A Pocket Guide to Adult HIV/AIDS Treatment provides treatment information in table format for easy reference in clinical settings: AIDSInfo: http://www.aidsinfo.nih.gov National HIV/AIDS Clinical Consultation Center Warmline: 1-800-933-3413 (toll free in the U.S.) Recommendations for HIV care and treatment are complex and change rapidly. In addition to the Pocket Guide and A Guide to Primary Care of People with HIV/AIDS , which the Pocket Guide supports, consult the following resources provided by the U.S. Department of Health and Human Services for frequently updated HIV treatment information: To order copies of the guide, contact: HRSA Information Center 1-888-275-ASK-HRSA (1-888-275-4772) toll free in the U.S. 2710 Prosperity Ave, Suite 200 Fairfax, VA 22031 The Pocket Guide can also be viewed or ordered on the HRSA HIV/AIDS Bureau website: http://www.hab.hrsa.gov U.S. Department of Health and Human Services ii Fe b r u a r y 2006 Ed i t i o n A Po c k e t G u ide t o Adu l t H I V/AIDS Tre a t me n t : Companion to A G u ide t o Pr i m a r y C a re o f Pe o p l e w i t h H I V/AIDS John G. Bartlett, MD Professor of Medicine Chief, Division of Infectious Diseases Director, AIDS Service The Johns Hopkins University School of Medicine Baltimore, Maryland A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Department of Health a nd Human Services Health Resources and Services Administration HIV/AIDS Bureau Parklawn Building, Room 7- 05 5600 Fishers Lane Rockville MD 20857 http://www.hab.hrsa.gov Publication d ate February, 2006 Acknowledgements Richard W. Dunning, MS, MHS, edited the August 2004 edition. Helen Schietinger, MA , ACRN, edited subsequent updates. Paul Pham, Pharm D, reviewed the manuscript. Cover artwork was created by Laura Spofford. Design and layout was done by Patrice Lincoln and Jim Concannon. U.S. Department of Health and Human Services iii Ta b l e o f C o n t e n t s References ............................................................................................................. v Important Information for Users of This Pocket Guide ................................... v i List of Abbreviations Used in This Pocket Guide ............................................ 1 Drug Information Drug Table 1. Antiretroviral Agent Characteristics ................................................... 2 Drug Table 2. Antiretroviral Agents, Class Adverse Reactions .................................. 8 Drug Table 3. Antiretroviral Agents, Adverse Reactions: ?Black Box? Warnings ...... 1 1 Drug Table 4. Combination Antiretroviral Therapy, Dose Adjustments .................. 1 2 Drug Table 5. Drug Interactions: Contraindicated Combinations ........................... 1 3 Drug Table 6. Drug Interactions: Nucleosides ........................................................ 1 4 Drug Table 7. Drug Interactions: Combinations with PIs or NNRTIs Requiring Dose Modi?cations ................................................................ 1 5 Antiretroviral Therap y Adult ART Table 1. When to Start Therapy ............................................................ 1 7 Adult ART Table 2. Suggested Minimum Target Trough Levels ............................... 1 7 Adult ART Table 3. Starting Regimens for Antiretroviral Na?ve Patients ................. 1 8 Adult ART Table 4. Advantages and Disadvantages of Antiretroviral Regimens ...... 1 9 Adult ART Table 5. Antiretroviral Regimens or Components That Are Not Generally Recommended ................................................. 2 0 Adult ART Table 6. Laboratory Monitoring ............................................................. 2 2 Adult ART Table 7. Resistance Mutations ............................................................... 2 3 Therapeutic Failure ............................................................................................... 2 5 Adult ART Table 8 . Methods to Achieve Readiness to Start HAART & Maintain Adherence ............................................................................... 2 7 Adult ART Table 9. National Cholesterol Education Program: Indications for Dietary or Drug Therapy for Hyperlipidemia .................................... 2 8 Adult ART Table 10. Drug Therapy for Hyperlipidemia ......................................... 2 9 A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Pregnancy and HI V Antiretroviral Therapy in Pregnancy ..................................................................... 30 Pregnancy Table 1. Preferred Antiretroviral Agents ............................................... 3 0 Pregnancy Table 2. Antiretroviral Agents: Pharmacokinetic and Toxicity Data ...... 3 1 Pregnancy Table 3. Antiretroviral Drugs for Delivery ............................................. 3 2 Pregnancy Table 4. Pregnancy Issues .................................................................... 3 3 Pregnancy Table 5. Clinical Scenarios and Management of Untreated Pregnant Patients Including C-Section ................................................... 3 3 Pregnancy Table 6. Clinical Scenarios and Management of Treated Pregnant Patients Including C-Section ................................................... 3 4 Pregnancy Table 7. Delivery Procedures and Therapy ........................................... 3 4 Prevention of HIV for Providers in Three Step s Step 1 : Screen Patients for Risk Behaviors ............................................................ 35 Step 2: Behavioral Interventions ........................................................................... 36 Step 3: Partner Counseling and Noti?cation .......................................................... 37 Opportunistic Infection s Adult OI Table 1. 2001 USPHS/IDSA Guidelines for Prevention of Opportunistic Infections ........................................................................ 3 8 Tuberculosis and HIV ............................................................................................ 4 2 Adult OI Table 2. Recommended Drug Regimens for Treatment of Latent TB in HIV Co-infected Adults ....................................................... 4 3 Adult OI Table 3. Monitoring of Patients on Latent TB Prophylaxis ........................ 4 4 Special Considerations for TB Treatment with HIV Co-infectio n ............................ 4 5 Adult OI Table 4. Treatment of Drug-Susceptible TB .............................................. 4 6 Adult OI Table 5. Doses of Antituberculosis Drugs ? First-line Drugs ..................... 4 7 Adult OI Table 6. Management of Opportunistic Infections .............................. 48 Occupational HI V Post e xposure Prophylaxis (PEP) Considerations in Occupational Exposure to HIV .................................................. 52 Occupational Postexposure Table 1. Exposure Contingencies ............................... 53 Occupational Postexposure Table 2. Indications for HIV PEP ................................ 5 4 Management of Health Care Workers (HCWs) With Potential HIV Exposure ......... 5 5 Occupational Postexposure Table 3. Recommended Regimens ............................. 5 7 Resources for Consultation ................................................................................... 5 7 U.S. Department of Health and Human Services v References: A Pocket Guide to Adult HIV/AIDS Treatment: ? The (DHHS) Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. (The Living Document: October, 6 2005). Available at http://www.aidsinfo.nih.gov/guidelines. ? 2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunode?ciency Virus. November 28, 2001. Available at http://www.aidsinfo.nih.gov. ? USPHS/IDSA. Treating Opportunistic Infections Among HIV-Infected Adults and Adolescents. MMWR Recommendations and Reports 53 (RR15):1-112, December 17, 2004. Available at http://www.aidsinfo. nih.gov. ? Public Health Service Task Force Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States. June 23, 2005. Available at http://www.aidsinfo.nih.gov. ? ATS/CDC Statement on Targeted Tuberculin Testing and Treatment of Latent Tuberculosis Infection. The MMWR Recommendations and Reports Vol. 49, No. RR-6, June 9, 2000. Available at http://www.cdc.gov/nchstp/tb. ? Incorporating HIV Prevention into the Medical Care of Persons Living with HIV: Recommendations of CDC, the Health Resources and Services Administration, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recommendations and Reports Vol. 52, No. RR-12, July 18, 2003. Available at http://www.aidsinfo.nih.gov. ? Integrating Nutrition Therapy into Medical Management of Human Immunode?ciency Virus. Clin Infect Dis 2003; 36; Suppl 2:S51-109. ? American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis, Am J Respir Crit Care Med 2003;167(4):603. Available at http://www.aidsinfo.nih.gov. ? Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and recommendations for Postexposure Prophylaxis. MMWR 2005;54:RR?9. Available at http:// www.aidsinfo.nih.gov. ? Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States: Recommendations from the U.S. Department of Health and Human Services. MMWR 2005;54:RR?2. Available at http://www.aidsinfo.nih.gov. A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Important Information for Users of This Pocket Guide This document is provided as an information resource for physicians and other health care professionals to guide them in the appropriate treatment of patients with HIV/AIDS. Recommendations for care and treatment change rapidly, and opinions can be controversial; therefore, physicians and other health care professionals are encouraged to consult other sources, especially manufacturers? package inserts, and con?rm the information contained in these tables. The individual physician or other health care professional should use his/her best medical judgment in determining appropriate patient care or treatment because no single reference or service can take the place of medical training, education, and experience. Although these tables have been carefully prepared and reviewed, the author makes no warranty as to the reliability, accuracy, timeliness, usefulness, or completeness of the information. The data presented herein are for informational purposes only. Determination of appropriate treatment is the responsibility of the treating physician. U.S. Department of Health and Human Services 1 Abbreviations Used in This Pocket Guide Drug Abbreviations ABC: abacavir ( Ziagen ) IVIG: intravenous immune globulin APV: amprenavir ( Agenerase ) LPV/r: lopinavir/ritonavir ( Kaletra ) ATV: atazanavir ( Reyataz ) NFV: nel?navir ( Viracept ) AZT: zidovudine ( Retrovir ) NNRTI: non-nucleoside reverse transcriptase inhibitor CBV: Combivir (AZT+3TC) NRTI: nucleoside reverse transcriptase inhibitor ddI: didanosine ( Videx ) NVP: nevirapine ( Viramune ) d4T: stavudine ( Zerit ) PI: protease inhibitor ddC: zalcitabine ( Hivid ) RBT: rifabutin ( Mycobutin ) DLV: delavirdine ( Rescriptor ) RTV: ritonavir ( Norvir ) EFV: efavirenz ( Sustiva ) r: ritonavir in dose <400 mg/day ENF: enfuvirtide ( Fuzeon , T-20 ) SQV: saquinavir ( Invirase, Fortovase ) FTC: emtricitabine ( Emtriva ) TPV: tipranavir ( Artivus ) FTV: Fortovase ( saquinavir , soft gel cap) 3TC: lamivudine ( Epivir ) FPV: fosamprenavir ( Lexiva ) T-20: enfuvirtide ( Fuzeon ) HU: hydroxyurea TDF: tenofovir ( Viread ) IDV: indinavir ( Crixivan ) TMP-SMX: trimethoprim sulfamethoxazole INH: isoniazid TZV: Trizivir (ABC+AZT+3TC) INV: Invirase ( saquinavir , hard gel cap) VZIG: varicella zoster immune globulin ZDV: zidovudine ( Retrovir ) Miscellaneous Abbreviations ART: antiretroviral therapy q: every EC: enteric coated qd: daily HAART: highly active antiretroviral therapy qid: four times per day IV: intravenous qm: monthly IM: intramuscular qod: every other day VL: viral load qw: every week bid: twice per day soln: solution biw: twice per week tid: three times per day CNS: central nervous system tiw: three times per week hs: bedtime (hour of sleep) TAMS: thymidine analogue assoc. mutations mo: month ULN: upper limit of normal po: by mouth A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Information Drug Table 1. Antiretroviral Agent Characteristics (Most common and/or important toxicities are in italics.) Drug Name Form Usual Adult Dose Food Effects Renal Failure Dosing Liver Failure Dosing Toxicity (main toxicity ? italics) CrCl 30-59 mL/min CrCl 10-29 mL/min CrCl < 10 or dialysis Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Abacavir (ABC, Ziagen ) 300 mg tab (see also: Trizivir); 20 mg/mL po soln 300 mg bid No effect Standard Usual Hypersensitivity : fever, rash, GI sx, dyspnea??? Combivir (CBV) AZT 300 mg + 3TC 150 mg (tab) 1 bid No effect Fixed formulation not recommended Usual AZT side effects? Didanosine ( Videx EC ; ddI)? 125, 200, 250, and 400 mg EC caps?? >60 kg <60 kg ? hr before or 2 hr after meal Separate dosing of ATV, TPV/r >60 kg 200 mg/d <60 kg 125 mg/d >60 kg 125 mg/d <60 kg 100 mg/d >60 kg 125 mg/d <60 kg 75 mg/d? Usual Pancreatitis, peripheral neuropathy, GI intolerance ? EC Caps 400 mg qd 250 mg qd with TDF 250 mg/d 200 mg/d Emtricitabine ( Emtriva , FTC) 200 mg cap 200 mg qd No effect 200 mg q72 h 200 mg q96 h Usual Minimal? HBV ?are ? Lamivudine ( Epivir ; 3TC) 150, 300 mg tab (see also: Combivir & Trizivir); 10 mg/mL po soln 150 mg bid or 300 mg qd No effect 150 mg x 1 then 100 mg/d 150 mg x 1 then 25-50 mg/kg/d Usual Minimal? HBV ?are ? U.S. Department of Health and Human Services 3 Epzicom 3TC 300 mg + ABC 600 mg 1 qd No effect Fixed formulation not recommended in renal failure Usual ABC hypersensitivity, HBV ?are ? Stavudine ( Zerit ; d4T) ? 15, 20, 30, 40 mg cap 1 mg/mL po soln Wt >60 kg: 40 mg bid Wt <60 kg: 30 mg bid No effect >60 kg 20 mg q 12 h <60 kg 15mg q 12 h >60 kg 20 mg q 24 h <60 kg 15 mg q 24 h >60 kg 20 mg q 24 h <60 kg 20 mg q 24 h? Usual Peripheral neuropathy, pancreatitis, lipoatrophy, ascending paresis (rare)? Tenofovir ( Viread , TDF) 300 mg tab (see also: Truvada) 300 mg qd Take with meal 300 mg q 48 hr 300 mg 2 days/wk 300 mg q 7 days? Usual Minimal. Renal toxicity (rare)? HBV ?are ? Trizivir (TZV) AZT 300 mg + 3TC 150 mg + ABC 300 mg (tab) 1 bid No effect Fixed formulation not recommended in renal failure Usual Hypersensitivity reaction (ABC), bone marrow suppression (AZT) , GI Intolerance (AZT)? HBV ?are ? Truvada TDF 300 mg + FTC 200 mg 1 qd No effect Fixed formulation not recommended in renal failure Usual Minimal. Renal toxicity, HBV ?are ? A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Table 1. Antiretroviral Agent Characteristics ? continued (Most common and/or important toxicities are in italics.) Drug Name Form Usual Adult Dose Food Effects Renal Failure Dosing Liver Failure Dosing Toxicity (main toxicity ? italics) CrCl 30-59 mL/min CrCl 10-29 mL/min CrCl < 10 or dialysis Zidovudine ( Retrovir , AZT) 100 cap, 300 mg tab (see also: Combivir & Trizivir) 10 mg/mL IV soln 10 mg/mL po soln 300 mg bid 200 mg bid No effect 300 mg bid 300 mg qd 100 mg tid Usual Peripheral neuropathy, stomatitis? Protease Inhibitors (PIs) Atazanavir ( Reyataz , AZT) 100, 150, and 200 mg capsules 400 mg qd; ATV 300 mg/RTV 100 mg qd. Boosting is often preferred and is required if ATV is combined with TDF or EFV Take with food Avoid concurrent buffered ddl, antacids Standard CPS* 7-9: 300 mg qd CPS* >9: Avoid Benign increase in indirect bilirubin, GI intolerance, transaminitis, prolongation of QTc (caution with conduction defects or drugs that do this) ?? Fosamprenavir ?? (FPV, Lexiva) 700 mg tabs 1400 mg bid or 700 mg/RTV 100 mg bid or 1400 mg/RTV 200 mg qd No effect Standard CPS* 5-8: 700 mg bid CPS* >9: Avoid Rash , GI intolerance , transaminitis, headache, hepatitis ?? U.S. Department of Health and Human Services 5 Indinavir (IDV, Crixivan ) 200, 333, 400 mg caps 800 mg q 8h; separate buffered ddI ? 1 hr IDV 400 mg/RTV 400 mg bid or # IDV 800 mg/RTV 100-200 mg bid # 1 hr before or 2 hr after meal unless with RTV Standard 600 mg q8h GI intolerance, nephrolithiasis , transaminitis, benign increase in indirect bilirubin ?? Lopinavir/ Ritonavir (LPV/r) ( Kaletra ) 200/50 mg tabs; LPV 80 mg + RTV 20 mg/mL po soln?? 400 mg LPV + 100 mg RTV (2 tabs) bid Soln: 5 mL bid No effect Standard ?? Transaminitis, GI intolerance (esp diarrhea), asthenia ?? Nel?navir (NFV, Viracept ) 250, 625 mg tabs 50 mg/g powder 1250 mg bid or 750 mg tid Take with high fat meal Standard ?? GI intolerance, diarrhea, transaminitis?? Ritonavir (RTV, Norvir ) 100 mg caps 600 mg/ 7.5 mL po soln 600 mg q12h #; separate ddI ? 2 h Food improves GI tolerance Standard ?? GI intolerance , paresthesia, transaminitis, taste perversion ?? Saquinavir ?? (SQV, Invirase) 200 mg caps 500 mg tabs SQV 1000 mg bid + RTV 100 bid ?? SQV 2000 mg qd + RTV 100 mg qd ?? Take within 2 hours of meal Standard ?? GI intolerance, transaminitis ?? Tipranavir (TPV, Apitivus) 250 mg caps 500 mg bid with RTV 200 mg bid Take TPV and RTV with food Standard CPS B or C: Avoid Hepatotoxicity ? monitor ALT, skin rash, GI intolerance, multiple drug interactions A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Table 1. Antiretroviral Agent Characteristics ? continued (Most common and/or important toxicities are in italics.) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Delavirdine (DLV, Rescriptor) 100, 200 mg tabs 400 mg tid No effect Standard ?? Rash Efavirenz ??? (EFV, Sustiva) 50, 100, 200 mg caps 600 mg tabs 600 mg hs Avoid high fat meal Standard ?? CNS x 2-3 wks, rash, hepatitis, false + cannibinoid test Nevirapine (NVP, Viramune) 200 mg tabs 50 mg/5 mL po susp 200 mg qd x14 days, then 200 mg bid No effect Standard Standard; give post dialysis Avoid Rash , hepatitis, hepatic necrosis esp women with CD4 >250 in ?rst 6 wks Fusion Inhibitors Enfuvirtide (ENF, Fuzeon, T-20) 90 mg single- use vials to be reconstituted with 1.1 mL H 2 0 90 mg (1 mL) SQ q12h into upper arm, anterior or abdomen (rotate sites) N/A Standard Usual Dose Site reactions U.S. Department of Health and Human Services 7 ? The combination of ddI & d4T ?should be used in pregnant women only when the potential bene?t clearly outweighs the potential risk.? Efavirenz should be avoided in ?rst trimester of pregnancy and used with caution in women with reproductive potential. Avoid APV liquid in pregnancy. ?? The following are no longer available: buffered ddI, lopinovir/r 133/33 mg cap, amprenavir, or Fortovase. ? Drug change or dose change could be considered on a case-by-case basis noting the risk of resistance with underdosing. ** Capsule is the preferred formulation due to high propylene glycol in the po solution; po soln contraindicated in pregnancy. ? Class adverse reaction: lactic acidosis with steatosis (see Drug Table 2). Most common with d4T, ddl, and AZT. # See Drug Table 4 for dosing recommendations when using dual PI, PI plus NRTI, or dual PI plus NNRTI. ? Give post dialysis * CPS=Child Pugh Score ?? Registry for hypersensitivity 1-800-270-0425 ?? More frequent monitoring required. Drug change or dose change could be considered on a case-by-case basis noting the risk of resistance with underdosing. ??? Efavirenz should be avoided in ?rst trimester of pregnancy and used with caution in women with reproductive potential. Avoid APV liquid in pregnancy. ?? Class adverse effects include lipodystrophy with hyperglycemia, fat redistribution, hyperlipidemia, and possible increased bleeding with hemophilia. ATV does not cause hyperlipidemia. All PIs may cause elevated transaminases (see Drug Table 2). ? 3TC, FTC, and TDF: Risk of ?are of chronic HBV if discontinued. A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Table 2. Antiretroviral Agents, Class Adverse Reactions Reaction Lactic acidosis Hepatotoxicity Hyper- glycemia Fat redistribution Hyper- lipidemia Rash De?nition Lactic acid >2 mmol/mL usually >5 mmol/mL Gr III = AST/ALT 5-10 X ULN GR IV = AST/ALT > 10 x ULN Fasting glucose >126 mg/dL Fat accumulation Lipoatrophy See Adult ART Table 5 DRESS* (NVP, ABC) SJS, TEN (NVP, EFV, DLV) ABC hypersensitivity Frequency 1.3% NRTI recipients with median onset at 4 mo NRTIs: d4T, ddI, AZT (lactic acidosis) PIs: (15-30%) NVP: 11% in ?rst 6 wks in women with baseline CD4 >250; possible hepatic necrosis and death NNRTI: (8-15%) 3-17% with PIs 4-50% ABC hypersensitivity: 5-8%, 90% in 1st 6 wks EFV, NVP: 8-16% most in 1st 6 wks Agents NRTIs: d4T+ddI>d4T> ddI>AZT; rare with 3TC, ABC, FTC or TDF NRTI: Lactic acidosis with steatosis NVP: Hepatic necrosis PIs, NNRTIs: transaminitis PIs Fat accumulation: PIs Lipoatrophy: NRTIs esp d4T Also occurs without antiretrovirals PI: esp RTV; not noted with ATV and reduced frequency with FPV NNRTI: NVP > EFV & DLV PIs: FPV, increased risk with sulfa allergy NRTI: ABC* U.S. Department of Health and Human Services 9 Risk Factors Prolonged use NRTI (esp d4T) Female, pregnancy, obesity, ribavirin, metformin HCV or HBV infection, ETOH, male sex NVP: baseline CD4 >250 in female, > 400 in male Pre-existing glucose intolerance No clear risks de?ned Risk for CVD: HBP, smoking, obesity, genes, prior MI/stroke, diabetes, age ABC: genetic predisposition NNRTI: 1st 12 wks Female Sx GI (abd pain, anorexia, nausea, vomiting), wasting, dyspnea, cardiac arrhythmias Most common: asymptomatic ALT/AST due to all PIs and NNRTIs NVP: may cause lethal hepatonecrosis Note: indirect bilirubin with IDV or ATV is clinically inconsequential but may cause jaundice Polyuria, polydipsia, polyphagia, weight loss Fat accumulation: abd (visceral), buffalo hump, breasts, lipomas Fat atrophy : face, extremities, buttocks Cardiovascular disease with stroke or MI/angina Triglycerides >2000 mg/dL - pancreatitis Common : MP rash Severe : Stevens-Johnson synd, TEN#, DRESS* NVP : hepatonecrosis with fever, rash, and/or GI sx 1st 16 wks ABC hypersensitivity: ? 2 systems involved 1st 6 wks Lab Lactate >2 mmol/mL; life-threatening if >10 mmol/mL LFTs; liver biopsy is usually not helpful. Fasting glucose >126 mg/dL Appearance is best ?lab test?, CT scan, MRI, waist and hip measurement, Bioelectric Impedence Analysis, DEXA, ultrasound triglycerides cholesterol, LDL cholesterol Eosinophilia : variable A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Table 2. ? continued Antiretroviral Agents, Class Adverse Reactions Reaction Lactic acidosis Hepatotoxicity Hyper- glycemia Fat redistribution Hyper- lipidemia Rash Treatment Lactate 2-5 mmol/mL + Sx -D/C NRTI if sx severe Lactate level is 5-10 mmol/mL: D/C NRTIs. Lactate >10 mmol/mL (medical emergency): D/C NRTIs + supportive care (ventilator, dialysis, IV HCO3) IV thiamine or ribo?avin (?) Post recovery: use low risk NRTIs (3TC, FTC, TDF) or avoid class Hypersensitivity reactions to ABC or NVP (fever, eosinophilia, rash, systemic response usually in ?rst 6-18 wks): D/C drug immediately and do not rechallenge Asymptomatic elevations of LFT (<10x ULN): repeat LFTs q 1-2 wks Symptomatic or elevations of LFT (>5?10x ULN) or hyperlactatemia or hypersensitivity (ABC or NVP): D/C ART or change regimen. Some ?treat through? asymptomatic ALT >10x ULN. ALT may return to baseline or persist; liver biopsy usually not helpful Use standard diabetes treatment with diet and exercise Preferred hypoglycemics are metformin or thiazolidinediones D/C PI only if uncontrolled hyperglycemia D/C d4T, ddI, AZT for fat atrophy Cosmetic surgery Exercise? Change PI to ATV or NNRTI Lipoatrophy : D/C d4T NECP guidelines (pg 29): ? General ? ? LDL cholesterol Statins ? Triglycerides ?brate Most rashes do not require drug discontinuation D/C drug if blisters, bullae, mucous membranes involved, fever, elevated ALT/AST Withdraw NNRTI if severe: mucous membrane involvement ( SJS ); blisters or bullae, epidermal necrosis ( TEN ), systemic reaction (fever, arthralgia, myalgias) Treatment: IV ?uids, antipyretics, pain management, care in burn unit. Role of steroids not clear. Do not rechallenge NVP and ABC: rash as component of DRESS* or ABC hypersensitivity or NVP hepatonecrosis reaction: D/C drug and supportive care Monitor During Therapy None LFTs at baseline and q 3-6 mo NVP : LFTs at wks 0,2,4,8,12,16 then q 3 mo Fasting glucose baseline, at 3-6 mo, then yearly Appearance Fasting lipid pro?le at baseline, at 3-6 mo post HAART initiation, then yearly. Appearance *DRESS: (Drug Rash, Eosinophilia, & Systemic Symptoms) Life threatening complication that is seen with NVP and ABC - usually in the ?rst 6 weeks of therapy ?Lifestyle changes: d/c smoking, diet, weight reduction, exercise, tx HBP and diabetes # TEN: Toxic epidermal necrolysis U.S. Department of Health and Human Services 11 Drug Table 3. Antiretroviral Agents, Adverse Reactions: ?Black Box? Warnings Agent Reaction Abacavir ? Fatal hypersensitivity reactions: do not restart ? Lactic acidosis and steatosis Amprenavir Oral soln contains large amounts of propylene glycol : avoid with renal failure, hepatic failure, pregnancy, & metronidazole Atazanavir None Delavirdine None Didanosine Fatal and nonfatal pancreatitis: do not restart Lactic acidosis with steatosis Fatal lactic acidosis when combined with stavudine in pregnancy Efavirenz None Emtricitabine Lactic acidosis with steatosis Enfuvirtide None Indinavir None Lamivudine Lactic acidosis with steatosis Patients with HBV infection should receive only dosage and formulations appropriate for treatment of HIV Lopinavir None Nel?navir None Nevirapine Hepatotoxicity including fulminant and cholestatic hepatitis & hepatic necrosis: monitor intensively in ?rst 18 wks of therapy Severe, life-threatening skin reaction including toxic epidermal necrolysis (TEN), Stevens- Johnsson syndrome, etc Do not restart if there is serious liver injury or serious drug reaction Ritonavir Potentially serious drug interactions with nonsedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot alkaloids Stavudine Lactic acidosis with steatosis Fatal and non-fatal pancreatitis Fatal lactic acidosis when combined with didanosine in pregnancy Tenofovir Lactic acidosis and steatosis; discontinuation in pts with HBV co-infection may cause exacerbation of acute HBV Tipranavir Hepatotoxicity including clinical hepatitis and hepatic decompensation Zalcitabine Severe peripheral neuropathy Pancreatitis (rare) Hepatic failure in patients with HBV infection (rare) Lactic acidosis and steatosis Zidovudine Hematologic toxicity : anemia & leucopenia Lactic acidosis and steatosis A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Table 4. Combination Antiretroviral Therapy, Dose Adjustments* RTV SQV NFV FPV LPV/r ATV NVP EFV IDV IDV 400+ RTV 400 bid or IDV/r 800/ 100-200 bid ND IDV 1200 + NFV 1250 bid IDV-SD APV-SD ND NR NVP-SD IDV 1000 q8h EFV-SD IDV- 1000 q8h or EFV SD/ IDV 800 bid/ RTV 200 bid RTV - SQV/r 1000/100 or 400/400 bid - FPV/r 1400/ 200 qd or 700/ 100 bid co-form- ulated ATV/r 300/100 qd NVP-SD RTV-SD EFV-SD RTV-SD SQV - - NFV- SD + SQV 1200 bid or SQV 800 tid ND SQV 1000 bid + LPV/r- SD SQV 1200 + ATV 400 qd NVP-SD + SQV/RTV 400/400 bid or 1000/100 bid EFV-SD + SQV/RTV 400/400 bid NFV - - - ND ND ND NVP-SD NFV-SD EFV-SD NFV-SD FPV - - - - NR ND ND EFV-SD FPV/r 1400/300 qd or 700/100 bid LPV - - - - - ND NVP-SD LPV/r 533/133 bid EFV-SD LPV/r 533/133 bid ATV - - - - - - ND EFV-SD + ATV/r 300/100 qd TPV ** * Doses are in mg; ND = Inadequate data; NR = Not recommended; SD = Standard dose; **TPV must be combined with RTV and should not be combined with any other PI U.S. Department of Health and Human Services 13 Drug Table 5. Drug Interactions: Contraindicated Combinations Class Contraindicated Agent ART Agents Alternatives Ca++ channel blocker Bepridil RTV, ATV, FPV, TPV - Antiarrythmics Flecainide, Propafenone RTV, LPV/r, TPV - Amiodarone, quinidine RTV, IDV, TPV Lipid lowering Simvastatin, Lovastatin All PIs, DLV Pravastatin or Fluvastatin, possibly Atorvastatin, Rosuvastatin Antimycobacterials Rifampin All PIs; all NNRTIs except EFV Use Rifabutin* Rifabutin DLV, SQV (unless used with RTV) - Rifapentine All PIs, NVP, DLV, EFV Rifampin or rifabutin Antihistamine Astemizole, Terfenadine All PIs, DLV, EFV Loratadine, Fexofenadine, Cetirizine, or Desloratidine Antineoplastics Irinoteacan ATV - GI Cisapride All PIs, DLV, EFV -H2 blockers, proton pump inhibitors DLV, ATV Neuroleptic Clozapine RTV -Pimozide All PIs - Psychotropic Midazolam? Triazolam All PIs, DLV, EFV Temazepam, Lorazepam Alprazolam DLV Ergot alkaloids Ergotamine All PIs, DLV, EFV Consider Sumatriptan Herbs St. John?s wort All PIs & EFV, DLV, NVP Alternative antidepressants Miscellaneous Fluticasone RTV and all RTV/PI combinations * See Drug Table 7, pg 14 for Rifabutin and antiretroviral dose adjustments ? Midazolam may be used with caution as a single dose given for a procedure A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Table 6. Drug Interactions: Nucleosides Drug AZT d4T ddI TDF Methadone AZT AUC 43%; no dose change; monitor for AZT toxicity d4T 27%; no dose change - No change in methadone or TDF levels ddI - Magni?es toxicity Use with caution - ddI 44% Pt >60 kg: 250 mg/d (ddI) Pt <60 kg: 200 mg/d (ddI) Ribavirin Inhibits AZT activation; avoid if possible No data Magni?es ddI toxicity; avoid No data ATV - - ddI EC: separate dosing due to food restrictions Avoid concomitant use unless ATV combined with RTV Cidofovir Ganciclovir Valgancyclovir Ganciclovir + AZT marrow toxicity Monitor CBC - - Combinations may decrease CrCl LPV/r No data No data No data TDF AUC 34% Standard doses and monitor for TDF toxicity TPV AZT AUC 31?42% Right dose? - TPV Cmin 44% with ddI EC Separate by 2 hrs U.S. Department of Health and Human Services 15 Drug Table 7. Drug Interactions: Combinations with PIs or NNRTIs Requiring Dose Modi?cations Class Agent ART Antifungal Ketoconazole IDV : IDV 600 mg tid RTV, LPV/r : Ketoconazole ? 200 mg/d, FPV ? 400 mg/d NVP : Not recommended Voriconazole Current use with RTV ( ? 400 mg/d) or EFV is contraindicated; no data for NNRTIs, NFV, ATV, TPV, FPV, LPV/r but bidirectional interaction anticipated; Monitor for toxicity; IDV is OK Itraconazole IDV and TPV: itraconazole dose ? 200 mg or monitor levels Oral contraceptives - Additional method of contraception recommended with: RTV, NFV, EFV, LPV/r, NVP, FPV. (IDV & ATV are OK) No data for SQV Anticonvulsants Phenobarbital, Phenytoin, Carbamazepine Avoid carbamazepine + IDV and phenytoin + LPV; all other combinations of NNRTIs or PIs & designated anticonvulsants should be given with caution and monitoring of anticonvulsant levels or consider valproic acid Methadone - NVP and EFV may decrease methadone substantially; monitor for withdrawal IDV has no interaction; other PIs may cause modest decrease in methadone levels and require monitoring for withdrawal Methadone decreases buffered ddI levels - consider ddI EC (no interaction). Antibiotics Clarithromycin RTV, LPV/r, TPV, DLV: Decrease clarithromycin dose in renal failure. EFV, ATV: Consider alternative (e.g. azithromycin) Erectile dysfunction Sildena?l PIs + DLV: ? 25 mg q48 h Vardena?l PIs + DLV: ? 2.5 mg/d Tadala?l PIs + DLV: ? 10 mg q72 h A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Drug Table 7. ? c o n t i n u e d Drug Interactions: Combinations with PIs or NNRTIs Requiring Dose Modi?cations Class Agent ART Anti- mycobacterials Rifabutin FPV 1400 mg bid + RBT 150 mg/d or 300 mg 3x/wk ATV 400 mg/d + RBT 150 mg qod or 150 mg 3x/wk EFV 600 mg/d + RBT 450-600 mg/d or 600 mg 3x/wk IDV 1000 mg q 8h + RBT 150 mg/d or 300 mg 3x/wk LPV/r 400/100 mg + RBT 150 mg qod or 3x/wk NFV 1000 mg tid + RBT 150 mg/d or 300 mg 3x/wk NVP standard + RBT standard RTV 600 mg bid + RBT 150 mg qod or 150mg 3x/wk RTV (maintain usual dose) + PI (standard dose) + RBT 150 mg qod or 3x/wk Rifampin All PIs & NNRTIs contraindicated except EFV using standard doses of rifampin; consider EFV daily dose of 800 mg qd Lipid Lowering Lovastatin, Simvastatin Avoid PIs and DLV; no data for EFV and NVP Atorvastatin Atorvastatin levels 480%?SQV/RTV, 70%?NFV, 9x?TPV, 150%?FPV, 590%?LPV/r; 43% EFV; No data?IDV, ATV, NVP Pravastatin Levels pravastatin 33%?LPV/r, 50% SQV/RTV; No data for other PIs or NNRTIs Miscellaneous Theophylline RTV : Monitor theophylline levels Warfarin RTV, DLV, EFV : Monitor INR closely if given with any PI or NNRTI Trazedone RTV : lowest dose + monitor CNS signs Desipramine RTV : Consider desipramine dose reduction Grapefruit juice IDV , SQV Ca channel blockers ATV, FPV, RTV: contraindicated Others: dose titration of Ca channel blockers + EKG monitoring Diltiazem All PIs: Reduce diltiazem dose 50% + monitor EKG ABC Antacids TPV ABC levels 35?45%; ABC dose? ATV and TPV levels ; give PI 2 hrs before or 1 hr after PPI ATV: Avoid PPI U.S. Department of Health and Human Services 17 A n t i re t r o v i r a l Th e r a py Adult ART Table 1. When to Start Therapy* Clinical Category CD4+ Count Viral Load Recommendation Symptomatic (AIDS or severe symptoms) Any value Any value Treat Asymptomatic, AIDS CD4+ < 200/mm 3 Any value Treat Asymptomatic CD4+ > 200/mm 3 but < 350/mm 3 Any value Offer treatment, but consider patient readiness, probability of adherence, potential side effects, and prognosis based on CD4 count, CD4 slope, and HIV viral load Asymptomatic CD4+ > 350/mm 3 > 100,000 c/mL Consider therapy or observe (Data inconclusive for either alternative) Asymptomatic CD4+ > 350/mm 3 < 100,000 c/mL Defer therapy and observe * There are special considerations for pregnant women; consult Pregnancy Tables 1-3 Adult ART Table 2. Suggested Minimum Target Trough Levels Drug Concentration APV 400 mg/mL IDV 100 mg/mL LPV 1000 mg/mL NFV 800 mg/mL RTV 2100 mg/mL SQV 100-250 mg/mL EFV 1000 mg/mL NVP 3400 mg/mL A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult ART Table 3. Starting Regimens for Antiretroviral Na?ve Patients NRTI-Based Regimens # of pills per day Preferred Regimens efavirenz + (lamivudine or emtricitabine) + (zidovudine or tenofovir DF) ? except for pregnant women or women with pregnancy potential 2?3 Alternative Regimens ? efavirenz + (lamivudine or emtricitabine) + (didanosine or stavudine or abacavir) - except for pregnant women or women with pregnancy potential 2?4 ? nevirapine + (lamivudine or emtracitabine) +(zidovudine or abacavir or tenofovir or stavudine* or didanosine) (Avoid in women with baseline CD4>250 and men with baseline CD4 > 400) 3?6 PI-Based Regimens # of pills per day Preferred Regimens lopinavir/ritonavir + (lamivudine or emtricitabine) + zidovudine 6?7 Alternative Regimens ? atazanavir + (lamivudine or emtricitabine) + (zidovudine or stavudine* or abacavir or didanosine) or (tenofovir + ritonavir) 3?6 ? fosamprenavir + (lamivudine or emtricitabine) + (zidovudine or stavudine* or abacavir or tenofovir or didanosine) 5?8 ? fosamprenavir/ritonavir + (lamivudine or emtricitabine) + (zidovudine or tenofovir or didanosine or stavudine* or abacavir) 5?8 ? indinavir + ritonavir? + (lamivudine or emtricitabine) + (zidovudine or tenofovir or didanosine or stavudine* or abacavir) 7?12 ? nel?navir + (lamivudine or emtricitabine) + (zidovudine or stavudine* or tenofovir or didanosine or abacavir) 5?8 ? saquinavir (Invirase) + ritonavir + (lamivudine or emtricitabine) + (zidovudine or stavudine* or tenofovir or didanosine or abacavir) 7-15 ? lopinavir/ritonavir + (lamivudine or emtricitabine) + (stavudine* or abacavir or tenofovir or didanosine) 5-7 Triple NRTI Regimen ? As Alternative to PI- or NNRTI-based regimens # of pills per day Alternative Regimens ? abacavir + lamivudine + zidovudine 2 * Stavudine is associated with higher rates of lipoatrophy and mitochondrial toxicity than other NRTIs ? Low-dose (100-400 mg) ritonavir U.S. Department of Health and Human Services 19 Adult ART Table 4. Advantages and Disadvantages of Antiretroviral Regimens Advantages Disadvantages NNRTIs Class? less lipodystrophy Save PI option Extensive experience Low genetic barrier to resistance Class resistance / Drug interactions High rate of rash reactions EFV Potent Low pill burden qd Once daily dosing CNS toxicity Teratogenic in ?rst trimester NVP Extensive experience in pregnancy No food effect ADR: hepatotoxicity + rash Contraindicated in women with baseline CD4 count >250 PI Class? extensive experience Save NNRTI option ADR? lipodystrophy Multiple drug interactions GI intolerance ATV Once daily dosing Low pill burden No hyperlipidemia ADR: Jaundice + PR interval prolongation Drug interaction with TDF and EFV LPV/r Potency Coformulated with RTV ADR: GI intoleranceReduced levels in pregnancy FPV/r Low pill burden No food effect Once daily dosing ADR: skin rash IDV/r No food requirement bid dosing with RTV boosting ADR: NephrolithisisRequirement for po ?uid NFV Substantial experience in pregnancy ADR: diarrhea High rate virologic failure Food requirement SQV/r Improved GI tolerance with Invirase ADR: GI intolerance NRTIs AZT/ 3TC/ ABC Coformulated No food effect Preserves PI and NNRTI options Higher rate of virologic failure if used alone ADR: ABC hypersensitivity NRTI pairs AZT/ 3TC* Extensive experience Coformulated No food effect ADR: GI intolerance + narrow suppression (AZT) HBV ?are when 3TC stopped d4T/ 3TC* No food effect Once daily ADR of d4T ** HBV ?are when 3TC stopped TDF/ 3TC* or FTC Well tolerated Once daily TDF + FTC coformulated HBV ?are when TDF, 3TC, or FTC stopped ddI/ 3TC* Once daily ADR: ddI** Food effect HBV ?are when 3TC stopped ABC/ 3TC* Once daily No food effect Coformulated ADR: ABC hypersensitivity HBV ?are when 3TC stopped * FTC is similar to 3TC; has longer intracellular half life and has less extensive experience ** ADRs- d4T lipoatrophy, lactic acidosis, peripheral neuropathy; ddI- peripheral neuropathy, pancreatitis and lactic acidosis A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult ART Table 5. Antiretroviral Regimens or Components That Are Not Generally Recommended Rationale Exception Antiretroviral Regimens Not Recommended Monotherapy ? Rapid development of resistance ? Inferior antiretroviral activity when compared to combination with three or more antiretrovirals Pregnant women with HIV-RNA <1,000 copies/mL using zidovudine monotherapy for prevention of perinatal HIV transmission Two-agent drug combinations ? Rapid development of resistance ? Inferior antiretroviral activity when compared to combination with three or more antiretrovirals For patients currently on this treatment, it may be reasonable to continue if virologic goals are achieved ABC + TDF + 3TC as a triple NRTI regimen High rate of virologic failure and resistance No exception TDF + ddI + 3TC High rate of virologic failure and resistance No exception TDF + ddI + NNRTI High rate of virologic failure Possible reduced CD4 response No exception Antiretroviral Components Not Recommended As Part of Antiretroviral Regimen Saquinavir hard gel capsule (Invirase) as single PI ? Poor oral bioavailability (4%) ? Inferior antiretroviral activity when compared to other protease inhibitors No exception d4T + ddI Reports of serious, even fatal, cases of lactic acidosis with hepatic steatosis When no other antiretroviral options are available and potential bene?ts outweigh the risks* ATV + IDV Potential for additive hyperbilirubinemia No exception FTC + 3TC No potential bene?t No exception Efavirenz in pregnancy Teratogenic in nonhuman primate When no other antiretroviral options are available and potential bene?ts outweigh the risks* U.S. Department of Health and Human Services 21 Adult ART Table 5. ? c o n t i n u e d Antiretroviral Regimens or Components That Are Not Generally Recommended Rationale Exception Antiretroviral Components Not Recommended As Part of Antiretroviral Regimen (continued) Amprenavir oral solution in: ? pregnant women ? children <4 yr old ? patients with renal or hepatic failure ? patients treated with metronidazole or disul?ram Oral liquid contains large amount of the excipient propylene glycol, which may be toxic in the patients at risk No exception d4T + ZDV Antagonistic No exception ddC + d4T or ddC + ddI Additive peripheral neuropathy No exception ATV + IDV Additive hyperbilirubinemia No exception FTC + 3TC Similar agents; no potential bene?t No exception Hydroxyurea ? Decreases CD4 count ? Augments d4T- and ddI-associated side effects, such as pancreatitis & peripheral neuropathy ? Inconsistent evidence of improved viral suppression ? Contraindicated in pregnancy (Pregnancy Category D) No exception Not Recommended As Part of Initial Antiretroviral Regimen DLV Modest antiretroviral effect * RTV as single PI GI intolerance * d4T + ddI Increased peripheral neuropathy, lactic acidosis, and pancreatitis * NFV + SQV High pill burden of 16-22 caps/day * TPV Tested and approved only for salvage * * Reasonable to use in unusual circumstances A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult ART Table 6. Laboratory Monitoring ? Baseline tests, CBC, chemistry pro?le including liver and renal function tests, PAP smear for female patients, Toxoplasma gondii IgG, VDRL (or RPR), anti-HCV, anti-HBc, and PPD (if no prior positive, see TB tables ) ? Con?rm HIV Ab+ if not documented ? Viral load at baseline (x2) and 2-8 wks after initiating therapy or new regimen, then every 3-4 months, clinical event, or signi?cant (3x or >0.5 log10 c/mL) change in VL ? CD4 count at baseline and then every 3-6 months ? Antiretroviral agent toxicity (see Drug Table 2, pg 8) ? Resistance tests Recommended - Virologic failure within 4 weeks of stopping ART - Suboptimal suppression - Acute HIV infection Consider - Chronic HIV infection, before therapy Not Usually Recommended - After discontinuation of drugs for more than 4 weeks - Viral load <1,000 c/mL U.S. Department of Health and Human Services 23 Adult ART Table 7. Resistance Mutations* Drug Major ? Minor ? Protease Inhibitors IDV 46 IL, 82 AFT, 84 V 10 IRV, 20 MR, 24 I, 32 I, 36 I, 54 V, 71 VI, 73 SA , 77 I, 90 M NFV 30 N, 90 M 10 FI, 36 I, 46 IL, 71 VL, 77 I, 82 AFTS, 84 V, 88 DS RTV 82 AFTS, 84 V 10 FIRV, 20 MR, 32 I, 33 F, 36 I, 46 IL, 50 V, 54 VL, 71 VT, 77 T, 90 M SQV 48 V, 90 M 10 IRV, 54 VL, 71 VT, 73 S, 77 I, 82 A , 84 V FPV 50 V, 84 V 10 FIRV, 32 I, 46 IL, 47 V, 54 LVM, 73 S, 82 AFST,90 M LPV/r 32 I, 47 VA , 82 AFTS 10 FIVR, 20 MR, 24 I, 31 I, 33 F, 46 IL, 50 V, 53 L, 54 VLAMTS, 63 P, 71 VT, 73 S, 90 M ATV 50 L, 84 V, 88 S 10 IFV, 16 E, 20 RMI, 24 I, 32 I, 33 IFV, 36 ILV, 46 I, 48 V, 54 LVMT, 60 E, 62 V, 71 VITL, 73 CSTA , 82 A , 90 M, 93 L TPV 33 I, 82 LT, 84 V 10 IV, 13 V, 20 MR, 35 G, 36 I, 43 T, 46 L, 47 V, 54 AMV, 58 E, 69 K, 74 P, 83 D, 90 M, 46 I, 54 V * Adapted from IAS -USA Topics HIV Med 2005; 13:125. See http://www.iasusa.org ? Major : usually develop ?rst; associated with decreased drug binding; Minor : also contribute to drug resistance; may affect drug binding in vitro less than primary mutations. Use of Major and Minor designations for NRTIs and NNRTIs has been suspended. A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult ART Table 7. ? c o n t i n u e d Resistance Mutations* Drug Codon Mutations Nucleosides and Nucleotides AZT 41 L, 44 D, 67 N, 70 R, 118 I, 210 W, 215 YF, 219 Q d4T 41 L, 44 D, 65 R, 67 N, 70 R, 118 I, 210 W, 215 YF, 219 QE 3TC 65 R, 184 VI FTC 65 R, 184 VI ddI 65 R, 74 V ABC 65 R, 74 V, 115 F, 184 V TDF 65 R Multinucleoside A- Q 151 M 62 V, 75 I, 77 L, 116 Y, 151 M Multinucleoside B 69 insertion 41 L, 67 N, 69 insert, 70 R, 210 W, 215 YF, 219 QE Multinucleoside TAMS 41 L, 67 N, 70 R, 210 W, 215 YF, 219 QE NNRTIs NVP 100 I, 103 N, 106 AM, 108 I, 181 CI, 188 CLH, 190 A DLV 103 N, 106 M, 181 C, 188 L, 236 L EFV 100 I, 103 N, 106 M, 108 I, 181 CI, 188 L, 190 SA , 225 H Multi-NNRTI resistance 103 N, 106 M, 188 L Multi-NNRTI resistance- accumulation 100 I, 106 A , 181 CI, 190 SA , 230 L * Adapted from IAS -USA Topics HIV Med 2005; 13:125. See http://www.iasusa.org U.S. Department of Health and Human Services 25 Therapeutic Failure De?nitions Virologic Failure: ? Failure to achieve VL <400 c/mL by 24 wks or <50 c/mL by 48 wks. Note: Most patients will have a decrease in VL of ? 1 log 10 c/mL at 1?4 weeks ? Viral suppression followed by repeated positive viral load Immunologic Failure: Failure to increase CD4 count 25-50 cells/mm 3 during ?rst year Note: Mean increase is about 150 cells/mm 3 in a year with HAART in treatment na?ve patients Clinical Failure: Occurrence or recurrence of HIV-related event ? 3 months after start of HAART Note: Must exclude immune reconstitution syndromes Management of Regimen Failure Assessment ? Adherence: Address cause and/or simplify regimen ? Tolerability - Change one drug within class - Change classes; e.g. PI-based HAART vs NNRTI-based HAART ? Pharmacokinetic Issues A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Therapeutic Failure ? c o n t i n u e d Virologic Failure De?nition: 1) HIV RNA > 400 c/mL (VL) after 24 weeks of treatment 2) VL > 50 c/mL after 48 weeks of treatment 3) Viral load detectable after achieving undetectable (viral rebound) VL indicating failure should be con?rmed; ?Blips? (isolated VL values of 50?1,000 c/mL) do not constitute failure if uncon?rmed Assessment: ? Review treatment history and prior resistance tests ? Access adherence, intolerance and pharmacokinetic issues (food/ fasting requirements, drug interactions, malabsorption) ? Distinguish between limited, intermediate, and extensive prior treatment and drug resistance ? The viral load that de?nes an indication for therapeutic intervention is in the range of 400?5000 c/mL; The threshold of 400 may result in multiple drug exposures and limited access to resistance tests (since a threshold of 1000 c/mL is often required to do the test); a delay to a threshold of 5000 c/mL risks accumulation of multiple resistance mutations including class resistance ? Perform resistance tests while the patient is receiving the failed regimen or within 4 weeks of stopping it ? Identify 2?3 active drugs for the next regimen; two active drugs are essential for viral supression ? If no resistance is demonstrated: consider continuation with emphasis on adherence, possibly with therapeutic drug monitoring ? With low level viremia (< 5000 c/mL) and limited drug exposure consider boosting a PI, or intensi?cation by adding a nucleoside or change therapy ? With intermediate or extensive prior drug exposure, consider an agent with a new mechanism of action (enfuvertide) usually combined with a PI including TPV or an experimental drug such as TMC 114 ? With extensive treatment failures, multiple resistance mutations and no available regimens likely to achieve virologic goals: the goal of therapy is to preserve immune function and avoid HIV-associated complications; HIV therapy should be continued U.S. Department of Health and Human Services 27 Adult ART Table 8. Methods to Achieve Readiness to Start HAART & Maintain Adherence Patient-related ? Negotiate a plan or regimen that the patient understands and to which she or he commits ? Take time needed, >2 visits, to ensure readiness before 1st prescription ? Recruit family, friends, peer and community support ? Use memory aids: timers, pagers, written schedule, pill boxes/ medication organizers ? Plan ahead: keep extra meds in key locations, obtain re?lls ? Use missed doses as opportunities to prevent future misses ? Active drug and alcohol use and mental illness predict poor adherence; race, sex, age, educational level, income, and past drug use do not Provider/Health Team-related ? Educate patient re: goals of therapy, pills, food effects, and side effects ? Assess adherence potential before HAART; monitor at each visit ? Ensure access at off-hours and weekends for answering questions or addressing problems ? Utilize full health care team; ensure med re?lls at pharmacy ? Consider impact of new diagnoses and events on adherence ? Provide training updates on adherence for all team members and utilize team to reinforce adherence ? Monitor adherence and intensify management in periods of low adherence ? Educate volunteers, patient-community representatives Regimen-related ? Avoid adverse drug interactions ? Simplify regimen re: dose frequency, pill burden, and food requirements ? Inform patient about side effects ? Anticipate and treat side effects A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult ART Table 9. National Cholesterol Education Program: Indications for Dietary or Drug Therapy for Hyperlipidemia Coronary Heart Disease Risk Status Goal Threshold for Diet Rx Threshold for Drug Rx No CHD & 0-1 Risks* LDL <160 mg/dL LDL ? 160 mg/dL LDL >190 mg/dL (LDL 160-190 Drug therapy optional) No CHD & ? 2 Risks* LDL <100 mg/dL LDL ? 130 mg/dL 10 Yr CHD Risk <10% ? LDL > 160 mg/dL 10 Yr CHD Risk 10- 20% ? LDL >130 mg/dL CHD or CHD equivalent: ? Clinical ASCVD ? ? Diabetes mellitus ? Multiple Risk Factors conferring 10 Yr risk of CHD of >20% ? LDL < 70 mg/dL LDL ? 100 mg/dL LDL >130 mg/dL (100-129 mg/dL: drug optional) Triglycerides are an independent consideration ? For patients with serum triglycerides >500 mg/dL the primary goal is reduction of triglycerides to prevent pancreatitis and reduce risk of CHD ? For patients with serum triglycerides 200 - 499 mg/dL reduction of non-HDL cholesterol becomes a secondary goal after reaching LDL goal Adapted from: JAMA 2001; 285:2486-2497; updated NCEP ? Circulation 2004; 110:227. Editors Note: This table is a basic condensation of complex guidelines. Readers are encouraged to consult and use the tools available on the NHLBI web site: http://www.nhlbi.nih.gov/ guidelines/cholesterol/ * CHD Risk Factors: Age (men >45 years; women >55 yrs or premature menopause without estrogen replacement); hypertension, current smoking, history of cardiovascular disease in ?rst degree relative (<55 years for male relative and <65 years for female relative), or serum HDL cholesterol <40 mg/dL. If high HDL (>60 mg/dL) subtract one risk factor. ? Atherosclerotic cardiovascular disease (ASCVD) includes peripheral artery disease, symptomatic carotid artery disease, and abdominal aortic aneurysm. ? Calculation of 10 year risk of CHD requires tables which may be found in the JAMA 2001;285:2486 or the NHLBI website: http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm U.S. Department of Health and Human Services 29 Adult ART Table 10. Drug Therapy for Hyperlipidemia (Recommendations of the ACTG [Dube MP et al, CID 2000; 31:1216]) Lipid Problem Preferred Alternative Comment Isolated high LDL Statin* Fibrate? Start low doses and titrate up; with PIs watch for myopathy High cholesterol and triglycerides Statin* or ?brate? Start one and add other Combination may increase risk of myopathy Isolated high triglycerides Fibrate? Statin* Combination may increase risk of myopathy NOTE: Optimal management of hyperlipidemia should begin with speci?c risk factor reduction interventions such as: low-fat diet; regular exercise; moderation of alcohol intake; smoking cessation, blood pressure control, and diabetes control (where applicable). The likelihood of success with drug therapy for hyperlipidemia is substantially reduced in the absence of such interventions. * Statin: Pravastatin 20 mg/day (max. 40 mg/day), ?uvastatin 20-40 mg/day, or atorvastatin 10 mg/day. Use particular caution when giving LPV/r or NFV with Atorvastatin; also see Table 5. Drug Interactions: Contraindicated Combinations . ? Fibrate: Gem?brozil 600 mg bid ? 30 minutes before meal or Feno?brate tablets (e.g. Tricor) 160 mg qd Micronized feno?brate (capsules) 67mg qd to start, max. dose 201 mg qd A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Pre g n a n c y a n d H I V Antiretroviral Therapy in Pregnancy Continually updated recommendations: US Department of Health and Human Services. Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the U.S. November 17, 2005. Available at: http://aidsinfo.nih.gov. Recommendation for antiretroviral drugs in pregnancy: All pregnant women with HIV infection should be treated. Goal of therapy: VL < 1000 c/mL Regimen: See Pregnancy Table 1 Pregnancy Table 1. Preferred Antiretroviral Agents NRTI Class ? Preferred: AZT/3TC ? Alternates: ddI, FTC, d4T, ABC ? Insuf?cient data: TDF ? Not recommended: ddC NNRTI Class ? Preferred: NVP (if baseline CD4 is < 250/mm 3 ) ? Not recommended: EFV and DLV PI Class ? Recommended: NFV (1250 mg bid), SQV/r (1000/100 mg bid) ? Alternatives: IDV, LPV/r, RTV ? Insuf?cient data: APV, FPV, ATV, TPV Entry Inhibitor Class ? Insuf?cient data: ENF U.S. Department of Health and Human Services 31 Pregnancy Table 2. Antiretroviral Agents: Pharmacokinetic and Toxicity Data* Agent FDA cat.** Experience in Pregnancy Nucleoside/nucleotide reverse transcriptase inhibitors ABC C No studies; concern for hypersensitivity ddI B Well tolerated; usual pharmacokinetics; concern for lactic acidosis; avoid ddI + d4T FTC B No studies 3TC C Well tolerated; usual pharmacokinetics d4T C Well tolerated; usual pharmacokinetics; concern for lactic acidosis; avoid ddI + d4T TDF B No studies; animal studies show bone abnormalties ddC C No studies; teratogenic in animals ZDV C Well tolerated; preferred agent Non-nucleoside reverse transcriptase inhibitor DLV C No studies EFV D Teratogenic; 4/142 birth defects; avoid in 1st trimester NFV C Well tolerated; contraindicated as initial Rx with CD4 > 250; single dose with labor causes high rates of resistance Protease inhibitors APV C No studies; oral solution is contraindicated ATV B No studies; theoretical concern for elevated indirect bilirubin FPV C No studies IDV C Low levels and theoretical concern for elevated indirect bilirubin LPV/r C No studies NFV B Well tolerated; extensive experience; use 1250 mg bid RTV B No studies SQV B Levels are low: use SQV: RTV 800/100 mg bid or 1000/100 mg bid TPV C No studies * June 23, 2005 ** Pregnancy categories: A=Controlled studies show no risk B=No evidence of risk in humans C=Risk cannot be excluded D=Positive evidence of risk A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Pregnancy Table 3. Antiretroviral Drugs for Delivery A. ACTG 076 Protocol (Should be used as part of ART regimen in all pregnant women, if possible) Antepartum: AZT 300 bid or 200 tid po, wk 14 until delivery Intrapartum: AZT IV 2 mg/kg over ?rst hr then 1 mg/kg/hr until delivery Postpartum: (Infant): AZT syrup 2 mg/kg po q 6h (or 1.5 mg/kg q 6h IV) x 6 wks B. Regimen for 2nd & 3rd Trimesters Standard ART, but: ? Include AZT * according to 076 protocol ? Treat based upon maternal clinical/immunologic status but avoid: EFV, HU, AZT & d4T, d4T & ddI, APV solution ? Previously untreated pregnant women with VL <1000 c/mL and CD4 >350 cells/mm 3 may be treated with AZT monotherapy, AZT + 3TC, or HAART C. Choices for Untreated Women Presenting In Labor and Their Infants NVP: 200 mg po onset labor; Infant: single 2 mg/kg po at 48-72 hrs AZT: 600 mg po onset labor and 300 mg po q3h until delivery PLUS 3TC 150 mg po onset labor and 150 mg po q12h until delivery; Infant: AZT 4mg/kg po q12h PLUS 3TC 2mg/kg po q12h for 7 days AZT: 2mg/kg IV bolus then 1mg/kg/hr IV infusion until delivery; Infant: AZT 2mg/kg po q6h for 6 wk (ACTG 076 Protocol) NVP + AZT: NVP:200 mg po onset labor PLUS AZT 2mg/kg IV bolus then 1 mg/kg/hr IV infusion until delivery; Infant: NVP single 2 mg/kg po at 48-72 hrs PLUS AZT 2mg/kg po q6h for 6 wk * Unless unacceptable side effects or toxicity or requires d4T-containing regimen ** AZT & d4T: pharmacologic antagonism; do not use together. APV oral solution (only) is contraindicated in pregnancy because it contains large quantities of propylene glycol, which cannot be metabolized in pregnancy. d4T & ddI: concerns about lactic acidosis; use only when other NRTIs have failed or caused unacceptable side effects/toxicity ( New Engl J Med 1999; 340:1723). EFV, HU: concerns about teratogenicity or birth defects; EFV: avoid in pregnancy. Drug Information A listing of antiretroviral drugs with information pertinent to their use in pregnancy may be found in Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States , Table 3. U.S. Department of Health and Human Services 33 Pregnancy Table 4. Pregnancy Issues Adverse Drug Reactions (ADR) Generally, pregnant women are at the same risk of ADRs as non-pregnant individuals, but some ADRs may be more common because of pregnancy-related physiologic changes: anemia (iron & folate de?ciency), nausea & vomiting (esp in 1st trimester), amniotransferase elevation. PIs may exacerbate pregnancy-related risk of hyperglycemia and NRTIs (especially d4T/ddI) increase risk of lactic acidosis. Risk for Perinatal HIV Transmission Viral load in plasma & genital tract (most signi?cant), primary infection or late stage HIV, low CD4 count, STDs/other co-infections, pre-term delivery, increasing duration of membrane rupture, placental disruption, invasive fetal monitoring or assessment, vaginal delivery, and lack of AZT prophylaxis. Post-Partum Risk Breast feeding: not recommended in U.S. Pregnancy Table 5. Clinical Scenarios and Management of Untreated Pregnant Patients Including C - Section Scenario 1: No prior ART ? Standard lab and clinical care ? HAART for VL > 1000 c/mL ? Include the 3?part 076 protocol (see Pregnancy Table 3A) ? Consider delay initial therapy until after 1st trimester Scenario 2: Currently receiving ART ? Continue therapy, but include AZT according to 076 protocol (see Pregnancy Table 3A) ? Option to stop in 1st trimester Scenario 3: Woman in labor no prior therapy?options are: ? Intrapartum AZT and 6?week course for neonate ? AZT/3TC during labor and 3 weeks for neonate ? Single dose NVP intrapartum and single dose for infant ? Two?dose NVP and intrapartum AZT and 6 weeks AZT for newborn Scenario 4: Woman has delivered ? Discuss HIV detection and implications ? Offer AZT to infant ? The mother should be evaluated for HIV management A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Pregnancy Table 6. Clinical Scenarios and Management of Treated Pregnant Patients Including C - Section Time of Presentation Recommended Management Early In Pregnancy (<36 Weeks) ? Continue ART with standard monitoring, but: o May consider discontinuation during 1st trimester: all drugs should be stopped and restarted simultaneously to reduce risk of resistance o Include AZT if tolerated; see cautions for antiretrovirals, Pregnancy Table 3 footnotes Late In Pregnancy ( ? 36 Weeks) ? Continue antiretroviral therapy including AZT without interruption during labor and delivery ? VL >1,000 copies/mL: Counsel that C -section is likely to reduce the risk of transmission to infant, but counsel about risks and bene?ts of all choices C -Section Planned But Presents in Labor or With Ruptured Membranes ? Initiate ACTG 076 Protocol, Intrapartum in Pregnancy Table 3A ? Rapid progression of labor: vaginal delivery ? If long labor anticipated: consider C -section after loading dose of AZT or give pitocin to expedite delivery Pregnancy Table 7. Delivery Procedures and Therapy Procedure Therapy Cesarean Section ? Schedule for 38 wk ? If on ART, IV AZT starting 3 hrs before C -section and continue all other antiretroviral drugs with the exception of d4T ? Infant: Use ACTG 076 Protocol, Postpartum (infant) In Pregnancy Table 3A Vaginal Delivery ? If on ART give IV AZT with initiation of labor and continue all other antiretroviral drugs with the exception of d4T ? Avoid rupture of membranes, fetal scalp electrodes, forceps delivery, and vacuum extractor ? Infant: If TREATED mother, use ACTG 076 Protocol, Postpartum (infant) in Pregnancy Table 3A If UNTREATED mother, use treatment from Pregnancy Table 3C which matches maternal regimen Antiretroviral Pregnancy Registry: www.APRegistry.com 1011 Ashes Dr, Wilmington NC 28405 Telephone: 800-258-4263 Fax: 800-800-1052 U.S. Department of Health and Human Services 35 Pre v e n t i o n o f H I V f o r Pr o v i de rs i n Th re e St e p s Step 1: Screen Patients for Risk Behaviors ? Behaviors and clinical factors associated with HIV, other STDs, and IV drug use (every visit) ? STD symptoms: most are asymptomatic (every visit) ? Pregnancy ? Screening tests Patients Test Routine ? All patients ? Syphilis serology: RPR or VDRL* ? All women ? Trichomonas wet mount or culture ? All women ? 25 years and sexually active ? Cervical specimen for C. trachomatis Consider ? All men and women not included above ? Screening for GC and C. trachomatis by urethral (men) or cervical (women) specimen or ?rst catch urine for NAAT* ? Anal receptive sex ? Anal swab for GC culture and, if available, for C. trachomatis ? Oral receptive sex ? Pharyngeal culture for GC ? Possible pregnancy ? Pregnancy test * Repeat RPR or VDRL annually. Consider repeating screening tests for N. gonorrhea and C. trachomatis annually or more frequently if sexually active, if screening previous test positive, or other high risk A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Step 2: Behavioral Interventions ? Prevention messages should be provided with each visit ? Communicate factors that in?uence transmission and risk reduction; i.e. abstinence, sex with condoms, sex exclusively with HIV-infected person(s). If sex with persons with unknown or negative serologic status, stress proper condom use. ? IDU Stop using drugs Enter substance abuse treatment If patient continues to use drugs: - Never reuse or share needles, water, or drug preparation equipment - Use only syringes from reliable sources (pharmacies) - Use new syringe; if not possible-boil or disinfect with bleach (http://www.cdcnpin.org) - Use sterile water to prepare drugs; otherwise use tap water - Use new or disinfected cooker and new cotton - Clean injection site with new alcohol swab - Safely dispose of needle ? Per act relative risks of HIV transmission - Condom vs no condom: 1:20 - Compared to insertive vaginal sex: receptive vaginal sex 2:1, receptive anal sex 10:1, insertive fellatio 1:10, insertive anal sex 1.3:1, receptive fellatio 1:5 (STD 2002;29:38) Note: Risks for condom use and acts are multiplicative; e.g, for the ratio for anal sex without a condom vs vaginal insertive sex with a condom is 100:1 ? Viral load: each log 10 reduction in viral load reduces probability of transmission 2.5 fold. ? Non-occupational postexposure prophylaxis: not endorsed by CDC due to ?uncertain effectiveness.? ? HAART recipients: decreases in VL probably reduces but risk transgression in behavior eliminates this bene?t; with structured treatment interruption, warn patient that viral load increases as does risk of transmission U.S. Department of Health and Human Services 37 Step 3: Partner Counseling and Noti?cation ? Laws: Follow local and state laws for reporting sex and needlesharing partners ? Initial Visit: Ask if all sex and needlesharing partners have been noti?ed ? Follow-ups: Ask about new sex or needlesharing partners who have not been noti?ed ? Referrals: All contacts should be referred to the Health Department; arrange for noti?cation and testing without identifying source; patients who elect not to notify partners should be referred to the Health Department to conduct these activities A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Opportunistic Infections Adult OI Table 1. 2001 USPHS/IDSA Guidelines for Prevention of Opportunistic Infections Pathogen Episode Indication* First Choice Alternatives Comment Strongly Recommended P. carinii 1 0 & 2 0 Primary CD4 < 200 or CD4 % <14, thrush, hx AIDS de?ning illness or FUO Secondary Hx PCP unless immune reconstitution: see comment TMP-SMX 1 DS/d ? or TMP-SMX 1 SS/d ? Dapsone 100 mg/d or Dapsone 50 mg/d + pyrimethamine 50 mg/wk + leucovorin 25 mg/wk or Dapsone 200 mg + pyrimethamine 75 mg + leukovorin 25 mg/wk or Aerosol pentamidine 300 mg/mo or Atovaquone 1500 mg/d or TMP-SMX 1 DS? 3x /wk Immune reconstitution recommendations: Discontinue primary & secondary prophylaxis if CD4 >200 cells/mm 3 for ? 3 mos Restart Prophylaxis: Restart prophylaxis if CD4 decreases to <200 cells/mm 3 Tuberculosis See Adult OI Tables 2 and 3 U.S. Department of Health and Human Services 39 Toxoplasmosis 1 0 + anti-Toxoplasma lgG and CD4 <100 cells/mm 3 TMP- SMX 1 DS ? qd TMP- SMX 1 SS? qd or Dapsone 50 mg/d + pyrimethamine 50 mg/wk + Leucovorin 25 mg/wk or Dapsone 200 mg/wk + pyrimethamine 75 mg/wk + Leucovorin 25 mg/wk or Atovaquone 1500 mg/d ? pyrimethamine 25 mg/d + Leucovorin 10 mg/d Immune reconstitution recommendations: Discontinue if CD4 >200 cells/mm 3 for ? 3 mos Restart Prophylaxis: CD4 falls to <100-200 cells/mm 3 2 0 Toxo tx unless immune reconstitution: see comment Sulfadiazine 500-1000 mg qid + Pyrimethamine 25-50 mg/d + Leucovorin 10-25 mg/d Clindamycin 300-450 mg q 6-8 hr + Pyrimethamine 25-50 mg/d+ Leucovorin 10-25 mg/d or Atovaquone 750 mg q 6-12 hr + Pyrimethamine 25 mg/d + Leucovorin 10 mg/d Immune reconstitution recommendations: Discontinue if HAART 6-12 mos, CD4 >200 cells/mm 3 , and asymptomatic Restart Prophylaxis: CD4 falls to <200 cells/mm 3 Mycobacterium avium complex 1 0 CD4 <50 cells/mm 3 Azithromycin 1200 mg/wk Clarithromycin 500mg bid Rifabutin?300 mg/d or Azithromycin 1200 mg / wk + Rifabutin? 300 mg/d Immune reconstitution recommendations: Discontinue if CD4 >100 cells/mm 3 for ? 3 mo 2 0 Hx MAC disease Clarithromycin 500 mg bid + Ethambutol 15 mg/kg/d ? Rifabutin? ? 300 mg/d Azithromycin 500 mg/d + Ethambutol 15 mg/kg/d ? Rifabutin? 300 mg/d Immune reconstitution recommendations: Discontinue if CD4 >100 cells/ mm 3 x >6 mo and Rx 12 mo and asymptomatic A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult OI Table 1. ? continued 2001 USPHS/IDSA Guidelines for Prevention of Opportunistic Infections Pathogen Episode Indication* First Choice Alternatives Comment Varicella 1 0 Chickenpox /shingles exposure + susceptible (no history of disease and varicella seronegative) VZIG 5 vials (6.25 mL) IM <96 h post exposure Acyclovir has been removed from OI prophylaxis guidelines due to lack of documented ef?cacy Cryptococcosis 2 0 Hx Cryptococcal meningitis Fluconazole 200 mg po qd Amphotericin B 0.6-1.0 mg/kg iv qw-tiw or itraconazole 200 mg capsule po qd Immune reconstitution recommendations: Discontinue if CD4 >100 X 6 mo and completed initial Rx and asymptomatic Cytomegalovirus 2 0 Prior end-organ disease Extra ocular: ganciclovir 5 mg/kg/day IV 5-7 days/wk, valganciclovir 900 mg/d, or foscarnet 90mg/kg IV qd or cidofovir 5 mg/kg q 2 weeks For retinitis: ganciclovir sustained release implant q 6-9 months plus valganciclovir 900mg/d or ganciclovir or foscarnet (above doses) Cidofovir 5 mg/kg IV qow with probenecid 2 grams po 3 hours before the dose followed by 1 gram po 2 hours after the dose, and 1 gram po 8 hours after the dose (total of 4 grams) or Fomivirsen 1 vial (330?g) injected into the vitreous, then repeated every 2-4 wks ? or Valganciclovir 900 mg po qd Immune reconstitution recommendations: Discontinue if CD4 >100-150 X 6 mo + no active disease + negative ophthal exam U.S. Department of Health and Human Services 41 Generally Recommended S. pneumoniae 1 0 All Patients with CD4 > 200 Pneumovax None Immune reconstitution: Consider reimmunization if CD4 increases to >200 and initial immunization was given when CD4 <200 Hepatitis B 1 0 Susceptible- (anti-HBc negative) HBV vaccine series None In?uenza 1 0 All patients In?uenza vaccine Rimantidine 100 mg bid Amantadine 100 mg bid Oseltamivir 75 mg qd Hepatitis A 1 0 Susceptible- (anti- HAV neg) and anti- HCV positive Hepatitis A vaccine series None * Indication is separately de?ned for: 1 0 = Primary: No prior infection with this pathogen 2 0 = Secondary: Prior infection with this pathogen ? SS= Single strength tablet, DS=double strength tablet ? Dose adjusted for concurrent PI/NNRTI ? Rifabutin reduces levels of clarithromycin by 50% (consider azithromycin if RBT is used) ? Added Rx needed to protect the contralateral eye and other organ systems A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Tuberculosis and HIV Latent TB and HIV Co -infection Candidates For Testing ? All HIV-infected patients without prior positive PPD test upon entry into HIV care ? Repeat testing annually for HIV-infected patients at risk of acquiring TB who have no prior positive tests ? All HIV-infected patients with prior negative skin test who are discovered to be contacts of pulmonary cases Indications For Treatment of Latent Tuberculosis Infection (MMWR 2000;49 RR-6) ? Positive PPD ( ? 5 mm induration) plus no prior completed prophylaxis or treatment for TB disease ? Recent contact with TB case (Recent contacts who are initially TST negative should have TST repeated 12 weeks after last exposure to TB case; those placed on prophylaxis should be discontinued if PPD negative at 12 weeks) ? History of inadequately treated TB that healed Patients meeting skin test positivity criteria should be evaluated to rule out active TB disease before initiating treatment U.S. Department of Health and Human Services 43 Adult OI Table 2. Recommended Drug Regimens for Treatment of Latent TB in HIV Co-infected Adults Regimen Adult Dosage (max) Criteria for Completion Comments Preferred Regimens All patients INH daily for 9 mos 300 mg qd + pyridoxine 50 mg qd 270 doses within 9 mos (up to 12 mos with interruptions) INH may be administered concurrently with NRTIs, PIs, or NNRTIs; contact with provider monthly INH twice-weekly for 9 mos 900 mg + pyridoxine 100 mg 2x/wk 76 doses within 9 mos (up to 12 mos with interruptions) Acceptable alternative for HIV-infected adults; DOT must be used with twice weekly dosing Alternative Regimen Contacts of isoniazid-resistant, rifampin-susceptible TB RIF daily for 4 mos? RIF 10 mg/kg (600 mg) RBT is alternative if patient is receiving HAART* 120 doses within 6 mos 8 week regimen: PZA + RIF No longer recommended due to excessive hepatotoxicity including 7 deaths (not in persons known to have HIV co-infection) MMWR 2003;52:735 Abbreviations: INH = isoniazid, RIF = rifampin, RBT= rifabutin, PZA = pyrazinamide, DOT = directly observed therapy * See Drug Table 7 for RBT & PI/NNRTI dose adjustments ? May not be used with patients taking PI/NNRTI with the exception of RTV/SQV, RTV, or EFV A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult OI Table 3. Monitoring of Patients on Latent TB Prophylaxis Latent TB Regimen Monitoring All patients ? Initial clinical evaluation ? Educate patients about side effects associated with LTBI treatment ? Advise to stop treatment and promptly seek medical evaluation if these occur INH ? Contact with patient monthly; LFTs at baseline and 3 mo* and with hepatitis sx ? Include careful questioning about side effects and a brief physical examination checking for evidence of hepatitis or other side effects Rifampin or rifabutin + PZA ? Clinic visits at 2,4,6, & 8 wks; CBC & LFTs at baseline, 2,4, & 6 wks or with symptoms? ? Include careful questioning about side effects and a brief physical examination checking for evidence of hepatitis or other side effects * INH: D/C if ALT 5X ULN or symptoms plus ALT ? 3X ULN ? Rifampin/rifabutin + PZA: D/C if ALT ? 5X ULN or if symptoms plus any abnormal LFTs U.S. Department of Health and Human Services 45 Special Considerations for TB Treatment with HIV Co-infection Treatment of Tuberculosis Disease American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis Am J Respir Crit Care Med 2003;167(4):603 Special Treatment Notes PREGNANCY: INH regimens preferred for pregnant women. Some experts would use RIF plus PZA as alternate regimen in HlV-infected pregnant women. PZA should be avoided during ?rst trimester. MDR-TB Exposure Expert consultation is recommended for persons who are likely to be infected with INH and RIF (multidrug) resistant-TB and at high risk of reactivation. ART/TB Treatment Interactions * Rifabutin should not be used with hard-gel saquinavir (as sole PI) or delavirdine. Rifampin/Rifabutin See Drug Table 7 Identical for General Population Except: ? CD4 <100/mm 3 : Continuation phase should be daily or 3x/week; once weekly rifapentine regimen should not be used ? Positive cultures at 2 months: ?Strongly consider ? 7 month continuation phase (total 9 mo) ? In absence of prior HIV therapy and CD4 < 350/mm 3 : delay antiretroviral drugs for 4-8 weeks ? RIF may be used with 2 NRTIs + EFV, RTV + SQV (Invirase or Fortovase) or AZT/3TC/ABC ? Rifabutin combined with other PIs and NNRTI requires dose adjustment of both; See: www.cdc.gov/nchstp/tb/ or www.medscape.com/updates/quickguid e ? When starting NNRTI or PI in patient receiving RIF, substitute rifabutin 2 weeks prior to NNRTI or PI to give a 2 week washout period for RIF ? Paradoxical reaction: Frequency is 7-36%; clinical features: high fever, increased adenopathy, CNS lesions, pulmonary in?ltrates and pleural effusions; treatment: symptomatic; if severe give prednisone 1 mg/kg and reduce dose at 1-2 weeks A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult OI Table 4. Treatment of Drug- Susceptible TB Drugs Phase 1 (8 weeks) Phase 2*: regimen, doses, minimal duration INH RIF PZA EMB 8 weeks ? 7 d/wk for 8 wks (56 doses) or ? 5 d/wk for 8 wks (40 doses) ? INH/RIF 7 d/wk for 18 weeks (126 doses) or ? INH/RIF 5 d/wk for 18 weeks (90 doses) or ? INH/RIF 2x/wk for 18 weeks ( 36 doses) INH RIF PZA EMB 2 wk/6 week 7 d/wk, for 2 wks (14 doses), then 2x/week for 6 wks (12 doses) INH/RIF 2x/wk for 18 weeks (36 doses) INH RIF PZA EMB 8 weeks 3 x/week for 8 weeks (24 doses) INH/RIF 3x/week for 18 weeks (54 doses) INH RIF EMB 8 weeks ? 7 d/week for 8 wks (56 doses) ? 5 d/week for 8 wks (40 doses) ? INH/RIF 7 d/week for 31 weeks (217 doses) or ? INH/RIF 5 d/wk for 31 weeks (155 doses) or ? INH/RIF 2x/wk for 31 weeks (62 doses) INH = isoniazide, RIF = rifampin, RPT = rifapentine, PZA = pyrazinamide, EMB = ethambutol * Patients with cavitation at baseline and positive cultures at 2 months should receive 31 week continuation phase for total of 9 months U.S. Department of Health and Human Services 47 Adult OI Table 5. Doses of Antituberculosis Drugs ? First-line Drugs Drug Daily l/wk 2x/wk 3x/wk INH 5 mg/kg (300)* 15 mg/kg (900) 15 mg/kg (900) 15 mg/kg (900) RIF 10 mg/kg (600) - 10 mg/kg (600) 10 mg/kg (600) RPT - - 10 mg/kg (600) - PZA (wt) 40-55 kg 56-75 kg 76-90 kg 1 gm 1.5 gm 2.0 gm - - - 2.0 gm 3.0 gm 4.0 gm 1.5 gm 2.5 gm 3.0 gm EMB (wt) 40-55 kg 56-75 kg 76-90 kg 800 mg 1200 mg 1600 mg - - - 2000 mg 2800 mg 4000 mg 1200 mg 2000 mg 2400 mg *Dose in mg/kg and (usual dose in mg) A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult OI Table 6. Management of Opportunistic Infections (MMWR 2004; 53 RR 15) Bartonella : Treat ? 3 mo ? Preferred: erythromycin 500 mg qid po or IV or doxycycline 100 mg bid po or IV x ? 3 mo ? Alternative: azithromycin 600 mg/d po or clarithromycin 500 mg bid po x ? 3 mo ? Note: If relapse: treat lifelong; CNS: Use IV or po doxycycline Candida Thrush: Treat 7?14 days ? Preferred: clotrimazole troches 10 mg po 5x/d or Nystatin susp 5 mL qid or pastilles 4?5 x/d or ?uconazole 100 mg po/d; all 7?14 days ? Fluconazole?refractory: Itraconazole oral solution ? 200 mg/d po or amphotericin B 0.3 mg/kg/d IV ? Recurrent disease: Consider chronic ?uconazole or itraconazole Candida Esophagitis: Treat 14?21 days ? Preferred: Fluconazole 100 mg/d (up to 400 mg/d) po or IV x 14?21 days ? Alternative: Itraconazole oral soln 200 mg/d, capsofungin 70 mg IV x 1, then 50 mg/d x 7 days or amphotericin B 0.3?0.7 mg/kg/d or voricomazole 200 mg/d po or IV or liposomal amphotericin 3?5 mg/kg/d Candida Vaginitis: Treat 3?7 days ? Preferred: Topical azole (clotrimazole, butoconazole, miconazole, ticonazole, terconazole) x 3?7 days or topical nystatin or ?uconazole 150 mg x 1 day or itraconazole 200 mg bid x 1 day or 200 mg/d x 3 days ? Recurrent: Daily topical azole Cryptococcoisis: Treat lifetime unless immune reconstitution ? Acute phase: Amphotericin B 0.7 mg/kg/d IV + ?ucytosine 25 mg/kg qid po x 14 days ? Consolidation phase: Fluconazole 400 mg/d po x 8 weeks ? Chronic maintenance phase: Fluconazole 200 mg/d po until CD4 > 100?200/mm 3 x ? 6 mo ? Alternative ? Acute phase: Amphotericin B 0.7 mg/kg/d x 14 days (without 5FC) or ?uconazole 400?800 mg po or IV qd ? flucytocine 25 mg/kg/ qid po ? Alternative ? Consolidation phase: Itraconazole 200 mg bid po ? Alternative ? Chronic maintenance phase: Itraconazole 200 mg/d po until CD4 > 100?200/mm 3 x ? 6 mo ? Note: Drain CSF if OP > 200 mL H 2 O Cryptosporidiosis ? Preferred: Symptomatic treatment + HAART ? Alternatives: Nitazoxanide 500 mg po bid or paromomycin 25?35 mg/kg/d in 2?3 doses U.S. Department of Health and Human Services 49 Adult OI Table 6. ? c o n t i n u e d Management of Opportunistic Infections (MMWR 2004; 53 RR 15) Cytomegalovirus retinitis ? Immediate sight-threatening lesions: Intraocular implant + valganciclovir 900 mg/d po ? Peripheral lesions: Valganciclovir 900 mg bid po x 14?21 days, then 900 mg/d ? Alternative: Ganciclovir 5 mg/kg q 12h IV x 14?21days, then 5 mg/kg/d or foscarnet 60 mg/kg IV q 8 h x 14?21 days, then 90?120 mg/kg/d single dose x 14 days or cidofovir 5 mg/kg/d weekly x 2 IV or 1 hr x 2 wks, then 5 mg/kg IV every other wk; patient must be hydrated with ? 1 L saline prior to cidofovir and receive probenecid 2 gm 3 hrs prior to cidofovir and 1 gm at 2 and 8 hrs after or fomivirsen intravitreal infections (relapses only) ? Maintenance therapy: - Preferred: Valganciclovir 900 mg po qd or foscarnet 90?120 mg/kg/d IV until: inactive disease, CD4 > 100?150 mm 3 x 6 mo and consultation with ophthalmologist - Implant: Need replacement q 6?8 mo if CD4 < 100?150/mm 3 - Alternative: Maintenance ganciclovir, cidofovir ? Immune reconstitution uveitis (IRU): periocular steroids or short course systemic steroids CMV esophagitis or colitis ? Preferred: Ganciclovir or foscarnet IV x 21?28 days or until symptoms resolve; valganciclovir po is appropriate if symptoms are not severe ? Maintenance: Not necessary except if there are relapses CMV pneumonia ? Indication to treat: Histologic evidence of disease and failure to respond to other pathogens CMV neurologic disease ? Preferred: Ganciclovir + foscarnet IV (above doses) until improvement ? Maintenance: Lifetime Hepatitis B ? Indication for treatment: HBV:(HbeAg pos or HBV DNA >10 5 /mL) + (liver disease by histopathology or ALT > 2x ULN) ? HBV + HAART: - Preferred: TDF/FTC or TDF/3TC - Alternative: (3TC or FTC) + adefovir or entecavir - Preferred eAg pos: Peginterferon x 48 weeks ? HBV without HAART: Adofovir, entecavir or peginterferon A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Adult OI Table 6. ? c o n t i n u e d Management of Opportunistic Infections (MMWR 2004; 53 RR 15) Hepatitis C ? Indications to treat: HCV RNA > 50 IU/mL, liver biopsy showing ?brosis or in?ammation, no contraindications, stable HIV and (?) CD4 > 200/mm 3 ? Preferred: Peginterferon alfa2a 180ug or peginterferon alfa 2b 1.5 mg/kg, each SC q 9 weekly + ribavirin 400 mg bid po x 48 weeks Herpes simplex: Moderate or severe mucocutaneous ? Preferred: Acyclovir 5 mg/kg q 8 h IV, then famciclovir 500 mg bid po or valacyclovir 1 gm bid po or acyclovir 400 mg tid po until lesions heal ? Acyclovir resistant: Foscarnet 120?200 mg/kg/d IV in 2?3 doses or cidofovir 5 mg/kg weekly until clinical response Herpes zoster ? Dermatomal: Famciclovir 500 mg tid po or valciclovir 1 gm tid po x 7?10 days ? Extensive cutaneous or visceral: Acyclovir 10 mg/kg q 8 h IV until response Microsporidiosis ? Preferred: HAART + symptomatic treatment ? Enterocytozoon bieneusi (80% of diarrheal disease due to microsporidia): Fumagillin 60 mg/d po ? Non- enterocytozoon bieneusi (20% of diarrheal disease): Albendazole 400 mg po bid until CD4 > 200/mm 3 ? Disseminated disease: Itraconazole 400 mg/d, albendazole 400 mg bid ( Brachiola or Trachipleistophora ) Mycobacterium avium ? Preferred: Clarithromycin 500 mg bid po plus ethambutol 15 mg/kg/d po ? rifabutin 300 mg/d po until treatment ? 12 mo + asymptomatic + CD4 > 100/mm 3 ? 6 mo ? Alternative: Azithromycin 500?600 mg/d po in place of clarithromycin ? Alternative ?3rd drug?: cipro?oxacin 500?750 mg bid po or levo?oxacin 500 mg/d po or amikacin 10?15 mg/kg/d IV ? Immune reconstitution: Moderately severe ? NSAIDs; severe or persistent ? prednisone 20?40 mg/d x 4?8 weeks Mycobacterium tuberculosis (see Adult OI Tables on tuberculosis) U.S. Department of Health and Human Services 51 Adult OI Table 6. ? c o n t i n u e d Management of Opportunistic Infections (MMWR 2004; 53 RR 15) Pneumocystis jiroveci (also known as Pneumocystis carinii ) ? Preferred: TMP?SMX 15?20 mg TMP/kg/d IV in 3?4 daily doses or 2 DS tid po x 21 days ? Alternative (IV therapy): Pentamidine 3?4 mg/kg IV infused over 1 hr or dapsone 100 mg/d po + TMP 15 mg/kg/d (3 daily doses) or primaquine 15?30 mg (base)/d po + clindamycin 600?900 mg q 6?8 h IV or 300?450 mg q 6?8 po or atovaquone 750 mg bid po (with food) ? PaO 2 < 70 mm/Hg room air or A?a gradient: Day 1?5 40 mg bid; Day 6?10 40 mg/d; Day 11?21 20 mg/d ? Maintenance - Preferred: TMP?SMX 1 DS/d or 1 DS bid po - Alternative: Dapsone 100 mg/d po or dapsone 50 mg/d + pyrimethamine 50 mg/wk po + leucovorin 25 mg/wk po or aerosolized pentamidine 300 mg q mo or atovaquone 1500 mg/d po; All until CD4 > 200/mm 3 x ? 3 mo Toxoplasmosis ? Preferred: Pyrimethamine 200 mg/d po x 1 then 50 mg/d (<60 kg) or 75 mg/d (> 60 kg) plus sulfadiazine 1000 mg q 6 h po (< 60 kg) or 1500 mg q 6 h po (> 60 kg) plus leucovorin 10?20 mg/d po (up to 50 mg/d) x ? 6 weeks ? Alternative: Pyrimethamine and leucovorin (above doses) plus 1) Clindamycin 600 mg q6 h IV or po or 2) Atovaquone 1500 mg bid po or 3) Azithromycin 900?1200 mg/d po 4) TMP?SMX 5 mg/kg TMP bid IV or atovaquone 1.5 gm bid po (with meals) ? Maintenance - Preferred: Sulfadiazine 500?1000 mg qid po + leucovorin 10?25 mg/d - Alternative: 1) Clindamycin 300?400 mg q 6?8 h plus pyrimethamine 25?50 mg/d + leucovorin 10?25 mg/d - 2) Atovaquone 750 mg q 6?12 h ? pyrimethamine 25 mg/d + leucovorin 10 mg/d Continue until CD4 ? 100/mm 3 , continue maintenance until CD4 >200/mm 3 x ? 6 months A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 O c c u p a t i o n a l H I V Po s t e x p o s u re Pr o p h y l a x i s ( P E P ) Considerations in Occupational Exposure to HIV PEP Guidelines Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis. MMWR Recommendations and Reports . September 30, 2005; 54 (RR-9):1. Available at http://www.cdc.gov/mmwr/ Risk of HIV transmission The risk of transmission continues to be related to exposure to infectious material and the source of that material. Exposure is de?ned as either percutaneous injury with a contaminated sharp object or exposure of mucous membranes or nonintact skin (skin that is abraded, chapped or with dermatitis) to infectious material. The current understanding of exposure contingencies is summarized in Occupational Postexposure Table 1. The risk of HIV transmission (without prophylaxis) is 0.3% (3/1,000) from percutaneous injury and 0.09% (9/10,000) from mucocutaneous exposure. The following are associated with increased risk of transmission: device (needle) with visible blood, needle placed in artery or vein, deep injury, large volume, high viral load. Ef?cacy of PEP The ef?cacy of AZT monotherapy prophylaxis is estimated to be 80% in retrospective case control series. To date there have been only six recorded prophylaxis failures associated with occupational exposures in the US. U.S. Department of Health and Human Services 53 Occupational Postexposure Table 1. Exposure Contingencies Exposure Element Explanation Material Blood or bloody body ?uid Established risk of transmission with occupational exposure CSF; pleural pericardial, peritoneal, amniotic and vaginal ?uids; semen Theoretical risk of transmission Urine, stool, nasal secretions, sputum, tears, vomitus (if not bloody) Not potentially infectious Type of Exposure Percutaneous Not severe More severe Solid needle or super?cial injury, etc. Large bore hollow needle, deep injury, or visible blood on needle/device Mucocutaneous Small volume Large volume Few drops Major splash Source of Infectiousness HIV positive Low risk High risk HIV positive and asymptomatic, viral load < 1500 c/mL HIV positive and symptomatic, AIDS, acute retroviral syndrome, or known high viral load Source unknown For example, deceased source person with no samples available for HIV testing A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Occupational Postexposure Table 2. Indications for HIV PEP Source Type of Exposure Percutaneous Muscocutaneous Not Severe* More Severe* Small Volume* Large Volume* HIV Positive Low Risk*? 2 drugs ? 3 drugs 2 drugs 2 drugs High Risk*? 3 drugs ? 3 drugs ? 3 drugs ? 3 drugs Source Unknown ? None or 2 drugs? None or 2 drugs? None or 2 drugs? None or 2 drugs? * See Occupational Postexposure Table 1 for explanation ? HIV resistance is a concern get expert consultation ? PEP is optional based on discussion of risk:benefit U.S. Department of Health and Human Services 55 Management of Health Care Workers (HCWs) W ith Potential HIV Exposure The importance of rapid action in the event of a potential exposure cannot be over-emphasized since PEP, if warranted, needs to be initiated within hours. Assessment Documentation of the nature and degree of the exposure and the HIV status of the source patient need to be identi?ed. Rapid testing of previously untested source patients is valuable in determining the need for PEP. The need for PEP and potential number of drugs may be determined by using Table 2. Initiation of HIV PEP Initiate PEP as soon as possible, preferably within hours after exposure, and continue for 4 weeks. From a practical point of view, PEP should be initiated if the source person is HIV-infected or thought to be infected, especially if the results of HIV serology likely to be delayed. PEP may be discontinued if the source is determined to be uninfected. The current recommended PEP regimens are listed in Table 3. The following drugs are not recommended because of the potential for adverse events: abacavir, delavirdine, zalcitabine, didanosine with stavudine, and nevirapine. During pregnancy efavirenz should be avoided because of the risk of teratogenic effects and the combination didanosine with stavudine because of toxicity concerns. Additionally, indinavir should be avoided because of side effects in the newborn. Health care workers taking PEP report adverse reactions at the rate of 17?47%. The most frequently reported reactions were nausea ? 27%, malaise and fatigue ? 23%. Of 503 HCW who prematurely (<28 days) stopped PEP, 24% did so because of adverse reactions. Regardless, the HCW should be advised on the need to complete the 4?week course of PEP. A Pocket Guide to Adult HIV /AIDS Treatment ? February , 200 6 Management of Health Care Workers (HCWs) W ith Potential HIV Exposure ? c o n t i n u e d Expert Consultation Consultation with an expert in HIV exposures and PEP is encouraged especially in the following instances: ? Initiation of PEP is delayed to > 24?36 hrs post-exposure ? The status of the source patient is unknown ? The HCW is currently pregnant or is breastfeeding ? The source patient is known to have a resistant HIV strain ? There are toxicity problems in the initiated regimen Monitoring ? Re-evaluate HCW at 72 hours, especially if additional information becomes available about the status of the source ? HIV serology testing should be conducted at baseline, and then at 6 weeks, 12 weeks, and 6 months after exposure; if the HCW experiences hepatitis C seroconversion after exposure, HIV serology should be conducted 12 months after exposure ? Tests for HIV (P24 Ag or HIV PCR) in HCW are not routinely recommended due to high rates of false positives; these tests should be done if there are symptoms compatible with the acute retroviral syndrome ? Toxicity monitoring Laboratory: CBC, liver and renal function tests at baseline and at 2 weeks; HCWs given indinavir should also have urinanalysis monitoring for crystalluria and hematuria Self Report: HCWs should be advised to report rash, fever, back or abdominal pain, dysuria, blood in urine, and symptoms of hyperglycemia; they should also be counseled on the possibility of drug interactions and advised to report these should they occur Prevention Warnings HCW with exposure to HIV should be counseled on measures to prevent secondary transmission including: avoidance of blood or tissue donations; pregnancy and breastfeeding, especially in the ?rst 6?12 weeks; and the use of condoms for sexual transmission. Seroconversions Report any Seroconversion to your local Health Department. U.S. Department of Health and Human Services 57 Occupational Postexposure Table 3. Recommended Regimens 2 Drug Regimen 3 Drug Regimen Lamivudine or emtricitabine plus zidovudine, stavudine or tenofovir Two nucleosides plus Preferred: lopinavir/ritonavir Alternates: atazanavir, fosamprenavir, ritonavir boosted indinavir, ritonavir boosted saquinavir or nel?navir* * Consider EFV if PI resistance in source and HCW has no pregnancy risk Resources for Consultation The following resources are available for consultation regarding HIV PEP: ? PEPline: http://www.ucsf.edu/hivcntr Telephone: 1-888-448-4911 ? HIV Pregnancy registry: http://www.apregistry.com/index.htm Telephone: 1-800-258-4263, email ?registry@nc.crl.com ? FDA (for reporting unusual or severe toxicity to antiretroviral agents) at http://www.fda.gov/medwatch Telephone: 1-800-332-1088 ? Report HIV infections in HCP and failures of PEP to local Health Department. ? HIV/AIDS Treatment Information Service: http://aidsinfo.nih.gov A Pocket Guide to Adult HIV/AIDS Treatment provides treatment information in table format for easy reference in clinical settings: AIDSInfo: http://www.aidsinfo.nih.gov National HIV/AIDS Clinical Consultation Center Warmline: 1-800-933-3413 (toll free in the U.S.) Drug Information ...................... Pages 2-16 Adult ART Tables .................... Pages 17-29 Pregnancy Tables ................... Pages 30-34 Prevention for Providers ....... Pages 35-37 Adult OI Tables ....................... Pages 38- 51 Occupa tional PEP .................. Pages 52-58 Recommendations for HIV care and treatment are complex and change rapidly. In addition to the Pocket Guide and A Guide to Primary Care of People with HIV/AIDS , which the Pocket Guide supports, consult the following resources provided by the U.S. Department of Health and Human Services for frequently updated HIV treatment information: