Indian J Med Res 121, April 2005, pp 415-423
415
The HIV pandemic has had a major impact on the
epidemiological dynamics of tuberculosis (TB). In
countries with a severe HIV epidemic, there has been
a dramatic rise in the notification rates for TB. Various
studies1-3 have domonstrated that persons co infected
with  Mycobacterium tuberculosis and HIV have a
5-8 per cent annual risk and a 30 per cent or greater
life time risk of developing active TB. The
mechanisms include reactivation of latent infection2,
rapid progression of primary infection3 or re-infection
with  Mycobacterium tuberculosis4.
The Joint United National Programme on HIV/
AIDS (UNAIDS) estimates that of the global total
of 37.8 million people living with HIV at the end of
2003, 70.1 per cent are in sub-Saharan Africa and
16.1 per cent are in South East Asia5. About one
third of those living with HIV worldwide are co-
infected with M. tuberculosis6. Since 68 per cent of
those co-infected live in sub-Saharan Africa, this
region carries the overwhelming burden of global
epidemic of HIV associated tuberculosis. In sub
Saharan Africa 20 to 67 per cent of patients with
pulmonary tuberculosis have been reported to be HIV
seropositive7. However, with 22 per cent of co-
infected individuals, South East Asia also bears a
considerable burden of HIV associated TB. In other
regions with a high number of AIDS cases, an
increased HIV prevalence rate has been noted among
TB patients8-10.
Key words Chemoprophylaxis - drug monitoring - drug toxicity - HIV - preventive therapy - tuberculosis
Preventive therapy for tuberculosis in HIV infected individuals
C. Padmapriyadarsini & Soumya Swaminathan
Tuberculosis Research Centre (ICMR), Chennai, India
Accepted February 4, 2005
The increased risk of developing tuberculosis (TB) among those infected with HIV has prompted
a need to reconsider the institution of preventive therapy/chemoprophylaxis with one or more
antituberculosis drugs. Prior to the initiation of preventive therapy for tuberculosis, it is essential
to rule out active TB. The target population for chemoprophylaxis among HIV seropositives
includes all Mantoux (PPD) positive individuals who do not have active tuberculosis and could
include all PPD negative individuals living in high prevalence region for TB. The optimal
duration of preventive therapy with single drug isoniazid, daily or twice weekly, should be
greater than six months to provide the maximum degree of protection against tuberculosis. The
effectiveness of preventive therapy should be evaluated at regular intervals by monitoring patients
for drug adherence, drug toxicity and for the development of tuberculosis. Though the impact of
preventive therapy on an individual basis may be rather small, widespread implementation
would have substantial impact on morbidity due to tuberculosis and some impact on mortality.
Till the vast majority of HIV positive individuals in the world can access antiretroviral therapy,
preventive therapy for tuberculosis should be offered at voluntary counselling and testing centres,
as part of a package of care that includes prophylaxis and treatment of opportunistic infections,
nutritional support and counselling.
416 INDIAN J MED RES, APRIL  2005
Over the last decade HIV has been the major cause
for the large increase in the incidence of tuberculosis
in populations with a high prevalence of HIV
infection. In south India, one of the early observations
in 1992 has shown that a significant proportion of
AIDS cases detected, had active tuberculosis11. The
increased risk of developing TB among those infected
with HIV has prompted a need to reconsider institution
of preventive measures to enable HIV seropositive
patients to avoid the risk of progression to clinical
TB. Four types of intervention are available for TB
control, namely, Case finding and Treatment,
Preventive therapy, Use of BCG vaccination, and
Environmental measures12. Emphasis in developing
countries has been on case finding and treatment and
on provision of BCG vaccination to infants. Preventive
therapy was not recommended except for infants
being breastfed by mothers with pulmonary
tuberculosis or other children under 5 yr of age living
with infectious persons13.
Preventive therapy (PT) or chemoprophylaxis
against TB is the use of one or more antituberculous
drugs (ATT) given to persons with latent infection
with M. tuberculosis in order to stop or prevent the
progression to active disease. Prior to the HIV
epidemic, its use in countries with a high prevalence
of tuberculosis was limited to childhood contacts of
active cases since these children have a higher risk
of progression to disseminated and severe forms of
disease. Evaluation of preventive therapy, before the
emergence of AIDS, involving over 100,000
participants in a placebo-controlled trial demonstrated
a reduction of 25-92 per cent in tuberculosis14. Several
studies have now demonstrated that PT is effective
in preventing progression of TB infection in individuals
dually infected with HIV and  M. tuberculosis,
although the efficacy is not 100 per cent (ranges from
60-90%). In addition, there is a suggestion that
chemoprophylaxis may delay HIV disease progression
amongst asymptomatic HIV infected individuals15.
The increased risk of developing active disease
associated with HIV infection has provoked a number
of questions, like who should receive prophylactic
therapy, how long to continue, whether isoniazid alone
is the most effective agents, role of secondary
prophylaxis, etc. Clinical trials are ongoing in these
areas.
Ideal candidate for chemoprophylaxis: In a study
under a methadone maintenance programme in New
York the risk of developing active tuberculosis in HIV
infected persons with positive tuberculin (PPD) skin
test reactions was shown to be as high as 7.9  per
cent per year2. All these cases occurred in patients
who did not take prophylactic isoniazid and occurred
among those with a positive PPD. Swaminathan
et al16 reported an incidence rate of 7.1 per 100 person
years in PPD positive and 6.9 per 100 person years
in PPD negative HIV positive individuals, in south
India. A meta-analysis17 of 7 randomized controlled
clinical trials to determine the efficacy of isoniazid
(INH) for the prevention of TB in tuberculin skin test
positive and negative individuals with HIV infection
revealed that in groups of tuberculin skin test positive
and negative persons, the risk ratio of TB was 0.41
(95% CI, 0.24-0.71) and 0.94 (95% CI, 0.52-1.38),
respectively and the difference in the effectiveness
of INH versus placebo between these groups was
statistically significant; consistency of results was
found across trials for all comparisons. Another meta-
analysis18, on the effectiveness of tuberculosis
preventive therapy in reducing the risk of active
tuberculosis and death in HIV infected persons,
analyzed 11 different preventive therapy trials with a
total of 8,130 randomized participants. The result
showed that the benefit was more in individuals with
a positive tuberculin skin test (RR 0.38, 95% CI 0.25
to 0.57) than in those with a negative test
(RR 0.83, 95% CI 0.58 to 1.18) (Table I). A positive
tuberculin skin test is defined as an induration of
>5 mm in HIV-1 seropositive persons. These
observations have led to the recommendation that all
HIV infected patients should undergo tuberculin skin
testing and persons with a positive test be offered
preventive therapy with INH, after ruling out active
tuberculosis.
A study among injecting drug users in Baltimore,
Maryland19 found that there was a considerable
change in the delayed type hypersensitivity (DTH)
status over time, particularly among HIV infected
persons with lower CD4 cell counts. Another study20
suggested that establishing the likelihood of
M. tuberculosis infection on grounds other than skin
testing is a more useful means for determining who
should receive prophylactic therapy. Recently, the
detection of interferon-gamma (IFN-? ) production by
417
peripheral blood mononuclear cells (PBMCs) in
response to TB antigens like ESAT-6 and Cfp 10 has
been suggested as a test for latent TB infection 21.
However, its utility in HIV infected persons has not
been established.  At present, there is no surrogate
test for M. tuberculosis latent infection that is
consistently better than the tuberculin skin test.
Factors such as community rates of infection and
active disease, demographic information, history of
exposure and abnormalities on chest radiographs can
all be used to identify the HIV infected patients at
highest risk. These individuals may be considered for
prophylactic therapy regardless of skin test results.
The Centers for Disease Control and Prevention
(CDC) has recommended that preventive therapy for
anergic HIV infected persons be considered if the
patient has had known contact with an active TB case
or belongs to a group in which the prevalence of TB
infection is high22. In areas endemic for TB and HIV,
PPD or tuberculin test may not be helpful in identifying
persons who could benefit from INH prophylaxis.
Among TB patients with HIV infection, up to 40 per
cent could be anergic. This further complicates the
issue of tuberculosis preventive therapy among
individuals infected with HIV.
Chemoprophylaxis in tuberculin negative HIV
infected persons
Tuberculin skin test negative, HIV infected persons
from high risk groups or from areas with a high
prevalence of M. tuberculosis infection may be at
increased risk of primary or reactivation tuberculosis.
Some experts recommend preventive therapy for
persons in this category. The efficacy of preventive
therapy in Mantoux or PPD negative HIV positive
persons has not been clearly established, most studies
showing it to be of limited value. In a meta-analysis 23
combining the various studies on efficacy of
preventive therapy in subjects with a negative PPD
test, INH was found to be significantly better than
placebo with a rate ratio of 0.82 (95% CI 0.50 to
1.36). Hence in HIV seropositive individuals, living
in a high prevalence TB region, with negative PPD
or in situations where tuberculin test cannot be
performed, chemoprophylaxis with INH will reduce
the risk of developing active TB in the short term to
around 60 per cent of what it would have been without
such treatment. Hence the target population for
preventive therapy among HIV seropositives includes
all PPD positive HIV infected individuals who do not
have active tuberculosis and when PPD testing is not
feasible like those living in areas with a high
prevalence of TB infection (>30%), among health
care workers, household contacts of TB patients,
among prisoners and miners and other selected groups
at high risk of acquisition or transmission of TB.
Prerequisite to initiate preventive therapy
Prior to starting an individual on preventive
treatment for tuberculosis, it is essential to ensure
that he/she does not have active tuberculosis. This is
done by a complete clinical examination along with a
chest X-ray and sputum smear examination for acid-
fast bacilli (AFB). It is advisable that chest X-ray is
done for every individual before considering
preventive therapy. Any HIV infected patient with
fever, cough or abnormal chest X-ray should not be
given preventive treatment until a full evaluation is
done to confirm that active TB disease is not present.
At times, it is difficult to exclude TB even when the
chest radiograph is normal and three sputum smears
are negative for AFB. Where mycobacterial culture
facilities are available, sputum culture can be used to
definitively diagnose TB24. In general, it is safe to
presume that completely asymptomatic individuals are
unlikely to have TB.
Duration of preventive therapy
A multicentric trial conducted in the USA, Mexico,
Brazil and Haiti25 demonstrated that the magnitude
of protection obtained from a regimen of isoniazid
(H) administered daily for 12 months was similar to
that obtained from a regimen of rifampicin (R) and
pyrazinamide (Z) administered daily for 2 months.
Moreover, it was noted that persons taking R and Z
for 2 months were significantly more likely (80%) to
complete therapy than those taking H for 12 months
(69%). However, due to several cases of fatal
hepatoxicity reported among HIV-negative
individuals on the RZ regimen, it is no longer
recommended for preventive therapy.  A study
amongst HIV infected persons in Uganda26 evaluated
a 6-month regimen with a placebo comparison group
and demonstrated a 70 per cent reduction in the
incidence of tuberculosis among persons in the
treatment group.
PADMAPRIYADARSINI & SWAMINATHAN: PREVENTIVE THERAPY FOR TB IN HIV SEROPOSITIVES
418 INDIAN J MED RES, APRIL  2005
Another trial by Halsey et al27 found similar overall
protection against tuberculosis in 2 groups of Mantoux
positive, HIV infected persons: those who took
partially supervised H twice weekly for 6 months and
those who took R and Z twice weekly for 2 months.
There was no significant difference in total mortality
rates at any time between both the groups (Table II).
Another trial in Ugandan adults infected with
HIV28 studied three regimens namely H daily for 6
months versus H with R daily for 3 months and H
with R and Z daily for 3 months along with a placebo
group; 80-89 per cent of different groups completed
treatment and the mean follow up duration was 15
months. This study28 demonstrated a 83 per cent
reduction in the incidence of tuberculosis among
persons in the treatment groups as compared to the
placebo group. It was also noted that the advantage
of shorter regimens was better patient compliance
and earlier sterilization of any lesions; however, the
risk of drug toxicity was higher.
There is evidence to suggest that preventive
therapy is efficacious in HIV positive persons with
tuberculin reactions >5 mm, and that optimal duration
of isoniazid preventive therapy (using a single drug)
should be greater than six months to provide the
maximum degree of protection against TB. Although
the American Thoracic Society29 has recommended
that isoniazid therapy be continued for 12 months in
persons with HIV infection, there are only few
studies comparing the efficacy of this approach with
that of either shorter or longer courses. There has
been some suggestion that the effect of prophylaxis
tends to wane, as time passes30. A randomized clinical
trial is currently underway at the Tuberculosis
Research Centre, Chennai to investigate a 6-month
regimen of ethambutol and isoniazid compared to a
3-yr regimen of isoniazid alone (in lieu of lifelong
therapy). The results of this trial should provide
information on the need for long-term prophylaxis.
Rhythm of administration of preventive therapy
HIV seropositive patients in Haiti27, who received
either isoniazid twice weekly for six months or
rifampicin with pyrazinamide twice weekly for 2
months were studied, the rate of development of
active TB was similar in the two groups after 3 yr;
but in group receiving rifampicin and pyrazinamide
had significantly more cases of active TB during the
first 10 months.
In another study in which isoniazid was
administered twice a week (10-15 mg/kg, with a
maximum dose of 900 mg) to a cohort of injecting
drug users under directly observed preventive therapy
(DOPT), support the efficacy of twice weekly
isoniazid preventive therapy31. Twice weekly
regimens with DOPT were used in the study with
the hope that supervised delivery of therapy would
enhance adherence with preventive therapy regimen.
Thus, the available data suggest that the protection
obtained from isoniazid preventive therapy regimens
may be the same whether the drug is administered
daily or twice a week.
Drug monitoring
(i) Adherence: Patients on preventive therapy should
be monitored during routine visits and by means of
surprise checks for adherence to the preventive
therapy, for drug toxicity and signs and symptoms of
developing active TB. Pill counts, self-report and
estimation of urinary acetyl INH may be useful in
assessing adherence. Patients who interrupt therapy
should be counselled about reasons for stopping
treatment. Preventive therapy should only be restarted
if the obstacles to adherence have been removed.
The aim is to provide at least 6 months of INH therapy
during a one year period.
(ii) Drug toxicity: Patients with symptoms suggestive
of toxicity to medication should be evaluated
immediately. Patients should be educated about
symptoms of hepatitis and instructed to attend the
clinic/OPD promptly should these occur.  No toxicity
from isoniazid was encountered in the Haitian study15.
In the study from Spain32, 9 of 86 (11%) patients who
started therapy had to discontinue it, in 6 cases
because of hepatotoxicity. In our experience at
Tuberculosis Research Centre preventive therapy with
isoniazid can be safely employed in HIV infected
patients, if baseline liver function tests are within
normal limits (unpublished observations). Another
study suggested an overall risk of death of 0.001 per
cent among subjects of all ages taking isoniazid for
preventive therapy33. Data on rates of adverse effects
419
in HIV infected individuals are not available; although
experience suggests that toxicity from anti-
tuberculosis drugs in advanced HIV disease is
frequent34. In a community based programme in
Florida35, of the 135 HIV infected patients who
received R with Z for 2 months under DOT for latent
TB infection, five had to discontinue treatment due
to side effects and allergic skin reaction (n=4) and
hepatitis (n=1). In the Ugandan HIV infected adults
trial28, it was noted that side effects were higher in
the 3 drugs group. In a meta-analysis17, it was noted
that compared to INH monotherapy short course
multidrug regimens were much more likely to require
discontinuation of treatment due to adverse effects.
(iii) Development of TB: Preventive therapy should
not be continued if the patient develops signs or
symptoms of TB. The suspected cases must be
properly evaluated for active TB and referred for
treatment.
Contraindication to preventive therapy
Preventive therapy is contraindicated in patients
with active tuberculosis and in patients with active
(chronic or acute) hepatitis. Isoniazid should be given
with caution to individuals who consume alcohol daily.
Active tuberculosis must be excluded before beginning
preventive therapy.
Chemoprophylaxis in special situations
Chemoprophylaxis in pregnancy: Chemoprophylaxis
for tuberculosis is recommended during pregnancy
for HIV infected women, who have a history of
exposure to active tuberculosis or after active TB
has been ruled out. INH with pyridoxine (to reduce
the risk of neurotoxcity) is the prophylactic agent of
choice36. Some may choose to initiate prophylaxis
after the first trimester to avoid teratogenicity.
Chemoprophylaxis in children: Infants born to HIV
infected mothers should have a Mantoux test (5-TU
PPD or 1-TU PPD RT23 with tween 80) at or before
age of 9-12 months and should be retested at least
every 2-3 yr36. Children exposed to those with active
TB, should be administered preventive therapy after
active TB has been ruled out. However, there have
been no clinical trials of preventive therapy in HIV
positive children.
Chemoprophylaxis in developing countries : In
many of the developing countries with a high
prevalence of HIV and TB, many HIV infected
individuals are likely to develop active TB. The first
priority of National TB Control Programme in such
settings, is to treat all active cases of TB, render them
non infectious and achieve a high cure rate. Although
it could be accepted that preventive therapy should
be offered to individuals who are diagnosed to be
infected with both HIV and latent TB, such preventive
therapy programme should not compromise or
undermine the priority of the TB control programme
of diagnosing and curing patients with infectious
tuberculosis.
Secondary prophylaxis
The rate of recurrent TB is higher in HIV-1
positive individuals than in HIV negative individuals
with both re-activation and new infections contributing
to recurrences37. A trial was conducted in Haiti38 to
determine whether post treatment INH prophylaxis
decreases the risk of recurrent TB. The rate of
recurrent TB among patients who had completed a
short course regimen was found to be 4.8 per 100
person years in HIV-1 infected individuals and 0.4
per 100 person years in uninfected individuals
(RR=10.7, 95% CI 1.4-81.6). Among HIV-1 positive
patients receiving INH for 6 months after TB
treatment, the TB recurrence rate was 1.4 per 100
person years and among HIV-1 positive patients
receiving placebo, it was 7.8 per 100 person years
(RR0.18, 95% CI 0.04-0.83). Another trial conducted
in South Africa39 to determine the efficacy of
secondary preventive therapy against TB among gold
miners, concluded that the overall incidence of
recurrent TB was reduced by 55 per cent among men
who received preventive therapy compared with those
who did not (RR =0.45, 95% CI 0.26-0.78). It also
showed that the absolute impact of secondary
preventive therapy to reduce TB recurrence was
highest among individuals with low CD4 cell counts.
Cost efficacy
Studies are being conducted to consider not just
the efficacy but the feasibility and cost efficacy of
preventive therapy in HIV infected people in countries
with a high prevalence of TB. The unit cost to prevent
PADMAPRIYADARSINI & SWAMINATHAN: PREVENTIVE THERAPY FOR TB IN HIV SEROPOSITIVES
420 INDIAN J MED RES, APRIL  2005
future TB disease should be evaluated against the
cost of successful treatment of TB cases under
programme conditions. The need for and provision of
preventive therapy should therefore depend on the
HIV situation and local resources. The impact of
preventive therapy on the prevalence of tuberculosis
in HIV infected persons in contemporary sub-Saharan
Africa40 showed that giving preventive therapy to
25 per cent of HIV-positive individuals with latent
tuberculosis infection leads to a 3.9 per cent reduction
in the prevalence of tuberculosis in 10 yr and a 5.1
per cent reduction in 20 yr. Doubling the preventive
therapy coverage to 50 per cent approximately
doubles the effect size, suggesting a linear relationship
within the 20-yr period. This model-based analysis
suggests that the impact of preventive therapy on
tuberculosis in the population is likely to be small
contrary to general belief.
Effect of preventive therapy on mortality
The combined estimate provided by a meta-
analysis23 showed some reduction in death rates in
those subjects with a positive tuberculin skin test who
took INH rather than placebo (RR=0.73, 95% CI 0.57-
0.95). In those with a negative tuberculin test, the
pooled relative risk for mortality was 1.02 (95% CI
0.89 to 1.17). The overall estimate for all subjects in
the trial did not differ significantly from unity,
confirming that no substantial protection was
conferred by interventions.
The Uganda efficacy study28 showed that survival
did not differ among the different groups but subjects
with anergy had a higher mortality rate than the PPD
positive subjects. Although the individual benefits may
be rather small, widespread implementation of
preventive therapy would have some impact on
mortality.
Evaluation of outcome of preventive therapy
Programmes or Centres that offer preventive
therapy should assess its effectiveness regularly. This
assessment should include attendance at scheduled
appointments, adherence (number of persons started
on preventive therapy and number completed), toxicity
and withdrawals from therapy due to toxicity, number
of suspected TB cases found by screening, and
monitoring of therapy. Individual records should be
maintained to document use of PT. Individual
information will be aggregated for regular reports,
which may be used in the TB programme to estimate
future drug requirements.
Current recommendations for preventive
therapy against TB in HIV infected persons
(i) WHO recommendation: Isoniazid is the
recommended drug (5 mg/kg - maximum 300 mg) as
daily, self-administered therapy for 6 months.
Individuals should be seen monthly and given only
one month’s supply of medication at each visit13.
(ii) CDC recommendation: Isoniazid is chosen for
prevention of tuberculosis in persons with HIV
infection, 9 months is recommended rather than
6 months41. Rifampicin and pyrazinamide may be
offered daily for 2 months to contacts of patients with
INH resistant, rifampicin susceptible TB.
(iii) American Thoracic Society : Isoniazid is
recommended for 12 months as prophylaxis in person
infected with HIV infection29.
Implementation of preventive therapy in India
In order to make an impact on the incidence of
tuberculosis in India, preventive therapy has to be
administered to a large number of people. Delivery
of preventive therapy will be limited by the number
of sites where a sufficient number of people know
their HIV status, or where there is sufficient demand
for and capacity of voluntary counselling and testing
(VCT) services. Preventive therapy should therefore
be promoted as an intervention for those living with
HIV, rather than as a primary strategy to control
the public health burden of tuberculosis.
Before a developing country can implement a
preventive therapy programme, it should be able to
readily identify HIV infected persons through
counselling services and there should be good
collaboration between the TB and AIDS
programmes. Most importantly, preventive therapy
should be organized and integrated into health
services and the cost of prevention must be
affordable or fully supported by state/district health
service.
421
Table I. Efficacy of isoniazid (INH) preventive therapy: results from three meta-analyses
Author Country Rate ratio (RR) or odds ratio (OR) for INH compared to no INH
(95% CI)
PPD positive PPD negative Total
Wilkinson et al23 Haiti, Kenya, OR 0.32 OR 0.82 OR 0.57
Uganda & U.S. (0.19 to 0.51) (0.50 to 1.36) (0.41 to 0.79)
Bucher et al17 Haiti, Mexico, RR 0.41 RR 0.94 RR 0.58
Zambia, USA, (0.24 to 0.71) (0.52 to 1.38) (0.39 to 0.87)
Uganda, Kenya
Woldehanna & Volmink18 11 trials RR 0.38 RR 0.83 RR 0.64
(0.25-0.57) (0.58 to 1.18) (0.51 to 0.81)
PPD, Purified protein derivative
Superscript numerals represent reference numbers
Table II. Studies of rifampicin containing regimens for Preventive therapy in HIV seropositive persons
Study reference Country Regimen Comments Relative Risk
Whalen et al28 Uganda 3RH, 3RHZ, Side effects 0.41, 0.51, 0.33. All
6H, Placebo higher with 3 drugs significantly lower compared
to placebo
Gordin25 USA, Mexico 12H, 2RZ Equivalent, better Breakdown rate 3.3 vs 2.4%
Haiti, Brazil adherence with 2RZ  at 37 months follow up
Mwinga et al30 Zambia 3RZ2, 6H2, Equivalent, No protective 0.58 and 0.62 compared
placebo effect after 18 months, no  to placebo
effect on mortality
Halsey27 Haiti 6H2, 2RZ2 H better in earlier months Breakdown rate 3.8 vs 5.0%
no difference later  at 4 years follow up
Narita et al35 Florida 2RZ, 12H RZ higher adherence rate.
Side effects higher with
2 drugs
Superscript numerals represent reference numbers
R, Rifampicin; H, isoniazid; Z, pyrazinamide
In India, collaboration between the National AIDS
Control Programme (NACP) and Revised National
Tuberculosis Control Programme (RNTCP) is being
strengthened. All symptomatic persons diagnosed to
have HIV infection VCT centres are referred to the
nearest microscopy centre to rule out tuberculosis.
In this setting, it would be feasible to offer
preventive therapy to those individuals who are found
not to have TB. Both isoniazid and co-trimoxazole
prophylaxis can be given in the same clinic under
close monitoring. If symptoms of TB develop at any
time, patients can be promptly investigated and
treated.
Following issues need to be clarified through future
research: (i) Ideal duration of preventative therapy
in TB-endemic areas: need for life-long prevention?
(ii) Operational research to identify ideal setting,
method of delivery, monitoring for exclusion of active
TB and adherence; and (iii) Preventive therapy for
TB in the era of highly active antiretroviral therapy
(HAART).
Conclusion
The evidence to date indicates that preventive
therapy for TB in HIV infected persons reduces the
incidence of TB by 50-60 per cent. The efficacy is
422 INDIAN J MED RES, APRIL  2005
higher in those who are tuberculin test positive.
Challenges to implementation in resource-constrained
settings include the exclusion of active TB disease
and monitoring for adherence and toxicity.
Recommendations for duration of preventive
therapy range from 6-12 months of isoniazid daily to
short term (2 or 3 months) regimens. The efficacy of
long-term (>12 months) regimens is currently being
investigated. In India, preventive therapy can be
offered to HIV positive persons detected at VCT
centres, who are referred to the nearest TB clinic. It
should be included in the package of care for HIV
positive persons, which would include ongoing
counselling and provision of prophylaxis and treatment
for opportunistic infections. Till the vast majority of
HIV positive individuals in the world can access
antiretroviral therapy, preventive therapy for TB will
continue to play a role in reducing the incidence of
TB thereby decreasing mortality and morbidity in this
population.
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Reprint requests: Dr Soumya Swaminathan, Deputy Director (Sr. Grade), Tuberculosis Research Centre (ICMR)
Mayor V.R. Ramanathan Road, Chetput, Chennai 600031, India
e-mail: doctorsoumya@yahoo.com