Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: A prospective cohort

Johns Hopkins University, School of Medicine, 1550 Orleans St., 1M.07 Baltimore, MD 21231, USA.
AIDS (London, England) (Impact Factor: 5.55). 04/2009; 23(5):631-6. DOI: 10.1097/QAD.0b013e328327964f
Source: PubMed


The World Health Organization recommends isoniazid preventive therapy (IPT) for preventing tuberculosis in HIV-infected adults, although few countries have instituted this policy. Both IPT and highly active antiretroviral therapy (HAART) used separately result in reductions in tuberculosis risk. There is less information on the combined effect of IPT and HAART. We assessed the effect of IPT, HAART or both IPT and HAART on tuberculosis incidence in HIV-infected adults in South Africa.
Two clinical cohorts of HIV-infected patients were studied. Primary exposures were receipt of IPT and/or HAART and the primary outcome was incident tuberculosis. Crude incident rates and incident rate ratios were calculated and Cox proportional hazards models investigated associations with tuberculosis risk.
Among 2778 HIV-infected patients followed for 4287 person-years, 267 incident tuberculosis cases were diagnosed [incidence rate ratio (IRR)=6.2/100 person-years; 95% CI 5.5-7.0]. For person-time without IPT or HAART, the IRR was 7.1/100 person-years (95% CI 6.2-8.2); for person-time receiving HAART but without IPT, the IRR was 4.6/100 person-years (95% CI 3.4-6.2); for person-time after IPT but prior to HAART, the IRR was 5.2/100 person-years (95% CI 3.4-7.8); during follow-up in patients treated with HAART after receiving IPT the IRR was 1.1/100 person-years (95% CI 0.02-7.6). Compared to treatment-naive patients, HAART-only patients had a 64% decreased hazard for tuberculosis [adjusted hazard ratio (aHR)=0.36; 95% CI 0.25-0.51], and patients receiving HAART after IPT had a 89% reduced hazard (aHR=0.11; 95% CI 0.02-0.78).
Tuberculosis risk is significantly reduced by IPT in HAART-treated adults in a high-incidence operational setting in South Africa. IPT is an inexpensive and cost-effective strategy and our data strengthen calls for the implementation of IPT in conjunction with the roll-out of HAART.

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    • "For example, a meta-analysis by Woldehanna and Volmink [21] shows that the provision of IPT to persons with HIV infection even in the absence of ART reduced the incidence of TB by 33% overall and by 64% among individuals with positive tuberculin skin test (TST) results, compared with placebo. Besides, observational studies suggest that IPT reduces the risks of TB and death during early ART [22] and that IPT and ART in combination result in a greater reduction in TB risk than does either treatment alone [22,23]. "
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    ABSTRACT: Activities to decrease the burden of tuberculosis (TB) among people living with HIV (PLHIV) include intensified TB case-finding (ICF), Isoniaizid (INH) preventive therapy (IPT) and infection control in health-care and congregate settings (IC). Information about the status of collaborative TB/HIV care services which decreases the burden of TB among PLHIV in Ethiopia is limited. The purpose of the study was to assess TB case finding and provision of IPT among PLHIV in Addis Ababa. A cross sectional, facility-based survey was conducted between June 2011 and August 2011. Data was collected by interviewing 849 PLHIV from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to analyze findings and the results are described in this report. The proportion of PLHIV who have been screened for TB during any one of their follow-up cares was 92.8%. Eighty eight (10.4%) of the study participants have been diagnosed for TB during their HIV follow-up cares. PLHIV who had never been diagnosed for TB before they knew their positive HIV status were nearly four times more likely to be diagnosed for TB during follow-up cares than those diagnosed before (AOR [95%CI]: 3.78 [1.69-8.43]). Nearly a third (28.7%) of all interviewed PLHIV self reported that they had been treated with IPT. It can be concluded that ICF for TB and IPT among PLHIV in Addis Ababa need boosting. Hence, it is recommended to put into practice the national and global guidelines to improve ICF and IPT among PLHIV in the city.
    BMC Public Health 01/2014; 14(1):52. DOI:10.1186/1471-2458-14-52 · 2.26 Impact Factor
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    • "Isoniazid preventive therapy (IPT) is one of the strategies to reduce TB infection among HIV patients IPT reduces TB risk by 32% overall and by 64% in the subset of patients with positive tuberculin skin tests and is the key TB preventive intervention prior to ART eligibility [22]. Study by Golub et al. [23] revealed lower TB incidence rates in HIV patients taking antiretroviral (ARV) and IPT compared to ARV alone (1.1 vs. 4.6 per 100 person years). "
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    ABSTRACT: Human immunodeficiency virus (HIV)-infected patients present complex immunological alterations. Multiple drugs that usually prescribed for prevention or treatment of opportunistic infections and antiretroviral pose these patients a higher risk of developing drug hypersensitivity. All antiretroviral agents and drugs to treat opportunistic infections have been reported to cause drug hypersensitivity reactions. Allergic reactions with antiretroviral are not restricted to older agents, although newer drugs usually more tolerated. Cutaneous adverse drug reactions are the most common manifestation of drug hypersensitivity in HIV, typically manifesting as maculopapular rash with or without systemic symptoms in the presence or absence of internal organ involvement. The onset of an allergic reaction is usually delayed. Severe drug hypersensitity reactions as erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis develop more often in HIV-infected patients compared to other populations. Mild to moderate rash without systemic symptom or organ involvement usually do not need drug discontinuation. Appropriate diagnosis and management of drug hypersensitivity reactions are essential, especially in patients with very low CD4+ T-cell count and multiple opportunistic infections. Clinicians should aware of different half-life of each drug when decided to stop the drug. Knowledge of the metabolism, recognition of the risk factors, and the ability to suggest the probability of particular drug as causative are also important points. A step wise rechallenge test or desensitization with the offending drug might be a preferable action and more commonly used in managing drug hypersensitivity in HIV-infected patients. Desensitization protocols have been successfully done for several antiretroviral and opportunistic infection drugs.
    01/2014; 4(1):54-67. DOI:10.5415/apallergy.2014.4.1.54
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    • "IPT added to ART has been shown to further reduce TB rates by a supplementary factor of around 0.31–0.63 [23], [24], [26] but without a further large increment to life expectancy. The long-term durability of this effect is unknown, but sustained suppression was observed when IPT was given in combination with ART continuously over 3 years [25]. "
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    ABSTRACT: To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART.
    PLoS ONE 10/2013; 8(9):e75466. DOI:10.1371/journal.pone.0075466 · 3.23 Impact Factor
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