Outcome of HIV-Associated Tuberculosis in the Era of Highly Active Antiretroviral Therapy

Department of Thoracic and HIV Medicine, Royal Free Hospital, Royal Free and University College London Medical School, London, United Kingdom. .
The Journal of Infectious Diseases (Impact Factor: 6). 12/2004; 190(9):1670-6. DOI: 10.1086/424676
Source: PubMed


The benefit of highly active antiretroviral therapy (HAART) in the treatment of patients coinfected with tuberculosis (TB) and human immunodeficiency virus (HIV) is unclear because of concerns about treatment-related complications.
We compared outcomes in patients starting TB treatment during the pre-HAART era (before 1996; n=36) with those in patients starting treatment during the HAART era (during or after 1996; n=60).
During a median of 3.6 years of follow-up, 49 patients died or had an AIDS event. Compared with patients in the pre-HAART group, those in the HAART group had a lower risk of death (cumulative at 4 years, 43% vs. 22%; P=.012) and of death or having an AIDS event (69% vs. 43%; P=.023). Event risk within the first 2 months of TB treatment was exceptionally high in patients with CD4(+) cell counts <100 cells/mm(3) and declined thereafter. HAART use during follow-up was associated with a marked reduction in event risk (adjusted hazard ratio, 0.38 [95% confidence interval, 0.16-0.91]).
HAART substantially reduces new AIDS events and death in coinfected patients. Those with a CD4(+) cell count <100 cells/mm(3) have a high event risk during the intensive phase of anti-TB treatment. These data should be taken into account when deciding to delay HAART in coinfected patients with CD4(+) cell counts <100 cells/mm(3).

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    • "Previous studies showed reductions in HIV-associated mortality and morbidity among TB/HIV co-infected individuals who start ART early [3,4]. Recent clinical trials demonstrated that early initiation of ART was safe, and was associated with increased survival [5-7]. "
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    ABSTRACT: In July 2011, the Malawi national HIV program implemented the integrated antiretroviral therapy (ART) and prevention of mother-to-child transmission (PMTCT) guidelines. Among the principle goals of the guidelines were increasing ART uptake among TB/HIV co-infected patients and treating TB/HIV patients with a different drug regimen. We, therefore, assessed the effects of the new guidelines on ART uptake, the factors associated with ART uptake and the frequency of ARV-related adverse events in TB/HIV co-infected patients. This was an observational cohort study using routine program data. All ART-naive adult TB/HIV co-infected patients starting TB treatment over the six months preceding and following implementation of 2011 integrated ART/PMTCT guidelines were included. A total of 685 adult TB/HIV co-infected patients were registered in the study; 377 (55%) before and 308 (45%) after the implementation of the new guidelines. ART uptake increased from 70% (240/308) before implementation of the new guidelines to 78% (262/377) after the inception of the new guidelines (P=0.013). The proportion of TB patients initiating ART within two weeks of starting TB treatment increased from 30% before implementation of the new guidelines to 46% after implementation of the new guidelines (p <0.001). The median time from the start of TB treatment to ART initiation dropped from 16 days (IQR 14-31) before the new guidelines to 14 days (IQR 9-20; p <0.004) after implementing the new guidelines. Factors associated with ART uptake were enrolment in HIV care before starting TB treatment and being a retreatment TB patient. The overall frequency of ARV-related adverse events was higher in patients on d4T/3TC/NVP (35%) than those on TDF/3TC/EFV (25%) but not significantly different (P=0.052). Implementation of the 2011 Malawi Integrated ART/PMTCT guidelines was associated with an overall increase in ART uptake among TB/HIV patients and with an increase in the number of patients initiating ART within two weeks of starting their TB treatment. However, the reduction in time between initiating TB treatment and starting ART was small suggesting that further measures must be implemented to facilitate ART uptake. Early enrolment in HIV care provides opportunities for timely ART initiation among TB patients.
    Full-text · Article · Feb 2014 · BMC Public Health
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    • "For example, age- and sex-standardized mortality rates decreased from 22.9% to 11.8% between 1993-95 and 1999-2001 in the Netherlands, probably because of widespread availability of HAART by 1999 [21]. Other studies have also shown that HAART may reduce the mortality in HIV-infected TB patients by as much as 60% [22]. Only 10.5% of the patients who received HAART died during follow-up compared to 29.6% of those who did not receive any ART in a study from North America [20]. "
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    ABSTRACT: Background HIV has fuelled the TB epidemic in sub-Saharan Africa. Mortality in patients co-infected with TB and HIV is high. Managing factors influencing mortality in TB patients might help reducing it. This study investigates factors associated with mortality including patients' HIV sero-status, CD4 cell count, laboratory, nutritional and demographic characteristics in AFB smear positive pulmonary TB patients. Methods We studied 887 sputum smear positive PTB patients, between 18 and 65 years of age receiving standard 8 months anti-TB treatment. Demographic, anthropometric and laboratory data including HIV, CD4 and other tests were collected at baseline and at regular intervals. Patients were followed for a median period of 2.5 years. Results Of the 887 participants, 155 (17.5%) died, of whom 90.3% (140/155) were HIV-infected, a fatality of 29.7% (140/471) compared to 3.6% (15/416) among HIV-uninfected. HIV infection, age, low Karnofsky score, CD4 cell counts and hemoglobin, high viral load, and oral thrush were significantly associated with high mortality in all patients. Conclusion Mortality among HIV-infected TB patients is high despite the use of effective anti-TB therapy. Most deaths occur after successful completion of therapy, an indication that patients die from causes other than TB. HIV infection is the strongest independent predictor of mortality in this cohort.
    Full-text · Article · Nov 2009 · BMC Public Health
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    • "Several papers have reported improved outcomes in HIV/TB co-infected cases in the era of HAART (Hung et al, 2003; Dheda et al, 2004). Study on these treated without HAART reported a mortality rate of 13.3% (Putong et al, 2002). "
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    ABSTRACT: HIV-infected patients with active tuberculosis (TB) having CD4 counts < 100/mm3 and who were antiretroviral therapy (ART) naïve were reviewed retrospectively to determine the outcomes of their tuberculosis infection. All patients received ART at or after receiving anti-TB treatment. Clinical manifestations, treatment regimens and outcomes were analyzed. Of 101 patients, 62 (61.4%) completed TB treatment. Of these, 53.2% were treated with a 6-month standard TB regimen, while the rest were treated with prolonged TB regimens. The median interval between anti-TB treatment and ART was 68 days (range: 0-381). Among the clinically cured patients 66.1% received rifampin concomitantly with nevirapine, and 32.3% received rifampin concomitantly with efavirenz. The treatment success rate was 75.6%, with a mortality rate of 6.1%. The risk factors for death were resistant TB (p = 0.03) and poor compliance (p < 0.05). Seven point nine percent had multi-drug resistant TB. Possible or probable immune reconstitution inflammatory syndrome (IRIS) was seen in 15 cases (14.9%). No life-threatening IRIS was reported, and it did not affect disease outcome (p = 0.5). A shorter time between anti-TB treatment and ART onset was associated with the occurrence of IRIS (31 days vs 90 days; p < 0.05). Regarding adverse drug effects, 44.6% had side effects due either to anti-TB drugs or ART. Sixty-six point one percent of them occurred within the first 2 months of TB treatment, and 43 (76.8%) had to stop or change either anti-TB treatment or ART. The mortality rate with TB and HIV on ART was low and the occurrence of IRIS did not carry any additional mortality.
    Full-text · Article · Nov 2007 · The Southeast Asian journal of tropical medicine and public health
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