Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

Abstract

BackgroundFor antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events.MethodsIn a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART.FindingsA total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar.InterpretationEarly initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability.Trial registrationCTRI/2011/12/002260

Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients

“…Experience derived from the treatment of other AIDS-defining illnesses, such as Pneumocystis jirovecii pneumonia and tuberculosis, show that prompt initiation of cART in antiretroviral-naïve patients leads to better clinical outcomes compared with deferred initiation. [46][47][48] Our findings also demonstrate evidence for better outcomes with concurrent cART and support its use even during induction chemotherapy for AIDS-related lymphomas (ARLs).…”

The Impact of Antiretroviral Therapy on Mortality in HIV Positive People during Tuberculosis Treatment: A Systematic Review and Meta-Analysis

“…Three studies explicitly reported on how death was ascertained or confirmed (Table 2) [38], [39], [45].…”

“…Where all patients were initiated on ART during TB treatment, the median start times occurred in month 2 or 3 after starting TB treatment [14], [25], [27], [32], [36], [37]. The variability in reporting between studies limited our ability to examine the mortality impact of different ART initiation times with respect to the start of TB treatment.…”

Immune reconstitution inflammatory syndrome in HIV infection: taking the bad with the good

“…The duration of TB therapy prior to the initiation of ART was shown to have an effect on the development of IRIS with longer TB treatment reducing the complication of IRIS. However, delayed HIV treatment increases the risk of all‐cause mortality leading to the recommendation of starting ART early, within 2 weeks, in patients with CD4 counts below 50 cells μ l −1 (Abdool Karim et al , ; Blanc et al , ; Havlir et al , ; Manosuthi et al , ; Sinha et al , ; Mfinanga et al , ; Amogne et al , ). It is thus anticipated that prevalence of TB‐IRIS will increase in HIV infection, making development of new preventive or treatment strategies more pressing.…”