Early versus Delayed Fixed Dose Combination Abacavir/Lamivudine/Zidovudine in Patients with HIV and Tuberculosis in Tanzania

Abstract

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.

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).…”

Paradoxical TB-IRIS in HIV-infected Adults: a Systematic Review and Meta-analysis

“…It compared early (2 weeks) versus delayed (8 weeks) ART, with a fixed dose combination of abacavir, lamivudine and zidovudine, among patients on TB treatment. This study reported no cases of TB-IRIS [65]. The median CD4 count in this study was 103 cells/μl.…”

“…The pooled estimate of incidence was 18% (95% CI: 16-21%). One study with unexpected findings that was not included in this systematic review (because there were no TB-IRIS cases) was an RCT conducted in Tanzania [65]. It compared early (2 weeks) versus delayed (8 weeks) ART, with a fixed dose combination of abacavir, lamivudine and zidovudine, among patients on TB treatment.…”

Integration of Antiretroviral Therapy with Tuberculosis Treatment

“…Further, the limited observational data available, show similar trends. A 70 patient pilot study of antiretroviral therapy initiation among patients (median CD4+ count = 103 cells/mm 3 ) observed two deaths in the early group (2 week) versus one death in the delayed group (8 weeks) (p=0.601) 10 .…”