Morbidity and mortality according to latest CD4+ cell count among HIV positive individuals in South Africa who enrolled in project Phidisa.

BACKGROUND: Short-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents. METHODS AND FINDINGS: A total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50-99, 100-199, 200-349, 350-499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm3. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200-349 (2.2/100 py), death rates were significantly lower (p<0.001), as expected, for those with 350-499 (0.9/100 py) and with 500+ cells (0.8/100 py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350-499 and 7.9 for 500+ cells) and lower than those with counts 200-349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events. CONCLUSION: Rates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350-499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.

Impact of lamivudine on HIV and hepatitis B virus-related outcomes in HIV/hepatitis B virus individuals in a randomized clinical trial of antiretroviral therapy in southern Africa.

OBJECTIVE: To examine HIV and hepatitis B virus (HBV)-related outcomes in HIV/HBV-coinfected participants in the PHIDISA II study by use of HBV-active vs. non-HBV-active antiretroviral therapy (ART). DESIGN AND METHODS: PHIDISA II was a randomized study of ART therapy in HIV-infected adults employing zidovudine along with didanosine, or lamivudine along with stavudine in a factorial 2x2 design. HIV/HBV-coinfected participants by randomization received HBV-active or non-HBV-active ART. The following outcomes of interest were examined: immunological recovery and HIV RNA suppression; hepatic flare; HBV DNA suppression; and mortality. RESULTS: HIV/HBV coinfection was present in 106 of 1771 (6%) of participants. Participants with HIV/HBV coinfection were more likely to be men, and have higher baseline alanine aminotransferase, lower albumin, and lower platelets than those with HIV monoinfection. Median CD4 cell gain and HIV RNA suppression was similar across all groups. Hepatic flare was observed in 9.4% of coinfected and 0.02% monoinfected participants. HBV DNA suppression (<55 IU/ml) at week 48 was observed in only 33% of those on lamivudine vs. 13% in those on no HBV-active drugs (P = 0.13). Mortality over follow-up was significantly greater in coinfected (17%) than monoinfected (11%) participants (P = 0.04). CONCLUSION: In summary, the use of lamivudine-containing ART in HIV/HBV participants in PHIDISA II resulted in little additional benefit over that of ART itself and failed to impact on the greater mortality in this group. These data provide strong support for recent guidelines advocating the use of tenofovir in all HIV-HBV-coinfected individuals initiating ART.

Instability of lopinavir/ritonavir capsules at ambient temperatures in sub-Saharan Africa: relevance to WHO antiretroviral guidelines.

WHO recommends lopinavir/ritonavir as an antiretroviral option in resource-limited countries. Lopinavir/ritonavir is recommended to be stored at 2-8 degrees C until dispensing, and afterwards, may be kept at < or = 25 degrees C for < or = 2 months. Anticipating lopinavir/ritonavir use in countries lacking adequate cold-chains, we assessed its physical and chemical stability at 35 and 45 degrees C. Although maintaining chemical stability for 4 weeks at 35 degrees C, at 45 degrees C the capsules clumped after 7 days, supporting a need for more temperature-stable formulations for hotter climates.