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Clinical Trial
. 2012 Feb;56(2):995-1000.
doi: 10.1128/AAC.05322-11. Epub 2011 Nov 28.

HIV-1 protease inhibitors and clinical malaria: a secondary analysis of the AIDS Clinical Trials Group A5208 study

Kimberly A Porter  1 , Stephen R Cole, Joseph J Eron Jr, Yu Zheng, Michael D Hughes, Shahin Lockman, Charles Poole, Tina S Skinner-Adams, Mina Hosseinipour, Doug Shaffer, Ronald D'Amico, Frederick K Sawe, Abraham Siika, Elizabeth Stringer, Judith S Currier, Tsungai Chipato, Robert Salata, James S McCarthy, Steven R Meshnick
Affiliations
Clinical Trial

HIV-1 protease inhibitors and clinical malaria: a secondary analysis of the AIDS Clinical Trials Group A5208 study

Kimberly A Porter et al. Antimicrob Agents Chemother. 2012 Feb.

Abstract

HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted.

Trial registration: ClinicalTrials.gov NCT00089505.

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Figures

Fig 1
Fig 1
Malaria-free survival in ACTG A5208 subjects, by treatment assignment. NVP, n = 219; LPV/r, n = 226.
Fig 2
Fig 2
Malaria-free survival in ACTG A5208 subjects, by trial and treatment assignment. (A) Trial 1. NVP, n = 73; LPV/r, n = 72 (B) Trial 2. NVP, n = 146; LPV/r, n = 154.
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