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

TitleHIV-1 protease inhibitors and clinical malaria: a secondary analysis of the AIDS Clinical Trials Group A5208 study.
Publication TypeJournal Article
Year of Publication2012
AuthorsPorter KA, Cole SR, Eron JJ, Zheng Y, Hughes MD, Lockman S, Poole C, Skinner-Adams TS, Hosseinipour M, Shaffer D, D'Amico R, Sawe FK, Siika A, Stringer E, Currier JS, Chipato T, Salata R, McCarthy JS, Meshnick SR
JournalAntimicrob Agents Chemother
Volume56
Issue2
Pagination995-1000
Date Published2012 Feb
ISSN1098-6596
KeywordsAdenine, Adult, Anti-HIV Agents, Deoxycytidine, Emtricitabine, Female, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Incidence, Lopinavir, Malaria, Nevirapine, Organophosphonates, Reverse Transcriptase Inhibitors, Ritonavir, Tenofovir, Treatment Outcome
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.

DOI10.1128/AAC.05322-11
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID22123685
PubMed Central IDPMC3264273
Grant List1-T32-AI070114-01A1 / AI / NIAID NIH HHS / United States
5U01AI068634-05 / AI / NIAID NIH HHS / United States
5U01AI068636-05 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States