title: HIV-1 protease inhibitors and clinical malaria: a secondary analysis of the AIDS Clinical Trials Group A5208 study.
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.
authors: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA. kimberly.porter@alaska.gov
authors: Kimberly A
authors: KA
authors: Porter
authors: Stephen R
authors: SR
authors: Cole
authors: Joseph J
authors: JJ
authors: Eron
authors: Yu
authors: Y
authors: Zheng
authors: Michael D
authors: MD
authors: Hughes
authors: Shahin
authors: S
authors: Lockman
authors: Charles
authors: C
authors: Poole
authors: Tina S
authors: TS
authors: Skinner-Adams
authors: Mina
authors: M
authors: Hosseinipour
authors: Doug
authors: D
authors: Shaffer
authors: Ronald
authors: R
authors: D'Amico
authors: Frederick K
authors: FK
authors: Sawe
authors: Abraham
authors: A
authors: Siika
authors: Elizabeth
authors: E
authors: Stringer
authors: Judith S
authors: JS
authors: Currier
authors: Tsungai
authors: T
authors: Chipato
authors: Robert
authors: R
authors: Salata
authors: James S
authors: JS
authors: McCarthy
authors: Steven R
authors: SR
authors: Meshnick
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D015994:Incidence; D061466:Lopinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D008288:Malaria / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D000068698:Tenofovir; D016896:Treatment Outcome
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D061466:Lopinavir; D019829:Nevirapine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir