Abstract:
Background: HIV protease inhibitors anti-Plasmodium falcipa-
rum activity in adults remains uncertain.
Methods: Adults with HIV CD4+ counts .200 cells/mm3 starting
antiretroviral therapy (ART) with P. falciparum subclinical para-
sitemia (Pf SCP) were randomized 1:1 to (step 1) protease inhibitor
lopinavir/ritonavir (LPV/r)-based (arm A) or nonnucleoside reverse
transcriptase inhibitor (nNRTI)-based ART (arm B) for 15 days. In
step 2, participants received nNRTI-based ART and trimethoprim/
sulfamethoxazole prophylaxis for 15 days. P. falciparum SCP
clearance was measured by polymerase chain reaction. The Fisher
exact test [95% exact confidence interval (CI)] was used to compare
proportions of P. falciparum SCP clearance (,10 parasites/mL on 3
occasions within 24 hours) between LPV/r and nNRTI arms at day
15. The Kaplan–Meier method and log-rank test were used to
compare time-to-clearance.
Results: Fifty-two adults from Kenya, Malawi, and Uganda with a
median age = 31 (Q1, Q3: 24–39) years, 33% women, with baseline
median CD4 + counts of 324 (259–404) cells/mm 3 , median HIV-1
RNA viremia of 5.18 log10 copies/mL (4.60–5.71), and median
estimated P. falciparum density of 454 parasites/mL (83–2219)
enrolled in the study. Forty-nine (94%) participants completed the
study. At day 15, there was no statistically significant difference in
the proportions of P. falciparum SCP clearance between the LPV/r
(23.1% clearance; 6 of the 26) and nNRTI (26.9% clearance; 7 of the
26) arms [between-arm difference 3.9% (95% CI, 221.1% to 28.4%;
P = 1.00)]. No significant difference in time-to-clearance was
observed between the arms (P = 0.80).
Conclusions: In a small randomized study of adults starting ART
with P. falciparum SCP, no statistically significant differences were
seen between LPV/r- and nNRTI-based ART in P. falciparum SCP
clearance after 15 days of treatment.
