Lopinavir/Ritonavir Monotherapy as Second-line Antiretroviral Treatment in Resource-Limited Settings: Week 104 Analysis of AIDS Clinical Trials Group (ACTG) A5230

Abstract

Background: The AIDS Clinical Trials Group (ACTG) A5230 study evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure (VF) on first-line human immunodeficiency virus (HIV) regimens in Africa and Asia.

Methods: Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000 copies/mL. All subjects received LPV/r 400/100 mg twice daily. VF was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models.

Results: One hundred twenty-three subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 of 123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39 of 41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400 copies/mL over 104 weeks on LPV/r monotherapy was 60% (95% CI, 50%-68%); 80%-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level <400 copies/mL at weeks 24, 48, and 104 revealed that 61%, 62%, and 65% were suppressed to <40 copies/mL, respectively.

Conclusions: LPV/r monotherapy after first-line VF with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.

Clinical trials registration: NCT00357552.

Keywords: ACTG 5230; intensification; protease inhibitor monotherapy; second-line antiretroviral therapy.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

The solid line and stars give the proportion of subjects with human immunodeficiency virus type 1 (HIV-1) RNA level

Figure 2.

Due to almost complete overlap in the populations with thymidine analogue mutations (TAMs) present and the K65R mutation absent, fully adjusted analyses were not possible. Multivariable analyses that adjusted for TAMs revealed little change in the unadjusted estimates presented. Multivariable analyses that adjusted for K65R revealed additional confounding with nonnucleoside reverse transcriptase inhibitor (NNRTI) use prior to study entry. *P < .05. Abbreviations: CI, confidence interval; EFV, efavirenz; HIV-1, human immunodeficiency virus type 1; HR, hazard ratio.

Figure 3.

Failure of lopinavir/ritonavir (LPV/r) monotherapy was defined as confirmed virologic failure (failure to suppress plasma human immunodeficiency virus type 1 [HIV-1] RNA level to 400 copies/mL after confirmed suppression to