Lopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings.

TitleLopinavir/ritonavir monotherapy after virologic failure of first-line antiretroviral therapy in resource-limited settings.
Publication TypeJournal Article
Year of Publication2012
AuthorsBartlett JA, Ribaudo HJ, Wallis CL, Aga E, Katzenstein DA, Stevens WS, Norton MR, Klingman KL, Hosseinipour MC, Crump JA, Supparatpinyo K, Badal-Faesen S, Kallungal BA, Kumarasamy N
JournalAIDS
Volume26
Issue11
Pagination1345-54
Date Published2012 Jul 17
ISSN1473-5571
KeywordsAcquired Immunodeficiency Syndrome, Adenine, Adult, Africa, Anti-HIV Agents, Deoxycytidine, Drug Administration Schedule, Drug Therapy, Combination, Emtricitabine, Female, Health Resources, Humans, India, Lopinavir, Male, Medication Adherence, Middle Aged, Mutation, Organophosphonates, Patient Selection, Pilot Projects, Reverse Transcriptase Inhibitors, Ritonavir, RNA, Viral, Surveys and Questionnaires, Tenofovir, Thailand, Treatment Failure, Viral Load
Abstract

OBJECTIVE: To evaluate virologic response rates of lopinavir/ritonavir (LPV/r) monotherapy as second-line antiretroviral treatment (ART) among adults in resource-limited settings (RLSs).

DESIGN: An open-label pilot study of LPV/r monotherapy in participants on first-line nonnucleoside reverse transcriptase inhibitor three-drug combination ART with plasma HIV-1 RNA 1000-200 000  copies/ml.

METHODS: Participants were recruited from five sites in Africa and Asia within the AIDS Clinical Trials Group (ACTG) network. All participants received LPV/r 400/100  mg twice daily. The primary endpoint was remaining on LPV/r monotherapy without virologic failure at week 24. Participants with virologic failure were offered addition of emtricitabine and tenofovir (FTC/TDF) to LPV/r.

RESULTS: Mutations associated with drug resistance were encountered in nearly all individuals screened for the study. One hundred and twenty-three participants were enrolled, and 122 completed 24 weeks on study. A high proportion remained on LPV/r monotherapy without virologic failure at 24 weeks (87%). Archived samples with HIV-1 RNA levels less than 400  copies/ml at week 24 (n=102) underwent ultrasensitive assay. Of these individuals, 62 had levels less than 40  copies/ml and 30 had levels 40-200  copies/ml. Fifteen individuals experienced virologic failure, among whom 11 had resistance assessed and two had emergent protease inhibitor mutations. Thirteen individuals with virologic failure added FTC/TDF and one individual added FTC/TDF without virologic failure. At study week 48, 11 of 14 adding FTC/TDF had HIV-1 RNA levels less than 400  copies/ml.

CONCLUSION: In this pilot study conducted in diverse RLS, LPV/r monotherapy as second-line ART demonstrated promising activity.

DOI10.1097/QAD.0b013e328353b066
Alternate JournalAIDS
PubMed ID22441252
PubMed Central IDPMC3443745
Grant ListD43 CA153722 / CA / NCI NIH HHS / United States
D43 TW006732 / TW / FIC NIH HHS / United States
P30 AI64518 / AI / NIAID NIH HHS / United States
R01 TW009237 / TW / FIC NIH HHS / United States
T84HA21123 / / PHS HHS / United States
U01 AI069484 / AI / NIAID NIH HHS / United States
U01 AI069484 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
U01AI069432 / AI / NIAID NIH HHS / United States
U01AI069518 / AI / NIAID NIH HHS / United States
U01AI38858 / AI / NIAID NIH HHS / United States
U19 AI067854 / AI / NIAID NIH HHS / United States