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Comparing the efficacy of efavirenz and boosted lopinavir using viremia copy-years.

ABSTRACT: HIV-1 plasma viral load during treatment can be highly variable. Thus, there is the need to find a measure of cumulative viremia that can be used to assess both the short- and long-term efficacy of highly active antiretroviral therapy (HAART). Here, we validate a measure of cumulative viremia to evaluate HAART efficacy.We accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico. We compared the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, against the cumulative plasma viral load, estimated as the area under the plasma viral load curve (AUVLC). High AUVLC indicates high cumulative viremia.There was a strong and significant association between the proportion of individuals achieving a viral load <50 and <400 copies/mL at week 48, with individuals suppressed having significant lower cumulative viremia. The median area was 7513 (25th-75th percentile [Q1-Q3] 6634-8180) if viral load <50 copies/mL and 7679 (Q1-Q3 6899-9373) if viral load ?50 copies/mL (p-value 0.0284). When the analysis was stratified by study arm, individuals on efavirenz had lower cumulative viremia than those on boosted lopinavir.Our findings suggest that cumulative viremia should be explored further as a tool to simultaneously evaluate the individual and public health efficacy of HAART. This is particularly relevant to the implementation and evaluation of the Treatment 2.0 strategy recently proposed by UNAIDS and the WHO, as a means to maximize the individual and public health benefit of HAART.

SUBMITTER: Lima VD

PROVIDER: S-EPMC4013478 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Comparing the efficacy of efavirenz and boosted lopinavir using viremia copy-years.

Lima Viviane D VD Sierra-Madero Juan J Wu Zunyou Z Singer Joel J Wood Evan E Hull Mark W MW Richard Harrigan Paul P Montaner Julio S G JS

Journal of the International AIDS Society 20140506

<h4>Introduction</h4>HIV-1 plasma viral load during treatment can be highly variable. Thus, there is the need to find a measure of cumulative viremia that can be used to assess both the short- and long-term efficacy of highly active antiretroviral therapy (HAART). Here, we validate a measure of cumulative viremia to evaluate HAART efficacy.<h4>Methods</h4>We accessed HAART efficacy using data from a randomized clinical trial conducted in Mexico. We compared the proportion of individuals achievin ...[more]

PMID: 24805184

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Project description:BackgroundAlbuvirtide (ABT), a fusion inhibitor against human immunodeficiency virus (HIV) infection, has good efficacy and tolerability for HIV treatment. However, there is a paucity of data regarding ABT-based regimen as second-line therapy. This current study evaluated the efficacy and safety of switching to ABT + ritonavir-boosted lopinavir (LPV/r) treatment in a cohort of HIV-infected individuals who failed initial treatment.MethodsThis retrospective comparative cohort study included patients who failed initial treatment and switched to either ABT + LPV/r (the ABT group) or two nucleotide reverse transcriptase inhibitors (NRTIs) + LPV/r (the NRTI group) between November 2019 and December 2020 in the People's Hospital of Zhaojue County in Liangshan Yi Autonomous Prefecture, China. All individuals were followed up from baseline to 12 weeks after conversion, or until the patient developed unacceptable toxic effects or was loss of follow-up. The proportion of patients who achieved virological suppression (viral load <50 copies/mL) at week 12 was considered a primary efficacy endpoint. Safety outcomes included the incidence of adverse events and laboratory abnormalities. All participants underwent resistance testing before regimen conversion. The linear regression model was applied to evaluate the association of CD4+ T cell count with the patient's clinical characteristics.ResultsA total of 71 patients were included in this study, the two groups were comparable at baseline in terms of age, sex, CD4+ T cell count, and viral load. The suppression of HIV-1 RNA to levels <50 copies/mL was achieved in 82.4% (28/31) and 29.7% (11/34) of patients in the ABT group and the NRTI group, respectively (P<0.001). Older age (P=0.016) and higher alkaline phosphatase (ALP) levels (P=0.038), but not rescue regimen, were associated with attenuated CD4+ T cell recovery. Most adverse events mild in severity, with abdominal pain as the most reported event in two groups (26.8%, 19/71), and no severe adverse events were detected.ConclusionsConversion to ABT + LPV/r therapy appears to be an effective and safe strategy. This treatment regimen has great potential to be generalized in the HIV-infected population, although further testing in a larger patient population is required to verify these results.

Project description:BackgroundNevirapine-based antiretroviral therapy is the predominant (and often the only) regimen available for children in resource-limited settings. Nevirapine resistance after exposure to the drug for prevention of maternal-to-child human immunodeficiency virus (HIV) transmission is common, a problem that has led to the recommendation of ritonavir-boosted lopinavir in such settings. Regardless of whether there has been prior exposure to nevirapine, the performance of nevirapine versus ritonavir-boosted lopinavir in young children has not been rigorously established.MethodsIn a randomized trial conducted in six African countries and India, we compared the initiation of HIV treatment with zidovudine, lamivudine, and either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 2 to 36 months of age who had no prior exposure to nevirapine. The primary end point was virologic failure or discontinuation of treatment by study week 24.ResultsA total of 288 children were enrolled; the median percentage of CD4+ T cells was 15%, and the median plasma HIV type 1 (HIV-1) RNA level was 5.7 log(10) copies per milliliter. The percentage of children who reached the primary end point was significantly higher in the nevirapine group than in the ritonavir-boosted lopinavir group (40.8% vs. 19.3%; P<0.001). Among the nevirapine-treated children with virologic failure for whom data on resistance were available, more than half (19 of 32) had resistance at the time of virologic failure. In addition, the time to a protocol-defined toxicity end point was shorter in the nevirapine group (P=0.04), as was the time to death (P=0.06).ConclusionsOutcomes were superior with ritonavir-boosted lopinavir among young children with no prior exposure to nevirapine. Factors that may have contributed to the suboptimal results with nevirapine include elevated viral load at baseline, selection for nevirapine resistance, background regimen of nucleoside reverse-transcriptase inhibitors, and the standard ramp-up dosing strategy. The results of this trial present policymakers with difficult choices. (Funded by the National Institute of Allergy and Infectious Diseases and others; P1060 ClinicalTrials.gov number, NCT00307151.).

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Comparing the efficacy of efavirenz and boosted lopinavir using viremia copy-years.

Publications

Comparing the efficacy of efavirenz and boosted lopinavir using viremia copy-years.

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