Abstract
Background: Nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) with boosted protease inhibitors are included in standardized first-line and second-line regimens. Recent World Health Organization (WHO) guidelines recommend a boosted protease inhibitor (PI) combined with 2 NRTIs or raltegravir as a second-line regimen.Objective: Ritonavir-boosted lopinavir (LPV/r) is known as a key second-line antiretroviral therapy (ART) in resource-limited settings. We carried out a meta-analysis to analyze virologic suppression and effectiveness of LPV/r-based second-line therapy in HIV-infected patients.Methods: In this meta-analysis, we searched randomized controlled trials and observational cohort studies to evaluate outcomes of second-line ART for patients with HIV who failed first-line therapy. A systematic search was conducted in Pubmed, Cochrane Library, and Embase from inception to January 2018. Outcomes included viral suppression, CD4 cell counts, drug resistance, adverse events, and self-reported adherence. We assessed comparative efficacy and safety in a meta-analysis. Data analysis was performed using RevMan 5.3 and Stata12.0.Results: Nine studies comprising 3,923 patients were included in the meta-analysis. The overall successful virologic suppression rate of the second-line regimen was 77% (ITT) and 87% (PP) at 48 weeks with a plasma HIV RNA load of <400 copies/mL. No statistical significance was found in CD4 cell count recoveries between LPV/r plus 2-3 NRTIs and simplified regimens (LPV/r plus raltegravir) at 48 weeks (P = 0.09), 96 weeks (P = 0.05), and 144 weeks (P = 0.73). Four studies indicated that the virus had low-level resistance to LPV/r, and the most common clinically significant PI-resistance mutations were 46I, 54V, 82A/82F, and 76V; however, no virologic failure due to LPV/r resistance was detected. In addition, no statistical significance was found between the two groups in self-reported adherence [relative risks (RR) = 1.03,95% confidence interval (CI) 1.00, 1.07, P = 0.06], grade 3 or 4 adverse events (RR = 0.84, 95% CI 0.64, 1.10, P = 0.20) or serious events (RR = 0.85, 95% CI 0.77, 1.17, P = 0.62).Conclusions: These results suggest that the LPV/r-based regimen demonstrates efficacious and low resistance as second-line antiretroviral therapy.Both LPV/r plus 2-3 NRTIs and LPV/r plus RAL regimens improved CD4 cell counts. There was no evidence of superiority of simplified regimens over LPV/r plus 2-3 NRTIs.
Highlights
Millions of adults and children who are infected with HIV in resource-limited regions have access to antiretroviral therapy (ART) based on World Health Organization (WHO) guidelines (Gilks et al, 2006; World Health Organization, 2013)
Systematic searches were conducted in Cochrane Library, Pubmed, and Embase databases for publications in English with key search words, including “HIV” and “ritonavir-boosted lopinavir.”
According to our search strategy, we identified 8,753 articles, 7,259 articles from Embase and 1,494 articles from Cochrane and Pubmed databases
Summary
Millions of adults and children who are infected with HIV in resource-limited regions have access to antiretroviral therapy (ART) based on World Health Organization (WHO) guidelines (Gilks et al, 2006; World Health Organization, 2013). In recent years, a growing number of patients have presented with first-line regimen (World Health Organization, 2013) failure and have been switched to second-line therapy (Long et al, 2010; Hamers et al, 2011; Hoen et al, 2011). Assessing the optimum second-line ART regimen in PLWHA who experience first-line therapy failure in resource-limited settings has important clinical, public health, and health policy considerations. Recent World Health Organization (WHO) guidelines recommend a boosted protease inhibitor (PI) combined with 2 NRTIs or raltegravir as a second-line regimen
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