Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART

Palacios, Rosario; Pérez-Hernández, Isabel; Martínez, M.a C. López; Mayorga, M; González-Domenech, Carmen M.; Omar, Mohamed; Olalla, Julián; Romero, Alberto; Romero, José María; Pérez-Camacho, Inés; Hernández-Quero, José; Santos, Juan Luis

doi:10.1007/s10096-016-2602-3

Cited by 13 publications

(14 citation statements)

References 14 publications

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“…Recently, Palacios and colleagues reported about the efficacy and safety of switching to ABC/3TC plus RPV in virologically suppressed HIV infected patients on HAART [ 11 ]. At 48 weeks, 78 patients (92%) were still on treatment with this same regimen and the efficacy was 88% and 96% by the intention to treat and the per protocol analyses, respectively.…”

Section: Resultsmentioning

confidence: 99%

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load

et al. 2018

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IntroductionA regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen.MethodsRetrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015.The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters.TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason.Patients’ follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit.Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters.Results and discussionIn this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942).Over a median follow-up of 2.9 years (IQR: 1.9–3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral blip, 1 due to VF, 1 for asthma, 1 patient’s decision, 1 due to enrolment in a study protocol].ConclusionsIn this retrospective study, long-term use of RPV plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not found to be affected by low CD4+ nadir or high pre-ART viral load.

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Section: Resultsmentioning

confidence: 99%

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load

et al. 2018

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“…Despite great advances in antiretroviral therapy in the last decade, several limitations remain including adverse effects, suboptimal adherence, tolerability problems and drug–drug interactions . Substitution of cART in stable, virologically suppressed patients with the aim of improving tolerability and convenience is a common practice in clinical settings . Data on the safety and durability of virological suppression following switches within or across antiretroviral classes have largely come from randomized controlled trials.…”

Section: Introductionmentioning

confidence: 99%

The treatment outcomes of antiretroviral substitutions in routine clinical settings in Asia; data from the TREAT Asia HIV Observational Database (TAHOD)

et al. 2017

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IntroductionAlthough substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV‐infected patients in non‐clinical trial settings in Asian countries.MethodsThe study population consisted of HIV‐infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within‐class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed.ResultsOf 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution.ConclusionsThe rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non‐clinical trial settings in Asian countries.

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“…The nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is FDA approved as a component of combination antiretroviral therapy (ART) that includes TFV disoproxil fumarate and FTC in a once-daily oral pill. RPV in combination with other antiretroviral drugs has been evaluated for efficacy as ART (7)(8)(9) and postexposure prophylaxis (10). RPV also has been developed in a nanoparticle long-acting formulation (RPV LA) to improve adherence (11,12).…”

mentioning

confidence: 99%

Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice

Melody

Roy

Kline

et al. 2020

J Virol

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As a long-acting formulation of the nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV LA) has been proposed for use as preexposure prophylaxis (PrEP) and the prevalence of transmitted RPV-resistant viruses can be relatively high, we evaluated the efficacy of RPV LA to inhibit vaginal transmission of RPV-resistant HIV-1 in humanized mice. Vaginal challenges of wild-type (WT), Y181C, and Y181V HIV-1 were performed in mice left untreated or after RPV PrEP. Plasma viremia was measured for 7 to 10 weeks, and single-genome sequencing was performed on plasma HIV-1 RNA in mice infected during PrEP. RPV LA significantly prevented vaginal transmission of WT HIV-1 and Y181C HIV-1, which is 3-fold resistant to RPV. However, it did not prevent transmission of Y181V HIV-1, which has 30-fold RPV resistance in the viruses used for this study. RPV LA did delay WT HIV-1 dissemination in infected animals until genital and plasma RPV concentrations waned. Animals that became infected despite RPV LA PrEP did not acquire new RPV-resistant mutations above frequencies in untreated mice or untreated people living with HIV-1, and the mutations detected conferred low-level resistance. These data suggest that high, sustained concentrations of RPV were required to inhibit vaginal transmission of HIV-1 with little or no resistance to RPV but could not inhibit virus with high resistance. HIV-1 did not develop high-level or high-frequency RPV resistance in the majority of mice infected after RPV LA treatment. However, the impact of low-frequency RPV resistance on virologic outcome during subsequent antiretroviral therapy still is unclear. IMPORTANCE The antiretroviral drug rilpivirine was developed into a long-acting formulation (RPV LA) to improve adherence for preexposure prophylaxis (PrEP) to prevent HIV-1 transmission. A concern is that RPV LA will not inhibit transmission of drug-resistant HIV-1 and may select for drug-resistant virus. In female humanized mice, we found that RPV LA inhibited vaginal transmission of WT or 3-fold RPV-resistant HIV-1 but not virus with 30-fold RPV resistance. In animals that became infected despite RPV LA PrEP, WT HIV-1 dissemination was delayed until genital and plasma RPV concentrations waned. RPV resistance was detected at similar low frequencies in untreated and PrEP-treated mice that became infected. These results indicate the importance of maintaining RPV at a sustained threshold after virus exposure to prevent dissemination of HIV-1 after vaginal infection and low-frequency resistance mutations conferred low-level resistance, suggesting that RPV resistance is difficult to develop after HIV-1 infection during RPV LA PrEP.

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Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART

Cited by 13 publications

References 14 publications

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load

The treatment outcomes of antiretroviral substitutions in routine clinical settings in Asia; data from the TREAT Asia HIV Observational Database (TAHOD)

Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice

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