Effectiveness of Protease Inhibitor/Nucleos(t)ide Reverse Transcriptase Inhibitor–Based Second-line Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus Type 1 Infection in Sub-Saharan Africa: A Systematic Review and Meta-analysis

Abstract

In sub-Saharan Africa, second-line ritonavir-boosted protease inhibitor–based antiretroviral therapy led to virological suppression in 69.3% of participants at week 48 and 61.5% at week 96, based on an intention-to-treat meta-analysis of 4558 participants (14 studies) and 2145 participants (8 studies), respectively.

Evolution of Protease Inhibitor Resistance in Human Immunodeficiency Virus Type 1 Infected Patients Failing Protease Inhibitor Monotherapy as Second-line Therapy in Low-income Countries: An Observational Analysis Within the EARNEST Randomized Trial

“…Despite varying subtypes, the pattern of resistance-mutations we found is similar to that in other studies of PI-based regimens [7,23,[29][30][31]. I47A was often followed by V32I, and developing I47A was associated with a lower odds of developing I54V and vice versa.…”

“…Many patients had virological failure without resistance, a well-known finding for PI-based regimens [4,[21][22][23]. Mutations in other viral regions (e.g.…”

Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

“… 13 We have previously reported on the large variations in the rates of switching to second-line ART in SSA, with higher rates reported in populations undergoing virological monitoring than in those without routine access to viral load testing, as also reflected in this study. 10 Emphasis has been placed on providing adherence support prior to changing ART for patients experiencing viraemia in SSA, given that re-suppression is frequently observed. In our cohort, it was common for viraemic patients to gain suppression while remaining on first-line ART.…”

“… 45 Interestingly, detection of NRTI resistance, most commonly M184V and TAMs, was found to predict significantly higher (rather than lower) odds of virological suppression on second-line ART. 10 One proposed explanation is that patients who develop resistance at failure of first-line ART may have higher levels of adherence (hence higher drug selective pressure) than subjects who fail without resistance. Furthermore, it is well established that NRTIs such as tenofovir and zidovudine retain significant residual antiviral activity in the presence of TAMs, and that this is enhanced by the concomitant presence of M184V and continuation of lamivudine.…”

A phase IV randomised, open-label pilot study to evaluate switching from protease-inhibitor based regimen to Bictegravir/Emtricitabine/Tenofovir Alafenamide single tablet regimen in Integrase inhibitor-naïve, virologically suppressed HIV-1 infected adults harbouring drug resistance mutations (PIBIK study): study protocol for a randomised trial

“…These studies however excluded individuals known to harbour HIV-1 drug resistance. It is well established that HIV-positive individuals that have either pre-treatment drug resistance (PDR) or limited drug resistance following failure of first-line ART achieve virological suppression on regimens comprising a bPI plus two nucleos(t)ide reverse transcriptase inhibitor (NRTIs) [9,10]. In contrast, in the SWITCHMRK study, switching virologically suppressed individuals from a bPI to the integrase inhibitor raltegravir resulted in an increased risk of virological failure relative to individuals maintained on the bPI.…”