Emergence of uncommon HIV‐1 non‐B subtypes and circulating recombinant forms and trends in transmission of antiretroviral drug resistance in patients with primary infection during the 2013‐2015 period in Marseille, Southeastern France

Abstract

Primary HIV-1 infections (PHI) with non-B subtypes are increasing in developed countries while transmission of HIV-1 harboring antiretroviral resistance-associated mutations (RAMs) remains a concern. This study assessed non-B HIV-1 subtypes and RAMs prevalence among patients with PHI in university hospitals of Marseille, Southeastern France, in 2005-2015 (11 years). HIV-1 sequences were obtained by in-house protocols from 115 patients with PHI, including 38 for the 2013-2015 period. On the basis of the phylogenetic analysis of the reverse transcriptase region, non-B subtypes were identified in 31% of these patients. They included 3 different subtypes (3A, 1C, 4F), 23 circulating recombinant forms (CRFs) (CRF02_AG, best BLAST hits being CRF 36_cpx and CRF30 in 7 and 1 cases, respectively), and 5 unclassified sequences (U). Non-B subtypes proportion increased significantly, particularly in 2011-2013 vs in 2005-2010 (P = .03). CRF02_AG viruses largely predominated in 2005-2013 whereas atypical strains more difficult to classify and undetermined recombinants emerged recently (2014-2015). The prevalence of protease, nucleos(t)ide reverse transcriptase, and first-generation nonnucleoside reverse transcriptase inhibitors-associated RAMs were 1.7% (World Health Organization [WHO] list, 2009/2.6% International AIDS Society [IAS] list, 2017), 5.2%/4.3%, and 5.2%/5.2%, respectively. Etravirine/rilpivirine-associated RAM (IAS) prevalence was 4.3%. Men who have sex with men (MSM) were more frequently infected with drug-resistant viruses than other patients (26% vs 7%; P = .011). The recent increase of these rare HIV-1 strains and the spread of drug-resistant HIV-1 among MSM in Southeastern France might be considered when implementing prevention strategies and starting therapies.

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

“…The prevalence of RPV-resistant isolates ranges from 4 to 10% in individuals who are treatment naive (26)(27)(28)(29)(30)(31)(32)(33) to 42 to 72% in individuals with viremia during non-RPVcontaining ART (34)(35)(36)(37)(38)(39)(40)(41). Three clinical studies evaluated the efficacy of RPV-containing regimens compared to EFV-containing regimens in treatment-naive individuals (the ECHO, THRIVE, and STaR trials), all of which identified multiple RPV-associated resistance mutations that arose in subjects on RPV-containing ART (42,43).…”

Changes in Primary HIV-1 Drug Resistance Due to War Migration from Eastern Europe

“…These genotypic changes do not confer consistently decreased susceptibility by themselves when viral strains are subjected to phenotypic testing [ 33 , 34 ]. Furthermore, studies of resistance pattern that emerge in patients receiving ART indicate that presence of polymorphisms before start of ART may provide a background facilitating emergence of specific selection pathways to secondary resistance[ 27 , 35 , 36 ].…”

Impact of HIV-1 subtypes on gross deletion in the nef gene after Korean Red Ginseng treatment

“…HIV-1 subtype B is the most common subtype in developed countries, and accounts for approximately 11%–12% of the global epidemic [ 4 ]. Primary HIV-1 infections with various non-B subtypes (hereafter called non-B) are increasing in developed countries [ [4] , [5] , [6] ]. There have been reports on the difference in disease progression among the patients infected with non-B [ [7] , [8] , [9] ].…”