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BackgroundCurrent knowledge on HIV-1 resistance to integrase inhibitors (INIs) is based mostly on subtype B strains. This contrasts with the increasing use of INIs in low- and middle-income countries, where non-B subtypes predominate.Materials and methodsHIV-1 drug resistance genotyping was performed in 30 HIV-1-infected individuals undergoing virological failure to raltegravir. Drug resistance mutations (DRMs) and HIV-1 subtype were characterized using Stanford HIVdb and phylogenetic analyses.ResultsOf the 30 integrase (IN) sequences, 14 were characterized as subtype F (47%), 8 as subtype B (27%), 7 as BF recombinants (23%) and 1 as a putative CRF05_DF (3%). In 25 cases (83%), protease and reverse transcriptase (PR-RT) sequences from the same individuals confirmed the presence of different BF recombinants. Stanford HIVdb genotyping was concordant with phylogenetic inference in 70% of IN and 60% of PR-RT sequences. INI DRMs differed between B and F IN subtypes, with Q148K/R/H, G140S and E138K/A being more prevalent in subtype B (63% versus 0%, P = 0.0021; 50% versus 0%, P = 0.0096; and 50% versus 0%, P = 0.0096, respectively). These differences were independent of the time on raltegravir therapy or viral load at the time of genotyping. INI DRMs in subtype F IN genomes predicted a lower level of resistance to raltegravir and no cross-resistance to second-generation INIs.ConclusionsAlternative resistance pathways to raltegravir develop in subtypes B and F IN genomes, with implications for clinical practice. Evaluating the role of HIV-1 subtype in development and persistence of mutations that confer resistance to INIs will be important to improve algorithms for resistance testing and optimize the use of INIs.

OBJECTIVES: To assess the prevalence and patterns of pre-treatment HIV drug resistance (PDR) and HIV-1 subtype in infants from Argentina with exposure to different antiretroviral drugs (ARVs) for the prevention of mother-to-child transmission (PMTCT). PATIENTS AND METHODS: HIV-1 genotyping was performed in 115 infants (median age = 2.3 months) born between 2007 and 2014 to screen for drug resistance mutations (DRMs) before starting first-line ART. HIV-1 subtype was characterized by phylogenetic and recombination analysis. RESULTS: Overall, DRMs were found in 34 of 115 infants (PDR level 30% to any ARV, 3.5% to PIs, 12% to NRTIs and 22% to NNRTIs). Of the 115 infants, 22 (19.1%) were ARV-unexposed. Another 93 were ARV-exposed: 28 (24.3%) to short-course zidovudine monotherapy ARV prophylaxis; 25 (21.7%) to nevirapine-based ARV prophylaxis; 12 (10.4%) to perinatal infant zidovudine prophylaxis + maternal combination ART with NNRTIs; and 28 (24.3%) to perinatal infant zidovudine prophylaxis+maternal combination ART with PIs. Transmitted drug resistance among ARV-unexposed infants was 32% (5% to PIs, 9% to NRTIs and 18% to NNRTIs). ART-exposed infants showed multi-class ARV resistance. Importantly, vertical transmission of a triple-class-resistant virus was confirmed in one case. Patterns of DRMs predicted high-level resistance to NNRTIs in a similar and high proportion (>50%) of infants with at least one DRM independently of ARV exposure. BF recombinants were found in 74%, subtype B in 20%, subtype C in 3% and novel AG and AB recombinants in 3%. CONCLUSIONS: PDR in HIV-1-infected children from Argentina is among the highest reported, jeopardizing successful lifelong suppressive ART as well as the efficacy of current PMTCT regimens. Fil: Aulicino, Paula. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Zapiola, Ines. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Kademian, Silvia. Ministerio de Salud; Argentina Fil: Valle, María M. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Subsecretaria de Planificacion y Contralor Sanitario. Direccion Provincial del Instituto Biologico "dr. Tomas Peron".; Argentina Fil: Fernandez Giuliano, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Toro, Rosana Isabel. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Subsecretaria de Planificacion y Contralor Sanitario. Direccion Provincial del Instituto Biologico "dr. Tomas Peron".; Argentina Fil: Barbas, Maria Gabriela. Ministerio de Salud; Argentina Fil: Cañizal, Ana M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Mayon, Paula. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Subsecretaria de Planificacion y Contralor Sanitario. Direccion Provincial del Instituto Biologico "dr. Tomas Peron".; Argentina Fil: Golemba, Marcelo Darío. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ortiz de Zarate, Marcela. No especifíca; Fil: Corazza, Marisa S.. Gobierno de la Provincia de Buenos Aires. Ministerio de Salud. Subsecretaria de Planificacion y Contralor Sanitario. Direccion Provincial del Instituto Biologico "dr. Tomas Peron".; Argentina Fil: Cudola, Analía. Ministerio de Salud; Argentina Fil: Mecikovsky, Débora. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Bologna, Rosa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Mangano, Andrea María Mercedes. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sen, Luisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

The study aimed to determine the prevalence of antiretroviral resistance associated mutations in HIV-1 infected pregnant woman treated in Buenos Aires metropolitan area (period 2008-2014). A total of 136 women with viral load = 500 copies/ml were included: 77 (56.6%) were treatment-naïve and 59 (43.4%) were antiretroviral-experienced patients either with current (n: 24) or previous (n = 35) antiretroviral therapy. Genotypic baseline resistance was investigated in plasma of antiretroviral-naïve patients and antiretroviral-experienced patients. The resistance mutations were identified according to the lists of the World Health Organization and the International Antiviral Society, respectively. Frequencies of resistance associated mutations detected in 2008-2011 and 2012-2014 were compared. A total of 37 (27.2%) women presented at least one resistance associated mutation: 25/94 (26.5%) in 2008-2011 and 12/42 (28.5%) in 2012-2014 (p > 0.05). Among naïves, 15 (19.5%) had at least one mutation: 10/49 (20.4%) in the period 2008-2011 and 5/28 (17.8%) in 2012-2014 (p > 0.05). The resistance mutations detected in naïves were associated with non nucleoside reverse transcriptase inhibitors, being K103N the most common mutation in both periods. In antiretroviral experienced patients, 22/59 (37.3%) had at least one resistance mutation. This study demonstrates a high frequency of resistance associated mutations which remained stable in the period analyzed. These levels suggest an increased circulation of HIV-1 antiretroviral resistant strains in our setting compared to previous reports from Argentina

Background: Rilpivirine-based regimens are now preferred or alternative first-line regimens according to many HIV treatment guidelines. Recently, a surveillance study conducted in Argentina determined that prevalence of pretreatment resistance to first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 10%. The aim of this study was to analyse the prevalence of resistance mutations to newer generation NNRTIs in the population starting ART in Argentina. Methods: We analysed the prevalence of resistance mutations to rilpivirine and etravirine (according to the IAS list), obtained through a nationally representative pretreatment HIV-drug resistance (PDR) surveillance study performed in Argentina in 2014–2015. Briefly, 25 ART-dispensing sites throughout the country were randomly chosen to enrol 330 adults starting ART. Samples were processed with Trugene (Siemens)® and analysed using the Stanford algorithm. Results: All 270 samples corresponding to participants with no prior exposure to antiretroviral drugs were included in this analysis. Median (IQR) age was 35 years (28–43); 66.7% were male; median (IQR) CD4+ T-cell count was 284 cells/mm3 (112–489). The prevalence of resistance to any antiretroviral was 16% (±5%) and prevalence of NNRTI RAMs was 13% (±4%). The prevalence of resistance to rilpivirine was 8% (±3%). Prevalence of resistance to etravirine was 4% (±3%). The most frequent mutations conferring resistance to rilpivirine were: E138A (n=6) and G190A (n=4). Conclusions: This PDR surveillance study showed concerning levels of HIV drug resistance (HIVDR) in Argentina, not only for first-generation NNRTIs but also to rilpivirine. In our setting, performing resistance testing would be necessary before prescription of ART even if a second-generation NNRTI-based regimen was used as first-line therapy. Fil: Bissio, Emiliano. Fundación Centro de Estudios Infectológicos; Argentina Fil: Barbás, Maria G. Laboratorio Central de Córdoba; Argentina Fil: Kademián, Silvia. Laboratorio Central de Córdoba; Argentina Fil: Bouzas, Maria B. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina Fil: Cudola, Analia Ester. Laboratorio Central de Córdoba; Argentina Fil: Fernández Giuliano, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Falistocco, Carlos. Ministerio de Salud de la Nación; Argentina