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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

Introduction : Surveillance of primary resistance to antiretroviral drugs is particularly important in pregnant population, in which infection by drug-resistant HIV has not only implications for maternal treatment, but could also jeopardize the efficacy of neonatal prophylaxis. We aim to describe the prevalence of resistance associated mutations (RAMs) in pregnant women with intrapartum HIV diagnosis in a public hospital of Buenos Aires, Argentina. Materials and Methods : Prospective pilot study (period from 2008 to October 2013). Plasma samples were tested for viral load by Versant HIV-1 RNA 3.0 (bDNA) and sequenced using HIV-1 TRUGENE ™ Genotyping Kit (Siemens). The prevalence of RAMs was analyzed according to World Health Organization (WHO) criteria. Results : Of 231 HIV-infected pregnant women assisted, 6% (n=14) had intrapartum diagnosis of HIV infection. 12 patients (85.7%) had previous pregnancies, 10 (71.4%) had inadequate prenatal care and 3 (23.1%) seroconverted during pregnancy. Maternal characteristics (expressed medians and ranges) were: age 25.5 (16–35) years; gestational age at birth: 39 (30–42) weeks; CD4 count: 500 (132–925) cells/µL; viral load: 9418 (1800–55299) copies/mL. No one had hepatitis B virus (HBV) or hepatitis C virus (HCV) coinfection; four (33.3%) had syphilis. Eight patients (57.1%) had vaginal delivery and six emergency C-section (42.9%). In six cases (46.2%), membrane rupture was spontaneous; four patients (28.6%) failed to receive intrapartum zidovudine (ZDV) infusion. In 12 patients a genotypic resistance test was performed: two (16.7%) had WHO RAMs corresponding to K103N mutation in both cases, conferring high-level resistance to nevirapine (NVP) and efavirenz. Two newborns (14.3%) were preterm. All received neonatal prophylaxis: ZDV in 1 case and combined prophylaxis (ZDV/3TC/NVP) in the remaining 13 (92.9%). All newborns were formula-fed. Two (14.3%) had congenital syphilis, one of whom died. One newborn was HIV-infected (positive proviral DNA at 24 hours of life, wild-type HIV). Conclusions : This pilot study suggests that levels of transmitted resistance in this high-risk population of pregnant women could be moderate to high. We preliminarily observed high-level resistance to NVP: if this finding is confirmed with a larger sample, it could potentially jeopardize the utility of this drug in the combined neonatal prophylaxis recommended in the absence of maternal antiretroviral therapy. (Published: 2 November 2014) Citation: Cecchini D et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19704 http://www.jiasociety.org/index.php/jias/article/view/19704 | http://dx.doi.org/10.7448/IAS.17.4.19704

The HIV epidemic in Argentina has changed since the first case was reported in 1982. Since the beginning of the 1990s, a decrease in the number parenterally acquired infections has been observed, with a marked increase in transmission through unprotected sexual contact (heterosexual and homosexual), and in the number of women living with HIV/AIDS [1]. Few prevalence studies have addressed the hepatitis B and C virus coinfection in Argentina. We performed this study in a large single clinic in Buenos Aires, taking care of more than 3,000 HIV patients. During a seven-month period (9/2004 to 3/2005), all HIV-positive patients ≥ 18 years old, who were followed up at our unit and who had their scheduled controls for HIV viral load (VL) at the Argentinean National Reference Centre for AIDS (CNRS), were invited to participate in the study. The study was approved by the Fernandez Hospital Ethics Committee. Patients gave their informed consent to be included in the study. Six hundred subjects were asked to enter the study, and 593 accepted. Studied population: 65.6% males, 64% young adults between 20 and 40 years old. The main route of HIV infection was through sexual contact (70%). Of the 593 samples, 52% (n=308) showed positive results for serological markers (HBcAb/HBsAg/anti-HCV) for hepatitis B or C coinfection. Coinfection rates and subjects characteristics are described in Table 1. Table 1 Demographics, rates of HCV/HBV coinfection, main routes of infection, median levels of CD4 cell count, HIV viral load, HAART, frequency of ALT level among HIV-positive patients studied HBV genotype A was identified in 85% of the samples with detectable HBV DNA, instead of genotype F, the most prevalent in our country among blood donors [2]. Among the 22 HBsAg-positive samples, four showed mutations in the rt domain of the pol gene. These samples belonged to patients who had a prolonged history of exposure to lamivudine (median: 25 months) and none of them had received tenofovir. This data reinforces the importance of adequate management of drugs with HBV/HIV dual activity when selecting antiretroviral therapies in coinfected patients, as stated in the last update of the European and North American guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [3,4]. The main isolated HCV genotype was 1 (65%), followed by genotype 3 (16.5%). Our study shows a change in the prevalence of HCV and HBV coinfection comparing with a previous report of the same geographical area [5], among people living with HIV/AIDS in Buenos Aires, the city with the highest prevalence of HIV in Argentina. A reduction in prevalence rates of dual HIV/HCV (from 58.5% in 1999 to 21%, p 0.000) and HIV/HBV coinfection (from 14.5% in 1999 to 3.7%, p 0.000) was observed. This could be related to the decreasing number of injecting drug users in our country because of the introduction of non-injecting recreational drugs and the increasing transmission through unprotected sex [1]. Despite the decrease in the rates of HCV/HIV and HBV/HIV coinfections the prevalence of those coinfections continues to be high and it could lead to the increase in the morbidity and mortality associated with liver disease, especially in the context of expanded antirretroviral therapy in Argentina. The epidemiological data presented in this study provides information for the development of prevention campaigns for hepatitis C through harm reduction policies and for hepatitis B vaccination programs among people living with HIV/AIDS.