Drug resistance mutations in HIV pol sequences from Argentinean patients under antiretroviral treatment: subtype, gender, and age issues.

We studied drug resistance mutations (DRMs) in 2623 pol sequences. Out of 94,828 amino acid substitutions that were detected, 8749 corresponded to nucleoside reverse transcriptase inhibitor (NRTI), 3765 to nonnucleoside reverse transcriptase inhibitor (NNRTI), and 7141 to protease inhibitor (PI) resistance-associated mutations. The most common DRMs were L10I, I54V, L90M, V82A, A71V, L10V, M46I, M184V, M41L, T215Y, D67N, L210W, K70R, N348I, V118I, K103N, Y181C, G190A, K101E, V108I, L100I, V90I, K101Q, and A98G. As expected, DRMs frequencies depended on viral genotype. The amounts of NRTI and PI resistance mutations among B and BF sequences from children were higher than among sequences from adults. The frequencies of PI and NRTI resistance mutations among B and BF sequences from adult men were higher than among sequences from women. Some of these observations can be explained in light of the available epidemiological information, but some cannot, indicating that further studies are needed to understand the antiretroviral resistance epidemics in Argentina.

HLA-driven convergence of HIV-1 viral subtypes B and F toward the adaptation to immune responses in human populations.

BACKGROUND: Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. METHODOLOGY/PRINCIPAL FINDINGS: We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. CONCLUSIONS: Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate.

HCV genotype distribution among HIV co-infected individuals in Argentina: Relationship with host and viral factors / Distribución de los genotipos de HCV entre individuos co-infectados con HIV en Argentina: su relación con factores del huésped y del virus

Coinfection with hepatitis C virus (HCV) in individuals infected with HIV is associated with a higher incidence of liver injury, hepatic decompensation, anddecreased survival than that observed in an HIVmonoinfected population. While prevalence studies on HIV/HCV coinfection have been performed in theU.S. and in some European countries, little is known about HCV genotype distribution in Latin America.The main objective was to evaluate the HCV prevalence and genotypes among HIV co-infected patients, and their relationship with HCV viral load, serumALT level and T lymphocyte CD4+ cell count. These data pursue to increase the knowledge from South America about a pressing problem from HIV-infectedpatients. Retrospectively collected specimens from 593 HIV-positive individuals in Argentina were tested foranti-HCV. These were analyzed for HCV-RNA qualitatively and quantitatively. The HCV genotype was determined by the RFLP method. One hundred andtwenty-nine (21.7%) HIV-infected individuals were anti-HCV positive; 65.9% of them exhibited detectable HCV- RNA. Genotype 1 (43, 1a/c; 9, 1b;and 5, 1a/c+1b) was present in 57, while 1, 14 and 13 were infected with genotype 2, 3 or a mix, respectively.Co-infected individuals were more likely to be male, without significant differences in age and CD4+ cell counts than HIV-monoinfected individuals.HCV infection prevalence in patients co-infected with HIV highlights the impending public health impact of this problem. Considering the increasingrate of HCV genotypes with lower response rates to treatment among HIV co-infected patients, antiretroviraltherapy success might be jeopardized by HCV coinfection.

La coinfección con el virus de hepatitis C (HCV) en individuos infectados con HIV está asociada con una mayor incidencia de injuria y descompensación hepática,y un menor tiempo de supervivencia respecto de la población mono-infectada por HIV. Mientras que diferentesestudios de prevalencia de la coinfecciónHIV/HCV se han llevado a cabo en Estados Unidos y países de Europa, la información de la distribución degenotipos de HCV en Latinoamérica es escasa. El objetivo de este estudio fue evaluar la prevalencia de HCVy la distribución de sus genotipos entre pacientes coinfectados con HIV, y su relación con la carga viral deHCV, los niveles séricos de ALT y el recuento de linfocitos T CD4+. Estos datos pretenden incrementar el conocimiento desde la región de Sudamérica acerca de este acuciante problema en pacientes infectados con HIV.Retrospectivamente se colectaron especímenes desde 593 pacientes infectados con HIV en Argentina enquienes se investigó la presencia de anticuerpos anti-HCV. Se pesquisó además la presencia de RNA viral deHCV tanto cualitativa como cuantitativamente. El genotipo de HCV se determinó por la técnica de RFLP.Ciento veintinueve (21.7%) individuos infectados con HIV fueron positivos para anti-HCV; 65.9% de ellos exhibieron RNA de HCV detectable. El genotipo 1(43, 1a/c; 9, 1b; y 5, 1a/c+1b) se presentó en 57 individuos, en tanto que 1, 14 y 13 estaban infectados porlos genotipos 2, 3 o mezcla de ellos, respectivamente. Predominó el sexo masculino entre los individuos concoinfección, en tanto que no se advirtieron diferencias significativas respecto de los pacientes infectados sólocon HIV en lo referido a edad y recuento de linfocitos T CD4+. La prevalencia de infección por HCV en pacientescoinfectados con HIV resalta el impacto de esta problemática en la salud pública. Considerando la creciente tasa de genotipos de HCV con menor respuestaal tratamiento entre los pacientes coinfectados con HIV, el efecto...

Analysis of HIV type 1 diversity in pregnant women from four Latin American and Caribbean countries.

Worldwide, the distribution of HIV-1 subtypes and intersubtype recombinants is not homogeneous. In Latin America and the Caribbean, HIV-1 subtype B predominates. However, in the south of Brazil and in countries of the Southern cone (Argentina, Chile, Paraguay, and Uruguay) there is a different distribution of viral subtypes and intersubtype recombinants. The aim of this work was to analyze HIV-1 diversity in a cohort of pregnant women (with primarily heterosexual acquisition of the infection) who were diagnosed with HIV-1 infection during their current pregnancy and who received ARVs during pregnancy for perinatal transmission prophylaxis. Analysis of 121 partial pol sequences from subjects enrolled in Argentina, Brazil, the Bahamas, and Mexico was performed by phylogenetic and recombinant characterization. Different prevalences of subtype B were observed (100% for specimens from Mexico and the Bahamas, 61% for Brazil, and 30% for Argentina). Subtypes C and F were found, along with BC, BF, FC, and CBF recombinants in specimens from Brazilians. A high prevalence of BF recombinants was found (70%) in specimens from Argentina. The different patterns of HIV- 1 subtypes and intersubtype recombinants in South America (Argentina and Brazil) compared to those in Central and North America should be considered in the design of future HIV-1 vaccine trials.

Distribución de subtipos y recombinantes del HIV: situación en la Argentina / Distribution of subtypes and recombinant of HIV: situation in Argentina

Soon after HIV (Human Immunodeficiency Virus) was discovered, its characteristics level of diversity and variability was established. So far, within HIV-1 it is known that there exist 3 main groups, 9 subtypes and at least 12 recombinant forms. Not only does this diversity affect taxonomy, but also prophylaxis and therapy for HIV infection. Numerous studies worldwide have demonstrated the influence this variability has on both diagnosis and monitoring assays as well as on the pathogenesis of HIV infection. In Argentina, from the molecular point of view, the epidemic shows a complex pattern. HIV-1 subtypes B and F have been described as well as a recombinant B/F form. Epidemiology and molecular data suggest high percentage levels and a great diversity of these recombinant forms in the heterosexual population.