HIV, HBV, and HCV molecular epidemiology among trans (transvestites, transsexuals, and transgender) sex workers in Argentina.

Commercial sex work is frequent among male-to-female transvestites, transsexuals and transgenders in Argentina, leading to high susceptibility to HIV, HBV, and HCV among other sexually transmitted infections. In a global context of scarce data on the trans sex workers population, this study was aimed to study the genomic characterization of these viruses. Plasma presence of HIV, HBV, and HCV genomic material was evaluated in samples from 273 trans sex workers. Genomic sequences of HIV-gag, pol, and vif-vpu genes, HBV-S gene, and HCV-5'UT and NS5B genes were obtained. Molecular characterization involved phylogenetic analysis and several in silico tools. Resistance-associated mutations in HIV and HBV pol genes were also analyzed. The HIV genomic characterization in 62 trans sex workers samples showed that 54.8% of the isolates corresponded to BF intersubtype recombinants, and 38.7% to subtype B. The remaining were classified as subtypes C (4.8%) and A (1.6%). HBV and HCV co-infection prevalence among HIV positive trans sex workers yielded rates of 3.2% and 6.5% respectively. Drug resistance-associated mutations were found in 12/62 (19%) HIV pol sequences, but none among HBV. Based on phylogenetic relationships, HIV isolates characterized as subtypes BF and B appeared intermingled with those from other high-risk groups. Despite trans sex workers declared not to have received antiviral treatment, complex drug resistance-associated mutation patterns were found in several HIV isolates. Planned prevention, screening, and treatment are needed to reduce further transmission and morbidity.

HIV-1 induces telomerase activity in monocyte-derived macrophages, possibly safeguarding one of its reservoirs.

Monocyte-derived macrophages (MDM) are widely distributed in all tissues and organs, including the central nervous system, where they represent the main part of HIV-infected cells. In contrast to activated CD4(+) T lymphocytes, MDM are resistant to cytopathic effects and survive HIV infection for a long period of time. The molecular mechanisms of how HIV is able to persist in macrophages are not fully elucidated yet. In this context, we have studied the effect of in vitro HIV-1 infection on telomerase activity (TA), telomere length, and DNA damage. Infection resulted in a significant induction of TA. This increase was directly proportional to the efficacy of HIV infection and was found in both nuclear and cytoplasmic extracts, while neither UV light-inactivated HIV nor exogenous addition of the viral protein Tat or gp120 affected TA. Furthermore, TA was not modified during monocyte-macrophage differentiation, MDM activation, or infection with vaccinia virus. HIV infection did not affect telomere length. However, HIV-infected MDM showed less DNA damage after oxidative stress than noninfected MDM, and this resistance was also increased by overexpressing telomerase alone. Taken together, our results suggest that HIV induces TA in MDM and that this induction might contribute to cellular protection against oxidative stress, which could be considered a viral strategy to make macrophages better suited as longer-lived, more resistant viral reservoirs. In the light of the clinical development of telomerase inhibitors as anticancer therapeutics, inhibition of TA in HIV-infected macrophages might also represent a novel therapeutic target against viral reservoirs.

Longitudinal analysis of the 5'UTR, E2-PePHD and NS5A-PKRBD genomic regions of hepatitis C virus genotype 1a in association with the response to peginterferon and ribavirin therapy in HIV-coinfected patients.

BACKGROUND: The rate of non-response to pegylated interferon plus ribavirin (peg-IFN+RBV) in HCV/HIV coinfected patients is higher than in HCV-monoinfected patients. In this sense, the contribution of HCV genetic variability is unknown. The 5' untranslated (5'UTR), the nonstructural 5A (NS5A) and the second envelope (E2) HCV genomic regions have been implicated to peg-IFN therapy response. The proteins appear to block interferon (IFN)-induced RNA-dependent protein kinase (PKR) and the 5'UTR may influence the viral lymphotropism. METHODS: We examined comparatively the pretreatment HCV variability between HIV coinfected and HCV monoinfected patients as well as assessed longitudinally the impact of peg-IFN+RBV on HCV variability when HIV is co-present. For this purpose, 15 HIV coinfected and 20 HCV monoinfected patients were compared. They were peg-IFN+RBV non-responders and infected with HCV 1a. RESULTS: Irrespectively of the HIV-coexistence, at baseline the amino acid variation in the NS5A-related domains was significantly higher than in the E2-PePHD (p<0.001). The number of amino acid variations (mean±SD) at the NS5A-ISDR domain was higher among HCV/HIV patients than HCV-monoinfected ones (1.80±0.77 vs. 0.95±1.05; p=0.009) but such difference was slightly lower when comparing NS5A-PKRBD sequences (2.47±1.13 vs. 1.60±1.57; p=0.06). No differences were found at the E2-PePHD (0±0 vs. 0.2±0.4). At intra-HIV coinfected patient level, only minor (HCV genetic analysis) or no (HCV substitution rate and quasispecies heterogeneity) changes were observed during therapy (basal, 24h, 4weeks, and 12weeks). CONCLUSIONS: Among HCV-1a/HIV coinfected and HCV-monoinfected peg-IFN+RBV non-responder patients, the HCV variability at the 5'UTR, E2-PePHD and NS5A-PKRBD/ISDR domains was mostly comparable exhibiting a low number of variations. Four well-defined amino acid substitutions in NS5A-ISDR domain appeared most frequently when HIV coexists. The interferon-based therapy did not exert any effect in the variation, selection or diversity in the above mentioned HCV regions that could influence clinical responsiveness to IFN therapy.

A clustering phenomenon among HCV-1a strains among patients coinfected with HIV from Buenos Aires, Argentina.

The human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes which lead to high coinfection rates. Among HIV-infected individuals such rates reached 21% in Argentina, being HCV-1a the most predominant subtype. In this work, 25 HCV subtype 1a (HCV-1a) strains from Argentinean patients coinfected with HIV were studied based on E2 and NS5A sequences. Phylogenetic analyses indicated that 12 strains were highly related to each other, constituting a highly supported (posterior probability = 0.95) monophyletic group that we called "M." The remaining HCV strains (group dispersed or "D") were interspersed along the phylogenetic trees. When comparing both groups of HCV-1a, 10 amino acid differences were located in functional domains of E2 and NS5A proteins that appeared to affect eventually the peptides binding to MHC-I molecules thus favoring immune escape and contributing to the divergence of HCV genotypes. Bayesian coalescent analyses for HCV-1a cluster M isolates indicated that the time to the most recent common ancestor (tMRCA) overlaps with the age estimated recently for the HIV-BF epidemic in Argentina. Furthermore, the genomic characterization based on pol gene analysis from HIV viremic patients showed that most HIV isolates from patients coinfected with HCV-1a cluster M were BF recombinants with identical recombination patterns. In conclusion, these results suggest the presence of an HCV-1a monophyletic cluster with a potential HIV co-transmission by phylogenetic analyses.

Telomerase activity in peripheral blood mononuclear cells from HIV and HIV-HCV coinfected patients.

Replicative senescence of peripheral blood mononuclear cells (PBMC) plays an important role in the pathophysiology of chronic viral infections. Although there are controversial reports concerning telomerase activity in HIV monoinfected subjects, no data on HIV-HCV coinfected individuals is available. In this cross-sectional study telomerase activity was quantified in non-stimulated and mitogen-stimulated PBMC lysates from HIV-1 monoinfected and HIV-HCV coinfected individuals using real-time PCR. Up-regulation of telomerase activity after mitogen stimulation was impaired in PBMC of HIV monoinfected and HIV-HCV coinfected patients. The lack of an appropriate induction of this enzymatic activity after stimulus could partly account for immunosuppressive conditions observed in such patients.

HCV genotype distribution among HIV co-infected individuals in Argentina: relationship with host and viral factors.

Coinfection with hepatitis C virus (HCV) in individuals infected with HIV is associated with a higher incidence of liver injury hepatic decompensation, and decreased survival than that observed in an HIV-monoinfected population. While prevalence studies on HIV/HCV coinfection have been performed in the U.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, serum ALT level and T lymphocyte CD4+ cell count. These data pursue to increase the knowledge from South America about a pressing problem from HIV-infected patients. Retrospectively collected specimens from 593 HIV-positive individuals in Argentina were tested for anti-HCV These were analyzed for HCV-RNA qualitatively and quantitatively. The HCV genotype was determined by the RFLP method. One hundred and twenty-nine (21.7%) HIV-infected individuals were anti-HCV positive; 65.9% of them exhibited detectable HCV-RNA. Genotype 1 (43, la/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 increasing rate of HCV genotypes with lower response rates to treatment among HIV co-infected patients, antiretroviral therapy success might be jeopardized by HCV coinfection.

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.(AU)

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...(AU)

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...