The effect of protease inhibitor-based dual antiretroviral regimens on CD4/CD8 ratio during the first year of therapy in ART-naïve patients with HIV-infection.

OBJECTIVES: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. METHODS: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/µL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. RESULTS: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. CONCLUSION: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.

Bioinformatic analysis of post-transmission viral readaptation in Argentine patients with acute HIV-1 infection.

During the acute phase of HIV-1 infection, a strong readaptation occurs in the viral population. Our objective was to analyze the post-transmission mutations associated with escape to the cytotoxic immune response and its relationship with the progression of the infection. In this study, a total of 17 patients were enrolled during acute/early primary HIV infection and 8 subjects that were the HIV positive partner resulting in 8 transmission pairs. Genotyping of the genetic polymorphisms of HLA class I A and B was performed using PCR-SSOP. Viral RNA extraction was from plasma. 570 single Gag-gene amplifications were obtained by limiting-dilution RT-PCR. Epitope prediction was performed with NetMHC CBS prediction server for the 19 HLA-A and B alleles. Cytotoxic response prediction was performed by using the IEDB Analysis Resource. From our results, we deduce that the transmitted CTL / gag escape frequency in the founder virus was at least double compared to the post-transmission events. Additionally, by means of an algorithm that combines these frequencies, we observed that the founder viruses better adapted to the HLA A / B alleles of the recipient could contribute to a greater progression of the infection. Our results suggest that there is a large adaptation of HIV-1 to the HLA A / B alleles prevalent in our population. However, despite this adaptive advantage, the virus needs to make "readjustments" through new escape and compensatory mutations. Interestingly, according to our results, this readaptation could have a role in the progression of the infection.

Factores asociados con la transición en adolescentes con infección HIV perinatal / Factors associated with transition of adolescents with perinatal mother-to-child HIV infection

Los avances terapéuticos de los niños con infección HIV lograron una gran sobrevida y llevaron el foco de la atención al manejo de la infección cada vez más compleja de niños experimentados y al desafío de preparar a los adolescentes para la transición hacia un centro de adultos. Para ello se diseñó un Programa de Transición con pasos definidos que se implementó en el 2007 en el Servicio de Infectología del Hospital JP Garrahan. Este estudio tiene por objetivos describir las características de los adolescentes con infección VIH/SIDA incluidos en el Programa de Transición y analizar los factores asociados a la transición. Entre junio de 2007 y diciembre de 2013, se incluyeron 230 pacientes. Presentan un estadio clínico e inmunológico avanzado, la vía de infección fue perinatal en 96.5%. Presentan experiencia a varios esquemas de tratamiento con una respuesta adecuada virológica e inmunológica: 62.9 % presentan carga viral indetectable. Se registró una adherencia al seguimiento en el Hospital Garrahan del 59%. Concurrió solo alguna vez el 46.3% de los pacientes. La transición se efectivizó en 131pacientes (57%) y tuvieron una transición exitosa el 72.3% de ellos. En el análisis bivariado se encontró que estar al cuidado del propio paciente y la adherencia a los controles se asoció significativamente como factor protector para transición no exitosa. La no escolarización mostró una tendencia al límite de la significación estadística a aumentar el riesgo de transición no exitosa así como el uso de drogas (AU)

Advances in the management of HIV-infected children have led to long-term survival and shifted the focus to the care of children with an increasing complexity of the infection and the challenge to prepare children for the transition to adult care. For this purpose, a Transition Program with well-defined steps was implemented at the Deapartment of Infectious Diseases in 2007. The aim of this study was to describe the features of adolescents with HIV/AIDS infection included in the Transition Program and analyze factors associated with transitioning. Between June 2007 and December 2013, 230 patients were included. The patients had a clinically and immunologically advanced state. Infection had been from mother to child in 96.5%. The children had received different treatment schemes with adequate virological and immunological response: 62.9% had a detectable viral load. Adherence to follow-up at the Garrahan Hospital was 59%; 46.3% came to the hospital only sporadically. Of all patients, 131 (57%) were transitioned and transition was successful in 72.3% of them. Bivariate analysis showed that the patient being in charge of their own transition and adherence to follow-up visits were significantly associated with a successful transition. Not attending school showed a borderline statistically significant trend towards increasing failure of transition, as did drug use (AU)

Etravirine in treatment-experienced, HIV-1-infected children and adolescents: 48-week safety, efficacy and resistance analysis of the phase II PIANO study.

OBJECTIVES: PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥ 6 to < 12 years) and adolescents (≥ 12 to < 18 years) over 48 weeks. METHODS: In a phase II, open-label, single-arm study, 101 treatment-experienced patients (41 children; 60 adolescents) with screening viral load (VL) ≥ 500 HIV-1 RNA copies/mL received etravirine 5.2 mg/kg (maximum dose 200 mg) twice a day (bid) plus OBR. RESULTS: Sixty-seven per cent of patients had previously used efavirenz or nevirapine. At week 48, the most common treatment-related grade ≥ 2 adverse event (AE) was rash (13%); 12% experienced grade 3 AEs. Only two grade 4 AEs occurred (both thrombocytopaenia, not etravirine related). At week 48, 56% of patients (68% children; 48% adolescents) achieved a virological response (VL<50 copies/mL; intent-to-treat, noncompleter=failure). Factors predictive of response were adherence > 95%, male sex, low baseline etravirine weighted genotypic score and high etravirine trough concentration (C0h ). Seventy-six patients (75%) completed the trial; most discontinuations occurred because of protocol noncompliance or AEs (8% each). Sixty-five per cent of patients were > 95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration-time curve over 12 h (AUC0-12h ; 5216 ng h/mL) and C0h (346 ng/mL) were comparable to adult target values. CONCLUSIONS: Results with etravirine 5.2 mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200 mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients.

Analysis of sequences of hepatitis C virus NS5A genotype 1 in HIV-coinfected patients with a null response to nitazoxanide or peg-interferon plus ribavirin.

Even though new drugs have been approved for treatment of hepatitis C virus (HCV) infection, the risk of drug-drug interactions and concern about overlapping toxicities has hindered the development of studies in HIV/HCV-coinfected individuals. Traditional treatment with pegylated interferon plus ribavirin (peg-IFN + RBV) is very expensive and has a low rate of sustained virological response in coinfected patients, especially if they are infected with HCV genotype 1. Nitazoxanide (NTZ) is a drug that is being evaluated for the treatment of chronic HCV infection, both in HCV-monoinfected and HIV/HCV-coinfected patients. Understanding the NTZ resistance mechanism could allow the development of resistance to be minimized and would expand the treatment options, mainly in special populations such as HIV/HCV-coinfected patients. Similarly to IFN, NTZ increases the activity of the cellular protein kinase activated by double-stranded RNA (PKR), a key kinase in the innate antiviral response. In order to elucidate whether sequence heterogeneity in the PKR-binding domain of HCV NS5A genotype 1 could influence the antiviral activity of either NTZ monotherapy or peg-IFN + RBV, baseline and end-of-therapy plasma samples from two groups of eleven non-responder HIV/HCV-coinfected patients that had received NTZ or peg-IFN + RBV were studied. Most of the HCV NS5A sequences examined at the end of therapy did not change from the baseline, even after 30 days course of antiviral therapy. An extensive comparison of HCV NS5A genotype 1 and 4 sequences from the database with reported IFN therapy outcome was performed in order to infer their phylogenetic relationships. The HCV genotype 1 NS5A nucleotide sequences from therapy-non-responder patients were intermingled amongst those from the database, irrespective of their IFN-therapy outcome. When comparing NS5A-PKRBD amino acid sequences, significant differences were observed in genotype 4, but not in genotype 1 (p < 0.0001 and p > 0.05, respectively). In conclusion, despite IFN and NTZ sharing the protein kinase activated by double-stranded RNA as their cellular target, the HCV genotype 1 strategy to counteract the IFN action mediated by NS5A ISDR/PKRBD does not explain drug resistance in HIV/HCV-coinfected patients. Other viral factors that are possibly involved are discussed as well.

Subgroup analysis of virological response rates with once- and twice-daily darunavir/ritonavir in treatment-experienced patients without darunavir resistance-associated mutations in the ODIN trial.

BACKGROUND: ODIN (once-daily darunavir in treatment-experienced patients) was a 48-week, phase III, randomized, open-label trial comparing once-daily (qd) darunavir/ritonavir (DRV/r) 800/100 mg with twice-daily (bid) DRV/r 600/100 mg, both with an optimized background regimen [OBR; at least two nucleoside reverse transcriptase inhibitors (NRTIs)], in treatment-experienced, HIV-1-infected adults with no DRV resistance-associated mutations (RAMs) at screening. Week 48 analyses of virological response by subgroups are reported. METHODS: A total of 590 patients were randomized to receive qd (n=294) or bid (n=296) DRV/r. Virological response (HIV-1 RNA <50 copies/mL) was assessed according to: screening HIV-1 RNA (≥ or <50000 copies/mL), CD4 cell count, prior protease inhibitor (PI) use, number of active NRTIs in the OBR, presence of mutations (primary PI mutations, PI RAMs or M184V/I), gender, age, race, HIV-1 clade and adherence. RESULTS: Baseline characteristics were well balanced between arms and across subgroups. Response rates were comparable between qd and bid DRV/r treatments for all subgroups examined. Response rates were 78.4 and 76.8% in the qd and bid treatment arms, respectively, in patients with baseline HIV-1 RNA ≤ 50000 copies/mL and 52.8% in both arms in those with > 50000 copies/mL. Response rates for the qd and bid treatment arms by baseline CD4 cell count were also similar (69.6 vs. 65.2% for <200 cells/µL; 72.2 vs. 74.8% for 200- <350 cells/µL; 77.0 vs. 74.3% for ≥ 350 cells/µL). CONCLUSIONS: DRV/r administered either qd or bid provided effective treatment for antiretroviral treatment-experienced patients with no DRV RAMs, with comparable response rates across all subgroups studied. Low patient numbers in specific subgroups may limit interpretation of these specific subgroup results.

The immunomodulatory nutritional intervention NR100157 reduced CD4+ T-cell decline and immune activation: a 1-year multicenter randomized controlled double-blind trial in HIV-infected persons not receiving antiretroviral therapy (The BITE Study).

BACKGROUND: The immunomodulatory nutritional product NR100157 was developed for human immunodeficiency virus (HIV)-infected individuals. We hypothesized that targeting the compromised gastrointestinal tract of HIV-infected individuals would result in systemic immunological benefits. METHODS: In a multicenter, randomized, controlled, double-blind trial, 340 HIV-1-positive adults not on antiretroviral therapy, with CD4(+) T-cell counts <800/µL, were given either NR100157 or an isocaloric and isonitrogenous control for 52 weeks. Primary outcome was CD4(+) T-cell count. Secondary outcomes included plasma viral load (pVL), safety, and tolerability. In a pilot study (n = 20), levels of CD4(+)CD25(+) and CD8(+)CD38(+) activation were measured (n = 20). The trial is registered at the Dutch Trial Register (NTR886) and ISRCTN81868024. RESULTS: At 52 weeks, CD4(+) T-cell decline showed a 40-cell/µL difference (P = .03) in the intention-to-treat population in favor of the immunomodulatory NR100157 (control vs active, -68 ± 15 vs -28 ± 16 cells/µL/year). The change in pVL from baseline was similar between groups (P = .81). In the pilot study, the percentage of CD4(+)CD25(+) was lower in the active group (P < .05) and correlated with changes in CD4(+) T-cell count (r = -0.55, P < .05). The percentage of CD8(+)CD38(+) levels was unaffected. CONCLUSIONS: The specific immunonutritional product NR100157 significantly reduces CD4(+) decline in HIV-1-infected individuals, and this is associated with decreased levels of CD4(+)CD25(+). (This nutritional intervention is likely to affect local gut integrity and gut-associated lymphoid tissue homeostasis, which in turn translates positively to systemic effects.) Clinical Trials Registration. ISRCTN81868024.

No reduction of HCV viral load in HIV patients co-infected with HCV genotype 1 during a 30 days course of nitazoxanide monotherapy.

There are two new drugs approved and several in development for treatment of chronic HCV; among them nitazoxanide (NTZ). Twelve HIV/HCV genotype 1 co-infected patients were enrolled prospectively to receive a 30 days course of oral NTZ 500 mg bid. This therapy was well tolerated in this group of HIV patients co-infected with HCV genotype 1. Nevertheless no changes in HCV viral load were observed during treatment in none of the patients evaluated. This data suggests that despite the promising results reported for HCV genotype 4 mono-infected patients, NTZ exhibit poor activity as monotherapy in HIV/HCV co-infected patients with genotype 1.

HCV RNA decline in the first 24 h exhibits high negative predictive value of sustained virologic response in HIV/HCV genotype 1 co-infected patients treated with peginterferon and ribavirin.

BACKGROUND: Treatment with Peg-interferon and ribavirin (PEG-IFN/RBV) for HIV patients co-infected with hepatitis C virus (HCV) genotype 1 has suboptimal rates of response. Viral kinetics has emerged as one of the best prognostic factors of treatment outcome. METHODS: Twenty HIV/HCV genotype 1 co-infected patients in treatment with PEG-IFN/RBV, had blood drawn at baseline, 24 h, 4, 12, 24, 48, and 72 weeks. HCV-RNA levels were evaluated at each time point. ROC curves were used to evaluate the log10 HCV-RNA decay at 24 h that exhibits the best predictive value of achieving response. Genomic characterization of HCV NS5A at both interferon sensitivity-determining region (ISDR) and protein-kinase binding (PKRBD) domains were performed in order to evaluate its heterogeneity and association with 24 h HCV-RNA decay and SVR. RESULTS: Non-responder patients exhibited a mean of 0.7 log10 (SD 0.74 log10) HCV-RNA decay at 24 h, whereas responder-patients presented 1.6 log10 (SD 0.28 log10), p = 0.04. A reduction in HCV viral load from baseline to 24 h of < 1.4 had a negative predictive value for achieving SVR of 100% and a positive predictive value of 50%. HCV genotype 1 isolates from patients with a decrease of HCV-RNA at 24 h > 1.4 log10, exhibited 3.1(SD 1.5) amino acids substitutions in ISDR and 4.8(SD 2.3) in PKRBD regions and 1.6(SD 0.7) and 2.4(SD 1.3), respectively, in those patients presenting lower reduction in HCV-RNA. CONCLUSIONS: HIV/HCV genotype 1 co-infected patients with a decrease in HCV-VL at 24 h > 1.4 log10 are more likely to achieve SVR when treated with PEG-IFN/RBV than those with lower levels of HCV-RNA decay. Along with other host-related and viral-related prognostic factors in HIV/HCV co-infected patients, this very early time point of evaluation could be of relevance in the management of HCV-specific treatment.

Antiviral activity of apricitabine in treatment-experienced HIV-1-infected patients with M184V who are failing combination therapy.

OBJECTIVES: Apricitabine (ATC) is a novel deoxycytidine analogue nucleoside reverse transcriptase inhibitor (NRTI) with significant antiviral activity in vitro, including activity against HIV-1 with reverse transcriptase mutations that confer resistance to other NRTIs. ATC has shown promising antiviral activity and good tolerability when given as monotherapy for 10 days in treatment-naïve HIV-1-infected patients. METHODS: In this Phase II randomized, double-blind study, 51 treatment-experienced HIV-1-infected patients with the reverse transcriptase mutation M184V who were failing therapy which included lamivudine (3TC) were randomized to receive twice-daily 600 mg ATC, 800 mg ATC or 150 mg 3TC for 21 days. Patients remained on their existing background regimen until day 21, when background therapy could be optimized according to genotype at screening. RESULTS: At day 21, the mean change in viral load was -0.71 and -0.90 log(10) HIV-1 RNA copies/mL in the 600 and 800 mg ATC groups, respectively, compared with a -0.03 log(10) change in the 3TC group. In patients with at least three thymidine analogue mutations (TAMs) at baseline, greater reductions in viral load were observed in the 800 mg ATC group at day 21 than in the 600 mg ATC group. Few genotypic changes were detected at day 21 [two patients (600 mg ATC) lost and three patients (800 mg ATC) gained a TAM] and all patients with detectable virus retained the M184V mutation. The safety profiles of the two ATC doses were similar to that of 3TC. CONCLUSIONS: Over the 21-day treatment period, ATC showed promising antiviral activity and was well tolerated in treatment-experienced patients with M184V, with or without additional TAMs.

Virological response with fully active etravirine: pooled results from the DUET-1 and DUET-2 trials.

The objective of this subanalysis of the Phase III DUET trials was to examine virological response to an etravirine-containing regimen in patients harbouring virus fully sensitive to etravirine. Full etravirine sensitivity was defined as fold change in 50% effective concentration (FC) ≤3 or weighted genotypic score ≤2. At Week 48 in the etravirine group, 74% of patients with etravirine FC ≤3 and 77% with etravirine genotypic score ≤2 had viral load <50 HIV-1 RNA copies/mL, versus 48% and 46%, respectively, in the placebo group (P < 0.0001). Response rates increased with baseline phenotypic sensitivity score, but were consistently higher with etravirine (56-82%) than placebo (2-72%). Similar observations were made in patients harbouring virus with full etravirine and darunavir sensitivity. Our findings support current recommendations to include three active agents in treatment-experienced patients' regimens.

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART.

OBJECTIVE: Determine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART). METHODS: A cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis. RESULTS: A total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44% received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2% and 20.2%, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females. CONCLUSIONS: Traditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings.

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART

OBJECTIVE: Determine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART). METHODS: A cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis. RESULTS: A total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44 percent received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2 percent and 20.2 percent, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females. CONCLUSIONS: Traditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.

Use of darunavir and enfuvirtide in a pregnant woman.

SUMMARY: A 41-year-old pregnant woman with multiple virological failures started darunavir, enfuvirtide, zidovudine and lamivudine at week 28 of pregnancy. During week 38, the patient had a viral load <400 copies/mL and a CD4 count of 180 cells/mm(3) (13%). The child was found to be in good health, with negative HIV-polymerase chain reactions at birth, at two and at six months.

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.

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...

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)

Hepatitis B virus genotype distribution and its lamivudine-resistant mutants in HIV-coinfected patients with chronic and occult hepatitis B.

Hepatitis B virus (HBV) genotypes were examined in HIV-infected patients with chronic and occult HBV infection. From a total population of 593 HIV-infected patients, 22 individuals (prevalence 3.7%) were found to be HBsAg while 72 (12.1%) were found to be anti-HBc alone. From them, 20 and 4 were HBV DNA positive, respectively. These last four patients are therefore considered to be HBV infected in an occult form. The genotypes could be determined in all 24 HBV-infected patients. HBV-A was the most common (20/24; 83.3%), followed by HBV-D (2/24; 8.3%) and HBV-F (1/24; 4.2%). The remaining sample exhibited mixed infection involving genotypes A and D as pure ones, thus also forming part of three intergenotypic recombinant forms exhibiting different mosaic S gene patterns. The sexual route of transmission was predominant among HBV genotype A-infected patients. Among the 24 HBV DNA-positive patients, point mutations related to lamivudine resistance were found in four strains. These viral strains showed a methionine-to-valine substitution at codon 204 (rtM204V) in association with an upstream B-domain change at rtL180M. Additionally, two of them exhibited the additional rtV173L mutation. The value of HBV molecular monitoring including both HBV viral genomic characterization and genotypic resistance profile in HIV-HBV-coinfected individuals is discussed.

Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors.

Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from diverse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For example, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.