Mitochondrial toxicity and caspase activation in HIV pregnant women.

To assess the impact of HIV-infection and highly active anti-retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV-infected and -treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation. The HIV pregnancies showed increased adverse perinatal outcome (OR: 4.81 [1.14-20.16]; P < 0.05) and decreased mtDNA content (42.66 ± 5.94%, P < 0.01) compared to controls, even higher in naïve participants. This depletion caused a correlated decrease in mitochondrial protein synthesis (12.82 ± 5.73%, P < 0.01) and function (20.50 ± 10.14%, P < 0.001), not observed in controls. Along pregnancy, apoptotic caspase-3 activation increased 63.64 ± 45.45% in controls (P < 0.001) and 100.00 ± 47.37% in HIV-pregnancies (P < 0.001), in correlation with longer exposure to nucleoside analogues. HIV-infected women showed increased obstetric problems and declined genetic and functional mitochondrial parameters during pregnancy, especially those firstly exposed to anti-retrovirals. The apoptotic activation of caspases along pregnancy is emphasized in HIV pregnancies promoted by nucleoside analogues. However, we could not demonstrate direct mitochondrial or apoptotic implication in adverse obstetric outcome probably because of the reduced sample size.

HIV-1 promonocytic and lymphoid cell lines: an in vitro model of in vivo mitochondrial and apoptotic lesion.

To characterize mitochondrial/apoptotic parameters in chronically human immunodeficiency virus (HIV-1)-infected promonocytic and lymphoid cells which could be further used as therapeutic targets to test pro-mitochondrial or anti-apoptotic strategies as in vitro cell platforms to deal with HIV-infection. Mitochondrial/apoptotic parameters of U1 promonocytic and ACH2 lymphoid cell lines were compared to those of their uninfected U937 and CEM counterparts. Mitochondrial DNA (mtDNA) was quantified by rt-PCR while mitochondrial complex IV (CIV) function was measured by spectrophotometry. Mitochondrial-nuclear encoded subunits II-IV of cytochrome-c-oxidase (COXII-COXIV), respectively, as well as mitochondrial apoptotic events [voltage-dependent-anion-channel-1(VDAC-1)-content and caspase-9 levels] were quantified by western blot, with mitochondrial mass being assessed by spectrophotometry (citrate synthase) and flow cytometry (mitotracker green assay). Mitochondrial membrane potential (JC1-assay) and advanced apoptotic/necrotic events (AnexinV/propidium iodide) were measured by flow cytometry. Significant mtDNA depletion spanning 57.67% (P < 0.01) was found in the U1 promonocytic cells further reflected by a significant 77.43% decrease of mitochondrial CIV activity (P < 0.01). These changes were not significant for the ACH2 lymphoid cell line. COXII and COXIV subunits as well as VDAC-1 and caspase-9 content were sharply decreased in both chronic HIV-1-infected promonocytic and lymphoid cell lines (<0.005 in most cases). In addition, U1 and ACH2 cells showed a trend (moderate in case of ACH2), albeit not significant, to lower levels of depolarized mitochondrial membranes. The present in vitro lymphoid and especially promonocytic HIV model show marked mitochondrial lesion but apoptotic resistance phenotype that has been only partially demonstrated in patients. This model may provide a platform for the characterization of HIV-chronicity, to test novel therapeutic options or to study HIV reservoirs.

Prediction of higher cost of antiretroviral therapy (ART) according to clinical complexity. A validated clinical index.

BACKGROUND: The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. OBJECTIVE: To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. METHODS: Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. RESULTS: In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). CONCLUSIONS: The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity.

Changes in the etiology, incidence and prognosis of acute lower respiratory track infections in human immunodeficiency virus patients.

AIM: To describe the incidence, the changes in the etiology and the prognosis of lower respiratory tract infection (LRTI) in HIV infected patients, presenting by the first time to the Emergency Department (ED), during years 2000-2010. STUDY DESIGN: Prospective collection of data. METHODS: Data were collected on the first visit of HIV-infected patients at our ED due to a LRTI, (defined according to the criteria of the European Respiratory Society), between 1/1/2000 and 31/12/2010. A series of epidemiological and laboratory variables as well as the need for admission to the intensive care unit (ICU). LRTI etiology were also collected. The influence ofthe mentioned variables on 30-day mortality were analyzed. RESULTS: One hundred thirty one patients were included. LRTI represented 27% of visits to the ED by HIV-infected patients. Mean age was 39±9 years. 72% of patients were males. 18% required admission to the ICU. The most frequent LRTI was pneumonia by P. jiroveci in 35 cases, bacterial penumonia in 27 and pulmonary tuberculosis in 20. LRTI incidence gradually reduced significantly over time from 6.13 × 1000 patients/year in year 2000 to 0.23 × 1000 patients/year in 2010 (p<0.05). Overall mortality was 14%. Logistic regression analysis showed that admission to ICU (p<0.004) and viral load (p<0.029) were independent variables predicting mortality. CONCLUSION: LRTI is a pathology with a decreasing incidence, probably related to the widespread utilization increased of HAART regimens. lts etiology has also been changing, but with a non negligible mortality, mostly when ICU admission was required.

Standardized representation, visualization and searchable repository of antiretroviral treatment-change episodes.

BACKGROUND: To identify the determinants of successful antiretroviral (ARV) therapy, researchers study the virological responses to treatment-change episodes (TCEs) accompanied by baseline plasma HIV-1 RNA levels, CD4+ T lymphocyte counts, and genotypic resistance data. Such studies, however, often differ in their inclusion and virological response criteria making direct comparisons of study results problematic. Moreover, the absence of a standard method for representing the data comprising a TCE makes it difficult to apply uniform criteria in the analysis of published studies of TCEs. RESULTS: To facilitate data sharing for TCE analyses, we developed an XML (Extensible Markup Language) Schema that represents the temporal relationship between plasma HIV-1 RNA levels, CD4 counts and genotypic drug resistance data surrounding an ARV treatment change. To demonstrate the adaptability of the TCE XML Schema to different clinical environments, we collaborate with four clinics to create a public repository of about 1,500 TCEs. Despite the nascent state of this TCE XML Repository, we were able to perform an analysis that generated a novel hypothesis pertaining to the optimal use of second-line therapies in resource-limited settings. We also developed an online program (TCE Finder) for searching the TCE XML Repository and another program (TCE Viewer) for generating a graphical depiction of a TCE from a TCE XML Schema document. CONCLUSIONS: The TCE Suite of applications - the XML Schema, Viewer, Finder, and Repository - addresses several major needs in the analysis of the predictors of virological response to ARV therapy. The TCE XML Schema and Viewer facilitate sharing data comprising a TCE. The TCE Repository, the only publicly available collection of TCEs, and the TCE Finder can be used for testing the predictive value of genotypic resistance interpretation systems and potentially for generating and testing novel hypotheses pertaining to the optimal use of salvage ARV therapy.

Newborn mice vaccination with BCG.HIVA²²² + MVA.HIVA enhances HIV-1-specific immune responses: influence of age and immunization routes.

We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA(222) prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8(+) T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA(222) compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA(222) and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA(222) to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.

Molecular characterization of heterologous HIV-1gp120 gene expression disruption in mycobacterium bovis BCG host strain: a critical issue for engineering mycobacterial based-vaccine vectors.

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261) and Mycobacteria spp. alpha-antigen promoter (in plasmid pJH222). Among 14 rBCG:HIV-1gp120 (pMV261) colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222) colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

Virological Outcome Measures During Analytical Treatment Interruptions in Chronic HIV-1-Infected Patients.

BACKGROUND: Analytical treatment interruptions (ATIs) are essential in research on HIV cure. However, the heterogeneity of virological outcome measures used in different trials hinders the interpretation of the efficacy of different strategies. METHODS: We conducted a retrospective analysis of viral load (VL) evolution in 334 ATI episodes in chronic HIV-1-infected patients collected from 11 prospective studies. Quantitative (baseline VL, set point, delta set point, VL, and delta VL at given weeks after ATI, peak VL, delta peak VL, and area under the rebound curve) and temporal parameters (time to rebound [TtR], set point, peak, and certain absolute and relative VL thresholds) were described. Pairwise correlations between parameters were analyzed, and potential confounding factors (sex, age, time of known HIV infection, time on ART, and immunological interventions) were evaluated. RESULTS: The set point was lower than baseline VL (median delta set point, -0.26; P < .001). This difference was >1 log10 copies/mL in 13.9% of the cases. The median TtR was 2 weeks; no patients had an undetectable VL at week 12. The median time to set point was 8 weeks: by week 12, 97.4% of the patients had reached the set point. TtR and baseline VL were correlated with most temporal and quantitative parameters. The variables independently associated with TtR were baseline VL and the use of immunological interventions. CONCLUSIONS: TtR could be an optimal surrogate marker of response in HIV cure strategies. Our results underline the importance of taking into account baseline VL and other confounding factors in the design and interpretation of these studies.

Enzymatic and extraenzymatic role of adenosine deaminase 1 in T-cell-dendritic cell contacts and in alterations of the immune function.

Adenosine deaminase 1 (ADA1) is an enzyme of the purine metabolism whose congenital defect leads to severe combined immunodeficiency (SCID). Although classically considered a cytosolic enzyme, early evidence from work in brain synaptosomes suggested that the enzyme could be an ectoenzyme. In lymphoid cells, ectoenzymatic activity of ADA1 was also found. The obvious role of this enzyme located on the cell surface of lymphocytes and monocytes was to deaminate adenosine, making it less available for uptaking and metabolism, and also for adenosine-receptor activation. Quite unexpectedly, ADA1 was shown to act extraenzymatically. In addition, cell surface ADA1-binding proteins have been identified. Interestingly, the interaction of ADA1 with these anchoring proteins leads to costimulation of T-cell activation. Recent studies performed with professional antigen-presenting cells and T lymphocytes have shown that ADA1 can bridge the two cell types together by a cross-linking established between different anchoring molecules in each cell. Some aspects of ADA action are similar to that of growth factors. In fact, ADA1 is a member of the adenosine deaminase growth factor (ADGF) family. Some molecular mechanisms that occur in ADA-related SCID and the role ADA1 may play in acquired immunodeficiency are also reviewed here.

Improvement of psychosocial adjustment to HIV-1 infection through a cognitive-behavioral oriented group psychotherapy program: a pilot study.

The present study evaluated the efficacy of a group therapy program in improving psychosocial adjustment to HIV infection, and tried to identify variables predictive of greater improvement. The outcome of 47 completing patients was analyzed, comparing the measures between T1 (1 month before therapy), and T2 (first session), and between T2 and T3 (last session) using the Wilcoxon matched-pairs signed-ranks test for each dimension of the Psychosocial Adjustment to Illness Scale (PAIS). The therapy consisted of 16 weekly 2-hour sessions following a structured time-limited cognitive-behavioral group psychotherapy program. During the intervention (between T2 and T3) a significant improvement was observed in health care orientation, vocational environment, domestic environment, sexual relation, extended family relationships, social environment, and total PAIS. There were no changes during baseline (between T1 and T2) in any of the PAIS subscales, or in the total PAIS score. Sexual route of transmission was independently associated with an improvement in health care orientation (beta = 2.525). Time since HIV diagnosis (beta = 0.022) and being employed (beta = 2.548) were independently associated with an improvement in adjustment to vocational environment. Men who have sex with men showed a poorer improvement in adjusting to family relations after the intervention (beta = -2.548). Finally, a lower CD4 count (beta = -0.005) and being employed (beta = 3.054) were independently associated with an improvement in adjustment to social environment. Our psychotherapy program improved psychosocial functioning in a heterogeneous sample of HIV-1-infected patients referred to a consultation-liaison psychiatry unit.

Polypharmacy and potential drug-drug interactions in an HIV-infected elderly population.

OBJECTIVE: Comorbidities associated with the ageing of the HIV+ population may require chronic treatment. Our aim is to determine the degree of polypharmacy and the number of potential drug-drug interactions, as well as the relationship between both variables in a HIV-infected population over the age of 65. METHODS: Descriptive transversal study targeting HIV+ patients aged ≥65, attended in a Spanish hospital in 2014. The prevalence of polypharmacy (≥5 drugs) and potential drug-drug interactions were assessed, and also risk factors associated with such. RESULTS: 265 subjects aged ≥65 years were identified, 197 of whom were on antiretroviral treatment and had data about their electronic prescription. 93% were polymedicated. The patients whose antiretroviral treatment included a non-nucleoside reverse transcriptase inhibitor (NNRTI) demonstrated a fourfold probability of being polymedicated. 65% of the patients showed at least one potential drug-drug interaction and 6.6% a severe potential drug-drug interaction. The risk of interaction was significantly associated with the number of prescribed drugs (incidence rate ratio per prescribed drug, CI 95%: 1.18 (1.14;1.22; p<0.0001) and with the use of protease inhibitors (PI) (incidence rate ratio, CI 95%: 1.65 (1.28;2.11; p=0.0001)). CONCLUSION: Polypharmacy has a high prevalence and is more common in patients treated with NNRTI. The number of potential drug-drug interactions increase with the number of prescribed drugs and is higher in those patients on PI.

Objetivo: Las comorbilidades asociadas al envejecimiento de la población VIH+ pueden requerir tratamientos crónicos. Nuestro objetivo es determinar el grado de polifarmacia y el número de interacciones farmacológicas potenciales, así como la relación entre ambas variables en un grupo de población VIH+ mayor de 65 años.Métodos: Estudio descriptivo transversal en pacientes VIH+≥65 años atendidos en un hospital español en 2014. Se evaluó la prevalencia de polimedicación (≥5 fármacos) y se analizaron las interacciones farmacológicas potenciales y los factores de riesgo asociados a ellas.Resultados: Se identificaron 265 sujetos ≥65 años, de los cuales 197 recibían tratamiento antirretroviral y tenían datos en la receta electrónica. El 93% estaban polimedicados. Los pacientes cuyo tratamiento antirretroviral incluía un inhibidor de la transcriptasa inversa no nucleósido (ITINN) presentaban una probabilidad cuatro veces mayor de estar polimedicados. El 65% de los pacientes presentó al menos una interacción potencial y el 6,6% una interacción potencial grave. El riesgo de interacciones se asoció significativamente al número de fármacos prescritos (razón de tasas de incidencia por fármaco prescrito con IC 95%: 1,18 (1,14;1,22; p<0.0001)) y a los inhibidores de la proteasa (IP) (razón de tasas de incidencia IC 95%: 1,65 (1,28;2,11; p=0,0001)).Conclusión: La prevalencia de la polifarmacia es muy alta y más frecuente en los pacientes tratados con ITINN. El número de interacciones farmacológicas potenciales aumenta con el número de fármacos prescritos y es mayor en los pacientes tratados con IP.

Antiretroviral activity of didanosine in patients with different clusters of reverse transcriptase mutations.

Patterns of mutations associated with didanosine (ddI) resistance are still a controversial issue. The correlation between different clusters of reverse transcriptase mutations with the short-term virological activity of ddI when added to a failing regimen was examined in 40 patients. The median fall in plasma viral load at week 4 was 0.67 log10 copies/ml. There was good correlation between the median fall in plasma HIV RNA levels and the number of nucleoside-associated (P = 0.0152) or thymidine-associated (P = 0.0142) mutations. In conclusion, ddI retained substantial antiretroviral activity when the number of nucleoside-associated or thymidine-associated mutations was less than four.

MicroRNA Profile in CD8+ T-Lymphocytes from HIV-Infected Individuals: Relationship with Antiviral Immune Response and Disease Progression.

BACKGROUND: The relationship between host microRNAs (miRNA), viral control and immune response has not yet been elucidated in the field of HIV. The aim of this study was to assess the differential miRNA profile in CD8+ T-cells between HIV-infected individuals who differ in terms of viral replication control and immune response. METHODS: miRNA profile from resting and CD3/CD28-stimulated CD8+ T-cells from uninfected individuals (HIV-, n = 11), Elite Controllers (EC, n = 15), Viremic Controllers (VC, n = 15), Viremic Progressors (VP, n = 13) and HIV-infected patients on therapy (ART, n = 14) was assessed using Affymetrix miRNA 3.1 arrays. After background correction, quantile normalization and median polish summarization, normalized data were fit to a linear model. The analysis comprised: resting samples between groups; stimulated samples between groups; and stimulated versus resting samples within each group. Enrichment analyses of the putative target genes were perfomed using bioinformatic algorithms. RESULTS: A downregulated miRNA pattern was observed when resting samples from all infected groups were compared to HIV-. A miRNA downregulation was also observed when stimulated samples from EC, ART and HIV- groups were compared to VP, being hsa-miR-4492 the most downregulated. Although a preferential miRNA downregulation was observed when stimulated samples were compared to the respective resting samples, VP presented a differential miRNA expression pattern. In fact, hsa-miR-155 and hsa-miR-181a were downregulated in VP whereas in the other groups, either an upregulation or no differences were observed after stimulation, respectively. Overall, functional enrichment analysis revealed that the predicted target genes were involved in signal transduction pathways, metabolic regulation, apoptosis, and immune response. CONCLUSIONS: Resting CD8+ T-cells do not exhibit a differential miRNA expression between HIV-infected individuals but they do differ from non-infected individuals. Moreover, a specific miRNA pattern is present in stimulated CD8+ T-cells from VP which could reflect a detrimental pattern in terms of CD8+ T-cell immune response.

Early virological failure in treatment-naive HIV-infected adults receiving didanosine and tenofovir plus efavirenz or nevirapine.

A 50% rate of early virological failure associated with the selection of resistance mutations was seen in a group of 14 antiretroviral-naive adults who initiated highly active antiretroviral therapy with tenofovir and didanosine plus efavirenz or nevirapine. At month 6, the mutations detected were K65R, L74V, L100I, K103N/R/T, Y181C and G190E/Q/S. These results argue against the use of tenofovir plus didanosine in HIV-infected antiretroviral-naive adults even when the third drug is a non-nucleoside reverse transcriptase inhibitor.

High rate of virological failure in maintenance antiretroviral therapy with didanosine and tenofovir.

We evaluated the virological outcome of tenofovir plus didanosine-based regimens in 67 HIV-suppressed patients. After a median follow-up of 26 months (IQR 10.5-40.5), 12 (18%) discontinued the therapy because of virological failure. At virological failure 'de novo' selected mutations were identified in 11 of the 12 failing patients, including the K65R mutation in seven patients. These results argue against the use of tenofovir-didanosine not only in naive patients, but also in previously suppressed patients.

Genotypic and phenotypic resistance patterns at virological failure in a simplification trial with nevirapine, efavirenz or abacavir.

BACKGROUND: The NEFA Study was a randomized study comparing nevirapine (NVP), efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors. OBJECTIVE: To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms. METHODS: Patients with virological failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml, were analysed for phenotypic susceptibility and HIV-1 mutations. RESULTS: Of the 460 patients included in the study, 51 (11%) experienced virological failure after 24 months of follow-up while on assigned study medication. A higher proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12 (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms. In general, there was a good concordance among genotype and phenotype resistance testing, except for ABC, stavudine and didanosine, where phenotypic resistance testing added valuable information (fold change in the median inhibitory concentration). CONCLUSIONS: Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy. Phenotypic resistance testing may be helpful in interpreting unclear genotypic results.

Early virological failure with a combination of tenofovir, didanosine and efavirenz.

OBJECTIVE: To describe the occurrence of a high early virological failure (VF) rate and development of resistance mutations in antiretroviral-naive patients receiving tenofovir, didanosine and efavirenz. METHODS: HIV-infected antiretroviral-naive patients with viral load > or =30 000 copies/ml were enrolled in a pilot randomized trial of tenofovir/didanosine (250 mg)/ efavirenz with (arm A) or without (arm B) lopinavir/r for the first 12 weeks. As six cases of early VF (a drop of <2 log at month 3, or a rebound of >1 log from the nadir) were detected (five in arm B and one in arm A who had previously stopped lopinavir/r) an unplanned interim analysis was performed. RESULTS: A total of 29 out of 36 enrolled patients completed at least 3 months of follow-up and were included in the interim analysis. An intent-to-treat analysis showed treatment failure in 7/15 (46.7%) patients in arm B (five VF, one lost, one switched) versus 2/14 (14.3%) in arm A (one lost, one switched) (P=0.109). The patient in arm A who interrupted lopinavir/r at day 3 and continued with tenofovir/didanosine/efavirenz later developed VF. At baseline, 6/6 VF patients had VL >100000 copies/ml and an advanced stage of disease (CD4 <200 plus CDC stage C or B3) versus 0/8 non-VF patients taking the triple drug regimen (P<0.001). At failure, G190S/E alone or associated with K103N and K101R mutations was detected in five patients, and K103N/L1001/V108l in the sixth patient. Additionally, L74V/I and K65R were detected in four and two patients, respectively. CONCLUSIONS: A high early virological failure rate and the occurrence of resistance mutations were detected in a group of antiretroviral-naive patients treated with tenofovir/didanosine/efavirenz.

Factors associated with severe impact of lipodystrophy on the quality of life of patients infected with HIV-1.

A standardized questionnaire was used to assess the impact of lipodystrophy (LD) on quality of life (QoL). Eighty-four consecutive asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected outpatients with clinical LD completed a modified version of the Dermatology Life Quality Index (DLQI) survey to measure the impact of body fat changes on their QoL. Body changes influenced dressing for 55 patients (65%), produced feelings of shame for 41 (49%), and disrupted sexual life for 23 (27%). There was a greater impact on the DLQI due to body changes among women, injection drug users, patients with abdominal or breast lipoaccumulation, and patients with a high number of non-LD side effects. Multivariate proportional odds model analysis showed that the severity of non-LD-associated side effects and the presence of breast lipoaccumulation were associated with impaired psychosocial functioning. Specific characteristics of patients, antiretroviral-based side effects, and breast lipoaccumulation exert a greater impact on QoL in HIV-1-infected patients with LD.

Factors associated with the immune response to hepatitis A vaccination in HIV-infected patients in the era of highly active antiretroviral therapy.

INTRODUCTION: HIV seropositivity is considered a risk factor for complications in hepatitis A virus (HAV) infection. HAV vaccination schedules are widely implemented in HIV-infected patients, but the immune response remains impaired. METHODS: We analysed the response to vaccination (antiHAV titres ≥20IU/l) in 282 HIV-infected patients included in a standard (1440 Elisa Units (EU) at 0, 6 months) or rapidly accelerated schedule (720 EU at 0, 7, 21 days and 6 months) between 1997 and 2009. Factors associated with the response to vaccination were analysed using logistic regression. RESULTS: The overall response rate was 73.4%. Male sex (OR: 0.16, 95% CI 0.05-0.51) and hepatitis C virus co-infection (OR: 0.30, 95% CI 0.14-0.74) were associated with a lower probability of response. Protective antibody response was associated with a higher CD4/CD8 ratio (OR: 3.69, 95% CI 1.3-10.5) and having received two doses of standard schedule (compared with patients receiving only one dose of the same schedule) (OR: 2.51, 95% CI 1.22-5.15). Three doses of the rapidly accelerated schedule were not more effective than a single dose of 1440 EU (OR: 1.32, 95% CI 0.48-3.63). CONCLUSION: The low responses observed in patients receiving a single dose suggest the need to emphasize adhesion to vaccination protocols to avoid failure. The CD4/CD8 ratio may be considered as an immune status marker which could help to better choose the moment of vaccination. Our findings underscore the importance of identifying strategies that optimize the timing and effectiveness of hepatitis A vaccination in HIV-infected patients and of the need for further studies on individual factors such as sex and hepatitis C co-infection that may affect the response to vaccination. Likewise, the sub-optimal effectiveness of three doses of 720 EU in the rapidly accelerated schedule, if confirmed in future studies, might lead to a revision of the current schedule recommended for HIV-infected travellers.