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A recent study has pointed out to CD32a as a potential biomarker of HIV-persistent CD4 cells. We have characterized the level and phenotype of CD32+ cells contained in different subsets of CD4 T-cells and its potential correlation with level of total HIV-DNA in thirty HIV patients (10 typical progressors naïve for cART, 10 cART-suppressed patients, and 10 elite controllers). Total HIV-DNA was quantified in different subsets of CD4 T-cells: Trm and pTfh cells. Level and immunephenotype of CD32+ cells were analyzed in these same subsets by flow cytometry. CD32 expression in Trm and pTfh subsets was similar in the different groups, and there was no significant correlation between the level of total HIV-DNA and the level of CD32 expression in these subsets. However, total HIV-DNA level was correlated with expression of CD127 (rho = -0.46, p = 0.043) and of CCR6 (rho = -0.418, p = 0.027) on CD32+ cells. Our results do not support CD32 as a biomarker of total HIV-DNA content. However, analyzing the expression of certain markers by CD32+ cells could improve the utility of this marker in the clinical setting, prompting the necessity of further studies to both validate our results and to explore the potential utility of certain markers expressed by CD32+ cells.

Human immunodeficiency virus (HIV)-infected patients (n = 153) failing antiretroviral therapy after exposure to compounds from all three drug families were monitored for 6 months after beginning a rescue intervention program including tenofovir (TDF). At 3 months, levels of HIV RNA in plasma dropped by a mean of 0.9 log(10) and the mean CD4 count increased by 52 cells/ micro l. At 6 months, HIV RNA levels had dropped by a mean of 1.06 log(10) and the mean CD4 count had increased by 49 cells/ micro l. Only five (3.7%) patients discontinued TDF use due to adverse events. In the multivariate analysis, the presence of M41L and/or L210W at baseline was the only viral determinant of a lower response to TDF.

BackgroundIn addition to traditional cardiovascular (CV) risk factors, antiretroviral therapy, lifestyle, and human immunodeficiency virus (HIV)-related factors may contribute to future CV events in persons with HIV (PWH).MethodsAmong participants in the global REPRIEVE randomized trial, we characterized demographics and HIV characteristics relative to ACC/AHA pooled cohort equations (PCE) for atherosclerotic CV disease predicted risk and CV health evaluated by Life's Simple 7 (LS7; includes smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and glucose).ResultsAmong 7382 REPRIEVE participants (31% women, 45% Black), the median PCE risk score was 4.5% (lower and upper quartiles Q1, Q3: 2.2, 7.2); 29% had a PCE score

Abstract Background It is known that being on antiretroviral therapy reduces the risk of HIV transmission through sex. However it remains unknown what the absolute level of risk of transmission is in a person on ART with most recent measured HIV plasma viral load Methods/Design The PARTNER study is an international, observational multi-centre study, taking place from 2010 to 2014 in which HIV serodifferent partnerships who at enrolment reported recently having had condom-less vaginal or anal sexual intercourse are followed over time, with 46 monthly reporting of transmission risk behaviour through a confidential self completed risk behaviour questionnaire and with 46 monthly HIV testing for the HIV negative partner. The objective is to study (i) the risk of HIV transmission to partners, in particular in partnerships that continue not to use condoms consistently and the HIV-positive partner is on therapy with a viral load Discussion This observational study will provide missing information on the absolute risk of HIV transmission for both vaginal and anal sex when the index case is on ART with a VL

Background: Evidence from clinical practice on the effects of switching from emtricitabine/tenofovir disoproxil fumarate (F/TDF) to emtricitabine/tenofovir alafenamide (F/TAF)-based triple-therapy (TT) regimens on renal parameters is limited. Objective: This retrospective analysis evaluated the effects on renal function of switching from F/TDF to F/TAF-based TT regimens with no change in third agent among people living with HIV (PLWH). Methods: Data were from a multicenter Spanish PLWH cohort. Patients with a baseline estimated glomerular filtration rate (eGFR-EPI) measurement, ≥1 follow-up measurement, ≥30 days treatment with F/TAF, and who switched from F/TDF to F/TAF with no change in third agent were included. Multivariate mixed linear models were used to evaluate change from baseline over time in eGFR-EPI. eGFR-EPI changes before and after switch were analyzed in a matched patient subgroup. Results: Overall, 340 patients were included. Mean (95% CI) eGFR-EPI in patients with baseline eGFR-EPI <90 ml/min/1.73m2 (n = 125) was 79.6 (78.0; 81.2) ml/min/1.73m2 at baseline and 81.3 (79.9; 82.7) ml/min/1.73m2 at 12 months after switch. In the patient-matched subgroup (n = 175), median annual eGFR-EPI declined −4.24 ml/min/1.73m2 while on F/TDF and increased +0.93 ml/min/1.73m2 after switch to F/TAF (P < 0.0001). In patients with baseline eGFR-EPI <90 ml/min/1.73m2, median annual eGFR-EPI increased +4.19 mL/min/1.73m2 after switch (P < 0.0001). Conclusion: Switching from F/TDF to F/TAF-based TT regimens while maintaining the same third agent numerically improved eGFR-EPI in PLWH with baseline eGFR-EPI <90 mL/min/1.73m2. eGFR-EPI improved significantly when comparing progression while on F/TDF vs progression after switch, confirming beneficial renal effects of switching to F/TAF in a clinical practice setting. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infection impairs mucosal immunity and leads to bacterial translocation, fueling chronic inflammation and disease progression. While this is well established, questions remain about the compositional profile of the translocated bacteria, and to what extent it is influenced by antiretroviral therapy (ART). Using 16S ribosomal DNA targeted sequencing and shotgun proteomics, we showed that HIV increases bacterial translocation from the gut to the blood. HIV increased alpha diversity in the blood, which was dominated by aerobic bacteria belonging to Micrococcaceae (Actinobacteria) and Pseudomonadaceae (Proteobacteria) families, and the number of circulating bacterial proteins was also increased. Forty-eight weeks of ART attenuated this phenomenon. We found that enrichment with Lactobacillales order, and depletion of Actinobacteria class and Moraxellaceae and Corynebacteriacae families, were significantly associated with greater immune recovery and correlated with several inflammatory markers. Our findings suggest that the molecular cross talk between the host and the translocated bacterial products could influence ART-mediated immune recovery. [ABSTRACT FROM AUTHOR]

Background: We have previously observed increased levels of inflammatory biomarkers and Th17 as well as Treg cells, but not other T-cell specific alterations, preceding immunodiscordance of successfully-treated HIV-infected subjects. Our hypothesis is that this could be related with potential alterations in myeloid-derived suppressor cells (MDSCs) and/or monocyte subsets. Methods: We determined the frequencies of MDSCs and monocyte subsets and the expression of several functional markers (CCR2, β 7-integrin, IDO, PDL1, CD11b) in HIV-infected subjects before treatment. We additionally analyzed follow-up samples after 24 months of suppressive cART in a subgroup of subjects. Bivariate regressions were performed, and correlations with soluble proinflammatory and bacterial translocation biomarkers, as well as with Th17/Treg ratio and anti-CMV titers were explored. Results: Increased frequencies of MDSCs, but normal distribution of monocyte subsets, preceded immunodiscordance. The expression of several functional markers, such as CCR2, CD16, CD11b and PDL1, on MDSCs and monocyte subsets was altered in this scenario. MDSC and monocyte-related functional markers were associated with soluble biomarkers and T-cell parameters. Several of these cellular alterations were not restored after 24 months of suppressive cART. Conclusion: An early immunosuppressive environment, characterized by the expansion of MDSCs and Tregs, precedes immunodiscordance and is related with a highly inflammatory status. [ABSTRACT FROM AUTHOR]

The HIV reservoir is the main barrier to eradicating HIV infection, and resting memory CD4 T (Trm) cells are one of the most relevant cellular component harboring latent proviruses. This is the first study analyzing the transcriptional profile of Trm cells, in two well-characterized groups of HIV patients with distinct mechanisms of viral replication control (spontaneous versus treatment-induced). We use a systems biology approach to unravel subtle but important differences in the molecular mechanisms operating at the cellular level that could be associated with the host's ability to control virus replication and persistence. Despite the absence of significant differences in the transcriptome of Trm cells between Elite Controllers (ECs) and cART-treated (TX) patients at the single gene level, we found 353 gene ontology (GO) categories upregulated in EC compared with TX. Our results suggest the existence of mechanisms at two different levels: first boosting both adaptive and innate immune responses, and second promoting active viral replication and halting HIV latency in the Trm cell compartment of ECs as compared with TX patients. These differences in the transcriptional profile of Trm cells could be involved in the lower HIV reservoir observed in ECs compared with TX individuals, although mechanistic studies are needed to confirm this hypothesis. Combining transcriptome analysis and systems biology methods is likely to provide important findings to help us in the design of therapeutic strategies aimed at purging the HIV reservoir. Key messages: HIV-elite controllers have the lowest HIV-DNA content in resting memory CD4 T cells. HIV-ECs show a particular transcriptional profile in resting memory CD4 T cells. Molecular mechanisms of enhanced adaptative and innate immune response in HIV-ECs. High viral replication and low viral latency establishment associate to the EC status. [ABSTRACT FROM AUTHOR]

Importance: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex.Objective: To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL.Design, Setting, and Participants: The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions.Exposures: Condomless sexual activity with an HIV-positive partner taking virally suppressive ART.Main Outcomes and Measures: Risk of within-couple HIV transmission to the HIV-negative partner.Results: Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up.Conclusions and Relevance: Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk. [ABSTRACT FROM AUTHOR]

Background and objectives: Cardiovascular disease is a major concern in HIV-infected patients. Lifetime risk estimations use the risk of developing it over the course of remaining lifetime, and are useful in communicating this risk to young patients. We aim to describe the prevalence of cardiovascular risk factors among a representative sample of HIV-infected subjects under antiretroviral therapy in Spain, and to estimate their lifetime risk of cardiovascular disease. Methods: Cross-sectional survey about cardiovascular risk factors in 10 HIV units across Spain. Lifetime risk assessed according to Barry was classified in two major categories: low and high lifetime risk. Results: We included 895 subjects, 72% men, median age 45.7 years; median CD4 lymphocyte count 598 cells/μl, median time since HIV diagnosis 11 years, median time on antiretroviral treatment 6.3 years, 87% had undetectable HIV viral load. Tobacco smoking was the most frequent risk factor (54%), followed by dyslipidemia (48.6%) and hypertension (38.6%). Estimated 10-year coronary risk (Framingham/Regicor Risk Score) risk was low (< 5%) in 78% of the patients, and intermediate (5–10%) in 20%. Lifetime risk estimation showed a high risk profile for 71.4% of the population studied, which was associated with increasing age, prolonged antiretroviral therapy and patient's place of origin. Conclusions: Modifiable cardiovascular risk factors in this population are very common. There are significant disparities between the low 10-year risk estimated with the Framingham/Regicor score and the higher lifetime risk in HIV patients on antiretroviral therapy. A more aggressive management of modifiable cardiovascular risk factors in these patients seems advisable. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. Simplified highly active antiretroviral therapy (HAART) regimens are becoming widely used, particularly as a result of the side effects of and difficult compliance with protease inhibitor (PI) therapy. However, the long-term efficacy of HAART has not been properly assessed. Methods. We performed a prospective study of 110 patients infected with human immunodeficiency virus type 1 (HIV-1) with undetectable virus load who discontinued PI therapy and initiated therapy with nevirapine without changing nucleoside analogues. Reasons for switching were treatment simplification (45%), lipodystrophy (24%), renal problems (23%), and dyslipidemia (8%). HIV-1 load, CD4 cell count, and fasting biochemistry profiles were performed at the time of switching (baseline) and every 3–4 months thereafter. The aim of the study was to evaluate the long-term efficacy and safety of this combination. Results. Sixty-eight patients (61.8%) had a duration of follow-up of 3 years. The mean increase in the CD4 cell count after 3 years was 90 cells/mL (13.8% from baseline). Virus loads remained undetectable in all patients but 9 (8.2%). Triglyceride levels dramatically improved at 12 months (a 75% decrease; P < .02) and remained statistically significant over time (P < .04). The same occurred with serum cholesterol levels: there was an initial reduction of 25% (P < .02) and at the end of the follow-up period (P < .015). However, at the long-term evaluation, complete normalization of mean serum cholesterol and triglyceride levels could not be achieved. Sixteen patients (14.5%) had to stop therapy as a result of nevirapine-associated side effects. Conclusions. The switching of a PI to nevirapine is a safe and well-tolerated option for maintaining long-term virological suppression and immunological control. Three years after starting nevirapine therapy, rates of hypercholesterolemia and hypertriglyceridemia improved, although normal cholesterol and triglyceride values were not achieved. [ABSTRACT FROM AUTHOR]

People living with HIV (PLWH) have an increased risk of cardiovascular (CV) disease, likely due to a higher prevalence of CV risk factors. We compared the age-standardized prevalence and management of CV risk factors in PLWH to that of the general population in Spain. Blood pressure, lipid, glucose, and anthropometric profiles were cross-sectionally compared along with the treatment of hypertension, dyslipidemia, and diabetes in a general population cohort and a PLWH cohort. Prevalence rates were standardized by the direct method by 10-year age groups in European standard populations and stratified by gender. We included 47,593 individuals aged 35 to 74 years, 28,360 from the general population cohort and 19,233 from the PLWH cohort. Compared to the general population, PLWH had a higher concentration of triglycerides (>35 mg/dL in women and >26 mg/dL in men) and a higher prevalence of smoking (>23% and >17%) and diabetes (>9.9% and >8.5%). The prevalence of treated diabetes, hypertension, and dyslipidemia were up to three-fold lower in both women and men living with HIV. There was a significant difference in PLWH compared to the general population in the lipid, glucose, and anthropometric profile. In addition, PLWH were less often treated for diagnosed diabetes, hypertension, and dyslipidemia. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infection is characterized by an early depletion of the mucosal associated T helper (CD4+) cells that impair the host immunity and impact the oral and gut microbiomes. Although, the HIV-associated gut microbiota was studied in depth, few works addressed the dysbiosis of oral microbiota in HIV infection and, to our knowledge, no studies on intervention with prebiotics were performed. We studied the effect of a six-week-long prebiotic administration on the salivary microbiota in HIV patients and healthy subjects. Also, the co-occurrence of saliva microorganisms in the fecal bacteria community was explored. We assessed salivary and feces microbiota composition using deep 16S ribosomal RNA (rRNA) gene sequencing with Illumina methodology. At baseline, the different groups shared the same most abundant genera, but the HIV status had an impact on the saliva microbiota composition and diversity parameters. After the intervention with prebiotics, we found a drastic decrease in alpha diversity parameters, as well as a change of beta diversity, without a clear directionality toward a healthy microbiota. Interestingly, we found a differential response to the prebiotics, depending on the initial microbiota. On the basis of 100% identity clustering, we detected saliva sequences in the feces datasets, suggesting a drag of microorganisms from the upper to the lower gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Introduction Asymptomatic patients with human immunodeficiency virus (HIV) infection are at increased risk of vascular disease. Whether asymptomatic HIV patients have increased prevalence or structural differences in coronary artery plaques is not clear. Methods Pubmed, Cochrane and Google Scholar were searched for articles evaluating asymptomatic HIV patients evaluated with coronary computed tomography. The prevalence of coronary stenosis (defined as >30% and >50%), of calcified coronary plaques (CCP) viewed as more ‘stable’ plaques, and of non-calcified coronary plaques (NCP) viewed as more ‘vulnerable’ plaques were the end points of interest. Results 9 studies with 1229 HIV patients and 1029 controls were included. No significant differences were detected about baseline cardiovascular risk profile. The prevalence of significant coronary stenosis >30% or >50% did not differ between HIV+ and HIV- patients (42% [37–44] and 46% [35–52] with an Odds Ratio [OR] of 1.38 [0.86–2.20] for >30% stenosis) and (15% [9–21] and 14% [7–22] with an OR of 1.11 [0.81–1.52]), respectively. The prevalence of calcified coronary plaques (CCP) (31% [24–32] and 21% [14–30] with an OR of 1.17 [0.63–2.16]) also did not differ among HIV+ and HIV- patients. On the contrary rates of NCP were >3-fold higher in HIV-positive patients [58% (48–60) and 17% (14–27) with an OR of 3.26 (1–30-8.18)], with an inverse relationship with CD4 cell count at meta-regression (Beta −0.20 [-0.35-0.18], p 0.04). Conclusion Asymptomatic HIV patients present a similar burden of coronary stenosis and calcified coronary artery plaques but significantly higher rates of non-calcific coronary plaques at computed tomography. The association between HIV infection, reduced CD4 cell counts and higher prevalence on non-calcific coronary artery plaques may shed light into the pathogenesis in HIV-associated coronary artery disease, stressing the importance of primary prevention in this population. [ABSTRACT FROM AUTHOR]

We assessed high-density lipoprotein (HDL) anti-inflammatory properties in a cohort of vertically HIV-infected adolescents. We hypothesized that proatherogenic mechanisms related to inflammation and immune activation during HIV infection may impair HDL functionality and impact on the atherosclerotic burden. Compared with healthy controls, HDL from HIV-infected adolescents presented impaired functionality, as determined by its ability to inhibit monocyte chemotaxis in vitro, which correlated with detectable viral loads (P = 0.044), lower CD4 nadir (P = 0.043), increased levels of CD4 T-cell activation (P = 0.018), higher C-reactive protein (P = 0.009), and a tendency toward thicker carotid intima-media thickness (P = 0.071). [ABSTRACT FROM AUTHOR]