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BackgroundThe main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use.MethodsA retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL.Results135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic.ConclusionsIn a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

Background The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. Methods A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. Results 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1–90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6–99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. Conclusions In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen’s effectiveness.

BackgroundPeople in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group.ObjectiveTo evaluate the differences among older adults with HIV according to their chronological age and the year of HIV diagnosis.MethodsCross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors [LTHS]) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL).ResultsWe evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996. Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis. LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB ConclusionsA LTHS and a 65 or over person are both "older adults with HIV," but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.

OBJECTIVE:We investigated the association of genetic polymorphisms in chemokine and chemokine receptor genes with poor immunological recovery in HIV patients starting combined antiretroviral therapy (cART) with low CD4 T-cell counts. METHODS:A case-control study was conducted in 412 HIV-infected patients starting cART with CD4 T-cell count

OBJECTIVES:Sexualized intravenous drug use, also known as slamsex, seems to be increasing among HIV-positive men who have sex with men (MSM). Physical and psychopathological symptoms have previously been reported in this population, although research on the subject of slamsex is scarce. The objectives of our study were to describe the psychopathological background of a sample of HIV-positive MSM who engaged in slamsex during the previous year and to compare physical, psychopathological, and drug-related symptoms between these participants and those who engaged in non-injecting sexualized drug use. DESIGN AND METHODS:Participants (HIV-positive MSM) were recruited from the U-Sex study in 22 HIV clinics in Madrid during 2016-17. All participants completed an anonymous cross-sectional online survey on sexual behavior and recreational drug use. When participants met the inclusion criteria, physicians offered them the opportunity to participate and gave them a card with a unique code and a link to access the online survey. The present analysis is based on HIV-positive MSM who had engaged in slamsex and non-injecting sexualized drug use. RESULTS:The survey sample comprised 742 participants. Of all the participants who completed the survey, 216 (29.1%) had engaged in chemsex, and of these, 34 (15.7%) had engaged in slamsex. Participants who engaged in slamsex were more likely to have current psychopathology (depression, anxiety, and drug-related disorders) than participants who engaged in non-injecting sexualized drug use. In addition, participants who engaged in slamsex more frequently reported high-risk sexual behaviors and polydrug use and were more often diagnosed with sexually transmitted infections (STIs) and hepatitis C than those who did not inject drugs. Compared with participants who did not inject drugs, participants who engaged in slamsex experienced more severe drug-related symptoms (withdrawal and dependence), symptoms of severe intoxication (loss of consciousness), and severe psychopathological symptoms during or after slamsex (eg, paranoid thoughts and suicidal behaviors). CONCLUSION:Slamsex is closely associated with current psychiatric disorders and severe drug-related and psychiatric symptoms.

T-cell exhaustion has been involved in the pathogenesis of HIV infection. We have longitudinally analyzed PD1 and Tim3 surrogate markers of T-cells exhaustion, in parallel with other markers of HIV progression, and its potential association with CD4 changes in treated and untreated infection.96 HIV patients, 49 of them followed in the absence of cART (cART-naïve group) and 47 after initiation of cART (cART group) were included and followed for a median of 43 [IQR: 31-60] months. PD1 and Tim3 expression, CD8 T-cells activation, recent thymic emigrants, activation/apoptosis and turnover of CD4 cells were assessed at baseline and during follow up. Univariate and multivariate associations with CD4 evolution were explored.Parameters significantly associated with CD4 depletion in cART-naïve group were: baseline level (p = 0.02) and variation (p = 0.002) of PD1 and Tim3 co-expression on CD8, and variation of CD95 expression on CD4 (p = 0.007). Parameters significantly associated with CD4 restoration in cART group were: baseline level of CD38+HLADR- subset of CD8 (p = 0.01), variation of PD1 expression on CD8 (p = 0.036), variation of Tim3 expression on CD4 (p = 0.039) and variation of CD95 expression on CD4 (p = 0.035).Our results suggest that PD1 and Tim3 markers of exhaustion have a pivotal role in CD4 dynamics in HIV patients and its down-regulation would be a desirable effect of immunotherapies aimed to restore CD4 T-cell pool during progression of HIV infection.

BACKGROUND:Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. DESIGN:Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. METHODS:We evaluated effectiveness (defined as maintenance of HIV-1-RNA

BACKGROUND:There are several contributors to HIV-pathogenesis or insufficient control of the infection. However, whether HIV/HCV-coinfected population exhibits worst evolution of HIV-pathogenesis remains unclear. Recently, some markers of immune exhaustion have been proposed as preferentially upregulated on T-cells during HIV-infection. Herein, we have analyzed T-cell exhaustion together with several other contributors to HIV-pathogenesis that could be affected by HCV-coinfection. PATIENTS AND METHODS:Ninety-six patients with chronic HIV-infection (60 HIV-monoinfected and 36 HIV/HCV-coinfected), and 20 healthy controls were included in the study. All patients were untreated for both infections. Several CD4 and CD8 T-cell subsets involved in HIV-pathogenesis were investigated. Non-parametric tests were used to establish differences between groups and associations between variables. Multivariate linear regression was used to ascertain the variables independently associated with CD4 counts. RESULTS:HIV-patients presented significant differences compared to healthy controls in most of the parameters analyzed. Both HIV and HIV/HCV groups were comparable in terms of age, CD4 counts and HIV-viremia. Compared to HIV group, HIV/HCV group presented significantly higher levels of exhaustion (Tim3+PD1- subset) in total CD8+ T-cells (p = 0.003), and higher levels of exhaustion in CD8+HLADR+CD38+ (p = 0.04), CD8+HLADR-CD38+ (p = 0.009) and CD8+HLADR-CD38- (p = 0.006) subsets of CD8+ T-cells. Interestingly these differences were maintained after adjusting by CD4 counts and HIV-viremia. CONCLUSIONS:We show a significant impact of HCV-coinfection on CD8 T-cells exhaustion, an important parameter associated with CD8 T-cell dysfunction in the setting of chronic HIV-infection. The relevance of this phenomenon on immunological and/or clinical HIV progression prompts HCV treatment to improve management of coinfected patients.