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Summary Background Factors affecting outcomes of SARS-CoV-2 infection in people living with HIV are unclear. We assessed the factors associated with SARS-CoV-2 diagnosis and severe outcomes among people living with HIV. Methods We did a retrospective cohort study using data from the PISCIS cohort of people with HIV in Catalonia (Spain) between March 1 and Dec 15, 2020. We linked PISCIS data with integrated health-care, clinical, and surveillance registries through the Public Data Analysis for Health Research and Innovation Program of Catalonia (PADRIS) to obtain data on SARS-CoV-2 diagnosis, chronic comorbidities, as well as clinical and mortality outcomes. Participants were aged at least 16 years in care at 16 hospitals in Catalonia. Factors associated with SARS-CoV-2 diagnoses and severe outcomes were assessed using univariable and multivariable Cox regression models. We estimated the effect of immunosuppression on severe outcomes (hospital admission for >24 h with dyspnoea, tachypnoea, hypoxaemia, asphyxia, or hyperventilation; or death) using Kaplan-Meier survival analysis. Findings We linked 20 847 (72·8%) of 28 666 participants in the PISCIS cohort with PADRIS data; 13 142 people had HIV. 749 (5·7%) people with HIV were diagnosed with SARS-CoV-2: their median age was 43·5 years (IQR 37·0–52·7), 131 (17·5%) were female, and 618 (82·5%) were male. 103 people with HIV (13·8%) were hospitalised, seven (0·9%) admitted to intensive care, and 13 (1·7%) died. SARS-CoV-2 diagnosis was more common among migrants (adjusted hazard ratio 1·55, 95% CI 1·31–1·83), men who have sex with men (1·42, 1·09–1·86), and those with four or more chronic comorbidities (1·46, 1·09–1·97). Age at least 75 years (5·2, 1·8–15·3), non-Spanish origin (2·1, 1·3–3·4), and neuropsychiatric (1·69, 1·07–2·69), autoimmune disease (1·92, 1·14–3·23), respiratory disease (1·84, 1·09–3·09), and metabolic disease (2·59, 1·59–4·23) chronic comorbidities were associated with increased risk of severe outcomes. A Kaplan-Meier estimator showed differences in the risk of severe outcomes according to CD4 cell count in patients with detectable HIV RNA (p=0·039) but no differences were observed in patients with undetectable HIV RNA (p=0·15). Interpretation People living with HIV with detectable HIV viraemia, chronic comorbidities, and some subpopulations could be at increased risk of severe outcomes from COVID-19. These groups should be prioritised in clinical management and SARS-CoV-2 vaccination programmes. Funding Fundacio "la Caixa". Translations For the Catalan, Spanish and Russian translations of the Summary see Supplementary Materials section.

Background: There are few shared assistance programs with Primary Health Care (PHC) in PLWH. The aim was to develop a Pilot Program of shared HIV care in PLWH ensuring proper HIV control. Methods: Design: Prospective pilot project of a shared care intervention.Setting: HIV specialized outpatient consultations for HIV infection at Son Espases University Hospital which serves 2000 patients. Subjects: Patients who attended HIV specialized consultation between January 1st and June 30th, 2017. Intervention: Basal questionnaire on health services used by patients. HIV Training Program on HIV in Primary Health Care (PHC). Pilot Program of shared assistance (PPAC) with PHC. Main Outcomes: Maintenance of undetectable HIV viral load, antiretroviral therapy (ART) adherence, AIDS and non-AIDS events, loss of follow up, and satisfaction questionnaire. Results: The basal questionnaire was filled out by 918 patients, with 108 (11.7%) patients reporting neither knowing nor having been visited by their GP. A total of 93 patients were included in the PPAC, with a mean age of 49.9 years (SD 11.7), and an average of 14.6 years since the HIV diagnosis. Eleven patients were followed up for less than six months and were excluded from the analysis. Median follow-up during the PPAC of the remaining 82 patients was 728 days (IQR 370-1070). Sixteen patients dropped out of the PPAC (19.5%), three died, three were lost to follow up, one was withdrawn due to medical criteria, and nine withdrew voluntarily.No patient presented any AIDS defining events, although eight patients presented non-AIDS events. All the patients had undetectable viral load (VL) and average ART adherence was 99.4% (SD1.4). The patient’s satisfaction score with PPAC was 8.64 (SD2.5).Conclusion: It is possible to establish shared care programs with PHC in selected patients with HIV infection, thereby reducing hospital visits while maintaining good adherence and virological control and achieving high patient satisfaction.

Objective: To assess lipoatrophy, other toxicities, and efficacy associated with abacavir as compared with stavudine in HIV-infected antiretroviral-naive patients. Methods: This was a prospective, randomized, open trial, stratified by viral load and CD4 cell count, conducted January 2001 to July 2004. Two hundred thirty-seven adult patients with HIV infection initiating antiretroviral therapy were assigned to receive abacavir (n = 115) or stavudine (n = 122), both combined with lamivudine and efavirenz. The primary endpoint was the proportion of patients with lipoatrophy as assessed by physician and patient observation at 96 weeks. Results: A lower proportion of patients assigned to abacavir developed clinical signs of lipoatrophy (4.8% vs. 38.3%; P < 0.001). These observations were confirmed by anthropometric data. Dual energy x-ray absorptiometry (DEXA) scans performed in 57 patients showed significantly greater total limb fat loss in the stavudine arm (-1579 vs. 913 g; P < 0.001). The lipid profile in abacavir patients presented more favorable changes in the levels of triglycerides (P = 0.03), high-density lipoprotein cholesterol (HDLc; P < 0.001), and apolipoprotein Al (P < 0.001) as well as in the ratio between total cholesterol and HDLc (P = 0.005). Throughout the study, a higher proportion of patients in the stavudine group received lipid-lowering agents as compared to the abacavir group (17% vs. 4%; P = 0.002). Similar virologic and immunologic responses were observed. Conclusions: Assuming the limitations inherent to clinical assessment, this study shows a notably weaker association of abacavir with lipoatrophy than stavudine. DEXA scans and anthropometric measurements supported the clinical findings. In addition, the lipid changes that occurred were more favorable in patients receiving abacavir.

Objetivos Describir la utilizacion de los tests de resistencia genotipica (TRG) por fracaso virologico en la practica clinica y la evolucion clinica y virologica a largo plazo de los pacientes en los que se solicitaron. Establecer los factores predictivos de fracaso virologico con tratamientos antirretrovirales (TARV) de rescate. Metodos Estudio observacional de los pacientes con infeccion por el virus de la inmunodeficiencia humana (VIH) a los que se solicito TRG por fracaso virologico (FV) en el periodo comprendido entre el 1/10/1999 y 31/12/2001. Se determinaron los factores predictivos de mala evolucion virologica mediante un analisis de regresion logistica. Resultados En el periodo de estudio, 196 pacientes precisaron TRG por FV (15%) de los seguidos en unas consultas especificas. Los TRG se solicitaron mayoritariamente a pacientes extensamente pretratados, con una media de 5 anos y una mediana de cinco combinaciones TARV. La mitad de los pacientes presentaban tres o mas mutaciones asociadas a analogos de la timidina (TAM), alguna mutacion asociada a analogos no nucleosidos (ANNTI) y cinco o mas mutaciones asociadas a inhibidores de proteasas (IP). En 143 (74%) se realizo un cambio de TARV en base al TRG recibido. En el analisis por intencion de tratar, el porcentaje de pacientes con carga viral (CV) plasmatica El incremento medio de los linfocitos CD4 fue de 59,74 y 94 cels./μl. Las variables predictivas de presentar CV > 400 cop./ml a los 12 meses, fueron tener una CV > 30.000 cop./ml odds ratio (OR) 6 (1,8-19,5) y haber acumulado tres o mas TAM OR 4,4 (1,3-15) al iniciar el TARV de rescate. Conclusion A pesar de que los TRG se solicitan en la practica clinica en pacientes en multifracaso, al instaurar TARV de rescate se consiguen mantener la CV plasmatica indetectables en el 40% de los pacientes en seguimiento a los 18 meses y con una respuesta inmunologica mantenida. Los factores que mejor predicen la evolucion virologica son la CV plasmatica y el numero de TAMbasales.

To describe the use of genotype resistance testing (GRT) for virological failure in clinical practice, and the long-term clinical and virological evolution in patients for whom it is requested. To identify the predictive factors of virological failure in patients with antiretroviral (ARV) salvage therapy.Observational study in HIV-infected patients for whom GRT was requested for virological failure (VF) in the period of 1 October 1999 to 31 December 2001. Logistic regression analysis was used to determine the predictive factors of virological progression.Over the period studied, 196 patients required GRT for VF (15%) among those monitored in specific units. GRT was mainly requested for patients who had been extensively pretreated for a mean of 5 years and with a median of 5 ARV combinations. Half the patients presented 3 or more mutations associated with thymidine analogs (TAMs), mutations associated with non-nucleoside analogs (NNRTIs), and 5 or more mutations associated with protease inhibitors (PIs). In 143 (74%) patients, the RTV regimen was changed on the basis of GRT results. In the intent-to-treat analysis, the percentage of patients with plasma VL400 cop/mL at 6, 12 and 18 months was 41%, 29% and 17%, respectively. In the on-treatment analysis, the results were 50%, 48% and 46%, respectively. Mean CD4 lymphocyte increase was 59.74 and 94 cells/mm 3. The variables predicting virological failure (plasma VL400 cop/mL) at 12 months were plasma VL30,000 cop/mL (OR 6, 1.8-19.5) and accumulation of 3 or more TAMs (OR 4.4, 1.3-15) at the start of ARV salvage therapy.Even though in clinical practice GRT is requested for patients with various treatment failures, when ART salvage treatment was started, plasma VL was undetectable and immunological response persisted in 40% of patients followed-up for 18 months. The factors best predicting virological evolution were VL and the number of baseline TAMs.

The number of HIV-infected individuals with prior multiple treatment failures is increasing as time passes by. The success of antiretroviral therapy in these patients is often compromised by the selection of drug-resistant viruses. Despite initial concerns, a rebound in AIDS cases among heavily treatment-experienced patients failing virologically their antiretroviral therapy has not occurred yet. In a multicenter study conducted in Spain, HIV-infected patients were assessed with prior failure to antiretrovirals from the three main drug families who presented during the last semester of the year 2003 with plasma HIV-RNA values above 1,000 copies/ml, despite good treatment adherence. The relationships between CD4+ T cell counts, viral loads and drug-resistant genotypes were examined. A total of 273 patients were identified in 12 centers (78% male, median age: 41 years). The mean viral load was 50,438 copies/ml and the mean CD4+ count was 328 cells/mul. Only 19.5% had less than 200 CD4+ T cells/mul. Most patients (95%) were receiving nucleoside reverse transcriptase inhibitors (NRTI) in their last antiretroviral regimen, while 63% were treated with protease inhibitors (PI) and 27% on non-nucleoside reverse transcriptase inhibitors (NNRTI). Overall, 97.4% had at least one drug resistance mutation (87.2% for NRTI, 68.5% for NNRTI, and 92.7% for PI). Using the virtual phenotype, resistance to three or more drugs within each class was recognized in 45.8% for NRTI, 40.7% for NNRTI, and 44.7% for PI. Moreover, cross-resistance to compounds from two or three drug families was recognized in 41% and 19.4% of patients, respectively. Nearly half of the patients had plasma HIV-RNA below 10,000 copies/ml and they showed significantly higher CD4 + counts than those with greater viremia (408 versus 259 cells/mul; P < 0.001). Patients with higher plasma viremia had significantly more drug resistance mutations than those with lower viremia. No favorable effect on viral load could be recognized for individual drug resistance mutations known to reduce viral fitness in vitro (i.e., rtM184V, rtL74V, rtK65R, proD30N, or proI50L). In summary, a large proportion of treatment-experienced patients failing their current antiretroviral regimen carry viruses with broad cross-resistant genotypes. Nearly half of the patients with these multi-drug resistant viruses had < 10,000 HIV-RNA copies/ml and 80% have more than 200 CD4 + T cells/mul. Thus, maintaining treatment HIV-infected individuals failing virologically and harboring drug-resistant viruses might ameliorate immunological deterioration until new drugs became available. J. Med. Virol. 77:23-28, 2005. (c) 2005 Wiley-Liss, Inc.

Introduction : In a previous interim 24-week virological safety analysis of the PROTEST study [1], initiation of Maraviroc (MVC) plus 2 nucleoside reverse-transcriptase inhibitors (NRTIs) in aviremic subjects based on genotypic tropism testing of proviral HIV-1 DNA was associated with low rates of virological failure. Here we present the final 48-week analysis of the study. Methods : PROTEST was a phase 4, prospective, single-arm clinical trial (ID: NCT01378910) carried on in 24 HIV care centres in Spain. Maraviroc-naive HIV-1-positive adults with HIV-1 RNA (VL) 10% in a singleton), initiated MVC with 2 NRTIs and were followed for 48 weeks. Virological failure was defined as two consecutive VL>50 c/mL. Recent adherence was calculated as: (# pills taken/# pills prescribed during the previous week)*100. Results : Tropism results were available from 141/175 (80.6%) subjects screened: 87/141 (60%) were R5 and 74/87 (85%) were finally included in the study. Their median age was 48 years, 16% were women, 31% were MSM, 36% had CDC category C at study entry, 62% were HCV+ and 10% were HBV+. Median CD4+ counts were 616 cells/mm 3 at screening, and median nadir CD4+ counts were 143 cells/mm 3 . Previous ART included PIs in 46 (62%) subjects, NNRTIs in 27 (36%) and integrase inhibitors (INIs) in 1 (2%). The main reasons for treatment change were dyslipidemia (42%), gastrointestinal symptoms (22%), and liver toxicity (15%). MVC was given alongside TDF/FTC in 40 (54%) subjects, ABC/3TC in 30 (40%), AZT/3TC in 2 (3%) and ABC/TDF in 2 (3%). Sixty-two (84%) subjects maintained VL