Suchergebnisse

IntroductionAim of the study was to evaluate possible disparities in access and/or risk of virological failure (VF) to the first antiretroviral (ART) regimen for migrants compared to Italian‐born patients and to assess determinants of failure for the migrants living with HIV.MethodsAll native and migrant naïve patients enrolled in ICONA in 2004–2014 were included. Firstly, variables associated to ART initiation were analyzed. In a second analysis, the primary endpoint was time to failure after at least six months of ART, defined as: (a) VF (first of two consecutive viral load (VL) >50 and >200 copies/mL); (b) treatment discontinuation (TD) for any reason; and (c) treatment failure (TF: confirmed VL >200 cp/mL or TD). A Poisson multivariable analysis was performed to control for confounders.ResultsA total of 5777 HIV‐pos ART‐naïve patients (1179 migrants and 4598 natives) were evaluated. Most migrants were from sub‐Saharan Africa (35.3%) and South‐Central America/Caribbean (29%). Median duration of residency in Italy was five years (IQR 1–10). Baseline characteristics significantly differed between the two groups (Table 1); in particular, lower CD4 counts and higher frequency of AIDS events were observed in migrants vs natives. When adjusting for baseline confounders, migrants presented a lower chance to initiate ART compared to natives (OR 0.78, 95% CI 0.65–0.93, p=0.006). After ART initiation, the incidence rate of VF >50 cp/mL was 15.5 per 100 person‐years (95% CI 12.8–18.8) in migrants and 8.9 in natives (95% CI 7.9–9.9), respectively. By multivariable analysis, migrants had a significantly higher risk of VF, both >50 cp/mL (OR 1.50, 95% CI 1.17–1.193, p=0.001) and >200 cp/mL (OR 1.59, 95% CI 1.23–2.05, p<0.001), and of TF (OR 1.15, 95% CI 1.00–1.32, p=0.045), while no differences were observed in TD risk. Among migrants, variables associated with a higher VF risk were age (for 10‐year increase, OR 0.96, 95% CI 0.93–0.98, p=0.002), unemployment (OR 1.96, 95% CI 1.20–3.20, p=0.007) and use of a boosted PI based‐regimen (OR 2.04, 95% CI 1.25–3.34, p=0.005 vs NNRTI‐based), while pregnancy was associated with TD (OR 3.73, 95% CI 2.36–5.90, p<0.001) and TF (OR 3.13, 95% CI 02.00–4.89, p<0.001).ConclusionsDespite the use of more potent and safer antiretroviral drugs in the last 10 years, and even in a setting of universal access to ART, migrants living with HIV still present barriers to ART initiation and increased risk of VF compared to natives.

IntroductionEmtricitabine/rilpivirine/tenofovir (EVP) is a fixed‐dose combination of antiretrovirals (ARV) approved by the European Medicines Agency in November 2011 and introduced in Italy in February 2013. It is a once‐a‐day single tablet and is licensed in Europe for use only in ARV‐naïve patients with a viral load (VL) ≤100,000 copies/mL.ObjectiveTo identify factors that may be associated with the use of EVP as first‐line regimen in HIV‐infected individuals starting cART from ARV‐naïve in Italy.MethodsClinical sites in ICONA Foundation Study in which ≥1 person had started EVP were selected for this analysis. From these we included all patients who started an EVP‐based cART regimen as well as those starting other cART regimens after the date of introduction of EVP at the site (after February 2013 in any case) and with a VL ≤100,000 copies/mL from ARV‐naïve. Characteristics at the time of starting cART were compared using chi‐square test and unadjusted and adjusted logistic regression analysis. Factors investigated included: gender, mode of HIV transmission, time from HIV diagnosis, CD4 count, nation of birth, AIDS, HCV‐status, age, CD8 count, VL, diabetes, smoking, total and HDL cholesterol, eGFR, blood glucose, level of education and employment and site location. Factors showing unadjusted associations with a p‐value of 10% or smaller, were retained in the multivariable model.ResultsWe identified 183 patients starting EVP and 173 starting the control regimen from 23 sites. The number of patients starting EVP included at each site ranged from 1 to 12 and the number of those starting the control regimen was similar. The most frequently used drugs in the concurrent group were: TDF (75%), FTC (74%), DRV (39%), ATV/r (26%), LPV/r (9%), EFV (13%) and RAL (14%). In univariable analysis, there were differences in median CD4 count (390 cells/mm3 in EVP versus 348 in controls, p=0.002), time from HIV diagnosis to starting cART (11 versus 3 months, p=0.001) and prevalence of students (6% versus 3%, p=0.07). No differences were observed for all other factors examined. The table shows estimates of the odds ratios (OR) for factors included in the multivariable model.ConclusionsCD4 count was higher in EVP‐treated patients compared to controls. Guidelines suggest avoiding initiation of EVP in presence of high VL, possibly explaining this residual difference in CD4. There was also a tendency to prescribe EVP to people with perceived lower adherence or hesitant to start or perhaps with a slow progressing disease.

IntroductionSerious non‐AIDS events (SNAE) are frequent in HIV patients receiving cART. Current CD4 count was shown to be more strongly associated with infective compared to not‐infective SNAE and unable to predict cardiovascular events. We investigated the relationship between baseline and current CD4 count and the risk of both infective and non‐infective SNAE in HIV‐positive patients according to current ART use.MethodsWe included all HIV‐positive persons enrolled in the ICONA Foundation Study cohort who had at least one follow‐up visit. SNAE were grouped in infective (pneumonia, sepsis, endocarditis and meningitis) and non‐infective (malignancies, chronic kidney disease, cardiovascular events, hepatic events and pancreatitis) aetiology. Incidence of these event groups were calculated overall and according to baseline and current CD4 count (grouped as 0–200, 201–350, 351–500, 501–750, and >750 cells/mm3). Participants' follow‐up accrued from the date of enrolment (baseline) to a diagnosis of SNAE or their last visit. An event was defined the first time one of the considered SNAE occurred so that each person contributed a single event. A Poisson regression model for each of the two endpoints was used.ResultsA total of 10,822 patients were included (25.3% females, 38.2% heterosexuals) and 26.6% had hepatitis co‐infections. Median age was 36 (IQR 31–42) years. Overall, 423 not‐infective and 385 infective SNAE were included. The most frequent non‐infective SNAE were malignancies (n=202) and the most frequent infective SNAE were pneumonia (n=289). Crude rates of non‐infective SNAE were 0.78, 1.08 and 0.80/100 PYFU, and those of infective SNAE were 1.00, 0.51 and 0.66/100 PYFU in ART naive, currently off and currently on ART patients, respectively. Higher current CD4 count was associated with reduced risk of both infective and non‐infective SNAE in naives and in patients on ART (Table 1). The association was less strong in the group which suspended ART (for non‐infective SNAE the p value for interaction between current log‐CD4 and ART‐status, p=0.004). Conversely, we found no association between baseline CD4 count and risk of non‐infective SNAE in people treated with ART (p value for interaction = 0.0001). When CVD were considered separately, there was no association with CD4 count (not shown).ConclusionsOur findings show that, differently from ART naive, in ART‐treated patients, non‐infective SNAE are predicted by current but not by baseline CD4, suggesting that immune restoration is crucial to prevent these events.

Abstract
An extended haplotype on chromosome 3 is the major genetic risk factor for severe COVID-19. The risk haplotype, which was inherited from Neanderthals, decreases the expression of several cytokine receptors, including CCR5. Recently, a study based on three general population cohorts indicated that the minor allele of one of the variants in the haplotype (rs17713054) protects against HIV infection. We thus expected this allele to be over-represented in highly exposed individuals who remain uninfected (exposed seronegative individuals, ESN). To perform a meta-analysis, we genotyped rs17713054 in three ESN cohorts of European ancestry exposed to HIV through different routes. No evidence of association was detected in the single cohorts. The meta-analysis also failed to detect any effect of the variant on protection from HIV-1. The same results were obtained in a Cox-regression analysis for the time to seroconversion. An in-vitro infection assay did not detect differences in viral replication as a function of rs17713054 genotype status. We conclude that the rs17713054 minor allele is not associated with the ESN phenotype and does not modulate HIV infection in vitro.