Suchergebnisse

IntroductionIn a recent clinical trial (ACTG 5257), no difference in viral failure (VF) of a first‐line cART containing atazanavir/r (ATV/r) or darunavir/r (DRV/r) was found [1]. For the endpoint of discontinuation due to intolerance, the regimen with DRV/r was superior to that of ATV/r (49% of the stops of ATV/r were attributed to jaundice or hyperbilirubinemia). These and other intolerances to ATV/r remain a concern for clinicians.MethodsParticipants in the ICONA Foundation Study who started cART with 2NRTI+ ATV/r or DRV/r while ART‐naïve were included. Several endpoints were evaluated: confirmed VF>200 copies/mL after six months of therapy, discontinuation of DRV/r or ATV/r for any reasons or because of intolerance/toxicity (as reported by the treating physician) and the combined endpoint of VF or stop. Survival analysis with Kaplan–Meier curves and Cox regression model stratified by clinical site was used. Patients' follow‐up accrued from cART initiation to the date of the event or to the date of last available visit/viral load.Results894 patients starting 2NRTI+ATV/r and 686 2NRTI+DRV/r when ART‐naïve on average in 2011 (IQR: 2010–2012) were studied. Most common NRTIs used were FTC/TDF (84%) and ABC/3TC (12%). Median age was 40 years, 22% females, 44% heterosexuals. Patients starting ATV/r were more likely to be hepatitis B/C infected (2% and 14% vs 1% and 9%, p=0.001), they started one year earlier (2011 vs 2012, p=0.001), were more likely to be enrolled in sites located in the north of Italy (63% vs 54%, p=0.04), started cART less promptly after HIV diagnosis (5 vs 2 months, p=0.02) and less likely to have started TDF/FTC (83% vs 85%, p=0.02). By two years of cART, 9.8% (95% CI 7.6–12.0) of those starting ATV/r experienced discontinuation due to intolerance/toxicity vs 6.5% in DRV/r group (95% CI 4.2–8.8, p=0.04). After controlling for several potential confounders (age, gender, nation of birth, mode of HIV transmission, hepatitis co‐infection status, AIDS diagnosis, nucleoside pair started, baseline CD4 count and viral load and year of starting cART) the relative hazard (RH) for ATV/r vs DRV/r was 2.01 (95% CI 1.23, 3.28, p=0.005). There were no statistical differences detected for any of the other outcomes.ConclusionsAlthough unmeasured confounding cannot be ruled out, our results seem to be consistent with those of the ACTG 5257. When all cause discontinuations were considered, or the composite endpoint of treatment failure, there was no difference between ATV/r‐ and DRV/r‐based regimens.

BackgroundHIV can spread into the central nervous system (CNS) early in the course of infection and this turns into intrathecal inflammation and neuronal damage. We aimed to investigate clinical and immunological parameters associated with elevated CSF VL in HIV‐infected ART‐naïve patients.Materials and MethodsHIV+ ART‐naïve patients underwent a comprehensive battery of neurocognitive (NC) tests and lumbar puncture (LP) for CSF HIV‐RNA detection. Plasma HIV‐RNA and peripheral T‐cell immune‐phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/CD8) were also assessed (flow cytometry). High‐CSF HIV RNA was defined as≥10000cp/mL (H‐CSF), while CSF HIV RNA<10000cp/mL characterized low VL patients (L‐CSF). Chi‐square and Mann‐Whitney tests were used. Parameters independently associated with CSF VL were explored by multivariate regression.ResultsA total of 131 patients were retrospectively enrolled. Forty‐two patients (32%) had CSF VL >10000 cp/mL.Table 1 shows the features of H‐ versus L‐CSF patients. Compared to L‐CSF patients, H‐CSF patients displayed lower current CD4+%, lower CD4/CD8 ratio and higher CD8%. No differences in NC tests performance were observed between groups (p=0.6). Regarding T‐cell immuno‐phenotypes, H‐CSF patients displayed a higher proportion of CD45R0+CD38+CD8+ (11 vs 7%, p=0.02) and lower expression of CD45RA+CD8+ % (16 vs 20%, p=0.007), in comparison to L‐CSF patients. In multivariate analysis CD45RA+CD8+ T‐cells % (OR 0.917, CI 95% 0.852–0.987, p=0.002) was associated with H‐CSF, even after adjustment for plasma VL, CD8 and CD4 count. Globally, in univariate CSF VL inversely correlated with CD45RA+CD8+ % (r=−0.223, p=0.0217) and CD127+CD4+ % (r= −0.204, p= 0.0225), while a positive association was found between CSF and plasma VL (r=0.303, p=0.0004) and CD8 % (r=0.211, p=0.016). In multivariate linear regression, in addition to positive association between plasma and CSF VL (β: 0.212, 95% CI 0.02–0.41, p=0.032), also CD45RA+CD8+ % were confirmed inversely associated to CSF VL (β: 0.21, 95% CI −0.5 to −0.002, p=0.036), adjusting for CD4/CD8 and CD4CD127 %.ConclusionsWe hereby describe a 32% prevalence of H‐CSF in a cohort of HIV+ ART‐naïve patients. Subjects with high‐CSF viral replication are mostly with higher systemic immune activation, in particular the percentage of naïve CD8 T‐cell is positively associated with CSF VL, irrespective of plasma VL. In HIV+ ART‐naïve patients, especially if featuring a hyperactivated T‐cell immune‐phenotype, lumbar puncture should be considered to further guide CNS‐targeted cART.

IntroductionIn the management of HIV, women and men generally undergo the same treatment pathway, with gender differences being given limited consideration. This is in spite of accumulating evidence that there are a number of potential differences between women and men which may affect response to treatment, pharmacokinetics, toxicities and coping. There are also notable psychological, behavioural, social and structural factors that may have a unique impact on women living with HIV (WLWH). Despite our increasing knowledge of HIV and advances in treatment, there are significant gaps in the data relating specifically to women. One of the factors contributing to this situation is the under‐representation of women in all aspects of HIV clinical research. Furthermore, there are clinical issues unique to women, including gynaecologic and breast diseases, menopause‐related factors, contraception and other topics related to women's and sexual health.MethodsUsing scoping review methodology, articles from the literature from 1980 to 2012 were identified using appropriate MeSH headings reflecting the clinical status of WLWH, particularly in the areas of clinical management, sexual health, emotional wellbeing and treatment access. Titles and abstracts were scanned to determine whether they were relevant to non‐reproductive health in WLWH, and papers meeting inclusion criteria were reviewed.ResultsThis review summarizes our current knowledge of the clinical status of WLWH, particularly in the areas of clinical management, sexual health, emotional wellbeing and treatment access. It suggests that there are a number of gender differences in disease and treatment outcomes, and distinct women‐specific issues, such as menopause and co‐morbidities, that pose significant challenges to the care of WLWH.ConclusionsBased on a review of this evidence, outstanding questions and areas where further studies are required to determine gender differences in the efficacy and safety of treatment and other clinical and psychological issues specifically affecting WLWH have been identified. Well‐controlled and adequately powered clinical studies are essential to help provide answers to these questions and to contribute to activities aimed at improving the health and wellbeing of WLWH.

IntroductionIn clinical trials, toxicity leading to discontinuation of tenofovir (TDF) is a rare occurrence (3% by two years)[1, 2]; however, in clinical practice it seems to be higher. Previous studies suggested that TDF toxicity is higher when it is co‐administered with ritonavir‐boosted protease inhibitors (PI/r)[3, 4]. The aim of this study is to assess the rate of TDF discontinuations in clinical practice and to explore associated factors.MethodsAll previously antiretroviral‐naïve patients initiating a TDF‐containing regimen were selected from the ICONA cohort, unless they were positive for hepatitis B. The primary outcome was TDF discontinuation (>30 days) regardless of the reason, the secondary was TDF discontinuation due to toxicity. All analyses were repeated for the isolated stop of TDF (no stop of associated drugs). The main reason for discontinuation as reported by the treating physicians was used to classify stops. Kaplan–Meier (KM) analysis and Cox proportional hazards model were used.ResultsA total of 3,303 naïve patients were enrolled: 674 (20.4%) were female, the median age was 38 years (32–45), 55% were on PI/r‐based regimen and 45% on NNRTI; 80% of calculated estimated glomerular filtration rates (eGFR) were >90 ml/min. The probability of discontinuation of TDF regardless of the reason was 10% (95% CI 8–11) at two years, 20% by eight years. The causes of discontinuation were: toxicity (33%), failure (10%), non‐adherence (21%), simplification (16%) and other/unknown causes (20%). The five‐year KM estimates in the PI/r vs. not PI/r groups were 23% vs. 10%, respectively (log‐rank p=0.0001), for the outcome of stopping regardless of the reason, and 8% vs. 4% (p=0.18) for discontinuation due to toxicity. In a multivariable Cox model, PI/r use and lower body weight were associated with increased risk of discontinuing TDF regardless of the reason; lower eGFR at baseline was associated with TDF discontinuation for toxicity and PI/r use was associated with isolated stop of TDF (Figure). No differences in rates of TDF discontinuations between PIs were found.ConclusionIn our cohort, the observed frequency of TDF discontinuations was low although higher than estimated in clinical trials (10% by two years). Co‐administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. This finding should guide further investigations of the mechanism that may have led to discontinuation of TDF in patients using PI/r.

IntroductionWe aimed to assess any factors associated with dysplasia regression and with HPV clearance in a cohort of HIV+ patients, with particular focus on cART and gender.MethodsAsymptomatic HIV+ patients of the San Paolo Infectious Disease (SPID) cohort who underwent anoscopy/gynaecological evaluation were enrolled. Anal/cervical brushing were analyzed for: HPV‐PCR detection/genotyping (HR‐HPV), cytologic abnormalities (Bethesda System 2001: LSIL‐HSIL). Demographics and HIV‐related parameters were evaluated at baseline. Activated CD8+/CD38+ lymphocytes were measured (flow citometry). Patients were examined at baseline (T0) and at 12–18 months visit (T1). HPV clearance was defined as negativisation of HPV at T1; SIL regression (SIL‐R) and progression (SIL‐P) were defined as change from HSIL/LSIL to a lower‐grade/absence of dysplasia and as change from absence of HSIL/LSIL to a higher‐grade dysplasia at T1, respectively. Mann Whitney test, Chi‐square test and multivariate logistic regression were used.ResultsA total of 189 patients were examined, 60 (32%) were women. One hundred fifty patients (79%) were HPV+, 113 (75%) harboured HR‐HPV; 103 (68%) showed LSIL/HSIL at T0 (32% of women and 65% of men) (all were HPV‐positive). No differences in demographics and HIV‐related markers were found between patients with SIL‐P (33, 41%) and patients with SIL‐R (47, 59%). HPV+ patients who cleared HPV (28, 18%) were found to be more frequently female, heterosexual infected, more frequently on cART and with lower Log10 HIV‐RNA and lower levels of CD8+/CD38+ % compared with HPV persistence group (Table 1).No differences in PI exposure were found between the two groups (p=.08). Interestingly, also when only HR‐HPV were considered, clearance was associated with exposure to cART (naïve 4%, vs cART 86%, p=.048). In multivariate analysis, heterosexuals (AOR 5.123, 95% CI 1.5–17.5 vs homosexuals) were independently associated to HPV clearance, whereas CD8+/CD38+% (AOR 0.44, 95% CI 0.65–1.01 for each % more) were predictive of HPV persistence.ConclusionsClose follow‐up of HPV and SIL should be promoted particularly in men and in untreated individuals. We cannot exclude behavioural variables linked to risky sex and reinfection.

IntroductionA recent meta‐analysis of 4 RCTs showed an increased rate of suicidality events (suicidal ideation or attempted/completed suicide) associated with efavirenz (EFV) compared to other regimens, but only a trend towards a higher rate of completed/attempted suicides, as only 17 events occurred. We investigated the association between EFV use and completed suicide.Materials and MethodsAll D:A:D participants were followed from study entry to the first of death, last study visit or 1 February 2013. Deaths are centrally validated using cause of death methodology, which assigns underlying, immediate and up to four contributing causes of death. Two endpoints were considered: 1) suicide or psychiatric disease as the underlying cause, and 2) suicide or psychiatric disease mentioned as an underlying, immediate or contributing cause of death (anywhere). Adjusted rate ratios were calculated using Poisson regression.ResultsA total of 4420 deaths occurred in 49,717 people over 371,333 person‐years (PY) (rate 11.9 per 1000 PY; 95% CI 11.6–12.3). A total of 193 deaths (rate 0.52; 0.45–0.59) had an underlying cause of suicide or psychiatric disease, and 482 deaths (1.30; 1.18–1.41) had suicide or psychiatric disease mentioned anywhere. A strong association with current CD4 count was seen: for suicide or psychiatric disease mentioned anywhere, rates were: 3.18 (2.55–3.80) for <200 cells/uL, 1.60 (1.29–1.90) for 201–350 cells/uL, 1.07 (0.86–1.29) for 351–500 cells/uL, 0.95 (0.80–1.09) for >500 cells/uL and 1.30 (1.18–1.41) for unknown. Highest rate of suicide or psychiatric deaths were seen in ART‐experienced people currently off ART, but no differences were seen according to current ART regimen, which remained after adjustment (Table 1). Consistent results were obtained when considering additional endpoints of suicide alone as the underlying cause and death from suicide or any possibly related cause (psychiatric disease, drug overdose, alcohol related, accidental or violent), as well as considering recent EFV use in the previous 3 and 6 months.ConclusionsThe finding of no higher death rates from suicide amongst those receiving EFV is reassuring. However, there is likely confounding by indication in our observational study. In light of conflicting results from RCTs, this potentially could suggest that in clinical practice EFV may be less frequently prescribed in those with underlying psychiatric conditions.

IntroductionEvidence from HIV‐negative cohorts suggests a link between osteoporosis and cardiovascular disease. We evaluated the presence and distribution of abdominal aortic calcifications (AAC) and its correlation with bone mineral density (BMD) and vertebral fractures (VF) in a cohort of HIV‐positive patients.Materials and MethodsIn this cross‐sectional study, 280 asymptomatic HIV‐positive patients from the SPID ("San Paolo" Infectious Diseases) cohort were submitted to lateral spine X‐ray and DXA. AAC was identified using the AAC‐8 score, which estimates the total length of calcification of the anterior and posterior aortic walls in front of vertebrae L1–L4. Low BMD was defined by T‐score or Z‐score <−1 at lumbar spine or femoral neck. VF were identified by morph‐metric analysis of X‐ray and were defined by the "spine deformity index" (SDI) ≥1 according to semiquantitative method by Genant. Associations between AAC, BMD and SDI were evaluated by univariate and multivariate logistic regression models. The relationship between the grade of AAC and SDI was evaluated by Spearman's correlation.ResultsAAC≥1 was present in 65 patients (23.2%); of these 15 patients showed moderate/severe calcifications (AAC>2). Low BMD was found in 163 patients (58.2%) and VF (SDI≥1) in 47/274 patients (17.1%). By univariate analysis, factors associated with AAC>=1 were: age (for additional 10 years older HR 3.81 [IC95% 2.64–5.51], p<0.0001) lower CD4 nadir (for additional 50 CD4 HR 0.89 [IC95% 0.82–0.97], p=0.01) AIDS‐diagnosis (HR 2.13 [IC95 % 1.11–4.08], p=0.02) and being on HAART (HR 2.75 [IC95% 1.28–5.90], p=0.009). In multivariate analysis, only age (OR 2.62, IC95% 1.72–3.99, p<0.0001) resulted significantly associated with AAC≥1. Patients with AAC≥1 had twofold increase in the risk of low BMD (HR 2.45 [IC95% 1.32–4.45], p=0.004) and VF (SDI>=1: HR 2.17 [IC95% 1.1–4.2], p=0.02) compared to patients without AAC. The grade of AAC was directly correlated with the grade of SDI (rho=0.16; p=0.008): AAC>2 determines a sixfold increase in the risk of VF (HR 6.44 [IC95% 2.21–18.79], p=0.0006). AAC≥1 predict VF independently from BMD, vitamin D status and bone turnover marker (Table 1).ConclusionsIn our HIV population, AAC resulted a strong predictor of both low BMD and VF, irrespective of factors involved in bone formation. The grade of AAC was directly correlated with the grade of VF.

IntroductionGlobal HIV‐1 prevalence is 35.3 million [1]; women comprise >50% of those infected. The majority of women may lack regular care and only one‐fourth are virologically suppressed [2]. ELLA is a cross‐sectional, non‐interventional study conducted across Europe, Latin America, Canada and Asia that describes barriers to care for HIV‐infected women and associations with disease stage, symptoms and health‐related quality of life (HRQoL).MethodsHIV‐infected women eligible for ELLA (≥18 years) completed: Barrier to Care Scale (BACS) comprising 12 items in four domains (Index range 0–12, Overall range 1–4, greater=more barriers, Overall score ≥2 considered severe); AIDS Clinical Trials Group (ACTG) Health Status Assessment comprising 21 items assessing 9 HRQoL domains (range 0–100, greater=better); and ACTG Symptom Distress Module comprising 20 symptoms rated on bother (range 0–4, greater=more bother). Healthcare providers documented medical history and HIV clinical data. Correlations of BACS response and last reported VL/CD4 count with HIV symptoms and HRQoL were analyzed. Spearman rank order was used to test correlations with statistical significance set at p<0.05.ResultsEnrollment: 1931 women from 30 countries; mean age 40 years (16.9% >50 years); 47.7% education <12 years; 36% unemployed; 82.9% urban residence. HIV was acquired heterosexually in 83.0%; 88.2% of subjects were on ART; 57.5% had VL<50 c/ml; mean CD4 was 540.5 c/µL. Mean [SD] BACS Index and Overall scores were 6.19 [3.47] (N=1818) and 2.09 [0.71] (N=1922), respectively. Stigma was a prominent barrier. Lower (better) BACS Index and Overall scores correlated with better HRQoL on all nine domains (p<0.0001). Lower VL and greater CD4 count were both correlated with better HRQoL for eight of nine domains (p<0.04, p≤0.0002, respectively) excepting pain. Lower BACS Index and Overall scores correlated with fewer symptom count and less symptom bother (p<0.0001). Fewer symptom count and less symptom bother correlated with better HRQoL on all nine domains (p<0.0001). While greater CD4 count correlated with fewer HIV symptoms and less bother (p<0.0001), VL did not significantly correlate with either.ConclusionsIn HIV‐infected women, reduced barriers to care correlated with fewer symptoms, less symptom bother and better HRQoL. Improved HRQoL may be mediated by greater CD4 counts and fewer symptoms. Better access to care may improve HRQoL outcomes in this population.

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.

IntroductionThe 48‐week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r‐based triple therapy. The DSMB recommended stopping study enrollment but continuing follow‐up of enrolled patients. We present the 96‐week efficacy analysis.Material and MethodsMulticentre, randomized, open‐label, non‐inferiority trial (non‐inferiority margin −10%). Treatment failure (TF) was defined as CVF (two consecutive HIV‐RNA >50 cp/mL) or discontinuation for any cause. In the monotherapy arm, patients with CVF re‐introduced their previous NRTIs and remained in the study if HIV‐RNA <50 copies/mL within 12 weeks of re‐intensification.Results101 patients evaluated (Figure 1): 85% males, 21% HCV‐positive, median (IQR) age of 42 (36–48) years, baseline CD4+ 576 (447–743) cells/µL. In the 96‐week analysis (ITT; TF=failure), efficacy was 64% (32/50) in the monotherapy arm and 63% (32/51) in the triple‐therapy arm (difference +1.3%, 95% CI −17.5–20.1). Fourteen patients in monotherapy and two in triple‐therapy arm had CVF; median HIV‐RNA was 136 (72–376) copies/mL. In monotherapy arm, no PI or NRTI associated resistance mutations were observed at CVF. All patients who re‐intensified re‐suppressed. In monotherapy arm, TF was more frequent in HCV‐co‐infected patients (64% vs 28%; p=0.041). In the secondary analysis (ITT; re‐intensification=success), 82% (41/50) in monotherapy arm and 63% (32/51) in triple‐therapy arm were on study at week 96 (difference +19.3%, 95% CI 2.2–36.3). SAEs occurred in four (8%) patients in the monotherapy arm (one left basal pneumonia, one acute coronary stenosis, one traumatic lesion, one nephrolithiasis) and two (4%) in the triple therapy arm (one sepsis, one renal failure). Drug‐related adverse events (AEs) leading to discontinuation were three (6%) in the monotherapy arm (two AEs occurred in patients after successful re‐intensification) and 12 (23.5%) in the triple‐therapy (p=0.023).ConclusionsDespite the small sample size, the primary 96‐week analysis showed that simplification to ATV/r monotherapy showed inferior efficacy to maintaining ATV/r triple‐therapy but appeared to be superior when re‐intensification was considered success.

IntroductionSexually transmitted diseases (STDs) data collected in HIV+ patients could be used as indicator of risky sexual behaviour possibly linked to HIV transmission. We described the STDs incidence over time and identified higher incidence factors.MethodologyAll patients in the ICONA Foundation Study enrolled after 1998 were included. STDs considered: any‐stage syphilis, human papilloma virus (HPV) diseases, gonococcal and non‐gonococcal urethritis, herpes simplex virus (HSV) genital ulcers, vaginitis and acute hepatitis B virus (HBV), hepatitis A virus (HAV), and hepatitis C virus (HCV) infections (only for non‐IVDU (intravenous drug user) patients). STDs incidence rate (IR): number of STDs divided by person years of follow‐up (PYFU). Calendar periods: 1998–2002, 2003–2007 and 2008–2012. Predictors of STDs occurrence were identified using Poisson regression and sandwich estimates for the standard errors were used for multiple STD events.ResultsData of 9,168 patients were analyzed (median age 37.3 (SD=9.3), 74% male, 30% MSM). Over 46,736 PYFU, 996 episodes of STDs were observed (crude IR 17.3/1,000 PYFU). Median (IQR) CD4/mmc and HIV‐RNA/mL at STD: 433 (251–600) and 10,900 (200–63,000). Highest crude IRs were observed for any‐stage syphilis (3.95, 95% CI 3.59–4.35), HPV diseases (1.96, 1.71–2.24) and acute hepatitis (1.72, 1.49–1.99). At multivariable analysis (variables of adjustment shown in Figure 1), age (IRR 0.82 per 10 years younger, 95% CI 0.77–0.89), MSM contacts (IRR 3.03, 95% CI 2.52–3.64 vs heterosexual) and calendar period (IRR 1.67, 95% CI 1.42–1.96, comparing 2008–2012 with 1998–2002) significantly increased the risk of acquiring STDs. Moreover, having a HIV‐RNA >50 c/mL (IRR 1.44, 95% CI 1.19–1.74 vs HIV‐RNA <50 c/mL) and current CD4+ cell count <100/mmc (IRR 4.66, 95% CI 3.69–5.89, p<0.001 vs CD4+ cell count >500) showed an increased risk of STDs. Being on ARV treatment significantly reduced the risk of developing an STD (IRR 0.37, 95% CI 0.32–0.43) compared to ART‐naïve people, even in the situation of temporary interruption of treatment (IRR 0.51, 95% CI 0.39–0.43) (see Figure 1).ConclusionsThe overall incidence of STDs has been increasing in the recent years. Interventions to prevent STDs and potential further spread of HIV infection should target the recently HIV diagnosed, the young population and MSM. Being on ARV treatment (potentially an indicator of whether a person is regularly seen for care) seems to reduce the risk of acquiring STDs independently of its viro‐immunological effect.

IntroductionTranslation of the evidence regarding the protective role of highly active antiretroviral therapy (HAART) on HIV sexual transmission rates into sexual behaviour patterns of HIV‐infected subjects remains largely unexplored. This study aims to describe frequency of self‐reported condom use among women living with HIV in Italy and to investigate the variables associated with inconsistent condom use (ICU).MethodsDIDI (Donne con Infezione Da HIV) is an Italian multicentre study based on a questionnaire survey performed during November 2010 and February 2011. Women‐reported frequency of condom use was dichotomized in "always" versus "at times"/"never" (ICU).ResultsAmong 343 women, prevalence of ICU was 44.3%. Women declared a stable partnership with an HIV‐negative (38%) and with an HIV‐positive person (43%), or an occasional sexual partner (19%). Among the 194 women engaged in a stable HIV‐negative or an occasional partnership, 51% reported fear of infecting the partner. Nonetheless, 43% did not disclose HIV‐positive status. Less than 5% of women used contraceptive methods other than condoms. At multivariable analysis, variables associated with ICU in the subgroup of women with a stable HIV‐negative or an occasional HIV‐unknown partner were: having an occasional partner (AOR 3.51, 95% confidence interval [CI] 1.44–8.54, p=0.005), and reporting fear of infecting the sexual partner (AOR 3.20, 95% CI 1.43–7.16, p=0.004). Current use of HAART together with virological control in plasma level did not predict ICU after adjusting for demographic, behavioural and HIV‐related factors. With regard to socio‐demographic factors, lower education was the only variable significantly associated with ICU in the multivariate analysis (AOR 2.27, 95% CI 1.07–4.82, p=0.03). No association was found between high adherence to HAART and ICU after adjusting for potential confounders (AOR 0.89, 95% CI 0.39–2.01, p=0.78).ConclusionsCurrently in Italy, the use of HAART with undetectable HIV RNA in plasma as well as antiretroviral adherence is not associated with a specific condom use pattern in women living with HIV and engaged with a sero‐discordant or an HIV‐unknown partner. This might suggest that the awareness of the protective role of antiretroviral treatment on HIV sexual transmission is still limited among HIV‐infected persons, at least in this country.

IntroductionThere is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV‐positive individuals. We investigated whether such differences exist in the D:A:D study.Materials and MethodsFollow‐up was from 01/02/99 until the earliest of death, 6 months after last visit or 01/02/13. Rates of initiation of lipid‐lowering drugs (LLDs), angiotensin‐converting enzyme inhibitors (ACEIs), anti‐hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or stroke at baseline, overall and in groups known to be at higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii) triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii) predicted 10‐year CVD risk >10%. Poisson regression was used to assess whether rates of initiation were higher in men than women, after adjustment for these factors.ResultsAt enrolment, women (n=13,039; median (interquartile range) 34 (29–40) years) were younger than men (n=36,664, 39 (33–46) years, p=0.001), and were less likely to be current smokers (29% vs. 39%, p=0.0001), to have diabetes (2% vs. 3%, p=0.0001) or to have hypertension (7% vs. 11%, p=0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs. 2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall, women received ICPs at a rate of 0.07/100 person‐years (PYRS) compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46), anti‐hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all significantly lower in women than men (Table 1). As expected, initiation rates of each intervention were higher in the groups determined to be at moderate/high CVD risk; however, within each high‐risk group, initiation rates of most interventions (with the exception of anti‐hypertensives) were generally lower in women than men. These gender differences persisted after adjustment for potential confounders (Table 1).ConclusionUse of most CVD interventions was lower among women than men in the D:A:D study. Our findings suggest that actions should be taken to ensure that both men and women are monitored for CVD and, if eligible, receive appropriate CVD interventions.

AbstractIntroductionConcerns about dolutegravir (DTG) tolerability in the real‐life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG‐based regimens from a large cohort of HIV‐infected individuals.MethodsWe performed a multicentre, observational study including all antiretroviral therapy (ART)‐naïve and virologically suppressed treatment‐experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG‐based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation.ResultsAbout 1679 individuals (932 ART‐naïve, 747 TE) were included. The one‐ and two‐year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART‐naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART‐naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART‐naïve (2.1%) and TE (1.7%) patients. In ART‐naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH) = 3.38, p = 0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH = 3.30, p = 0.009). TE patients starting a DTG‐based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR) = 2.50, p = 0.037 for ABC‐based triple‐therapies, aHR = 3.56, p = 0.012 for tenofovir‐based) and for toxicity (aHR = 5.26, p = 0.030 for ABC‐based, aHR = 6.60, p = 0.024 for tenofovir‐based). The one‐ and two‐year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group.ConclusionsIn this large cohort, DTG showed excellent efficacy and optimal tolerability both as first‐line and switching ART. The low risk of treatment‐limiting toxicities in ART‐naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice.