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IntroductionSeveral resistance mutations have been shown to affect viral fitness, and the presence of certain mutations might result in clinical benefit for patients kept on a virologically failing regimen due to an exhaustion of drug options. We sought to quantify the effect of resistance mutations on CD4 slopes in patients undergoing episodes of viral failure.Materials and MethodsPatients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test during the episode were included. Mutations were identified using the IAS‐US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log‐scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope.ResultsA total of 2731 patients experiencing a median of 1 (range 1–4) episodes were included in this analysis. The prevalence of any resistance per episode was 88.4%; NNRTI resistance was most common (78.5%). Overall, CD4 counts declined by 17.1 (−19.7; −14.5) cells per year; this decline was less marked with partial viral suppression (current HIV RNA more than 1.5 log below the setpoint; p=0.01). In multivariable models adjusting for viral load, CD4 decline was slower during episodes with detected resistance compared to episodes without detected resistance (21.0 cells/year less, 95% CI 11.75–30.31, p<0.001). Among those with more than one resistance mutation, there was only weak evidence that class‐specific mutations had any effect on the CD4 slope (Table 1). The effects of individual mutations (incl. M184V) were explored, but none were significantly associated with the CD4 slope; for these comparisons, a Bonferroni‐corrected p‐value level was 0.003.ConclusionsIn our study population, detected resistance was associated with slightly less steep CD4 declines. This may be due to a biological effect of resistance on CD4 slopes, or other unmeasured factors such as poor adherence among individuals without resistance. Among individuals with detected drug resistance, we found no evidence suggesting that the presence of individual mutations was associated with beneficial CD4 slope changes.

IntroductionEuroSIDA has previously reported a poorer clinical prognosis for HIV‐positive individuals in Eastern Europe (EE) as compared with patients from other parts of Europe, not solely explained by differences in patient characteristics. We explored regional variability in self‐reported HIV management at individual EuroSIDA clinics, with a goal of identifying opportunities to reduce the apparent inequalities in health.MethodsA survey (www.chip.dk/eurosida/csurvey) on HIV management was conducted in early 2014 in all currently active EuroSIDA clinics. Responders in EE were compared with clinics in all other EuroSIDA regions combined (non‐EE). Characteristics were compared between regions using Fishers exact test.ResultsA total of 80/97 clinics responded (82.5%, 12/15 in EE, 68/82 in non‐EE). Participating clinics reported seeing a total of 133,532 patients [a median of 1300 per clinic (IQR 700–2399)]. The majority of clinics requested viral load and CD4 measurements at least every six months for patients on as well as off ART (EE 66.7%, non‐EE 75%, p=0,72). Significantly fewer EE clinics performed resistance tests before ART as well as upon treatment failure (Figure 1). Half of the EE clinics indicated following WHO guidelines (EE 50%, non‐EE 7.4%, p<0.0001), whereas most non‐EE clinics followed EACS guidelines (non‐EE 76.5%, EE 41.7%, p=0.017). The majority of EE clinics and ¼ non‐EE clinics indicated deferral of ART initiation in asymptomatic individuals until CD4 ≤350 cells/mm3 (Figure 1). There were no significant regional differences in screening haematology, liver or renal function, which the majority of clinics reported to do routinely. However, EE clinics reported screening significantly less for cardiovascular disease (CVD), and only about half screened for tobacco use, alcohol consumption and drug use (Figure 1). Screening for cervical cancer and for anorectal cancer was low in both regions (Figure 1).ConclusionsWe found significant regional variability in self‐reported HIV management across Europe, with less resistance testing, screening for CVD and substance use in EE. EE clinics indicated deferral of ART initiation for longer than non‐EE clinics. Adherence to international guidelines for cervical cancer screening was poor in both regions. Whether differences in HIV management are reflected in clinical outcomes deserves further investigation.

IntroductionAlthough prostate cancer (PCa) incidence is lower in HIV+ men than in HIV− men, the usefulness of prostate‐specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV− men. We aimed to describe the kinetics and predictive value of PSA in HIV+ men.MethodsMen with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed models were used to describe kinetics.ResultsSixty‐one men were included with a median six (IQR 2–9) years follow‐up. Time between last sample and PCa was seven (4–11) months. Cases and controls were well matched at first sample, with a median age of 51 (IQR 48–57) and CD4 of 437 (243–610) cells/mm3. Median tPSA [2.8 (IQR: 1.6–4.6) and 0.8 (0.5–1.2) µg/L] and fPSA [0.4 (0.2–0.8) and 0.3 (0.2–0.4) µg/L] levels were higher in cases than controls at first sample. Both tPSA and fPSA increased significantly over time in cases (Figure 1), to a median at last sample of 6.1 (4.7–9.5) and 0.9 (0.6–1.3) µg/L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5–1.4) and 0.2 (0.2–0.4) µg/L (Figure). Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2‐fold higher 4.7 (CI: 1.7–12.9) and 5.4 (1.7–17.4)]. Elevated tPSA values in cases were detectable ≥5 years before PCa (p<0.01). Testosterone [overall median 19.4 (IQR 15.3–23.9) nmol/L at first sample) and SHBG [50.0 (34.0–66.0) nmol/L] levels were similar in cases and controls at first and last sample (all p>0.7). The most informative predictor of PCa was tPSA (AUC=0.9), followed by fPSA (0.8). Testosterone (AUC = 0.5) and SHBG (0.5) were poor predictors of PCa. Overall, tPSA level >4 µg/L had 99% specificity and 37% sensitivity. Performance was best in the year prior to PCa (specificity: 99%, sensitivity: 88%).ConclusionsPSA was highly predictive of PCa in HIV+ men. Our results indicate that PSA screening in HIV+ men may be useful, and further work is needed to identify potentially age‐related cut‐offs to maximize sensitivity and specificity to identify those for further evaluation at early stages of PCa.

BackgroundUse of unboosted atazanavir (ATV400) is approved in the US but not in Europe [1]. Due to pharmacokinetic interactions it should not be used with tenofovir but can be used with abacavir/lamivudine (ABC/3TC) [1, 2,3]. Effectiveness data of ATV400+ABC/3TC as a switch strategy in clinical routine however are scant.MethodsWe evaluated treatment outcomes of ATV400+ABC/3TC in pre‐treated subjects in the EuroSIDA cohort with undetectable HIV‐1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c/mL) and a snapshot analysis at 48, 96 and 144 weeks. Virological failure (VF) was defined as a confirmed plasma HIV‐1 RNA >50 c/mL.ResultsWe included 258 subjects: 176 (68%) male, median age 46 (IQR 41, 53) y, 225 (87.2%) white, hepatitis virus co‐infection 36%, median baseline CD4 at switch 540 cells (360, 700), time with VL≤ 50 c/mL 45 (24, 69) months. The median calendar year of switching was 2008 (2006, 2010). The 3rd drug in previous regimen was ATV/r in 70 (27.1%), other PI/r in 25 (9.7%), and other 163 (63.2%); 85 (32.9%) had previously failed with a PI. The virological response at 48/96/144 weeks was, respectively, 89.5 [95% CI 85.1, 92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or stop for any reason) and the risk of VF was 8.3/7.6/7.6%. In the snapshot analysis HIV‐RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL in 6.6/5.4/4.3%. Only 0.8/1.9/3.5% discontinued due to adverse events. There was a high rate of discontinuations due to other reasons or with VL missing in window. In a multivariate adjusted analysis, we observed an association between VF and nadir CD4 count (RH 0.60 [0.39, 0.93] per 100 cells higher), time with VL≤50 c/mL (RH 0.89 [0.81, 0.98] per 6 months longer) and previous failure with a PI (3.04 [1.36, 6.80]). There was no association with gender, age, hepatitis virus co‐infection, CD4 count at time of switching or third drug used in the previous regimen.ConclusionsA switch to ATV400+ABC/3TC in selected subjects with HIV‐RNA below 50 c/mL is associated with relatively low rates of VF and discontinuation due to adverse events. Use might be considered in those with long‐term suppression and without prior PI failure. Larger cohorts are required to further define the appropriate selection criteria.