Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Abstract 192: Stroke in the WARCEF Trial

Background The Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial found no difference between warfarin and aspirin in heart failure patients in sinus rhythm for the outcome of first to occur of 84 ischemic strokes (IS), 7 intracerebral hemorrhages or 531 deaths. Pre-specified secondary analysis showed a 48% HR reduction (p=0.005) in IS risk for warfarin vs. aspirin. We examined this IS benefit for warfarin in post-hoc analyses. Methods We used the Wilcoxon rank sum test, stratified by prior IS or TIA, to compare the distributions of mRS among warfarin and aspirin IS patients in WARCEF. Median (md) scores and interquartile ranges (IQR) are shown for warfarin and aspirin arms, respectively. We used Fisher’s exact test to compare the effect of warfarin vs. aspirin on fatal IS; a stratified exact test to compare proportions of severe (mRS 3-5) IS; and stratified Poisson regression to compare IS subtypes. Results Twenty-nine (2.5%) of 1142 patients on warfarin and 55 (4.7%) of 1163 on aspirin had IS. The warfarin IS rate (0.72 per 100 patient years [/100PY]) was lower than for aspirin (1.36/100PY). There were no differences between warfarin and aspirin IS patients in baseline mRS (md 1, IQR, 2, N=29 vs. md 1, IQR 2, N=55); fatal IS (3/29, 10.3% vs. 6/55, 10.9%, p=1.0), or post-IS (after 90+30 days) mRS (md 2, IQR 3, n=23 vs. md 2, IQR 3, n=48, p=0.437). There were also no differences between warfarin and aspirin in change from baseline to post-IS mRS (md 1, IQR 3, n=23 vs. md 1, IQR 3, n=48, p=0.884). Cardioembolic IS was significantly less frequent on warfarin than on aspirin (9 [0.22/100PY] vs. 22 [0.55/100PY], p=0.012). The warfarin arm showed trends to fewer severe (mRS 3-5) IS (3/23 [13.0%] vs. 16/48 [33.3%], p=0.086) and a lower rate of IS of potential cardioembolic etiology (15 [0.37/100PY] vs. 27 [0.67/100PY] p=0.063). There was no difference between warfarin and aspirin in rate of non-cardioembolic IS (5 [0.12/100PY] vs. 6 [0.15/100PY], p=0.768). Conclusions Warfarin appears superior to aspirin in reducing the frequency of cardioembolic IS in heart failure patients in sinus rhythm. This is supported by trends to lower frequencies of severe IS and potentially cardioembolic IS in patients on warfarin compared to aspirin

Warfarin and aspirin in patients with heart failure and sinus Rhythm

BACKGROUND: It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS: We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS: The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS: Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized