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

Treatment switches during pregnancy among HIV-positive women on antiretroviral therapy at conception

Objectives: To describe antiretroviral therapy (ART) use and clinical status, at start of and during pregnancy, for HIV-positive women receiving ART at conception, including the proportion conceiving on drugs (efavirenz and didanosine) not recommended for use in early pregnancy.Methods: Women with a pregnancy resulting in a live-birth after 1995 (n = 1537) were identified in an observational cohort of patients receiving HIV care at 12 clinics in the UK by matching records with national pregnancy data. Treatment and clinical data were analysed for 375 women conceiving on ART, including logistic regression to identify factors associated with changing regimen during pregnancy.Results: Of the 375 women on ART, 39 (10%) conceived on dual therapy, 306 (82%) on triple therapy and 30 (8%) on more than three drugs. In total, 116 (31%) women conceived on a regimen containing efavirenz or didanosine (69 efavirenz, 54 didanosine, seven both). Overall, 38% (143) changed regimen during pregnancy, of whom 44% (n = 51) had a detectable viral load around that time. Detectable viral load was associated with increased risk of regimen change [adjusted odds ratio 2.97, 95% confidence interval (CI) (1.70-5.19)], while women on efavirenz at conception were three times more likely to switch than women on other drugs [3.40, (1.84-6.25)]. Regimen switching was also associated with year at conception [0.89, (0.83-0.96)].Conclusion: These findings reinforce the need for careful consideration of ART use among women planning or likely to have a pregnancy in order to reduce viral load before pregnancy and avoid drugs not recommended for early antenatal use. (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkin

The Cost-Effectiveness and Value of Information of Three Influenza Vaccination Dosing Strategies for Individuals with Human Immunodeficiency Virus

Influenza vaccine immunogenicity is diminished in patients living with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect information (EVPI) of three alternative influenza vaccine dosing strategies intended to increase immunogenicity in those patients.A randomized, multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults: two standard doses over 28 days (Strategy A), two double doses over 28 days (Strategy B) and a single standard dose of influenza vaccine (Strategy C), administered prior to the 2008 influenza season. The comparator in our analysis was practice in the previous year, in which 82.8% of HIV/AIDS received standard-dose vaccination (Strategy D). A Markov cohort model was developed to estimate the monthly probability of Influenza-like Illness (ILI) over one influenza season. Costs and quality-adjusted life years, extrapolated to the lifetime of the hypothetical study cohorts, were estimated in calculating incremental cost-effectiveness ratios (ICER) and EVPI in conducting further research.298 patients with median CD4 of 470 cells/µl and 76% with viral load suppression were randomized. Strategy C was the most cost-effective strategy for the overall trial population and for suppressed and unsuppressed individuals. Mean ICERs for Strategy A for unsuppressed patients could also be considered cost-effective. The level of uncertainty regarding the decision to implement strategy A versus C for unsuppressed individuals was high. The maximum acceptable cost of reducing decision uncertainty in implementing strategy A for individuals with unsuppressed pVL was $418,000--below the cost of conducting a larger-scale trial.Our results do not support a policy to implement increased antigen dose or booster dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine for individuals with HIV in Canada.ClinicalTrials.gov NCT00764998

Search for Massive Long-lived Highly Ionising Particles with the ATLAS Detector at the LHC

A search is made for massive highly ionising particles with lifetimes in excess of 100 ns, with the ATLAS experiment at the Large Hadron Collider, using 3.1 pb(-1) of pp collision data taken at root s = 7 TeV. The signature of energy loss in the ATLAS inner detector and electromagnetic calorimeter is used. No such particles are found and limits on the production cross section for electric charges 6e <= vertical bar q vertical bar <= 17e and masses 200 GeV <= m <= 1000 GeV are set in the range 1-12 pb for different hypotheses on the production mechanism. (C) 2011 CERN. Published by Elsevier B.V. All rights reserved