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Background:  Substantial gaps remain in understanding the trade-offs between the costs and benefits of choosing alternative human immunodeficiency virus (HIV) prevention strategies, including test-and-treat (expanded HIV testing combined with immediate treatment) and PrEP (initiation of preexposure prophylaxis by high-risk uninfected individuals) strategies., Methods:  We develop a mathematical epidemiological model to simulate HIV incidence among men residing in Los Angeles County, California, aged 15-65 years, who have sex with men. We combine these incidence data with an economic model to estimate the discounted cost, effectiveness (quality-adjusted life-years [QALYs]), and incremental cost-effectiveness ratios of various HIV prevention strategies using a societal perspective and a lifetime horizon., Results:  PrEP and test-and-treat yield the largest reductions in HIV incidence, and are highly cost-effective ($27 863/QALY and $19 302/QALY, respectively) relative to status quo and at a US willingness-to-pay threshold of $150 000/QALY saved. Status quo and 12 test-and-treat and PrEP strategies determine the frontier for efficient decisions. More aggressive strategies are costlier, but more effective, albeit with diminishing returns. The relative effectiveness of PrEP is sensitive to the initial HIV prevalence rate, PrEP and antiretroviral therapy (ART) adherence and initiation rates, the probabilities of HIV transmission, and the rates of sexual partner mixing., Conclusions:  PrEP and test-and-treat offer cost-effective alternatives to the status quo. The success of these strategies depends on ART and PrEP adherence and initiation rates. The lack of evidence on adherence behaviors toward PrEP, therefore, warrants further studies., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Data on effectiveness of preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV)-uninfected women attempting conception with HIV-infected male partners are limited to observational studies., Methods: To explore the benefits of PrEP for conception, we developed a model to estimate the average annual probability of a woman remaining HIV-uninfected and having a child ("successful" outcome) via condomless sex with an HIV-infected male. The outcome likelihood is dependent upon parameters defining HIV-1 infectivity. We simulated 2 scenarios: optimal (condomless sex acts limited to the ovulation window), and suboptimal (acts not limited to ovulation)., Results: In the optimal scenario when the male is on antiretroviral therapy (ART), the average annual probability of the successful outcome is 29.1%, increasing to 29.2% with the addition of PrEP (P = .45). In the suboptimal scenario, the probability is 26.8% with ART alone versus 27.3% with ART/PrEP (P < .0001). Older maternal age reduces the probability of success in both scenarios, particularly after age 30., Conclusions: In our model, PrEP provides little added benefit when the HIV-infected male partner is on ART, condomless sex is limited to the ovulation window, and other modifiable transmission risks are optimized. Older female age decreases the probability of success by increasing the number of condomless sex acts required for conception., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: There is evidence to suggest that antiretroviral therapy (ART) and testing for human immunodeficiency virus (HIV) reduce the probability of transmission of HIV. This has led health officials across the United States to take steps toward a test-and-treat policy. However, the extent of the benefits generated by test-and-treat is debatable, and there are concerns, such as increased multidrug resistance (MDR), that remain unaddressed., Methods: We developed a deterministic epidemiologic model to simulate the HIV/AIDS epidemic for men who have sex with men (MSM) in Los Angeles County (LAC). We calibrated the model to match the HIV surveillance data from LAC across a 10-year period, starting in 2000. We then modified our model to simulate the test-and-treat policy and compared epidemiologic outcomes under the test-and-treat scenario to the status quo scenario over the years 2012-2023. Outcome measures included new infections, deaths, new AIDS cases, and MDR., Results: Relative to the status quo, the test-and-treat model resulted in a 34% reduction in new infections, 19% reduction in deaths, and 39% reduction in new AIDS cases by 2023. However, these results are counterbalanced by a near doubling of the prevalence of MDR (9.06% compared to 4.79%) in 2023. We also found that the effects of increasing testing and treatment were not complementary., Conclusions: Although test-and-treat generates substantial benefits, it will not eliminate the epidemic for MSM in LAC. Moreover, these benefits are counterbalanced by large increases in MDR.

Background: The Botswana antiretroviral program began in 2002 and currently treats 42,000 patients, with a goal of treating 85,000 by 2009. The World Health Organization (WHO) has begun to implement a surveillance system for detecting transmitted resistance that exceeds a threshold of 5%. However, the WHO has not determined when this threshold will be reached. Here we model the Botswana government's treatment plan and predict, to 2009, the likely stochastic evolution of transmitted resistance., Methods: We developed a model of the stochastic evolution of drug-resistant strains and formulated a birth-death Master equation. We analyzed this equation to obtain an analytical solution of the probabilistic evolutionary trajectory for transmitted resistance, and used treatment and demographic data from Botswana. We determined the temporal dynamics of transmitted resistance as a function of: (i) the transmissibility (i.e., fitness) of the drug-resistant strains that may evolve and (ii) the rate of acquired resistance., Results: Transmitted resistance in Botswana will be unlikely to exceed the WHO's threshold by 2009 even if the rate of acquired resistance is high and the strains that evolve are half as fit as the wild-type strains. However, we also found that transmission of drug-resistant strains in Botswana could increase to approximately 15% by 2009 if the drug-resistant strains that evolve are as fit as the wild-type strains., Conclusions: Transmitted resistance will only be detected by the WHO (by 2009) if the strains that evolve are extremely fit and acquired resistance is high. Initially after a treatment program is begun a threshold lower than 5% should be used; and we advise that predictions should be made before setting a threshold. Our results indicate that it may be several years before the WHO's surveillance system is likely to detect transmitted resistance in other resource-poor countries that have significantly less ambitious treatment programs than Botswana.

Summary: In high-income countries after World War II, the widespread availability of effective antimicrobial therapy, combined with expanded screening, diagnosis, and treatment programmes, resulted in a substantial decline in the incidence of syphilis. However, by the turn of the 21st century, outbreaks of syphilis began to occur in different subpopulations, especially in communities of men who have sex with men. The reasons for these outbreaks include changing sexual and social norms, interactions with increasingly prevalent HIV infection, substance abuse, global travel and migration, and underinvestment in public-health services. Recently, it has been suggested that these outbreaks could be the result of an interaction of the pathogen with natural immunity, and that syphilis epidemics should be expected to intrinsically cycle. We discuss this hypothesis by examining long-term data sets of syphilis. Today, syphilis in western Europe and the USA is characterised by low-level endemicity with concentration among population subgroups with high rates of partner change, poor access to health services, social marginalisation, or low socioeconomic status. [Copyright &y& Elsevier]