Kelly-Jean Heymer

Serosorting may increase the risk of HIV acquisition among men who have sex with men.

Background: Serosorting, the practice of seeking to engage in unprotected anal intercourse with partners of the same HIV status as oneself, has been increasing among men who have sex with men. However, the effectiveness of serosorting as a strategy to reduce HIV risk is unclear, especially since it depends on the frequency of HIV testing. Methods: We estimated the relative risk of HIV acquisition associated with serosorting compared with not serosorting by using a mathematical model, informed by detailed behavioral data from a highly studied cohort of gay men. Results: We demonstrate that serosorting is unlikely to be highly beneficial in many populations of men who have sex with men, especially where the prevalence of undiagnosed HIV infections is relatively high. We find that serosorting is only beneficial in reducing the relative risk of HIV transmission if the prevalence of undiagnosed HIV infections is less than ∼20% and ∼40%, in populations of high (70%) and low (20%) treatment rates, respectively, even though treatment reduces the absolute risk of HIV transmission. Serosorting can be expected to lead to increased risk of HIV acquisition in many settings. In settings with low HIV testing rates serosorting can more than double the risk of HIV acquisition. Conclusions: Therefore caution should be taken before endorsing the practice of serosorting. It is very important to continue promotion of frequent HIV testing and condom use, particularly among people at high risk.

Chlamydial infection and spatial ascension of the female genital tract: a novel hybrid cellular automata and continuum mathematical model

Sexually transmitted chlamydial infection initially establishes in the endocervix in females, but if the infection ascends the genital tract, significant disease, including infertility, can result. Many of the mechanisms associated with chlamydial infection kinetics and disease ascension are unknown. We attempt to elucidate some of these processes by developing a novel mathematical model, using a cellular automata-partial differential equation model. We matched our model outputs to experimental data of chlamydial infection of the guinea-pig cervix and carried out sensitivity analyses to determine the relative influence of model parameters. We found that the rate of recruitment and action of innate immune cells to clear extracellular chlamydial particles and the rate of passive movement of chlamydial particles are the dominant factors in determining the early course of infection, magnitude of the peak chlamydial time course and the time of the peak. The rate of passive movement was found to be the most important factor in determining whether infection would ascend to the upper genital tract. This study highlights the importance of early innate immunity in the control of chlamydial infection and the significance of motility-diffusive properties and the adaptive immune response in the magnitude of infection and in its ascension.

Available evidence does not support serosorting as an HIV risk reduction strategy.

Recent data highlighted the association between penetration of antiretrovirals in the central nervous system (CNS) and neurocognitive impairment in HIVpositive patients. Existing antiretrovirals have been ranked according to a score of neuropenetration, which was shown to be a predictor of anti-HIVactivity in the CNS and improvement of neurocognitive disorders [1]. Main factors affecting drug penetration are known to be protein binding, lipophilicity and molecular weight [2]. Moreover, active translation by membrane transporters (such as p-glycoprotein) could be a key mechanism of passage [3]. The use of raltegravir (RGV), a novel antiretroviral drug targeted to inhibit the HIV preintegrase complex, is increasing worldwide due to its efficacy and tolerability. However, penetration of RGV in the CNS has not been yet elucidated. In fact, prediction of RGV neuropenetration according to molecular characteristics is controversial. Intermediate protein binding (83%) and large volume of distribution (273 l) could suggest a high distribution beyond extracellular spaces [4]. On the contrary, low lipophilicity (oil/water partition coefficient at pH 7.4 of 2.80) and intermediate molecular weight (482.51 Da) suggest a limited diffusion. Furthermore, in-vitro studies suggest that RGV is substrate of p-glycoprotein, although this efflux pump has not been identified to significantly affect plasma pharmacokinetics [5]. In any case, no data concerning RGV passage into cerebrospinal fluid of animals or humans have yet been published.

Treatment for prevention of HIV transmission in a localised epidemic: the case for South Australia

BACKGROUND Discussion is currently taking place among international HIV/AIDS groups around increasing HIV testing and initiating earlier use of antiretroviral therapy (ART) among people diagnosed with HIV as a method to reduce the spread of HIV. In this study, we explore the expected epidemiological impact of this strategy in a small population in which HIV transmission is predominantly confined to men who have sex with men (MSM). METHODS A deterministic mathematical transmission model was constructed to investigate the impacts of strategies that increase testing and treatment rates, and their likely potential to mitigate HIV epidemics among MSM. Our novel model distinguishes men in the population who are more easily accessible to prevention campaigns through engagement with the gay community from men who are not. This model is applied to the population of MSM in South Australia. RESULTS Our model-based findings suggest that increasing testing rates alone will have minimal impact on reducing the expected number of infections compared to current conditions. However, in combination with increases in treatment coverage, this strategy could lead to a 59-68% reduction in the number of HIV infections over the next 5 years. Targeting men who are socially engaged with the gay community would result in the majority of potential reductions in incidence, with only minor improvements possible by reaching all other MSM. CONCLUSIONS Investing in strategies that will achieve higher coverage and earlier initiation of treatment to reduce infectiousness of HIV-infected individuals could be an effective strategy for reducing incidence in a population of MSM.

What Impact Might the Economic Crisis have on HIV Epidemics in Southeast Asia

OBJECTIVE To evaluate the potential impact of the current global economic crisis (GEC) on the spread of HIV. DESIGN To evaluate the impact of the economic downturn we studied two distinct HIV epidemics in Southeast Asia: the generalized epidemic in Cambodia where incidence is declining and the epidemic in Papua New Guinea (PNG) which is in an expansion phase. METHODS Major HIV-related risk factors that may change due to the GEC were identified and a dynamic mathematical transmission model was developed and used to forecast HIV prevalence, diagnoses, and incidence in Cambodia and PNG over the next 3 years. RESULTS In Cambodia, the total numbers of HIV diagnoses are not expected to be largely affected. However, an estimated increase of up to 10% in incident cases of HIV, due to potential changes in behavior, may not be observed by the surveillance system. In PNG, HIV incidence and diagnoses could be more affected by the GEC, resulting in respective increases of up to 17% and 11% over the next 3 years. Decreases in VCT and education programs are the factors that may be of greatest concern in both settings. A reduction in the rollout of antiretroviral therapy could increase the number of AIDS-related deaths (by up to 7.5% after 3 years). CONCLUSIONS The GEC is likely to have a modest impact on HIV epidemics. However, there are plausible conditions under which the economic downturns can noticeably influence epidemic trends. This study highlights the high importance of maintaining funding for HIV programs.

An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia.

BACKGROUND As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. METHODS Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. RESULTS It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0-42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector

Evaluation of the potential impact of the global economic crisis on HIV epidemics in Southeast Asia

17860 per infection averted (median,

Available evidence does not support serosorting as an HIV risk reduction strategy

13651-24287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. CONCLUSIONS The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.