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Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. [ABSTRACT FROM AUTHOR]

The activation status can dictate the fate of an HIV-infected CD4+ T cell. Infected cells with a low level of activation remain latent and do not produce virus, while cells with a higher level of activation are more productive and thus likely to transfer more virions to uninfected cells during cell-to-cell transmission. How the activation status of infected cells affects HIV dynamics under antiretroviral therapy remains unclear. We develop a new mathematical model that structures the population of infected cells continuously according to their activation status. The effectiveness of antiretroviral drugs in blocking cell-to-cell viral transmission decreases as the level of activation of infected cells increases because the more virions are transferred from infected to uninfected cells during cell-to-cell transmission, the less effectively the treatment is able to inhibit the transmission. The basic reproduction number R0 of the model is shown to determine the existence and stability of the equilibria. Using the principal spectral theory and comparison principle, we show that the infection-free equilibrium is locally and globally asymptotically stable when R0 is less than one. By constructing Lyapunov functional, we prove that the infected equilibrium is globally asymptotically stable when R0 is greater than one. Numerical investigation shows that even when treatment can completely block cell-free virus infection, virus can still persist due to cell-to-cell transmission. The random switch between infected cells with different activation levels can also contribute to the replenishment of the latent reservoir, which is considered as a major barrier to viral eradication. This study provides a new modeling framework to study the observations, such as the low viral load persistence, extremely slow decay of latently infected cells and transient viral load measurements above the detection limit, in HIV-infected patients during suppressive antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Background: The Joint United Nations Programme updated a goal of 95-95-95 targets for the endgame of HIV. We investigate the optimal strategy of health resource allocation to improve HIV testing in both high-risk and general populations in China. Methods: We developed a mathematical model by integrating epidemiological, demographical and behavioural data from 12 high-risk and 2 general populations to evaluate the impact of various HIV testing strategies on HIV incidence in China. We identified the optimal testing strategy that maximizes the number of HIV diagnoses at a given cost and calculated the cost of detecting one new HIV case. Results: We estimated the current annual spending on HIV testing to be US$366.8 million. The largest proportion of spending has been allocated to pregnant women (25.90%), followed by the general male (20.33%), and general female (20.06%). With this allocation strategy, an estimated 37.55% (37,546/100,141) of annual new infections would be diagnosed. Overall, it required $9771 for each new HIV case detection. After optimizing HIV testing resource allocation of the same investment amount, the proportion of investment allocation was the highest in low-risk MSM (26.65%), followed by the PWID (21.01%), and high-risk MSM (0.93%). With the optimized strategy, we estimated that 67,684 (67.59%) of annual new infections would be diagnosed. The cost required for one HIV case detection was reduced to $5619/case. If the budget for HIV testing increased to 5-10 times the baseline level, healthcare sources may be then shifted to lowrisk populations. Conclusions: Optimizing resource allocation for HIV testing in high-risk populations would result in a higher HIV diagnosis rate and lower cost per HIV case detection. [ABSTRACT FROM AUTHOR]

Development times of eggs, larvae and pupae of vectors of onchocerciasis (Simulium spp.) and of Onchocerca volvulus larvae within the adult females of the vectors decrease with increasing temperature. At and above 25°C, the parasite could reach its infective stage in less than 7 days when vectors could transmit after only two gonotrophic cycles. After incorporating exponential functions for vector development into a novel blackfly population model, it was predicted that fly numbers in Liberia and Ghana would peak at air temperatures of 29°C and 34°C, about 3°C and 7°C above current monthly averages, respectively; parous rates of forest flies (Liberia) would peak at 29°C and of savannah flies (Ghana) at 30°C. Small temperature increases (less than 2°C) might lead to changes in geographical distributions of different vector taxa. When the new model was linked to an existing framework for the population dynamics of onchocerciasis in humans and vectors, transmission rates and worm loads were projected to increase with temperature to at least 33°C. By contrast, analyses of field data on forest flies in Liberia and savannah flies in Ghana, in relation to regional climate change predictions, suggested, on the basis of simple regressions, that 13-41% decreases in fly numbers would be expected between the present and before 2040. Further research is needed to reconcile these conflicting conclusions. [ABSTRACT FROM AUTHOR]