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Background: China's National Free Antiretroviral Treatment Program (NFATP) has substantially reduced morbidity and HIV/AIDS incidence since 2003. However, HIV resistance to antiretroviral drugs (ARVs) has been a major challenge for the current treatment of HIV/AIDS in China. Methods: In the current study, we established a nested dynamic model to predict the multi-drug resistance dynamics of HIV among the heterosexual population and evaluated the impact of intervention measures on the transmission of drug resistance. We obtained an effective reproductive number Red from each sub-model held at different stages of the dynamic model. Meanwhile, we applied Bayesian phylogenetic methods to infer the weighted average effective reproductive number Reg from four HIV subtypes that sampled from 912 HIV-positive patients in China. It is an original and innovative method by fitting Red to Reg by Markov Chain Monte Carlo (MCMC) to generate unknown parameters in Red. Results: By analyzing the HIV gene sequences, we inferred that the most recent common ancestor of CRF01AE, CRF07BC, CRF08BC, and CRFBC dated from 1994, 1990, 1993 and 1990, respectively. The weighted average effective reproductive number Reg dropped from 1.95 in 1994 to 1.73 in 2018. Considering different interventions, we used a macro dynamic model to predict the trend of HIV resistance. The results show that the number of new infections and total drug resistance under the baseline parameter (S1) are 253,422 and 213,250 in 2025, respectively. Comparing with the numbers under the target treatment rate (S2), they were 219,717 and 236,890, respectively. However, under the ideal treatment target (S3, the treatment rate reaches 90% and the treatment success rate reaches 90%), the number of new infections shows a declining trend and will decrease to 46,559 by 2025. Compared with S1 and S2, the total number of resistance also decreased to 160,899 in 2025. Conclusion: With the promotion of NFATP in China, HIV resistance to ARVs is inevitable. The strategy of increasing the treatment rate would not only ineffectively curb the epidemic, but also deteriorate drug resistance issue. Whereas, a combination of intervention strategies (the treatment rate reaches 90% and the treatment success rate reaches 90%) can greatly reduce both infection and drug resistance rate than applying one strategy alone. [ABSTRACT FROM AUTHOR]

Background: To project the impact of partner reduction on preventing new HIV infections among men who have sex with men (MSM) under varying conditions of enhanced HIV testing and treatment (T&T) and condom use in Beijing, China. Methods and findings: A complex network model was fitted to predict the number of new HIV infections averted from 2014 to 2023 under four scenarios of sexual behavior risk reduction (S)—: Male sexual partners decrease (reduced by a random value m from 1–50) while condom use increases (risk constant p is a random value between 0.2 and 1]); : Both sexual partners and condom use decrease (m 1, 50; p 1, 1.8); : Sexual partners reduce (m 1, 10) while condom use increases or decreases (p 0.2, 1.8); : Only MSM with ≥100 male sexual partners reduce their partners (m 1, 50) while condom use increases (p 0.2, 1). HIV prevalence will reach 23.2% by 2023 among Beijing MSM if T&T remains at the 2013 level. The three most influential factors are: T&T coverage; partner reduction (m); and the background risk (p). Under scenarios 1–4 of sexual behavioral changes with enhanced T&T interventions, the cumulative HIV new infections prevented over the 10 years will be 46.8% for (interquartile range [IQR] 32.4%, 60.1%); 29.7% for (IQR 18.0%, 41.4%), 23.2% for (IQR 12.2%, 37.0%) and 11.6% for (IQR 4.0%, 26.6%), respectively. The reproduction number R0 could drop below 1 if there were a substantial reduction of male sexual partners and/or expanded condom use. Conclusion: Partner reduction is a vital factor within HIV combination interventions to reduce HIV incidence among Beijing MSM, with substantial additional benefits derived from condom use. T&T without substantial partner reduction and increased condom use is less promising unless its implementation were extremely (and improbably) efficient. [ABSTRACT FROM AUTHOR]

Objective: To project the HIV/AIDS epidemics among men who have sex with men (MSM) under different combinations of HIV testing and linkage to care (TLC) interventions including antiretroviral therapy (ART) in Beijing, China. Design: Mathematical modeling. Methods: Using a mathematical model to fit prevalence estimates from 2000–2010, we projected trends in HIV prevalence and incidence during 2011–2020 under five scenarios: (S1) current intervention levels by averaging 2000–2010 coverage; (S2) increased ART coverage with current TLC; (S3) increased TLC/ART coverage; (S4) increased condom use; and (S5) increased TLC/ART plus increased condom use. Results: The basic reproduction number based upon the current level of interventions is significantly higher than 1 ( confidence interval (CI), 1.83–2.35), suggesting that the HIV epidemic will continue to increase to 2020. Compared to the 2010 prevalence of 7.8%, the projected HIV prevalence in 2020 for the five prevention scenarios will be: (S1) Current coverage: 21.4% (95% CI, 9.9–31.7%); (S2) Increased ART: 19.9% (95% CI, 9.9–28.4%); (S3) Increased TLC/ART: 14.5% (95% CI, 7.0–23.8%); (S4) Increased condom use: 13.0% (95% CI, 9.8–28.4%); and (S5) Increased TLC/ART and condom use: 8.7% (95% CI, 5.4–11.5%). HIV epidemic will continue to rise () for S1–S4 even with hyperbolic coverage in the sensitivity analysis, and is expected to decline () for S5. Conclusion: Our transmission model suggests that Beijing MSM will have a rapidly rising HIV epidemic. Even enhanced levels of TLC/ART will not interrupt epidemic expansion, despite optimistic assumptions for coverage. Promoting condom use is a crucial component of combination interventions. [ABSTRACT FROM AUTHOR]

Analysis of changes in viral load after initiation of treatment with potent antiretroviral agents has provided substantial insights into the dynamics of human immunodeficiency virus type 1. We built a simple mathematics model to study the effect of latent-infected resting memory CD4+ T cells during the HIV infection and highly active anti-retroviral therapy (HAART). Through analysis of eight patients who received HAART in China, we have an insight into the mechanisms of resting memory CD4+ T cells in HIV infection. Simulations show that new infections still exist in the eight patients even under the HAART. Also, because of the long half-life of resting infected memory CD4+ T cells, removal of HIV from patient could take considerably longer time or be unattainable. [ABSTRACT FROM AUTHOR]

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible. [ABSTRACT FROM AUTHOR]

mathematical model describing the antiretroviral therapy of Enfuvirtide on HIV-1 patients is developed. The effect of Enfuvirtide (formerly called T-20) by impulsive differential equations is modeled by two different drug elimination kinetics, the first-order elimination kinetics and the Michaelis-Menten elimination kinetics. The model is a non-autonomous system of differential equations. For a time-dependent system, the disease-free equilibrium is mainly studied. Its stability, when the therapy is taken with perfect adherence, is obtained. To ensure the disease-free equilibrium remains stable, the analytical thresholds for dosage and dosing intervals are determined. The effects of supervised treatment interruption are also explored. It is shown that the supervised treatment interruption can be worse than no therapy at all. [ABSTRACT FROM AUTHOR]

Abstract: Recently, the first drug in a new class of antiretroviral HIV drugs was approved, the fusion inhibitor enfuvirtide. We develop a mathematical model that describes the binding of the virus to T cells. We model the effect of enfuvirtide upon this process using impulsive differential equations. We find equilibria and determine stability in the case of no therapy and then when therapy is taken with perfect adherence. We determine analytical thresholds for the dosage and dosing intervals to ensure the disease-free equilibrium remains stable. We also explore the effects of partial adherence. Our theoretical results suggest that partial adherence may, at times, be worse than no therapy at all, but at other times may in fact as good as perfect adherence. It follows that patients should be counselled on the importance of adherence to this new antiretroviral drug. [ABSTRACT FROM AUTHOR]