Dynamical properties and thresholds of an HIV model with super-infection.

Super-infection by multiple HIV-1 subtypes, previously thought restricted to high risk groups, has now been reported in the general heterosexual populations at relatively the same incidence rate as in high risk groups. We present a simple deterministic HIV model with super-infection by two HIV-1 subtypes. Mathematical characteristics including the basic reproductive number $(\mathcal{R}_0)$, invasion threshold $(\mathcal{R}_{21},\mathcal{R}_{12})$ and conditions for asymptotic stability are derived. In the absence of super-infection the model exhibits competitive exclusion, and all equilibria are globally attracting if they exist except for the disease free which is a saddle for $\mathcal{R}_0>1.$ The results show that the subtype with the dominant reproductive number exceeding unity dominates the weaker subtype forcing it to extinction regardless of the size of the reproductive number. On the other end, super-infection may promote subtype co-existence whenever the minimum of the subtype specific reproductive numbers $(\mathcal{R}_1,\mathcal{R}_2)$ and the invasion reproductive numbers $(\mathcal{R}_{12},\mathcal{R}_{21})$ exceed unity. Our results demonstrate that if the partial reproductive numbers $(\mathcal{R}_1~\mbox{and}~\mathcal{R}_2 )$ and the invasion reproductive number for the weaker subtype $(\mathcal{R}_{21})$ satisfy $\mathcal{R}_2<1,~\mathcal{R}_1>1~\mbox{and}~\mathcal{R}_{21}>1,$ then primary infection by subtype $1$ may stay the extinction of subtype $2$ despite its relatively low reproductive fitness. For certain parameter ranges, hysteresis (including backward bifurcation) occurs with possible differences in the asymptotic level of disease prevalence. Super-infection may thus facilitate the continued re-generation of reproductively noncompetent subtypes whose subtype specific reproductive numbers will be less than unity while at the same time allowing for the mutual coexistence and persistence of multiple strains. Persistence and co-existence of multiple strains has detrimental effect on vaccine design and development and administration of ART where one or more of the strains are drug resistant.

Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India.

In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex (insertive, receptive or both), but little is known about sexual mixing between identity groups. Both role segregation (taking only the insertive or receptive role) and the extent of assortative (within-group) mixing are known to affect HIV epidemic size in other settings and populations. This study explores how different possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India, affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describing HIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data from Bangalore. We extended previous models of MSM role segregation to allow each of the identity groups to have both insertive and receptive acts, in differing ratios, in line with field data. The models were used to explore four different mixing scenarios ranging from assortative (maximising within-group mixing) to disassortative (minimising within-group mixing). A simple model was used to obtain insights into the relationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence under different mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore. With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixing tended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When the complex model was fit to HIV prevalence data, large differences in the level of assortative mixing were seen between the fits identified using different mixing scenarios, but little difference was projected in future HIV prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was modelled, targeted at the different identity groups. For intervention strategies targeting the receptive or receptive and versatile MSM together, the overall impact was very similar for different mixing patterns. However, for PrEP scenarios targeting insertive or versatile MSM alone, the overall impact varied considerably for different mixing scenarios; more impact was achieved with greater levels of disassortative mixing.

Investigating alcohol consumption as a risk factor for HIV transmission in heterosexual settings in sub-Saharan African communities.

Alcohol consumption and abuse is widespread in sub-Saharan Africa where most HIV infections occur and has been associated with risky sexual behaviors. It may therefore be one of the most common, potentially modifiable HIV risk factors in this region. A deterministic system of ordinary differential equations incorporating heterogeneity and biased sexual preferences is formulated to assess the effects of alcohol consumption on the transmission dynamics of the disease in heterosexual settings. Extensive qualitative analysis of the model is carried out and epidemic threshold such as the alcohol-induced reproductive number (RA), and equilibria are derived and their stabilities examined. The disease-free equilibrium is found to be globally attracting whenever the reproductive number is less than unity. In the model, heterosexuality is the source of transmissions, and therefore, targeting a reduction of the basic reproductive number (R0) should be primary objective for any intervention programme. We show that the preference to form partnerships amongst the heterogeneous groups influences the severity of disease and its evolution, and consequently the rate of partnership formation between females and alcohol consumers and their relative infectiousness over nondrinkers has a huge positive correlation with the alcohol-induced reproductive number and hence the epidemic. The proportion or absolute number of drinkers is shown to have minimal influence on the disease dynamics, and in a community with alcohol consumers, it is more prudent to reduce their risk sexual behavior rather than to fight the spread of alcohol consumption. Thus, intervention measures targeted at reducing heterogeneous group interactions and behavior change are the key to disease control in these settings.

Modelling HIV/AIDS in the presence of an HIV testing and screening campaign.

Preventing and managing the HIV/AIDS epidemic in South Africa will dominate the next decade and beyond. Reduction of new HIV infections by implementing a comprehensive national HIV prevention programme at a sufficient scale to have real impact remains a priority. In this paper, a deterministic HIV/AIDS model that incorporates condom use, screening through HIV counseling and testing (HCT), regular testing and treatment as control strategies is proposed with the objective of quantifying the effectiveness of HCT in preventing new infections and predicting the long-term dynamics of the epidemic. It is found that a backward bifurcation occurs if the rate of screening is below a certain threshold, suggesting that the classical requirement for the basic reproduction number to be below unity though necessary, is not sufficient for disease control in this case. The global stabilities of the equilibria under certain conditions are determined in terms of the model reproduction number R(0). Numerical simulations are performed and the model is fitted to data on HIV prevalence in South Africa. The effects of changes in some key epidemiological parameters are investigated. Projections are made to predict the long-term dynamics of the disease. The epidemiological implications of such projections on public health planning and management are discussed.

Modeling HIV/AIDS and tuberculosis coinfection.

An HIV/AIDS and TB coinfection model which considers antiretroviral therapy for the AIDS cases and treatment of all forms of TB, i.e., latent and active forms of TB, is presented. We begin by presenting an HIV/AIDS-TB coinfection model and analyze the TB and HIV/AIDS submodels separately without any intervention strategy. The TB-only model is shown to exhibit backward bifurcation when its corresponding reproduction number is less than unity. On the other hand, the HIV/AIDS-only model has a globally asymptotically stable disease-free equilibrium when its corresponding reproduction number is less than unity. We proceed to analyze the full HIV-TB coinfection model and extend the model to incorporate antiretroviral therapy for the AIDS cases and treatment of active and latent forms of TB. The thresholds and equilibria quantities for the models are determined and stabilities analyzed. From the study we conclude that treatment of AIDS cases results in a significant reductions of numbers of individuals progressing to active TB. Further, treatment of latent and active forms of TB results in delayed onset of the AIDS stage of HIV infection.

Modelling the effects of pre-exposure and post-exposure vaccines in tuberculosis control.

Epidemic control strategies alter the spread of the disease in the host population. In this paper, we describe and discuss mathematical models that can be used to explore the potential of pre-exposure and post-exposure vaccines currently under development in the control of tuberculosis. A model with bacille Calmette-Guerin (BCG) vaccination for the susceptibles and treatment for the infectives is first presented. The epidemic thresholds known as the basic reproduction numbers and equilibria for the models are determined and stabilities are investigated. The reproduction numbers for the models are compared to assess the impact of the vaccines currently under development. The centre manifold theory is used to show the existence of backward bifurcation when the associated reproduction number is less than unity and that the unique endemic equilibrium is locally asymptotically stable when the associated reproduction number is greater than unity. From the study we conclude that the pre-exposure vaccine currently under development coupled with chemoprophylaxis for the latently infected and treatment of infectives is more effective when compared to the post-exposure vaccine currently under development for the latently infected coupled with treatment of the infectives.

Tuberculosis transmission model with chemoprophylaxis and treatment.

A tuberculosis model which incorporates treatment of infectives and chemoprophylaxis is presented. The model assumes that latently infected individuals develop active disease as a result of endogenous re-activation, exogenous re-infection and disease relapse, though a small fraction is assumed to develop active disease soon after infection. We start by formulating and analyzing a TB model without any intervention strategy that we extend to incorporate chemoprophylaxis and treatment of infectives. The epidemic thresholds known as reproduction numbers and equilibria for the models are determined, and stabilities analyzed. The reproduction numbers for the models are compared to assess the possible community benefits achieved by treatment of infectives, chemoprophylaxis and a holistic approach of these intervention strategies. The study shows that treatment of infectives is more effective in the first years of implementation (approximately 10 years) as treatment results in clearing active TB immediately and there after chemoprophylaxis will do better in controlling the number of infectives due to reduced progression to active TB.

Effects of public health educational campaigns and the role of sex workers on the spread of HIV/AIDS among heterosexuals.

This paper presents a sex-structured model for heterosexual transmission of HIV/AIDS in which the population is divided into three subgroups: susceptibles, infectives and AIDS cases. The subgroups are further divided into two classes, consisting of individuals involved in high-risk sexual activities and individuals involved in low-risk sexual activities. The model considers the movement of individuals from high to low sexual activity groups as a result of public health educational campaigns. Thus, in this case public health educational campaigns are resulting in the split of the population into risk groups. The equilibrium and epidemic threshold, which is known as the basic reproductive number (R0), are obtained, and stability (local and global) of the disease-free equilibrium is investigated. The model is extended to incorporate sex workers, and their role in the spread of HIV/AIDS in settings with heterosexual transmission is explored. Comprehensive analytic and numerical techniques are employed in assessing the possible community benefits of public health educational campaigns in controlling HIV/AIDS. From the study, we conclude that the presence of sex workers enlarges the epidemic threshold R0, thus fuels the epidemic among the heterosexuals, and that public health educational campaigns among the high-risk heterosexual population reduces R0, thus can help slow or eradicate the epidemic.

Age and sex structured model for assessing the demographic impact of mother-to-child transmission of HIV/AIDS.

Age and sex structured HIV/AIDS model with explicit incubation period is proposed as a system of delay differential equations. The model consists of two age groups that are children (0-14 years) and adults (15-49 years). Thus, the model considers both mother-to-child transmission (MTCT) and heterosexual transmission of HIV in a community. MTCT can occur prenatally, at labour and delivery or postnatally through breastfeeding. In the model, we consider the children age group as a one-sex formulation and divide the adult age group into a two-sex structure consisting of females and males. The important mathematical features of the model are analysed. The disease-free and endemic equilibria are found and their stabilities investigated. We use the Lyapunov functional approach to show the local stability of the endemic equilibrium. Qualitative analysis of the model including positivity and boundedness of solutions, and persistence are also presented. The basic reproductive number ([Symbol: see text](0)) for the model shows that the adult population is responsible for the spread HIV/AIDS epidemic, thus up-to-date developed HIV/AIDS models to assess intervention strategies have focused much on heterosexual transmission by the adult population and the children population has received little attention. We numerically analyse the HIV/AIDS model to assess the community benefits of using antiretroviral drugs in reducing MTCT and the effects of breastfeeding in settings with high HIV/AIDS prevalence ratio using demographic and epidemiological parameters for Zimbabwe.

Sex-structured HIV/AIDS model to analyse the effects of condom use with application to Zimbabwe.

We present a sex-structured model for heterosexual transmission of HIV/AIDS in a community. The model is formulated using integro-differential equations, which are shown to be equivalent to delay differential equations with a time delay due to incubation period. The sex-structured HIV/AIDS model divides the population into a two sex-structure consisting of females and males. The threshold and equilibria for the model are determined and stabilities are examined. We extend the model to focus on the effects of condom use as a single-strategy approach in HIV prevention in the absence of any treatment. Initially we model the use of male condoms and further extend the model to incorporate the use of both female and male condoms. The model includes two primary factors in condom use to control HIV that are condom efficacy and compliance. The exposure risk of infection after each intervention is obtained. Basic reproductive numbers for these models are computed and compared to assess the effectiveness of male and female condom use in a community. The models are numerically analysed to assess the effectiveness of condom use on the transmission dynamics of HIV/AIDS using demographic and epidemiological parameters for Zimbabwe. The study demonstrates the use of sex-structured HIV/AIDS models in assessing the effectiveness of female and male condom use as a preventative strategy in a heterosexually active population.