Uncertainties in predicting the demographic impact of AIDS

A model giving the demographic impact of AIDS is analysed to examine the sensitivity of the projections when various complicating features are included. The model deals with age and sexual partner change rate as continuous variables and uses a device to specify arbitrary correlations between the ages of the people who form sexual partnerships. The device ensures consistency, in that the amount of partner formation is the same regardless of whether the partnerships are counted from the point of view of males or females. Arbitrary correlation between partner change rate and fertility is also permitted. The results show the uncertainty in model predictions that population growth will reduce over the next 20 years to approximately zero in parts of East Africa severely affected by the AIDS epidemic. The main sources of uncertainty in the model predictions are assumptions concerning the correlation between ages in a partnership, the correlation between partner change rate and fertility, the incubation period of AIDS, and the variability of the female partner change rate.     

A model of HIV-1 transmission for urban areas of Africa

A model of the transmission dynamics of HIV-1, appropriate to urban areas of Africa, is presented and its behaviour explored through numerical studies. The model is a two-sex model with age-dependent demographic and behavioural parameters. Adults are classified by age, sex, risk group, and epidemiologic status. HIV-1 is transmitted to adults heterosexually, and to infants and children vertically and parenterally. Numerical studies show that, while AIDS will slow population growth, growth rates do not become negative for reasonable parameter values. The sex and age patterns of infection are explored, as is the potential economic impact of changes in the sex and age composition of the population.     

The transmission dynamics of the human immunodeficiency virus type 1 in the male homosexual community in the United Kingdom: the influence of changes in sexual behaviour

This paper examines the transmission dynamics of human immune deficiency virus type 1 (HIV-1) in the male homosexual population in the U.K. via numerical studies employing a mathematical model representing the principal epidemiological process. The model is based on an assumption of proportionate mixing between different sexual-activity classes (defined by the rate of sexual partner change per unit of time) and incorporates heterogeneity in sexual activity, distributed infection and incubation periods and the recruitment of susceptibles to the sexually active population. The sensitivity of model predictions to various assumptions and parameter assignments is examined. Numerical studies of model behaviour focus on the influence of changes in the magnitudes of the transmission parameters, associated with three periods of infectiousness during the incubation period of acquired immune deficiency syndrome (AIDS), on the magnitude and duration of the epidemic and on the level of the endemic equilibrium state. Predicted temporal trends in the incidence of AIDS are shown to be particularly sensitive to changes in the intensities and durations of the stages of infectiousness. Most of the paper addresses the influence of changes in sexual behaviour on the magnitude and duration of the epidemic. Numerical simulations show that the manner in which behavioural changes occur and who is influenced by such changes (i.e. infecteds or susceptibles, the sexually active population or new recruits to this population) have a major impact on the future timecourse of the epidemic. The greatest reduction in the incidence of AIDS over the coming decades is induced by changes in the rate of sexual-partner change among the sexually active population, particularly those currently infected. The time periods at which changes in behaviour occur, in relation to the starting point of the epidemic (assumed to be 1979), are also of particular significance to the future pattern of the incidence of disease and infection. Changes in behaviour early on in the timecourse of the epidemic have a much greater impact than equivalent changes at latter time points. On the basis of limited data on the pattern of change in sexual behaviour among the male homosexual community in the U.K., numerical studies of model behaviour tentatively suggest that the epidemic is at, or near to, a period of peak incidence of the disease AIDS. Analyses suggest that, following the peak in incidence, there will be a period of slow decline over many decades provided recent changes in behaviour are maintained in the coming years.(ABSTRACT TRUNCATED AT 400 WORDS)     

Development,Calibration and Performance of an HIV Transmission Model Incorporating Natural History and Behavioral Patterns: Application in South Africa

Understanding HIV transmission dynamics is critical to estimating the potential population-wide impact of HIV prevention and treatment interventions. We developed an individual-based simulation model of the heterosexual HIV epidemic in South Africa and linked it to the previously published Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International Model, which simulates the natural history and treatment of HIV. In this new model, the CEPAC Dynamic Model (CDM), the probability of HIV transmission per sexual encounter between short-term, long-term and commercial sex worker partners depends upon the HIV RNA and disease stage of the infected partner, condom use, and the circumcision status of the uninfected male partner. We included behavioral, demographic and biological values in the CDM and calibrated to HIV prevalence in South Africa pre-antiretroviral therapy. Using a multi-step fitting procedure based on Bayesian melding methodology, we performed 264,225 simulations of the HIV epidemic in South Africa and identified 3,750 parameter sets that created an epidemic and had behavioral characteristics representative of a South African population pre-ART. Of these parameter sets, 564 contributed 90% of the likelihood weight to the fit, and closely reproduced the UNAIDS HIV prevalence curve in South Africa from 1990–2002. The calibration was sensitive to changes in the rate of formation of short-duration partnerships and to the partnership acquisition rate among high-risk individuals, both of which impacted concurrency. Runs that closely fit to historical HIV prevalence reflect diverse ranges for individual parameter values and predict a wide range of possible steady-state prevalence in the absence of interventions, illustrating the value of the calibration procedure and utility of the model for evaluating interventions. This model, which includes detailed behavioral patterns and HIV natural history, closely fits HIV prevalence estimates.     

Decreasing HIV-1 seroprevalence in young adults in a rural Ugandan cohort.

OBJECTIVE--To assess the trend in HIV-1 seroprevalence in an adult population in Uganda. DESIGN--An observational cohort study with four year follow up. SETTING--A cluster of 15 villages in rural Uganda. SUBJECTS--All residents of the 15 villages--about 10,000 people. MAIN OUTCOME MEASURE--Prevalence of HIV-1 infection as assessed by enzyme immunoassay. RESULTS--During the five year period the overall standardised seroprevalence of HIV-1 showed little change; 8.2% in 1990, 7.6% in 1994. Among males aged 13-24 years the prevalence decreased from 3.4% to 1.0% (P for trend < 0.001); among females of the same age the corresponding values were 9.9% and 7.3%. The decrease was greatest in males aged 20-24 years and females aged 13-19 years. CONCLUSION--This is the first report of a decline in HIV-1 prevalence among young adults in a general population in sub-Saharan Africa with high overall HIV-1 prevalence. It is too early to conclude that the epidemic in this population is in decline, but the results of this study should be reason for some cautious optimism and encourage the vigorous pursuit of AIDS control measures.     

Gonococcal infection and human fertility in sub-Saharan Africa.

An analysis is presented of the influence of Neisseria gonorrhoeae on human population growth in regions of sub-Saharan Africa where gonococcal infections are prevalent in sexually active adults. Combining epidemiological and demographic data within the framework of a mathematical model, we show that gonorrhoea has a major impact on fertility and, concomitantly, on net population growth in areas with a high prevalence of untreated infections. Specifically, a 20% prevalence in sexually active adults is predicted to induce a 50% reduction in net population growth. Model predictions are in good agreement with observed data from Uganda, and the sensitivity of the prediction to various complications, such as heterogeneity in sexual behaviour, is assessed. The analysis suggests that the predicted increase in fertility arising from expanded sexually transmitted disease (STD) control programmes in Africa to help combat the spread of human immunodeficiency viruses (HIV-1 and HIV-2) will help to offset the predicted demographic impact of AIDS in the worst afflicted areas. In other areas the rise in fertility associated with effective STD control will need to be countered by the linkage of STD control programmes with family planning initiatives.     

Modeling AIDS as a function of other sexually transmitted disease.

The spread of AIDS, as with any sexually transmitted disease, will depend on the pattern of sexual activity. Both the proportion of the population who have high partner exchange rates and the extent to which that proportion interacts with the remainder of the population are likely to be important determinants of the AIDS epidemic. However, it does not seem likely that surveys could obtain sufficiently reliable information of this nature for use in an accurate model of the AIDS epidemic. On the other hand, such information is implicitly contained in the epidemiology of other sexually transmitted diseases (STDs). Therefore a method is suggested of calculating the parameters of a model of the AIDS epidemic by comparing it with the epidemiology of another STD. The result is a model that predicts the likelihood of infection by the AIDS virus as a function of time and an individual's history of STD. It is suggested that further work along these lines may lead to a quantitative approach to assessing the importance of various STDs as cofactors in the spread of AIDS.     

AIDS as a zoonosis? Confusion over the origin of the virus and the origin of the epidemics

Based on findings demonstrating the simian ancestry of HIV, AIDS has been reported to be a zoonosis. However, this theory has never been proved and must seriously be questioned. Several arguments show that HIV-AIDS is not a zoonosis. (i) If AIDS were a zoonosis, there must be evidence of AIDS being directly acquired from an animal species, as is rabies, a disease that is directly acquired from animals. (ii) Despite long-term and frequent human exposure to SIV-infected monkeys in Africa, only 11 cross-species transmission events are known, and only four of these have resulted in significant human-to-human transmission, generating HIV-1 groups M and O and HIV-2 groups A and B. The closest relatives of SIVcpz (HIV-1 group N) and of SIVsm (HIV-2 groups C-H) are extremely rare, with only six HIV-1 group N-infected patients and only single individuals known to be infected by HIV-2 groups C-H. SIV, while capable of cross-species transmission, is thus poorly adapted for disease and epidemic spread. If AIDS were a zoonosis that is capable of significant human-to-human spread, there would be a plethora of founder subtypes and groups. (iii) Human exposure to SIV is thousands of years old, but AIDS emerged only in the 20th century. If AIDS were a zoonosis that spread into the human population, it would have spread to the West during slave trade. (iv) Experimental transmission of SIVs to different species of monkeys is often well controlled by the new host, showing that the virus and not the disease is transmitted. Therefore, we conclude that cross-species transmission of SIV does not in itself constitute the basis for a zoonosis. Transmission per se is not the major requirement for the generation of the AIDS epidemic. All HIVs do derive from simian species, but AIDS does not qualify as a zoonosis and this explanation cannot in itself account for the origin of AIDS epidemic. It is important to distinguish AIDS from true zoonoses (e.g. rabies) because research is needed to understand the processes by which animal viruses cause sustained human-to-human transmission, epidemics and even pandemics. Much is known about emerging viruses, but almost nothing is known about emerging viral diseases.     

Phylodynamics of HIV-1 subtype B among the men-having-sex-with-men (MSM) population in Hong Kong

The men-having-sex-with-men (MSM) population has become one of the major risk groups for HIV-1 infection in the Asia Pacific countries. Hong Kong is located in the centre of Asia and the transmission history of HIV-1 subtype B transmission among MSM remained unclear. The aim of this study was to investigate the transmission dynamics of HIV-1 subtype B virus in the Hong Kong MSM population. Samples of 125 HIV-1 subtype B infected MSM patients were recruited in this study. Through this study, the subtype B epidemic in the Hong Kong MSM population was identified spreading mainly among local Chinese who caught infection locally. On the other hand, HIV-1 subtype B infected Caucasian MSM caught infection mainly outside Hong Kong. The Bayesian phylogenetic analysis also indicated that 3 separate subtype B epidemics with divergence dates in the 1990s had occurred. The first and latest epidemics were comparatively small-scaled; spreading among the local Chinese MSM while sauna-visiting was found to be the major sex partner sourcing reservoir for the first subtype B epidemic. However, the second epidemic was spread in a large-scale among local Chinese MSM with a number of them having sourced their sex partners through the internet. The epidemic virus was estimated to have a divergence date in 1987 and the infected population in Hong Kong had a logistic growth throughout the past 20 years. Our study elucidated the evolutionary and demographic history of HIV-1 subtype B virus in Hong Kong MSM population. The understanding of transmission and growth model of the subtype B epidemic provides more information on the HIV-1 transmission among MSM population in other Asia Pacific high-income countries.     

Sexual risk behaviour among the youth in the era of HIV/AIDS in South Africa

The paper discusses factors associated with sexual risk behaviour, i.e. failure to use condoms consistently during sexual intercourse, among unmarried sexually experienced youths in South Africa. Data from the 'Transitions to Adulthood in the Context of AIDS in South Africa' surveys of 1999 and 2001 were analysed to identify factors associated with high sexual risk behaviour among the youth. The multinomial regression models for male and female youths were fitted separately for the 1999 and 2001 data sets. The results show increasingly consistent use of condoms during sexual intercourse and that high sexual risk behaviour among youths is predominantly determined by social factors such as 'ever-pregnant' or 'ever made pregnant', 'ever given something for sex', age of sexual partner, currently in school, pressured by friends to have sex, peer influence on safe sex and education level for males. There is evidence that availability of contraception information is important in strategic interventions that seek to change the sexual behaviour of the youth in South Africa.     

Different Epidemic Potentials of the HIV-1B and C Subtypes

HIV, the cause of AIDS in humans, is characterized by great genetic heterogeneity. In particular, HIV-1 group M subtypes are responsible for most of the infections worldwide. We investigate the demographic history of HIV-1B and HIV-1C subtypes in South Africa and Brazil using both a parametric and a nonparametric approach based on coalescent theory. Our results show that although both subtypes are spreading exponentially in Brazil, the HIV-1C growth rate is about twice that of Brazilian HIV-1B or South African HIV-1C, providing evidence, for the first time, of a different epidemic potential between two HIV-1 subtypes. The present study not only may have important consequences for devising future vaccination and therapeutic strategies, but also offers additional evidence that skyline plots are indeed a simple and powerful tool for monitoring and predicting the behavior of viral epidemics.Reviewing Editor: Dr. Yves Van de Peer     

AIDS and HIV-1 Infection: Clinical Entities in Geriatric Dentistry1

The number of AIDS cases in individuals 50 years of age or older in the United States is reported to exceed 9000. Contaminated blood and blood transfusions are major contributors to HIV-1 infection in this age group. Sexual transmission and infection through intravenous drug abuse are also potential avenues of HIV-1 transmission in the older population. AIDS presents with a variety of clinical manifestations, including dementia, frequently seen in non-HIV-1-infected older people. Neurological deficiencies associated with AIDS are very common and may lead to misdiagnosis in the elderly. The observed incubation period of HIV-1 infection is longer than previously estimated, increasing the risk of older individuals exposed to HIV-1 in the past to develop AIDS. Oral manifestations may present as one of the early clinical signs of AIDS. Little is known concerning AIDS in the geriatric population. It demands consideration by dental professionals treating older individuals belonging to one of the exposure categories of the disease.     

Using mathematical models to understand the AIDS epidemic

The most urgent public-health problem today is to devise effective strategies to minimize the destruction caused by the AIDS epidemic. This complex problem will involve medical advances and new public-health and education initiatives. Mathematical models based on the underlying transmission mechanisms of the AIDS virus can help the medical/scientific community understand and anticipate its spread in different populations and evaluate the potential effectiveness of different approaches for bringing the epidemic under control. Before we can use models to predict the future, we must carefully test them against the past spread of the infection and for sensitivity to parameter changes. The long and extremely variable incubation period and the low probability of transmitting the AIDS virus in a single contact imply that population structure and variations in infectivity both play an important role in its spread. The population structure is caused by differences between people in numbers of sexual partners and the use of intravenous drugs and because of the way in which people mix among age, ethnic, and social groups. We use a simplified approach to investigate the effects of variation in incubation periods and infectivity specific to the AIDS virus, and we compare a model of random partner choices with a model in which partners both come from similar behavior groups.     

Transmission Dynamics of an SIS Model with Age Structure on Heterogeneous Networks

Infection age is often an important factor in epidemic dynamics. In order to realistically analyze the spreading mechanism and dynamical behavior of epidemic diseases, in this paper, a generalized disease transmission model of SIS type with age-dependent infection and birth and death on a heterogeneous network is discussed. The model allows the infection and recovery rates to vary and depend on the age of infection, the time since an individual becomes infected. We address uniform persistence and find that the model has the sharp threshold property, that is, for the basic reproduction number less than one, the disease-free equilibrium is globally asymptotically stable, while for the basic reproduction number is above one, a Lyapunov functional is used to show that the endemic equilibrium is globally stable. Finally, some numerical simulations are carried out to illustrate and complement the main results. The disease dynamics rely not only on the network structure, but also on an age-dependent factor (for some key functions concerned in the model).     

Molecular cloning and phylogenetic analysis of human immunodeficiency virus type 1 subtype C: a set of 23 full-length clones from Botswana

To better understand the virological aspect of the expanding AIDS epidemic in southern Africa, a set of 23 near-full-length clones of human immunodeficiency virus type 1 (HIV-1) representing eight AIDS patients from Botswana were sequenced and analyzed phylogenetically. All study viruses from Botswana belonged to HIV-1 subtype C. The interpatient diversity of the clones from Botswana was higher than among full-length isolates of subtype B or among a set of full-length HIV-1 genomes of subtype C from India (mean value of 9. 1% versus 6.5 and 4.3%, respectively; P < 0.0001 for both comparisons). Similar results were observed in all genes across the entire viral genome. We suggest that the high level of HIV-1 diversity might be a typical feature of the subtype C epidemic in southern Africa. The reason or reasons for this diversity are unclear, but may include an altered replication efficiency of HIV-1 subtype C and/or the multiple introduction of different subtype C viruses.     

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.     

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1

The HIV-1 epidemic in sub-Saharan Africa is driven largely by heterosexual transmission of non-subtype B viruses, of which subtypes C and A are predominant. Previous studies of subtype B and subtype C transmission pairs have suggested that a single variant from the chronically infected partner can establish infection in their newly infected partner. However, in subtype A infected individuals from a sex worker cohort and subtype B individuals from STD clinics, infection was frequently established by multiple variants. This study examined over 1750 single-genome amplified viral sequences derived from epidemiologically linked subtype C and subtype A transmission pairs very early after infection. In 90% (18/20) of the pairs, HIV-1 infection is initiated by a single viral variant that is derived from the quasispecies of the transmitting partner. In addition, the virus initiating infection in individuals who were infected by someone other than their spouse was characterized to determine if genital infections mitigated the severe genetic bottleneck observed in a majority of epidemiologically linked heterosexual HIV-1 transmission events. In nearly 50% (3/7) of individuals infected by someone other than their spouse, multiple genetic variants from a single individual established infection. A statistically significant association was observed between infection by multiple genetic variants and an inflammatory genital infection in the newly infected individual. Thus, in the vast majority of HIV-1 transmission events in cohabiting heterosexual couples, a single genetic variant establishes infection. Nevertheless, this severe genetic bottleneck can be mitigated by the presence of inflammatory genital infections in the at risk partner, suggesting that this restriction on genetic diversity is imposed in large part by the mucosal barrier.     

UN says up to half the teenagers in Africa will die of AIDS

According to the Joint UN Programme on HIV/AIDS report, AIDS will cause early death in as many as half of the teenagers living in southern Africa. In Botswana, demographers have predicted that two-thirds of the 15-year-olds will die of AIDS before the age of 50. In terms of global estimates, the report indicated that there are 34.3 million people infected with HIV, of whom 1.3 million are children under the age of 15. The impact of the AIDS epidemic is accounted for in the erosion of all key measures of a nation's health, especially in much of sub-Saharan Africa. These key measures include economic development, educational attainment, and child survival. Although there are a few success stories in the countries of Uganda and Thailand, which show that strong prevention campaigns and increased condom use help in curbing the epidemic, the report revealed the need for a massive increase in political will.     

The replicative fitness of primary human immunodeficiency virus type 1 (HIV-1) group M, HIV-1 group O, and HIV-2 isolates

The main (M) group of human immunodeficiency virus type 1 (HIV-1) is responsible for the global AIDS epidemic while HIV-1 group O (outlier) and HIV type 2 are endemic only in west and central Africa. The failure of HIV-2 and especially HIV-1 group O to spread following the initial zoonotic jumps is not well understood. This study was designed to examine the relative replicative capacities between these human lentiviruses. A pairwise competition experiment was performed with peripheral blood mononuclear cells with eight HIV-2 isolates, 6 group O viruses, and 15 group M viruses of subtype A (2 viruses), B (5 viruses), C (4 viruses), D (2 viruses) and CRF01_AE (2 viruses). HIV-1 group M isolates of any subtype were typically 100-fold-more fit than group O or HIV-2 strains when competed in peripheral blood mononuclear cells from various humans. This order in replicative fitness was also observed when virus pairs were added to human dendritic cells and then cocultured with primary, quiescent T cells, which is the model for HIV-1 transmission. These results suggest that reduced replicative and transmission fitness may be contributing to the low prevalence and limited geographical spread of HIV-2 and group O HIV-1 in the human population.     

Epidemiology and the emergence of human immunodeficiency virus and acquired immune deficiency syndrome

Although acquired immune deficiency syndrome (AIDS) was first described in the USA in 1981, there is evidence that individual cases occurred considerably earlier in Central Africa, and serological and virological data show human immunodeficiency virus (HIV) was present in the Democratic Republic of Congo (DRC) as far back as 1959. It is likely that HIV-1 infection in humans was established from cross-species transmission of simian immunodeficiency virus of chimpanzees, but the circumstances surrounding this zoonotic transfer are uncertain. This presentation will review how causality is established in epidemiology, and review the evidence (a putative ecological association) surrounding the hypothesis that early HIV-1 infections were associated with trials of oral polio vaccine (OPV) in the DRC. From an epidemiological standpoint, the OPV hypothesis is not supported by data and the ecological association proposed between OPV use and early HIV/AIDS cases is unconvincing. It is likely that Africa will continue to dominate global HIV and AIDS epidemiology in the near to medium-term future, and that the epidemic will evolve over many decades unless a preventive vaccine becomes widely available.