Estimating the resources required in the roll-out of universal access to antiretroviral treatment in Zimbabwe.

OBJECTIVES: To develop projections of the resources required (person-years of drug supply and healthcare worker time) for universal access to antiretroviral treatment (ART) in Zimbabwe. METHODS: A stochastic mathematical model of disease progression, diagnosis, clinical monitoring and survival in HIV infected individuals. FINDINGS: The number of patients receiving ART is determined by many factors, including the strategy of the ART programme (method of initiation, frequency of patient monitoring, ability to include patients diagnosed before ART became available), other healthcare services (referral rates from antenatal clinics, uptake of HIV testing), demographic and epidemiological conditions (past and future trends in incidence rates and population growth) as well as the medical impact of ART (average survival and the relationship with CD4 count when initiated). The variations in these factors lead to substantial differences in long-term projections; with universal access by 2010 and no further prevention interventions, between 370 000 and almost 2 million patients could be receiving treatment in 2030-a fivefold difference. Under universal access, by 2010 each doctor will initiate ART for up to two patients every day and the case-load for nurses will at least triple as more patients enter care and start treatment. CONCLUSIONS: The resources required by ART programmes are great and depend on the healthcare systems and the demographic/epidemiological context. This leads to considerable uncertainty in long-term projections and large variation in the resources required in different countries and over time. Understanding how current practices relate to future resource requirements can help optimise ART programmes and inform long-term public health planning.

Tuberculosis screening of migrants to low-burden nations: insights from evaluation of UK practice.

Tuberculosis (TB) primarily occurs in the foreign-born in European countries, such as the UK, where increasing notifications and the high proportion of foreign-born cases has refocused attention on immigrant (new entrant) screening. We investigated how UK primary care organisations (PCOs) screen new entrants and whether this differs according to TB burden in the PCOs (incidence < 20 or ≥ 20 cases per 100,000 per annum). An anonymous, 20-point questionnaire was sent to all 192 UK PCOs asking which new entrants are screened, who is screened for active TB/latent TB infection (LTBI) and the methods used. Descriptive analyses were undertaken. Categorical responses were compared using the Chi-squared test. 177 (92.2%) out of 192 PCOs responded; all undertook screening action in response to abnormal chest radiographs, but only 107 (60.4%) screened new entrants for LTBI. Few new entrants had active TB diagnosed (median 0.0%, interquartile range (IQR) 0.0-0.5%) but more were identified with LTBI (median 7.85%, IQR 4.30-13.50%). High-burden PCOs were significantly less likely to screen new entrants for LTBI (OR 0.26, 95% CI 0.12-0.54; p<0.0001). Among PCOs screening for LTBI, there was substantial deviation from national guidance in selection of new entrant subgroups and screening method. Considerable heterogeneity and deviation from national guidance exist throughout the UK new entrant screening process, with high-burden regions undertaking the least screening. Forming an accurate picture of current front-line practice will help to inform future development of European new entrant screening policy.

Men who have sex with men and women in Bangalore, South India, and potential impact on the HIV epidemic.

OBJECTIVE: The aim of this study was to quantify differences in patterns of sexual behaviour among men who have sex with men and women (MSMW) compared with men who have sex with men only (MSMO), and to examine the extent to which bisexual behaviour may act as a bridge for introducing HIV infection into the general population. METHODS: A cross-sectional survey in Bangalore city in 2006, which sampled men seeking sex with men in public places and hammams (bath houses where transgender individuals sell sex to men). RESULTS: Among a sample of 357 men reporting same-sex behaviour; 41% also reported sex with a woman in the past year and 14% were currently married to a woman, only two of whom had informed their wives about having sex with men. Condom use was very inconsistent with all male partners, while 98% reported unprotected vaginal sex with their wives. MSMW reported lower rates of risky behaviour with other men than MSMO: fewer reported selling sex (17% vs 58%), or receptive anal sex with known (28% vs 70%) or unknown (30% vs 59%) non-commercial partners. CONCLUSION: Bisexual behaviour was common among men seeking sex with men sampled in this survey. Although MSMW reported lower rates of risky sexual behaviour with male partners than MSMO, inconsistent condom use with both male and female partners indicates a potential means of HIV transmission into the general population. HIV prevention programmes and services should reach bisexual men who potentially expose their male and female partners to HIV.

Measuring trends in age at first sex and age at marriage in Manicaland, Zimbabwe.

OBJECTIVE: To identify reporting biases and to determine the influence of inconsistent reporting on observed trends in the timing of age at first sex and age at marriage. METHODS: Longitudinal data from three rounds of a population-based cohort in eastern Zimbabwe were analysed. Reports of age at first sex and age at marriage from 6837 individuals attending multiple rounds were classified according to consistency. Survival analysis was used to identify trends in the timing of first sex and marriage. RESULTS: In this population, women initiate sex and enter marriage at younger ages than men but spend much less time between first sex and marriage. Among those surveyed between 1998 and 2005, median ages at first sex and first marriage were 18.5 years and 21.4 years for men and 18.2 years and 18.5 years, respectively, for women aged 15-54 years. High levels of reports of both age at first sex and age at marriage among those attending multiple surveys were found to be unreliable. Excluding reports identified as unreliable from these analyses did not alter the observed trends in either age at first sex or age at marriage. Tracing birth cohorts as they aged revealed reporting biases, particularly among the youngest cohorts. Comparisons by birth cohorts, which span a period of >40 years, indicate that median age at first sex has remained constant over time for women but has declined gradually for men. CONCLUSIONS: Although many reports of age at first sex and age at marriage were found to be unreliable, inclusion of such reports did not result in artificial generation or suppression of trends.

The role of testing and counselling for HIV prevention and care in the era of scaling-up antiretroviral therapy.

OBJECTIVE: HIV Testing and Counselling (TC) programmes are being scaled-up as part of efforts to provide universal access to antiretroviral treatment (ART). METHODS AND FINDINGS: Mathematical modelling of TC in Zimbabwe shows that if universal access is to be sustained, TC must include prevention counselling that enables behaviour change among infected and uninfected individuals. The predicted impact TC is modest, but improved programmes could generate substantial reductions in incidence, reducing need for ART in the long-term. CONCLUSIONS: TC programmes that focus only on identifying those in need of treatment will not be sufficient to bring the epidemic under control.

Fewer partners or more condoms? Modelling the effectiveness of STI prevention interventions.

BACKGROUND: Some advocates of HIV prevention have counterposed programmes aimed at reducing numbers of sex partners to programmes aimed at increasing condom use. In this polarised debate, arguments about their relative effectiveness have been based on limited evidence. OBJECTIVES: To explore the theoretical impact of changing partner acquisition rates and condom use on the population level incidence of sexually transmitted infections different in different populations. METHODS: A standard deterministic compartmental model of the transmission dynamics of a sexually transmitted disease is solved numerically. The change in behaviour required to prevent a single case of infection is calculated for a range of scenarios. RESULTS: When the transmission probability per sex act is low across partnerships, the incidence of infection responds similarly to changes in partner numbers and numbers of unprotected sex acts. High transmission probabilities alter the relationships, with the effectiveness of increasing condom use improving as the background number of unprotected sex acts decreases. The divergence in patterns of impact is marked when there is heterogeneity in the transmission probability per act across partnerships. CONCLUSIONS: Both reducing numbers of sex partners and increasing condom use can lower the incidence of sexually transmitted infections. Unfortunately, there is no simple and general rule that will allow the efficiency of interventions to be calculated. Heterogeneity in transmission probability across infections, which may occur for both bacterial and viral infections, can reduce the effectiveness of condom use as an intervention if that use is inconsistent.

Interpreting declines in HIV prevalence: impact of spatial aggregation and migration on expected declines in prevalence.

BACKGROUND: Declines in the prevalence of HIV might occur due to natural epidemic dynamics rather than changes in risk behaviour. Determining the cause of an observed decline is important in understanding the epidemiology of HIV. OBJECTIVE: To explore how patterns of recruitment and interactions between subpopulations in different areas influence the predicted decline in the prevalence of HIV in the absence of reductions in risk behaviour. METHODS: A deterministic mathematical model of the heterosexual transmission of HIV in high prevalence endemic settings incorporating various patterns of recruitment to high-risk behaviour groups, population growth and migration was solved numerically. The possibility that apparent trends are generated or obscured through aggregating data from across areas experiencing different epidemics is also considered. RESULTS: Declines in the prevalence of HIV can occur even if individuals do not change behaviour, raising the possibility that epidemic downturns could be wrongly attributed to interventions. This effect is greatest when individuals do not enter higher risk groups to compensate for reductions in size caused by deaths from AIDS and when migration is non-random with respect to risk or infectious status and migration patterns change as the epidemic matures. In contrast, aggregating prevalence data from subregions with different epidemic profiles tends to mask declines in prevalence. CONCLUSIONS: Interpreting surveillance data is important in understanding widespread responses to HIV epidemics. The results show that understanding patterns of adoption of risk behaviours and patterns of migration is important in interpreting declines in the prevalence of HIV.

Seroepidemiology as basis for design of a human papillomavirus vaccination program.

We have performed a serological survey of HPV type 16-antibody prevalence by age and sex in Sweden and used it as a basis for modelling the optimal vaccination strategies in this population. Samples of 3,317 subjects were tested for HPV16-specific antibodies. The observed age-specific seroprevalences along with sexual behaviour data were used to infer parameter values for a mathematical model representing Sweden and the preventive effect of possible strategies estimated. By the year 2055, vaccination of females starting at age 12 in 2008 was most efficient, estimated to prevent 5.8 million cumulative HPV16 infections. Catch-up programs had a strong additional preventive effect. Vaccination also targeting males increased protective effect by about 4%, but had lower preventive effect per vaccination given. Addition of an HPV serosurvey to existing models and data has enabled us to estimate effect of different vaccination strategies, optimized to the HPV epidemiology in our population.

Measuring effectiveness in community randomized trials of HIV prevention.

BACKGROUND: Complicated HIV transmission dynamics make it unclear how to design and interpret results from community-randomized controlled trials (CRCT) of interventions to prevent infection. METHODS: Mathematical modelling was used to investigate the effectiveness of interventions to prevent HIV transmission aimed at high-risk groups and factors related to the chance of recording a statistically significant result. RESULTS: Behaviour change by high-risk groups can substantially reduce HIV incidence in the whole population, although its effect is sensitive to the structure of the sexual network and the phase of the epidemic. There is a delay between the behaviour change happening and its full effect being realized in the low-risk group and this can pull the measured incidence rate ratio towards one and reduce the chance of recording a statistically significant result in a CRCT. Our simulations suggest that only with unrealistically favourable study conditions would a statistically significant result be likely with 5 years follow-up or less. Small differences in the epidemiological parameters between communities can lead to misleading incidence rate ratios. Behaviour change independent of the intervention can increase the epidemiological impact of the intervention and the chance of recording a statistically significant result. CONCLUSIONS: HIV prevention interventions, especially those targeted at high-risk groups may take longer to work at the population level and need more follow-up time in a CRCT to generate statistically significant results. Mathematical modelling can be used in the design and analysis of CRCTs to understand how the impact of the intervention could develop and the implications this has for statistical power.

Sexual identity and its contribution to MSM risk behavior in Bangaluru (Bangalore), India: the results of a two-stage cluster sampling survey.

In India, there are categories of MSM (hijras, kothis, double-deckers, panthis and bisexuals), which are generally associated with different HIV-risk behaviors. Our objective was to quantify differences across MSM identities (n = 357) and assess the extent they conform to typecasts that prevail in policy-orientated discourse. More feminine kothis (26%) and hijras (13%) mostly reported receptive sex, and masculine panthis (15%) and bisexuals (23%) insertive anal sex. However, behavior did not always conform to expectation, with 25% and 16% of the sample reporting both insertive and receptive anal intercourse with known and unknown noncommercial partners, respectively (p < 0.000). Although behavior often complied with stereotyped role and identity, male-with-male sexual practices were fluid. Reification of these categories in an intervention context may hinder our understanding of the differential HIV risk among MSM.

Behaviour change in generalised HIV epidemics: impact of reducing cross-generational sex and delaying age at sexual debut.

BACKGROUND: Sexual behavioural change is essential to prevent HIV infections in Africa and statistical analysis of risk factors at the individual-level may be used to design interventions. The importance of reducing cross-generational sex (young women having sex with older men) and delaying age at first sex on the spread of HIV at the population-level has been presumed but not scientifically investigated and quantified. METHODS: A mathematical model of heterosexual spread of HIV was developed to predict the population-level impact of reducing cross-generational sex and delaying sexual debut. RESULTS: The impact of behaviour change on the spread of HIV is sensitive to the structure and reaction of the sexual network. Reducing cross-generational sex could have little impact on the risk of infection unless it is accompanied by a reduction in the number of risky sexual contacts. Even peer-to-peer sexual mixing can support high endemic levels of HIV. The benefit of delaying sexual debut is comparatively small and is reduced if males continue to prefer young partners or if young women spend more time unmarried. In Manicaland, Zimbabwe, if older men were to use condoms as frequently as young men, the reduction in risk of infection could exceed that generated by a two-year delay in first sex. CONCLUSIONS: At the individual-level avoiding sex with older partners and delaying sexual debut can decrease the risk of infection but at the population-level these interventions may do little to limit the spread of HIV without wider-ranging behavioural changes throughout the sexual network.

Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland.

Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed.

Declines in HIV prevalence can be associated with changing sexual behaviour in Uganda, urban Kenya, Zimbabwe, and urban Haiti.

OBJECTIVE: To determine whether observed changes in HIV prevalence in countries with generalised HIV epidemics are associated with changes in sexual risk behaviour. METHODS: A mathematical model was developed to explore the relation between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection, and sampling biases in ANC populations were explored to determine which factors maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared with the observed prevalence data in urban Haiti, urban Kenya, urban Cote d'Ivoire, Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia. RESULTS: Recent downturns in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d'Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual behaviour. CONCLUSIONS: Changes in patterns of HIV prevalence in urban Kenya, Zimbabwe, and urban Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are consistent with behaviour change and not the natural course of the HIV epidemic.

Criteria for detecting and understanding changes in the risk of HIV infection at a national level in generalised epidemics.

Identification of causes of changes in prevalence and incidence of HIV at a national level is important for planning future prevention and intervention needs. However, the slow progression to disease and the sensitive and stigmatising nature of the associated behaviours can make this difficult. Changing rates of incidence are to be expected as an epidemic progresses, but separating background changes from those brought about by changes in behaviour and interventions requires careful analysis. This paper discusses the criteria required to determine whether observed changes in HIV prevalence are the result of changes in behaviour.

Behavioural data as an adjunct to HIV surveillance data.

BACKGROUND: Second generation surveillance for HIV aims to improve the validity and utility of routine serial HIV prevalence data. It includes the collection of data on sexual behaviour and sexually transmitted disease prevalence. METHODS: This paper reviews the function of sexual behaviour data in HIV surveillance and the methods used to determine which behaviours are monitored and how changes in behaviour can be assessed. RESULTS: Sexual behaviour data provide a poor predictor of the future spread of HIV, but these data can provide corroboration of changes in HIV incidence and assist in attributing changes to particular aspects of risk. Significance tests should be used to assess changes in behaviour, but this requires transparent reporting of methods and sample sizes. CONCLUSIONS: Collection of behavioural data will provide important retrospective information about the HIV epidemic progress and should not be neglected because of the focus on improving HIV sero-surveillance.

Patterns of uptake of treatment for self reported sexually transmitted infection symptoms in rural Zimbabwe.

OBJECTIVES: To determine the extent of self reported symptoms perceived to be related to sexually transmitted infections and the patterns of subsequent treatment seeking behaviour in a predominantly rural population of Zimbabwe. METHODS: A population based survey of 4331 men and 5149 women was conducted in rural Zimbabwe during 1998-2000. Structured confidential interviews collected data on self reported sexually transmitted infection symptoms, treatment seeking behaviour, sociodemographic characteristics, and sexual behaviour. RESULTS: 25% of men aged 17-54 years report experiencing genital sores and 25% of men report experiencing urethral discharge; 30% of women aged 15-44 years report experiencing vaginal discharge. The lifetime number of sexual partners, age, and years of sexual activity were all significant predictors of symptoms for both men and women (all p values <0.001). 92% of men and 62% of women had sought treatment for their symptoms in the past year (p value <0.001). Men and women were equally likely to have sought treatment at a local hospital or clinic, but women were much less likely than men to have sought treatment at a different hospital or clinic. Among those who had sought treatment, men sought treatment faster than women and were more likely to report being "very satisfied" with their treatment than women. CONCLUSIONS: The gender differences in treatment seeking are of major concern for control efforts and further work on determining the reasons for these should be a priority. This would inform the likely impact of both increasing availability of local services and further reducing the stigma faced by those wishing to access such services.

HIV infection and reproductive health in teenage women orphaned and made vulnerable by AIDS in Zimbabwe.

AIDS has increased the number of orphans and vulnerable children (OVCs) in sub-Saharan Africa who could suffer detrimental life experiences. We investigated whether OVCs have heightened risks of adverse reproductive health outcomes including HIV infection. Data on HIV infection, sexually transmitted infection (STI) symptoms and pregnancy, and common risk factors were collected for OVCs and non-OVCs in a population survey of 1523 teenage children in eastern Zimbabwe between July 2001 and March 2003. Multivariate logistic regression was used to test for statistical association between OVC status, adverse reproductive health outcomes and suspected risk factors. Amongst women aged 15-18 years, OVCs had higher HIV prevalence than non-OVCs (3.2% versus 0.0%; p = 0.002) and more common experience of STI symptoms (5.9% versus 3.3%; adjusted odds ratio = 1.75, 95% CI 0.80-3.80) and teenage pregnancy (8.3% versus 1.9%; 4.25, 1.58-11.42). OVCs (overall), maternal orphans and young women with an infected parent were more likely to have received no secondary school education and to have started sex and married, which, in turn, were associated with poor reproductive health. Amongst men aged 17-18 years, OVC status was not associated with HIV infection (0.5% versus 0.0%; p = 1.000) or STI symptoms (2.7% versus 1.6%; p = 0.529). No association was found between history of medical injections and HIV risk amongst teenage women and men. High proportions of HIV infections, STIs and pregnancies among teenage girls in eastern Zimbabwe can be attributed to maternal orphanhood and parental HIV. Many of these could be averted through further female secondary school education. Predicted substantial expanded increases in orphanhood could hamper efforts to slow the acquisition of HIV infection in successive generations of young adults, perpetuating the vicious cycle of poverty and disease.