Rob Dorrington

Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies

Leigh Johnson and colleagues estimate the life expectancies of HIV positive South African adults who are taking antiretroviral therapy by using information from 6 programmes between 2001 and 2010.

Male Circumcision for HIV Prevention in High HIV Prevalence Settings: What Can Mathematical Modelling Contribute to Informed Decision Making?

Experts from UNAIDS, WHO, and the South African Centre for Epidemiological Modelling report their review of mathematical models estimating the impact of male circumcision on HIV incidence in high HIV prevalence settings

Sentinel surveillance of sexually transmitted infections in South Africa: a review

Objectives: To review studies of sexually transmitted infection (STI) prevalence in South Africa between 1985 and 2003 in selected sentinel populations. To examine how STI prevalence varies between populations and to identify the limitations of the existing data. Methods: Studies of the prevalence of syphilis, chancroid, granuloma inguinale, lymphogranuloma venereum, gonorrhoea, chlamydia, trichomoniasis, bacterial vaginosis, candidiasis, and herpes simplex virus type 2 (HSV-2) were considered. Results were included if they related to women attending antenatal clinics or family planning clinics, commercial sex workers, individuals in the general population (household surveys), patients with STIs, patients with genital ulcer disease (GUD), or men with urethritis. Results: High STI prevalence rates have been measured, particularly in the case of HSV-2, trichomoniasis, bacterial vaginosis and candidiasis. The aetiological profile of GUD appears to be changing, with more GUD caused by HSV-2 and less caused by chancroid. The prevalence of gonorrhoea and syphilis is highest in “high risk” groups such as sex workers and attenders of STI clinics, but chlamydia and trichomoniasis prevalence levels are not significantly higher in these groups than in women attending antenatal clinics. Conclusions: The prevalence of STIs in South Africa is high, although there is extensive variability between regions. There is a need for STI prevalence data that are more nationally representative and that can be used to monitor prevalence trends more reliably.

The effect of changes in condom usage and antiretroviral treatment coverage on human immunodeficiency virus incidence in South Africa: a model-based analysis.

This study aims to assess trends in human immunodeficiency virus (HIV) incidence in South Africa, and to assess the extent to which prevention and treatment programmes have reduced HIV incidence. Two models of the South African HIV epidemic, the STI (sexually transmitted infection)–HIV Interaction model and the ASSA2003 AIDS and Demographic model, were adapted. Both models were fitted to age-specific HIV prevalence data from antenatal clinic surveys and household surveys, using a Bayesian approach. Both models suggest that HIV incidence in 15–49 year olds declined significantly between the start of 2000 and the start of 2008: by 27 per cent (95% CI: 21–32%) in the STI–HIV model and by 31 per cent (95% CI: 23–39%) in the ASSA2003 model, when expressed as a percentage of incidence rates in 2000. By 2008, the percentage reduction in incidence owing to increased condom use was 37 per cent (95% CI: 34–41%) in the STI–HIV model and 23 per cent (95% CI: 14–34%) in the ASSA2003 model. Both models also estimated a small reduction in incidence owing to antiretroviral treatment by 2008. Increased condom use therefore appears to be the most significant factor explaining the recent South African HIV incidence decline.

The contribution of maternal HIV seroconversion during late pregnancy and breastfeeding to mother-to-child transmission of HIV

Background:The prevention of mother-to-child transmission (PMTCT) of HIV has been focused mainly on women who are HIV positive at their first antenatal visit, but there is uncertainty regarding the contribution to overall transmission from mothers who seroconvert after their first antenatal visit and before weaning. Method:A mathematical model was developed to simulate changes in mother-to-child transmission of HIV over time, in South Africa. The model allows for changes in infant feeding practices as infants age, temporal changes in the provision of antiretroviral prophylaxis and counseling on infant feeding, as well as temporal changes in maternal HIV prevalence and incidence. Results:The proportion of mother-to-child transmission (MTCT) from mothers who seroconverted after their first antenatal visit was 26% [95% confidence interval (CI): 22% to 30%] in 2008, or 15,000 of 57,000 infections. It is estimated that by 2014, total MTCT will reduce to 39,000 per annum, and transmission from mothers seroconverting after their first antenatal visit will reduce to 13,000 per annum, accounting for 34% (95% CI: 29% to 39%) of MTCT. If maternal HIV incidence during late pregnancy and breastfeeding were reduced by 50% after 2010, and HIV screening were repeated in late pregnancy and at 6-week immunization visits after 2010, the average annual number of MTCT cases over the 2010–2015 period would reduce by 28% (95% CI: 25% to 31%), from 39,000 to 28,000 per annum. Conclusion:Maternal seroconversion during late pregnancy and breastfeeding contributes significantly to the pediatric HIV burden and needs greater attention in the planning of prevention of MTCT programs.

The effect of syndromic management interventions on the prevalence of sexually transmitted infections in South Africa

OBJECTIVES Few studies have assessed the effect of syndromic management interventions on the prevalence of sexually transmitted infections (STIs) at a population level. This study aims to determine the effect of syndromic management protocols that have been introduced in South Africa since 1994. STUDY DESIGN A mathematical model of sexual behaviour patterns in South Africa was used to model the incidence of HIV, genital herpes, syphilis, chancroid, gonorrhoea, chlamydial infection, trichomoniasis, bacterial vaginosis and vaginal candidiasis. Assumptions about health seeking behaviour and treatment effectiveness were based on South African survey data. The model was fitted to available STI prevalence data. MAIN OUTCOME MEASURES Reductions in STI prevalence due to syndromic management. RESULTS Between 1995 and 2005, there were significant reductions in the prevalence of syphilis, chancroid, gonorrhoea, trichomoniasis and chlamydial infection. In women aged between 15 and 49, syndromic management resulted in a 33% (95% CI: 23-43%) decline in syphilis prevalence, a 6% (95% CI: 3-11%) reduction in gonorrhoea prevalence, a 5% (95% CI: 1-13%) reduction in the prevalence of bacterial vaginosis and a substantial decline in chancroid. However, syndromic management did not significantly reduce the prevalence of other STIs. For all STIs, much of the modelled reduction in STI prevalence between 1995 and 2005 can be attributed to either increased condom usage or AIDS mortality. CONCLUSIONS Syndromic management of STIs can be expected to decrease the prevalence of curable STIs that tend to become symptomatic, but has little effect on the prevalence of STIs that are mostly asymptomatic.

The effect of early initiation of antiretroviral treatment in infants on pediatric AIDS mortality in South Africa: a model-based analysis.

Background: Guidelines for treatment of pediatric HIV have recently changed to recommend that all infants who are identified as HIV-infected should start antiretroviral treatment (ART) immediately, regardless of their immunologic or clinical status. This study aims to assess the likely impact of this change in guideline in South Africa. Methods: A mathematical model was developed to simulate mother-to-child transmission of HIV, disease progression, and death of HIV-infected children <15 years of age. The model is calibrated to South African data sources, including prevention of mother-to-child transmission program coverage data, pre-ART survival data, ART program statistics, and pediatric HIV prevalence studies. Results: Relative to what would be expected in the absence of early ART initiation, the number of infant AIDS deaths over the 2010–2025 period is expected to drop by 23.6% (95% confidence interval [CI]: 22.5–24.5%) at current levels of polymerase chain reaction (PCR) diagnosis, and by 34.2% (95% CI: 32.7–35.6%) if PCR diagnosis increases to 80% of perinatally infected infants at 2 months. However, the pediatric HIV disease burden has shifted toward older children in recent years. The effect of early ART on total pediatric AIDS mortality during the 2010–2025 period is therefore modest: a 9.8% reduction (95% CI: 7.9–12.6%) at current levels of PCR diagnosis, and a 14.2% reduction (95% CI: 11.4–18.2%) if PCR coverage increases to 80% of perinatally infected infants. Conclusion: The changes in ART guidelines for infants will have a significant impact on pediatric AIDS mortality at young ages, but further efforts are required to reduce the substantial growing AIDS mortality in older children.

Mortality trends and differentials in South Africa from 1997 to 2012: second National Burden of Disease Study

BACKGROUND The poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997-2012 and develop national, population group, and provincial estimates of the levels and causes of mortality. METHOD We used underlying cause of death data from death notifications for 1997-2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassified HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison. FINDINGS All-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29·1%) followed by cerebrovascular disease (7·5%) and lower respiratory infections (4·9%). All-cause age-standardised death rates were 1·7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2·2 times higher in black Africans compared to whites, and 1·4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial differences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence. INTERPRETATION This study shows the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality differentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Differences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data. FUNDING South African Medical Research Councils Flagships Awards Project.

A Bayesian approach to uncertainty analysis of sexually transmitted infection models.

Objectives To propose a Bayesian approach to uncertainty analysis of sexually transmitted infection (STI) models, which can be used to quantify uncertainty in model assessments of policy options, estimate regional STI prevalence from sentinel surveillance data and make inferences about STI transmission and natural history parameters. Methods Prior distributions are specified to represent uncertainty regarding STI parameters. A likelihood function is defined using a hierarchical approach that takes account of variation between study populations, variation in diagnostic accuracy as well as random binomial variation. The method is illustrated using a model of syphilis, gonorrhoea, chlamydial infection and trichomoniasis in South Africa. Results Model estimates of STI prevalence are in good agreement with observations. Out-of-sample projections and cross-validations also show that the model is reasonably well calibrated. Model predictions of the impact of interventions are subject to significant uncertainty: the predicted reductions in the prevalence of syphilis by 2020, as a result of doubling the rate of health seeking, increasing the proportion of private practitioners using syndromic management protocols and screening all pregnant women for syphilis, are 43% (95% CI 3% to 77%), 9% (95% CI 1% to 19%) and 6% (95% CI 4% to 7%), respectively. Conclusions This study extends uncertainty analysis techniques for fitted HIV/AIDS models to models that are fitted to other STI prevalence data. There is significant uncertainty regarding the relative effectiveness of different STI control strategies. The proposed technique is reasonable for estimating uncertainty in past STI prevalence levels and for projections of future STI prevalence.

Second National Burden of Disease Study South Africa: national and subnational mortality trends, 1997–2009

Abstract Background Global Burden of Diseases, Injuries, and Risk Factors Study 2010 results show continued limitations of data quality and availability in most of the African region. Focused efforts in South Africa, however, have contributed to improved completeness and availability of mortality data, such that South Africa is currently undertaking a second National Burden of Disease Study. Mortality estimates have been developed nationally and for the nine provinces for 1997–2009. Methods Vital registration data obtained for 1997–2009 were adjusted for completeness using indirect demographic techniques. A regression approach was used to identify misclassified AIDS deaths, and garbage codes were proportionally redistributed by age, sex, and population group. Injury deaths were estimated from additional data sources. Age-standardised mortality rate (ASMR) trends for the nine provinces were calculated using ASSA 2008 population estimates and the WHO age standard. Findings All-cause mortality peaked in 2006 and thereafter started to decline. ASMRs showed a two-fold difference between the highest-affected and lowest-affected provinces for the 1997–2009 period. ASMR from HIV/AIDS increased threefold since 1997 with provincial variation, while mortality from non-HIV-related tuberculosis declined. Mortality rates from non-communicable diseases decreased over the period nationally but increased for some provinces and remained stable for others as a result of differing trends in hypertensive heart disease and respiratory diseases. Nationally, preliminary analyses for 2009 show that HIV/AIDS was responsible for the highest number of deaths (31·2%; n=194 322 of 622 300 deaths), followed by cerebrovascular disease (6·2%; n=38 666), tuberculosis (5·4%; n=33 375), lower respiratory infections (5·2%; n=32 568), and ischaemic heart disease (4·4%; n=27 688). However, tuberculosis and interpersonal violence ranked among the top five causes for males, while hypertensive heart disease and ischaemic heart disease featured for females. Interpretation The downward trend in HIV/AIDS mortality can be attributed to the extensive antiretroviral treatment rollout since 2005. Differential provincial mortality trends reflect the different stages of epidemiological transition and differential health services in the provinces, providing relevant information for policy makers to address inequalities. Funding South African Medical Research Council.