Thomas Rehle

National HIV incidence measures - new insights into the South African epidemic

BACKGROUND AND OBJECTIVES Currently South Africa does not have national HIV incidence data based on laboratory testing of blood specimens. The 2005 South African national HIV household survey was analysed to generate national incidence estimates stratified by age, sex, race, province and locality type, to compare the HIV incidence and HIV prevalence profiles by sex, and to examine the relationship between HIV prevalence, HIV incidence and associated risk factors. METHOD The detection of recent infections was performed on confirmed HIV-positive samples, using the BED capture enzyme immunoassay optimised for dried blood spot (DBS) specimens. BED HIV incidence calculations applied adjustment procedures that were recently revised and approved by the Centers for Disease Control and Prevention for subtype C blood specimens. RESULTS HIV incidence in the study population aged 2 years and older was 1.4% per year, with 571,000 new HIV infections estimated for 2005. An HIV incidence rate of 2.4% was recorded for the age group 15-49 years. The incidence of HIV among females peaked in the 20-29-year age group at 5.6%, more than six times the incidence found in 20-29-year-old males (0.9%). Among youth aged 15-24 years, females account for 90% of the recent HIV infections. Non-condom use among youth, current pregnancy and widowhood were the socio-behavioural factors associated with the highest HIV incidence rates. CONCLUSIONS The HIV incidence estimates reflect the underlying transmission dynamics that are currently at work in South Africa. The findings suggest that the current prevention campaigns are not having the desired impact, particularly among young women.

A decline in new HIV infections in South Africa: estimating HIV incidence from three national HIV surveys in 2002, 2005 and 2008.

Background Three national HIV household surveys were conducted in South Africa, in 2002, 2005 and 2008. A novelty of the 2008 survey was the addition of serological testing to ascertain antiretroviral treatment (ART) use. Methods and Principal Findings We used a validated mathematical method to estimate the rate of new HIV infections (HIV incidence) in South Africa using nationally representative HIV prevalence data collected in 2002, 2005 and 2008. The observed HIV prevalence levels in 2008 were adjusted for the effect of antiretroviral treatment on survival. The estimated “excess” HIV prevalence due to ART in 2008 was highest among women 25 years and older and among men 30 years and older. In the period 2002–2005, the HIV incidence rate among men and women aged 15–49 years was estimated to be 2.0 new infections each year per 100 susceptible individuals (/100pyar) (uncertainty range: 1.2–3.0/100pyar). The highest incidence rate was among 15–24 year-old women, at 5.5/100pyar (4.5–6.5). In the period 2005–2008, incidence among men and women aged 15–49 was estimated to be 1.3/100 (0.6–2.5/100pyar), although the change from 2002–2005 was not statistically significant. However, the incidence rate among young women aged 15–24 declined by 60% in the same period, to 2.2/100pyar, and this change was statistically significant. There is evidence from the surveys of significant increases in condom use and awareness of HIV status, especially among youth. Conclusions Our analysis demonstrates how serial measures of HIV prevalence obtained in population-based surveys can be used to estimate national HIV incidence rates. We also show the need to determine the impact of ART on observed HIV prevalence levels. The estimation of HIV incidence and ART exposure is crucial to disentangle the concurrent impact of prevention and treatment programs on HIV prevalence.

Accuracy of serological assays for detection of recent infection with HIV and estimation of population incidence: a systematic review

We systematically reviewed the accuracy of serological tests for recent infections with HIV that have become widely used for measuring population patterns incidence of HIV. Across 13 different assays, sensitivity to detect recent infections ranged from 42-100% (median 89%). Specificity for detecting established infections was between 49.5% and 100% (median 86.8%) and was higher for infections of durations longer than 1 year (median 98%, range 31.5-100.0). For four different assays, comparisons were made between assay-derived population incidence estimates and a reference incidence estimate. The median percentage difference between the assay-derived incidence and reference incidence was 26.0%. Serological assays have reasonable sensitivity for the detection of recent infection with HIV, but are vulnerable to misclassifying established infections as recent-potentially leading to biases in incidence estimates. This conclusion is highly qualified by the apparent absence of a standardised approach to assay evaluation. There is an urgent need for an internationally agreed framework for evaluating and comparing these tests.

Beyond detuning: 10 years of progress and new challenges in the development and application of assays for HIV incidence estimation.

In the ongoing battle against HIV/AIDS, it is critical that we are able to measure and monitor HIV incidence, that is the number of new infections during a period of time, usually expressed as number of infections/person-years of observation or as an annual percentage of the population that acquire infection. Knowledge of HIV incidence is necessary to understand transmission patterns; to provide a rational basis for targeting prevention efforts; to evaluate interventions to reduce transmission; and to predict or project the burden of HIV infection in different demographic and risk populations. Reliable information on HIV incidence is especially important to support prevention programs in the low-income and middleincome countries that continue to bear a disproportionate share of the global burden of the HIVepidemic. Improved estimates of HIV incidence are essential to evaluate

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.

Epidemiological and demographic HIV/AIDS projections: South Africa

The Epidemic Projection Package (EPP) recently developed by the UNAIDS Reference Group on Estimates, Models and Projections and the Spectrum model program developed by the Futures Group were used to model the South African HIV epidemic, project future trends in HIV/AIDS and estimate the demographic impact of AIDS. The national HIV prevalence surveys among pregnant women from 1990–2001 and the first national, population-based HIV survey in 2002 served as the data sets used to calibrate the input HIV prevalence values for the model. The scenario created by the model showed that a dramatic rise in HIV prevalence during the 1990s has peaked in 2002 with 4.69 million infected people and it is projected that the epidemic in South Africa has now begun to level off. Adult (15–49 years) incidence rates have decreased substantially in the past five years since 1997 (4.2%) and are expected to reach a level of 1.7% in 2003. The annual number of deaths due to AIDS is projected to peak with 487 320 AIDS deaths in the year 2008. By 2020, the total population of South Africa is expected to be 23% smaller than it would be without AIDS, however, a negative population growth rate is not expected during the projection period. Life expectancy at birth is expected to hit a low of 45.6 years in the time period 2005–2010, which is 22 years less than it would have been in the absence of AIDS. Ten years from now over 2.5 million AIDS orphans are projected for South Africa. Models play an important role in estimating HIV variables that are difficult to measure. Projections of the future HIV/AIDS burden in South Africa underscore the importance of acting now to reduce the number of new infections and plan for medical and social care needs.

Rates of HIV testing and diagnosis in South Africa: successes and challenges.

Background:UNAIDS aims for 90% of HIV-positive individuals to be diagnosed by 2020, but few attempts have been made in developing countries to estimate the fraction of the HIV-positive population that has been diagnosed. Methods:To estimate the rate of HIV diagnosis in South Africa, reported numbers of HIV tests performed in the South African public and private health sectors were aggregated, and estimates of HIV prevalence in individuals tested for HIV were combined. The data were integrated into a mathematical model of the South African HIV epidemic, which was additionally calibrated to estimates of the fraction of the population ever tested for HIV, as reported in three national household surveys. Results:The fraction of HIV-positive adults who were undiagnosed declined from more than 80% in the early 2000s to 23.7% [95% confidence interval (95% CI) 23.1–24.3] in 2012. The undiagnosed proportion in 2012 was substantially higher in men (31.9%, 95% CI 29.7–34.3) than in women (19.0%, 95% CI 17.9–19.9). Projected probabilities of experiencing disease progression (CD4+ cell count <350 cells/&mgr;l) without diagnosis are more than 50% for most HIV-positive adults over the age of 40. The fraction of HIV-positive adults who are undiagnosed is projected to decline to 8.9% by 2020 if current targets (10 million tests per annum) are met. Conclusion:South Africa has made significant progress in expanding access to HIV testing, and at current testing rates, the target of 90% of HIV-positive adults diagnosed by 2020 is likely to be reached. However, uptake is relatively low in men and older adults.

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.

Prevention of transfusion-associated Hiv transmission in Kinshasa, Zaire: Hiv screening is not enough

The purpose of this study was to develop a strategy to reduce transfusion-related HIV transmission which went beyond the limits of routine HIV screening of blood donors. Current blood transfusion practices were assessed in 1044 patients for whom staff physicians had requested a transfusion between 5 September and 19 October, 1988. Children under 5 years of age with malaria, and pregnant women with acute anaemia requiring blood transfusion were the two highest risk groups. Many of the transfusions were given without an obvious medical indication; 22.7% (214 out of 955) of the recipients were transfused without prior laboratory tests [haemoglobin (Hb) or haematocrit (Hct)], 7.2% with Hb greater than 6g/100ml or Hct greater than 25% and 16.6% without clinical signs of severe anaemia (pulse less than 100/min without shortness of breath). The data of this study were used to organize a workshop for all the physicians responsible for blood transfusions in Kinshasa and two nearby health zones. A consensus statement on the indications for blood transfusion was developed. Subsequently, transfusion centres adopted this consensus statement instead of previous guidelines.