Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting.

OBJECTIVE: Despite World Health Organization recommendations, concerns about promoting resistance have impeded implementation of isoniazid preventive therapy (IPT) for tuberculosis (TB). We describe characteristics of TB in individuals previously exposed to IPT as part of 'Thibela TB', a cluster-randomized trial of community-wide IPT in gold miners in South Africa. DESIGN: Case series including participants who were dispensed IPT, attended at least one follow-up visit and were subsequently treated for TB. METHODS: TB episodes were detected through surveillance and through follow-up if IPT was stopped early. Drug susceptibility data were compared with TB episodes detected through surveillance in control clusters (where IPT use was minimal) and a laboratory substudy of mycobacterial sputum culture from TB suspects in control clusters. RESULTS: Among 126 eligible individuals (125 men, median age 43 years), median time from starting IPT to TB treatment was 316 days (interquartile range 174-491). Ninety-four of the 126 (75%) were first episodes. Eighty-nine of 103 (86%) tested HIV-infected, with the median CD4 cell count of 196 cells/microl (n = 51). Sixty-four of 108 (59%) with known treatment outcomes were cured or completed treatment. Among 71 isolates with drug susceptibility results available, 12.1% [95% confidence interval (CI) 5.0-23.3] and 7.7% (95% CI 0.2-36.0) from first and retreatment episodes, respectively, had isoniazid resistance, compared with 6.0% (95% CI 3.1-10.2) and 18.7% (95% CI 10.6-29.3) in control clusters and 11.8% (95% CI 8.2-16.3) among first TB episodes in the laboratory substudy. CONCLUSION: TB after recent IPT has prevalence of drug resistance similar to background and treatment outcomes typical of this setting. These data support wider implementation of IPT.

Age at first sex and HIV infection in rural Zimbabwe.

Beginning sexual activity introduces an individual to the risk of acquiring sexually transmitted infections. In this study, cross-sectional behavioral data linked to HIV-status from 4,138 men and 4,948 women interviewed in rural Zimbabwe are analyzed to investigate the distribution and consequences of early first sex. We find that age at first sex (at a median age of 19 years for males and 18 years for females) has declined among males over the past 30 years but increased recently among females. Those in unskilled employment, those not associated with a church, and women without a primary education begin to have sex earlier than others. Early sexual debut before marriage precedes a lifetime of greater sexual activity but with more consistent condom use. Women who begin to have sex earlier than others of their age are more likely to be infected with HIV. This finding can be explained by their having a greater lifetime number of sexual partners than those whose first sexual experience occurs later.

Evaluating the proximate determinants framework for HIV infection in rural Zimbabwe.

BACKGROUND: Risk factors for HIV infection can act at one of several causal levels, making interpretation of results problematic. One suggested solution has been a proximate determinants framework, in which risk factors are grouped into "underlying", "proximate" and "biological" determinants. METHODS: A baseline, cross-sectional survey of HIV serostatus and potential risk factors was carried out among 9480 adults in Zimbabwe. Associations were assessed separately for men and women using logistic regression models; data were only included for those who reported sexual debut. The predictive ability of proximate determinants describing both individual and partnership characteristics was assessed along with that of the underlying determinants. The significance of the underlying determinants once adjusted for proximate determinants was then evaluated. Finally, the relationship between the underlying determinants and some of the key proximate determinants was explored. RESULTS: The two most important proximate determinants for men and women were lifetime number of sexual partners and symptoms of sexually transmitted infections (p<0.001). After adjustment for all proximate determinants, some underlying determinants were still significant, particularly age group, marital status and community (p<0.001). CONCLUSIONS: Although proximate determinants could explain the action of many underlying determinants, several of the latter remained significant after adjustment for the proximate determinants. Hence, the proximate determinants were probably not measured completely. An important determinant of an individual's risk of HIV infection is the HIV status of their sexual partners. This was not measured in this survey, and may be related to the individual's age (as a predictor for the age of the partner), marital status and community prevalence. However, it will be measured in a subsequent survey of this cohort.

HIV decline associated with behavior change in eastern Zimbabwe.

Few sub-Saharan African countries have witnessed declines in HIV prevalence, and only Uganda has compelling evidence for a decline founded on sexual behavior change. We report a decline in HIV prevalence in eastern Zimbabwe between 1998 and 2003 associated with sexual behavior change in four distinct socioeconomic strata. HIV prevalence fell most steeply at young ages-by 23 and 49%, respectively, among men aged 17 to 29 years and women aged 15 to 24 years-and in more educated groups. Sexually experienced men and women reported reductions in casual sex of 49 and 22%, respectively, whereas recent cohorts reported delayed sexual debut. Selective AIDS-induced mortality contributed to the decline in HIV prevalence.

Beer halls as a focus for HIV prevention activities in rural Zimbabwe.

OBJECTIVE: The authors conducted an assessment of the role of beer halls in the HIV epidemic of rural Zimbabwe as part of the ongoing identification of risky places for the targeting of prevention activities. STUDY: A population-based survey of 9480 adults collected data on number of visits to beer halls in the last month, together with sociodemographics, sexual behavior, and HIV infection from 1998-2000. RESULTS: Fifty percent of men, but only 4% of women, had been to a beer hall in the last month. They reported higher levels of sexual behavior and stronger associations with commercial sex than those who had not been to a beer hall. A recent visit to a beer hall was also associated with HIV infection (men: odds ratio [OR] = 1.9, P <0.001; women: OR = 1.7, P = 0.001) and with ever having experienced urethral/vaginal discharge or genital sores. Only 225 respondents experienced an HIV prevention activity at a beer hall in the last 6 months. CONCLUSIONS: Beer hall attendance is associated with high-risk behavior for HIV infection and cofactor sexually transmitted infections. Beer halls represent an underused focus for HIV prevention.

The population impact of HIV on fertility in sub-Saharan Africa.

OBJECTIVES: To examine new evidence from studies on the estimates of the fertility rate ratio comparing HIV-infected and uninfected women, of the population change in total fertility attributable to HIV, and to review the evidence of changes in fertility in HIV-uninfected women. DESIGN: A review and analysis of data from the many individual studies that have examined the associations between HIV/AIDS and fertility. METHODS: Data from sub-Saharan Africa were collected from published studies, personal communications and the Demographic and Health Surveys. A mathematical model was used to demonstrate the impact of the HIV/AIDS epidemic on the number of births in Uganda. RESULTS: Fertility was lower among HIV-infected women than HIV-uninfected women, with the exception of those aged 15-19 years, in whom the selective pressure of sexual debut on pregnancy and HIV infection led to higher fertility rates among the HIV infected. This fertility differential resulted in a population-attributable decline in total fertility of 0.37% (95% confidence interval 0.30%, 0.44%) for each percentage point of HIV prevalence. The evidence for fertility changes in HIV-uninfected women was ambiguous. An estimated reduction of 700 000 births occurred in Uganda, as a result of the reduced fertility in HIV-infected women and premature mortality among reproductive age women. CONCLUSION: Large fertility differentials existed between HIV-infected and uninfected women, with substantial variation by age. The extent to which these could be attributed to the direct impact of the epidemic on both infected and uninfected women, as opposed to pre-existing differences in their fertility, merits further study.

Comparison of household-survey estimates with projections of mortality and orphan numbers in sub-Saharan Africa in the era of HIV/AIDS.

The United Nations publishes estimates of HIV prevalence, AIDS mortality, and orphan numbers for all countries of the world. It is important to assess the validity of these model-based estimates since they underpin much policy concerned with care and prevention. Household surveys that ask questions about the survival of children's parents (orphanhood) offer an independent source of data with which these estimates can be compared. Survey estimates of maternal and paternal orphans are significantly lower than model estimates for 40 surveys in 36 countries of sub-Saharan Africa (p < 0.001, p = 0.002). This is probably because adult mortality from causes other than AIDS is lower than assumed in the models, although under-reporting of orphanhood in surveys may also play a role. Reducing adult mortality from causes other than AIDS brings the model estimates into close agreement with the surveys. This suggests that the fraction of orphans attributable to AIDS is greater than estimated previously.

Age-specific back-projection of HIV diagnosis data.

A method for reconstructing the HIV infection curve from data on both HIV and AIDS diagnoses is enhanced by using age as a covariate and by using the diagnosis data to estimate parameters that were previously assumed known. Maximum likelihood estimation is used for parameters of the induction distribution. Each of the set of parameters that specify the baseline rate of infection over time and the set of parameters giving the relative susceptibility over age are estimated by maximizing the likelihood subject to a smoothness requirement. We find that estimating the extra parameters is feasible, producing estimates with good precision. Including age as a covariate gives 90 per cent confidence intervals for the HIV incidence curve that are about 20 per cent narrower than those obtained when age data are not used.