Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial.

OBJECTIVES: We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART). DESIGN: An open-label, multicentre, randomized trial. METHODS: Peripheral neuropathy was self-reported at 12-weekly clinic visits. Cox regression models (excluding participants reporting preexisting peripheral neuropathy at ART initiation), considered sex; pre-ART WHO stage, age and CD4(+) cell count; CD4(+) cell count versus no CD4(+) cell count monitoring; and time-updated CD4(+) cell count, weight and use of stavudine, isoniazid and didanosine. RESULTS: Four hundred and twenty-one out of 3316(13%) patients reported preexisting peripheral neuropathy at ART initiation. Median (interquartile range, IQR) follow-up in 2895 participants without preexisting peripheral neuropathy was 4.9 (4.7-5.4) years. Three hundred and fifty-four (12%) took stavudine as first-line substitution and 518 (18%) took isoniazid during follow-up. Two hundred and ninety (11%) participants developed a new peripheral neuropathy episode, an incidence of 2.12 per 100 person-years. Eighteen (0.1%) had a grade 3/4 episode. Independent predictors of peripheral neuropathy were current stavudine use [adjusted hazard ratio (a)HR 4.16 (95% confidence interval, 95% CI 3.06-5.66], current isoniazid use [aHR 1.59 (95% CI 1.02-2.47)] and current didanosine use [aHR 1.60 (95% CI 1.19-2.14)]. Higher risks were independently associated with higher pre-ART weight [aHR (per+5 kg) 1.07 (95% CI 1.01-1.13)] and older age aHR (per 10 years older) 1.29 (95% CI 1.12-1.49), but there was no significant effect of sex (P = 0.13), pre-ART CD4(+) cell count (P = 0.91) or CD4(+) cell count monitoring (P = 0.73). CONCLUSION: Current stavudine, didanosine or isoniazid use continue to increase peripheral neuropathy risks, as does older age and weight at ART initiation; however, we found no evidence of increased risk in women in contrast to previous studies. The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended. All patients receiving isoniazid, either as part of antituberculosis (TB) chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.

Symptomatic hyperlactataemia in adults on antiretroviral therapy: a single-centre experience.

OBJECTIVE: There are limited data on symptomatic hyperlactataemia caused by antiretroviral therapy (ART) in resource-limited settings. We assessed individuals who developed symptomatic hyperlactataemia on ART in an outpatient clinic in South Africa. DESIGN: A retrospective record review was performed on patients attending the clinic from January 2004 to December 2005. RESULTS: Thirty-five patients, all on stavudine-containing regimens, developed symptomatic hyperlactataemia. The incidence in this population was 20.5 cases per 1 000 person-years of ART with an associated mortality of 21%. The major risk factor was being female (risk ratio (RR) 3.27). Significant clinical symptoms preceding symptomatic hyperlactataemia include nonspecific gastrointestinal symptoms, weight loss, and development of symptomatic neuropathy. CONCLUSIONS: The incidence of symptomatic hyperlactataemia in our population was high. Simple clinical measures, such as neuropathy symptoms and monitoring of weight, may alert the clinician to impending symptomatic hyperlactataemia. Early diagnosis expedites safe outpatient care and switching of ART regimens without interruption, in many cases.

Operational effectiveness and 36 week HIV-free survival in the South African programme to prevent mother-to-child transmission of HIV-1.

OBJECTIVE: Previous studies on the operational effectiveness of programmes to reduce transmission of HIV from mother-to-child (PMTCT) in Africa have generally been hospital-based pilot studies with short follow-up periods. METHOD: Prospective cohort study to evaluate the routine operational effectiveness of the South African National PMTCT Programme, primarily measured by HIV-free survival at 36 weeks post-delivery. Three of eighteen pilot sites participating in the programme were selected as they reflected differences in circumstances, such as HIV prevalence, socioeconomic status and rural-urban location. A total of 665 HIV-positive mothers and their infants were followed. RESULTS: HIV-free survival at 36 weeks varied significantly across sites with 84% in Paarl, 74% in Umlazi and 65% in Rietvlei (P = 0.0003). Maternal viral load was the single most important factor associated with HIV transmission or death [hazard ratio (HR), 1.54; 95% confidence interval (CI), 1.21-1.95]. Adjusting for health system variables (fewer than four antenatal visits and no antenatal syphilis test) explained the difference between Rietvlei and Paarl (crude HR, 2.27; 95% CI, 1.36-3.77; adjusted HR, 1.81; 95% CI, 0.93-3.50). Exposure to breastmilk feeding explained the difference between Umlazi and Paarl (crude HR, 1.74; 95% CI, 1.06-2.84; adjusted HR, 1.41; 95% CI, 0.81-2.48). CONCLUSION: Ever breastfeeding and underlying inequities in healthcare quality within South Africa are predictors of PMTCT programme performance and will need to be addressed to optimize PMTCT effectiveness.

Rape perpetration by young, rural South African men: Prevalence, patterns and risk factors.

Sexual violence is a well-recognised global health problem, but there has been remarkably little research on men as perpetrators. The objectives of this paper are to describe the prevalence, patterns and factors associated with rape of an intimate partner and a woman who was not a partner with men aged 15-26 years in rural South Africa. The analysis presented here is of data collected during a baseline survey of participants in a cluster randomised controlled trial of an HIV behavioural intervention. A total of 1370 male volunteers were recruited from 70 rural South African villages. They completed a questionnaire asking about background, sexual practices and perpetration of rape and intimate partner violence. Among these men 16.3% had raped a non-partner, or participated in a form of gang rape; 8.4% had been sexually violent towards an intimate partner; and 79.1% had done neither. The mean age of first rape was 17 years. There was overlap between rape of a non-partner and partner, in that 44.3% of men who raped an intimate partner had also raped a non-partner, but overall the great majority of men who raped did not disclose both types of rape. The factors associated with rape of an intimate partner and non-partner had similarities and differences. After adjusting for the other variables, both forms of rape were strongly associated with ever having been physically violent to a partner, having had transactional sex with a casual partner and more sexual partners. Non-partner rape was also associated with peer-related variables, including gang membership and peer pressure to have sex, and also drug use. Non-partner rape was more common among wealthier and relatively more socially advantaged men. Both types of rape were associated with having more adverse childhood experiences. There was considerable overlap between rape-associated factors and known HIV risk factors, suggesting a need for further research on the interface of rape and HIV, and integrated prevention programming.

Gender inequalities, intimate partner violence and HIV preventive practices: findings of a South African cross-sectional study.

The aim of the paper is to investigate associations between a range of markers of gender inequity, including financial, psychological and physical violence, and two proximal practices in HIV prevention, namely discussion of HIV between partners and the woman suggesting condom use. The paper presents an analysis of data from a cross-sectional study of a representative sample of women from three South African Provinces which was primarily undertaken as an epidemiological study of gender-based violence. A multi-stage sampling design was used with clusters sampled with probability proportional to number of households. Households were randomly selected from within clusters. One randomly selected woman aged 18-49 years was interviewed in each selected home. One thousand three hundred and six women were interviewed (90.3% of eligible women). One thousand one hundred sixty four women had a partner in the previous year and were asked questions related to HIV prevention and gender inequalities in the relationship. The results indicate that discussion of HIV was significantly positively associated with education, living in Mpumalanga Province, the man being a migrant, the woman having multiple partners in the past year and having no confidante. It was significantly negatively associated with living in the Northern Province, the relationship being poor and there being a substantial age difference between partners. The woman suggesting condom use was significantly positively associated with her education, her having multiple partners, domestic violence prior to the past year and financial abuse. It was negatively associated with the relationship being poor. We conclude that this suggests that some indicators of gender inequalities are significantly associated with discussion of HIV and condom use but the direction of association found was both positive and negative. This highlights the need for a more nuanced understanding of gender inequalities and their relationship to HIV risk. Suggestions for key research questions are made.