Goodstart: a cluster randomised effectiveness trial of an integrated, community-based package for maternal and newborn care, with prevention of mother-to-child transmission of HIV in a South African township.

BACKGROUND: Progress towards MDG4 for child survival in South Africa requires effective prevention of mother-to-child transmission (PMTCT) of HIV including increasing exclusive breastfeeding, as well as a new focus on reducing neonatal deaths. This necessitates increased focus on the pregnancy and early post-natal periods, developing and scaling up appropriate models of community-based care, especially to reach the peri-urban poor. METHODS: We used a randomised controlled trial with 30 clusters (15 in each arm) to evaluate an integrated, scalable package providing two pregnancy visits and five post-natal home visits delivered by community health workers in Umlazi, Durban, South Africa. Primary outcomes were exclusive and appropriate infant feeding at 12 weeks post-natally and HIV-free infant survival. RESULTS: At 12 weeks of infant age, the intervention was effective in almost doubling the rate of exclusive breastfeeding (risk ratio 1.92; 95% CI: 1.59-2.33) and increasing infant weight and length-for-age z-scores (weight difference 0.09; 95% CI: 0.00-0.18, length difference 0.11; 95% CI: 0.03-0.19). No difference was seen between study arms in HIV-free survival. Women in the intervention arm were also more likely to take their infant to the clinic within the first week of life (risk ratio 1.10; 95% CI: 1.04-1.18). CONCLUSIONS: The trial coincided with national scale up of ARVs for PMTCT, and this could have diluted the effect of the intervention on HIV-free survival. We have demonstrated that implementation of a pro-poor integrated PMTCT and maternal, neonatal and child health home visiting model is feasible and effective. This trial could inform national primary healthcare reengineering strategies in favour of home visits. The dose effect on exclusive breastfeeding is notable as improving exclusive breastfeeding has been resistant to change in other studies targeting urban poor families.

Value of a mobile information system to improve quality of care by community health workers.

INTRODUCTION: We will be unable to achieve sustained impact on health outcomes with community health worker (CHW)-based interventions unless we bridge the gap between small scale efficacy studies and large scale interventions. Effective strategies to support the management of CHWs are central to bridging the gap. Mobile phones are broadly available, particularly in low and middle income countries (LAMIC's), where the penetration rate approaches 100%. In this article we describe how mobile phones may be combined with mobile web-based technology to assist in the management of CHWs in two projects in South Africa. METHODS: This paper is a descriptive one, drawing lessons from two Randomised Controlled Trials (RCT's), outlining how a mobile phone information system can be utilized to enhance the quality of health interventions. We organized our comprehensive management and supervision system around a previously published management framework. The system is composed of mobile phones utilized by CHWs and a web-based interface utilized by CHW supervisors. Computerized algorithms were designed with intervention and assessment protocols to aid in the real-time supervision and management of CHWs. RESULTS: CHWs used mobile phones to initiate intervention visits and trigger content to be delivered during the course of intervention visits. Supervisors used the web-based interface for real-time monitoring of the location, timing, and content of intervention visits. Additional real-time support was provided through direct support calls in the event of crises in the field. CONCLUSION: Mobile phone-based information system platforms offer significant opportunities to improve CHW-delivered interventions. The extent to which these efficiency gains can be translated into realized health gains for communities is yet to be tested.

Early cessation of breastfeeding amongst women in South Africa: an area needing urgent attention to improve child health.

BACKGROUND: Breastfeeding is a critical component of interventions to reduce child mortality. Exclusive breastfeeding practice is extremely low in South Africa and there has been no improvement in this over the past ten years largely due to fears of HIV transmission. Early cessation of breastfeeding has been found to have negative effects on child morbidity and survival in several studies in Africa. This paper reports on determinants of early breastfeeding cessation among women in South Africa. METHODS: This is a sub group analysis of a community-based cluster-randomized trial (PROMISE EBF) promoting exclusive breastfeeding in three South African sites (Paarl in the Western Cape Province, and Umlazi and Rietvlei in KwaZulu-Natal) between 2006 and 2008 (ClinicalTrials.gov no: NCT00397150). Infant feeding recall of 22 food and fluid items was collected at 3, 6, 12 and 24 weeks postpartum. Women's experiences of breast health problems were also collected at the same time points. 999 women who ever breastfed were included in the analysis. Univariable and multivariable logistic regression analysis adjusting for site, arm and cluster, was performed to determine predictors of stopping breastfeeding by 12 weeks postpartum. RESULTS: By 12 weeks postpartum, 20% of HIV-negative women and 40% of HIV-positive women had stopped all breastfeeding. About a third of women introduced other fluids, most commonly formula milk, within the first 3 days after birth. Antenatal intention not to breastfeed and being undecided about how to feed were most strongly associated with stopping breastfeeding by 12 weeks (Adjusted odds ratio, AOR 5.6, 95% CI 3.4 - 9.5 and AOR 4.1, 95% CI 1.6 - 10.8, respectively). Also important was self-reported breast health problems associated with a 3-fold risk of stopping breastfeeding (AOR 3.1, 95%CI 1.7 - 5.7) and the mother having her own income doubled the risk of stopping breastfeeding (AOR 1.9, 95% CI 1.3 - 2.8). CONCLUSION: Early cessation of breastfeeding is common amongst both HIV-negative and positive women in South Africa. There is an urgent need to improve antenatal breastfeeding counselling taking into account the challenges faced by working women as well as early postnatal lactation support to prevent breast health problems.

Infant feeding practices at routine PMTCT sites, South Africa: results of a prospective observational study amongst HIV exposed and unexposed infants - birth to 9 months.

BACKGROUND: We sought to investigate infant feeding practices amongst HIV-positive and -negative mothers (0-9 months postpartum) and describe the association between infant feeding practices and HIV-free survival. METHODS: Infant feeding data from a prospective observational cohort study conducted at three (of 18) purposively-selected routine South African PMTCT sites, 2002-2003, were analysed. Infant feeding data (previous 4 days) were gathered during home visits at 3, 5, 7, 9, 12, 16, 20, 24, 28, 32 and 36 weeks postpartum. Four feeding groups were of interest, namely exclusive breastfeeding, mixed breastfeeding, exclusive formula feeding and mixed formula feeding. Cox proportional hazards models were fitted to investigate associations between feeding practices (0-12 weeks) and infant HIV-free survival. RESULTS: Six hundred and sixty five HIV-positive and 218 HIV-negative women were recruited antenatally and followed-up until 36 weeks postpartum. Amongst mothers who breastfed between 3 weeks and 6 months postpartum, significantly more HIV-positive mothers practiced exclusive breastfeeding compared with HIV-negative: at 3 weeks 130 (42%) versus 33 (17%) (p < 0.01); this dropped to 17 (11%) versus 1 (0.7%) by four months postpartum. Amongst mothers practicing mixed breastfeeding between 3 weeks and 6 months postpartum, significantly more HIV-negative mothers used commercially available breast milk substitutes (p < 0.02) and use of these peaked between 9 and 12 weeks. The probability of postnatal HIV or death was lowest amongst infants living in the best resourced site who avoided breastfeeding, and highest amongst infants living in the rural site who stopped breastfeeding early (mean and standard deviations: 10.7% ± 3% versus 46% ± 11%). CONCLUSIONS: Although feeding practices were poor amongst HIV-positive and -negative mothers, HIV-positive mothers undertake safer infant feeding practices, possibly due to counseling provided through the routine PMTCT programme. The data on differences in infant outcome by feeding practice and site validate the WHO 2009 recommendations that site differences should guide feeding practices amongst HIV-positive mothers. Strong interventions are needed to promote exclusive breastfeeding (to 6 months) with continued breastfeeding thereafter amongst HIV-negative motherswho are still the majority of mothers even in high HIV prevalence setting like South Africa.

Human leukocyte antigen class I (A, B, C) and II (DRB1) diversity in the black and Caucasian South African population.

A cross-section of black and Caucasian South Africans (N = 302) were genotyped at high resolution (class I HLA-A, -B, -C and class II HLA-DRB1). Five new class I alleles (A*30:01:02, A*30:02:02, A*68:27, B*42:06, and B*45:07) and one new confirmatory allele (A*29:11) were identified in the black population. Alleles and haplotypes showed expected differences between the black and Caucasian populations, with the black population, on average, showing a broader spectrum of allele representation (less single allele dominance). The most prevalent alleles at the four loci in the black population were A*30:01, B*58:02, C*06:02, and DRB1*13:01 and in the Caucasian population were A*02:01:01, B*07:02:01, C*07:01, and DRB1*03:01. HLA-B, and HLA-C loci showed the strongest overall linkage disequilibrium (LD) and HLA-B/HLA-C two locus haplotypes also showed the strongest LD (D'(ij)) in both population groups. Bw allotype representation was similar between the two populations; however C allotypes differed significantly (C1 higher representation in Caucasians; C2 higher representation in blacks). HLA-A Supertype family phenotypic frequencies did not differ between the two populations, but four (B08, B27, B58, and B62) HLA-B Supertype families differed significantly. However, vaccine coverage estimation came close to 100% in both population groups, with inclusion of only four Supertype families (A1, A2, B7, B58).

An effectiveness study of an integrated, community-based package for maternal, newborn, child and HIV care in South Africa: study protocol for a randomized controlled trial.

BACKGROUND: Progress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission (PMTCT) of HIV and also addressing neonatal mortality. This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable, community-based care in South Africa in order to reach the poor. A number of key implementation gaps affecting progress have been identified. Implementation gaps for HIV prevention in neonates; implementation gaps for neonatal care especially home postnatal care; and implementation gaps for maternal mental health support. We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission (PMTCT) of HIV. METHODS: The trial is a cluster randomized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal, South Africa. The trial consists of 30 randomized clusters (15 in each arm). A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed. Sample size was based on increasing HIV-free survival from 74% to 84%, and calculated to be 120 pregnant women per cluster. Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally. The intervention is home based with community health workers delivering two antenatal visits, a postnatal visit within 48 hours of birth, and a further four visits during the first two months of the infants life. We are undertaking programmatic and cost effectiveness analysis to cost the intervention. DISCUSSION: The question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up, which requires effectiveness studies in a health systems context, adapting and testing Asian community-based studies in various African contexts.

Operational effectiveness of guidelines on complete breast-feeding cessation to reduce mother-to-child transmission of HIV: results from a prospective observational cohort study at routine prevention of mother-to-child transmission sites, South Africa.

OBJECTIVE: Until 2006, HIV-positive women who chose to exclusively breast-feed were advised to completely stop breast-feeding by 6 months. We investigated operational feasibility and predictors of complete breast-feeding cessation (CBC). DESIGN: A prospective observational cohort study at 3 routine prevention of mother-to-child transmission sites, South Africa. METHODS: Data on "complete breast-feeding cessation at 24 weeks" and "not breast-feeding (NBF) for 4 days before the last follow-up visit at or before 24 weeks" were gathered during home visits (3, 5, 7, 9, 12, 16, 20, and 24 weeks). The main subgroup of interest for this analysis was women practicing exclusive breast-feeding/predominant breast-feeding at 3 weeks. Univariate analysis, logistic regression, Kaplan-Meier Survival analysis, and Cox regression were performed. RESULTS: Eighty-eight women (43.6%) reported CBC. "Health staff suggesting formula use: [OR(a) 4.39 (1.76-10.97)] and "infant hospitalization" [OR(a) 3.27 (1.37-7.79)] were the only significant predictors of CBC. The probability of NBF at 5, 7, 9, 12, 16, 20, and 24 weeks was 2.8% [95% confidence interval (CI) 1.8% to 3.8%], 4.3% (3.0% to 5.6%), 5.9% (4.4% to 7.4%, 9.8% (7.9% to 11.7%), 16.1 (13.8% to 18.4%), 23.1% (20.5% to 25.7%), and 37.6% (34.6% to 40.6%), respectively. Infant HIV status [hazard ratio 5.5 95% CI 2.4 to 12.5] was the only predictor of infant death. NBF was not protective against 9-month infant HIV or death in univariate and multivariable analysis. CONCLUSIONS: At programmatic level, CBC by 24 weeks is uncommon, and success seems unrelated to predetermined social, economic, and environmental (acceptable, feasible, affordable, sustainable, and safe AFASS) criteria. Thus at this level, activities that encourage CBC (amongst women meeting AFASS criteria) need to be identified and tested.

The epidemiology of HIV in South African workplaces.

OBJECTIVE: To determine the prevalence and distribution of HIV in South African workplaces. DESIGN: : Cross-sectional HIV prevalence and knowledge, attitudes and practices surveys, conducted in 22 public and private sector organizations in all nine provinces of South Africa on full-time, formally employed personnel who provided consent to participate. OUTCOME MEASURES: The primary outcome was HIV prevalence. RESULTS: The crude HIV prevalence among the 32 015 participants was 10.9%. HIV prevalence was higher among men (11.3%) than among women (9.8%) and among black Africans (16.6%) than among other race groups (2.7%). Although managers and employees with post-school education had a lower HIV prevalence than lower skilled employees, this only partly accounted for the race differences. CONCLUSION: The HIV prevalence within an organization is not entirely explained by the race, age and sex structure of the workforce. This indicates that there is some other factor that is associated with the organization and has an impact on HIV prevalence.

An overview of HIV/AIDS workplace policies and programmes in southern Africa.

BACKGROUND: Workplace programmes refer to a range of company-based interventions including the institution of an HIV/AIDS policy, voluntary counselling and testing (VCT), and antiretroviral therapy (ART) provision. OBJECTIVE: To review the existing information on workplace policies and programmes in southern Africa, and ascertain the common accomplishments in and challenges to implementation and efficacy. METHODS: Given the paucity of peer-reviewed academic publications, information for this review was also drawn from working papers, symposia proceedings, and case studies. A convenience sample of 17 key informants was identified, and semi-structured interviews were conducted. RESULTS: Workplace policies and programmes of varying sophistication are proliferating in large companies and selected sectors. Accomplishments include the institution of a legal apparatus that safeguards against discriminatory practices, the high prevalence of HIV education programmes, the growing provision of VCT, and the development of supply-chain initiatives that may enable smaller companies to develop HIV programmes. Challenges include poor recognition and monitoring of legal violations by management and unions, lack of monitoring and evaluation (M&E) methodologies for workplace HIV prevention programmes, persistent stigma in the workplace resulting in poor uptake of HIV testing, and low enrollment into workplace ART programmes. CONCLUSION: The existing literature indicates a wide variation in workplace policies and programmes currently in place in southern Africa. The effectiveness of workplace interventions at the firm level, including prevention and treatment programmes is difficult to assess with currently available data. Further research on workplace programmes that addresses operational challenges to implementation and develops M&E strategies is urgently needed.

Effectiveness of the WHO/UNICEF guidelines on infant feeding for HIV-positive women: results from a prospective cohort study in South Africa.

BACKGROUND: The World Health Organization (WHO) and UNICEF recommend that HIV-positive women should avoid all breastfeeding only if replacement feeding is acceptable, feasible, affordable, sustainable and safe. Little is known about the effectiveness of the implementation of these guidelines in developing country settings. OBJECTIVE: To identify criteria to guide appropriate infant-feeding choices and to assess the effect of inappropriate choices on infant HIV-free survival. METHOD: Prospective cohort study of 635 HIV-positive mother-infant pairs across three sites in South Africa to assess mother to child transmission of HIV. Semistructured questionnaires were used during home visits between the antenatal period and 36 weeks after delivery to collect data concerning appropriateness of infant feeding choices based on the WHO/UNICEF recommendations. RESULTS: Three criteria were found to be associated with improved infant HIV-free survival amongst women choosing to formula feed: piped water; electricity, gas or paraffin for fuel; and disclosing HIV status. Using these criteria as a measure of appropriateness of choice: 95 of 311 women who met the criteria (30.5%) chose to breastfeed and 195 of 289 women who did not meet the criteria (67.4%) chose to formula feed. Infants of women who chose to formula feed without fulfilling these three criteria had the highest risk of HIV transmission/death (hazard ratio, 3.63; 95% confidence interval, 1.48-8.89). CONCLUSIONS: Within operational settings, the WHO/UNICEF guidelines were not being implemented effectively, leading to inappropriate infant-feeding choices and consequent lower infant HIV-free survival. Counselling of mothers should include an assessment of individual and environmental criteria to support appropriate infant-feeding choices.

Operational effectiveness of single-dose nevirapine in preventing mother-to-child transmission of HIV.

OBJECTIVE: To determine the operational effectiveness of the South African programme for preventing mother-to-child transmission (PMTCT) of HIV in reducing rates of early transmission of infection. METHODS: Participants were mother-infant pairs who participated in the South African PMTCT programme between October 2002 and November 2004. This was a prospective cohort study. Three sites in different provinces were selected to represent differences in socioeconomic status and HIV prevalence. Data on antenatal care and labour ward care were obtained from maternal interviews and from reviews of medical records. A total of 665 mother-infant pairs in which the mother was HIV-positive were recruited and 588 (88.4%) were followed up at 3 or 4 weeks postpartum to determine the HIV status and vital status of the infant. FINDINGS: Rural participants were significantly poorer and their health care was significantly worse. Women of higher socioeconomic status and those who received better counselling were more likely to be treated with nevirapine. Rates of early HIV transmission ranged from 8.6% to 13.7%. Maternal viral load was the only statistically significant risk factor for transmission. After adjusting for maternal viral load and prevalence of low birth weight, the odds of transmission were 1.8 times higher at the rural site. Controlling for having had > or = 4 antenatal visits and any delivery complication reduced the odds of transmission to 1.5 higher at the rural site. CONCLUSION: Rates of early transmission of HIV in an operational setting using single-dose nevirapine administered both to mother and child are similar to those obtained in clinical trials. Scaling up access to antiretroviral regimens for women will further reduce transmission to infants.

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.

Viral dynamics and CD4+ T cell counts in subtype C human immunodeficiency virus type 1-infected individuals from southern Africa.

Defining viral dynamics in natural infection is prognostic of disease progression and could prove to be important for vaccine trial design as viremia may be a likely secondary end point in phase III HIV efficacy trials. There are limited data available on the early course of plasma viral load in subtype C HIV-1 infection in Africa. Plasma viral load and CD4+ T cell counts were monitored in 51 recently infected subjects for 9 months. Individuals were recruited from four southern African countries: Zambia, Malawi, Zimbabwe, and South Africa and the median estimated time from seroconversion was 8.9 months (interquartile range, 5.7-14 months). All were infected with subtype C HIV-1 and median viral loads, measured using branched DNA, ranged from 3.82-4.02 log10 RNA copies/ml from 2-24 months after seroconversion. Viral loads significantly correlated with CD4+ cell counts (r=-0.5, p<0.0001; range, 376-364 cells/mm3) and mathematical modeling defined a median set point of 4.08 log10 (12 143 RNA copies/ml), which was attained approximately 17 months after seroconversion. Comparative measurements using three different viral load platforms (bDNA, Amplicor, and NucliSens) confirmed that viremia in subtype C HIV-1-infected individuals within the first 2 years of infection did not significantly differ from that found in early subtype B infection. In conclusion, the course of plasma viremia, as described in this study, will allow a useful baseline comparator for understanding disease progression in an African setting and may be useful in the design of HIV-1 vaccine trials in southern Africa.

Epidemiology of HIV in South Africa--results of a national, community-based survey.

OBJECTIVE: To determine HIV prevalence in the South African population and to investigate risk factors for HIV. METHODS: A national sample of 10 197 households was selected. One child (aged 2 - 14 years), one youth (15 - 24 years) and one adult (25 years and older) were randomly selected from each household. Consenting respondents were interviewed about their socio-demographic characteristics and asked to give an oral mucosal transudate sample to test anonymously for HIV. Differential response rates were compared using unweighted data. The Orasure HIV-1 device in combination with the Vironostika HIV UNI-Form II plus O enzyme-linked immunosorbent assay kits were used to collect oral fluid specimens for HIV testing. HIV prevalence within subgroups was compared using Rao and Scott's adjusted chi-square. Relative risk was calculated using Poisson regression. All analysis was on the weighted data. RESULTS: Of the 10 197 households selected, 7 249 (71.1%) were included in the study. Of the 13 518 individuals selected, 9 963 (73.7%) were interviewed. Of these, 8 428 (62.3%) agreed to HIV testing and had valid results. HIV prevalence in the general population was 11.4% (12.8% in females and 9.5% in males). Blacks had the highest prevalence (12.9%), compared with whites (6.2%), coloureds (6.1%) and Indians (1.6%). Informal settlements in urban areas had the highest HIV prevalence (21.6%). The findings of this study are consistent with South African Department of Health estimates based on the 2002 antenatal survey. CONCLUSION: The Nelson Mandela/Human Sciences Research Council survey included all race, sex and age groups. It is therefore the most reliable and valid source of information on the extent and distribution of the HIV epidemic in South Africa.

Novel and promiscuous CTL epitopes in conserved regions of Gag targeted by individuals with early subtype C HIV type 1 infection from southern Africa.

Characterization of optimal CTL epitopes in Gag can provide crucial information for evaluation of candidate vaccines in populations at the epicenter of the HIV-1 epidemic. We screened 38 individuals with recent subtype C HIV-1 infection using overlapping consensus C Gag peptides and hypothesized that unique HLA-restricting alleles in the southern African population would determine novel epitope identity. Seventy-four percent of individuals recognized at least one Gag peptide pool. Ten epitopic regions were identified across p17, p24, and p2p7p1p6, and greater than two-thirds of targeted regions were directed at: TGTEELRSLYNTVATLY (p17, 35%); GPKEPFRDYVDRFFKTLRAEQATQDV (p24, 19%); and RGGKLDKWEKIRLRPGGKKHYMLKHL (p17, 15%). After alignment of these epitopic regions with consensus M and a consensus subtype C sequence from the cohort, it was evident that the regions targeted were highly conserved. Fine epitope mapping revealed that five of nine identified optimal Gag epitopes were novel: HLVWASREL, LVWASRELERF, LYNTVATLY, PFRDYVDRFF, and TLRAEQATQD, and were restricted by unique HLA-Cw*08, HLA-A*30/B*57, HLA-A*29/B*44, and HLA-Cw*03 alleles, respectively. Notably, three of the mapped epitopes were restricted by more than one HLA allele. Although these epitopes were novel and restricted by unique HLA, they overlapped or were embedded within previously described CTL epitopes from subtype B HIV-1 infection. These data emphasize the promiscuous nature of epitope binding and support our hypothesis that HLA diversity between populations can shape fine epitope identity, but may not represent a constraint for universal recognition of Gag in highly conserved domains.

South African national household survey of HIV/AIDS prevalence, behavioural risks and mass media impact--detailed methodology and response rate results.

OBJECTIVES: To describe the methodology used in a recent survey of HIV/AIDS in South Africa and to present the response rates. METHODS: A cross-sectional, national household-based survey was conducted using second-generation surveillance procedures. A complex multistage sampling technique was used to create a master sample of 1,000 census enumerator areas out of a total of 86,000 nationally. Aerial photographs were taken and used to randomly select more than 10,197 households and ultimately 13,518 individuals from a sampling frame of 31,321 people. Phase 1 of the study involved notifying the household residents about the study and collecting key demographic information on respondents aged 2 years and older. This information was used to randomly select up to 3 respondents from each household: 1 adult (25 years and older), 1 youth (15-24 years), and 1 child (2-14 years). In phase 2 nurses interviewed respondents and collected oral fluid specimens for HIV testing. In the case of children aged 2-11 years, parents or guardians were interviewed, but HIV testing was performed on the selected children. Questionnaire data were anonymously linked with HIV test results. RESULTS: A total of 9,963 persons agreed to be interviewed and 8,840 were tested for HIV, yielding a response rate of 73.7% and 65.4% respectively. However, only 8,428 (62.3%) HIV test results were correctly matched with behavioural data. The results showed that those tested for HIV did not differ from those not tested in terms of key determinants. CONCLUSION: It is possible to use community-based surveys to study the prevalence of HIV in the general population.

Hierarchical targeting of subtype C human immunodeficiency virus type 1 proteins by CD8+ T cells: correlation with viral load.

An understanding of the relationship between the breadth and magnitude of T-cell epitope responses and viral loads is important for the design of effective vaccines. For this study, we screened a cohort of 46 subtype C human immunodeficiency virus type 1 (HIV-1)-infected individuals for T-cell responses against a panel of peptides corresponding to the complete subtype C genome. We used a gamma interferon ELISPOT assay to explore the hypothesis that patterns of T-cell responses across the expressed HIV-1 genome correlate with viral control. The estimated median time from seroconversion to response for the cohort was 13 months, and the order of cumulative T-cell responses against HIV proteins was as follows: Nef > Gag > Pol > Env > Vif > Rev > Vpr > Tat > Vpu. Nef was the most intensely targeted protein, with 97.5% of the epitopes being clustered within 119 amino acids, constituting almost one-third of the responses across the expressed genome. The second most targeted region was p24, comprising 17% of the responses. There was no correlation between viral load and the breadth of responses, but there was a weak positive correlation (r = 0.297; P = 0.034) between viral load and the total magnitude of responses, implying that the magnitude of T-cell recognition did not contribute to viral control. When hierarchical patterns of recognition were correlated with the viral load, preferential targeting of Gag was significantly (r = 0.445; P = 0.0025) associated with viral control. These data suggest that preferential targeting of Gag epitopes, rather than the breadth or magnitude of the response across the genome, may be an important marker of immune efficacy. These data have significance for the design of vaccines and for interpretation of vaccine-induced responses.

Sequence conservation and antibody cross-recognition of clade B human immunodeficiency virus (HIV) type 1 Tat protein in HIV-1-infected Italians, Ugandans, and South Africans.

We determined immune cross-recognition and the degree of Tat conservation in patients infected by local human immunodeficiency virus (HIV) type 1 strains. The data indicated a similar prevalence of total and epitope-specific anti-Tat IgG in 578 serum samples from HIV-infected Italian (n=302), Ugandan (n=139), and South African (n=137) subjects, using the same B clade Tat protein that is being used in vaccine trials. In particular, anti-Tat antibodies were detected in 13.2%, 10.8%, and 13.9% of HIV-1-infected individuals from Italy, Uganda, and South Africa, respectively. Sequence analysis results indicated a high similarity of Tat from the different circulating viruses with BH-10 Tat, particularly in the 1-58 amino acid region, which contains most of the immunogenic epitopes. These data indicate an effective cross-recognition of a B-clade laboratory strain-derived Tat protein vaccine by individuals infected with different local viruses, owing to the high similarity of Tat epitopes.