Mark Colvin

Hierarchical Targeting of Subtype C Human Immunodeficiency Virus Type 1 Proteins by CD8+ T Cells: Correlation with Viral Load

ABSTRACT 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.

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 Scotts 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.

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.

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.

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.

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.

HIV infection and asymptomatic sexually transmitted infections in a rural South African community

The objective was to determine the prevalence of HIV and other sexually transmitted infections STIs in a rural community. A population based survey of adults in 110 homesteads was conducted in 1995. A questionnaire on demographics, sexual practices and history of STDs was administered. Neisseria gonorrhoeae and Chlamydia trachomatis infections were detected using ligase chain reaction LCR assay of urine. The seroprevalence of syphilis rapid plasma reagin RPR and Treponema pallidum haemagglutination assay TPHA and HIV infection ELISA was determined. Among 259 subjects the prevalence of HIV was 10.5 , N. gonorrhoeae 4.5 , C. trachomatis 6.1 and active syphilis 8.8 . All infections were asymptomatic. Forty per cent of sexually active men had more than one concurrent sexual partner. Only 14 of subjects had ever used condoms. The STI epidemic is being promoted by high levels of asymptomatic infections, high partner concurrency and low condom use.

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.

Neuropsychological function in solvent-exposed South African paint makers.

Neuropsychological and neurological function were investigated in 228 organic solvent exposed paint manufacturing workers in two factories. Solvent exposure was expressed as both American Conference of Governmental Industrial Hygienists 1990 Threshold Limit Value equivalents and total hydrocarbon parts per million. The World Health Organization (WHO) neurobehavioral core test battery, the Neurobehavioural Evaluation System--2 (NES-2), and the UNISA Neuropsychological Assessment Procedure (UNAP) were used to measure outcomes, and a Vibratron II was used to measure peripheral vibration sensation. Exposures were generally below the Threshold Limit Value, and no exposure effect was found. Possible explanations for this finding are discussed, including low exposure, exposure, and outcome misclassification, together with inappropriateness, nonvalidity, and relative insensitivity of neuropsychological tests. Only age predicted Vibratron score. Some tests were clearly inappropriate for use in developing countries. Neuropsychological tests were sensitive to educational level, age, alcohol consumption, and cultural indicators. The WHO tests in particular showed good construct validity for neuropsychological functions and should be more formally validated for use in developing countries. Nevertheless, a major problem of cultural dependence is evident for all neuropsychological tests used in this study, and methods for bypassing this problem in less developed settings are discussed.

Social factors affecting HIV/AIDS in South Africa: Editorial overview

In the absence of a straightforward medical inoculation or cure, understanding of the spread of HIV/AIDS and advice about how to intervene to limit its spread should be largely social scientific in nature. Therefore, the social sciences should provide the main components of the relevant knowledge~base. The very considerable regional differences of social phenomena require a particu~ lar mobilisation of social science knowledge about each particular society or regional grouping of like societies. This special issue is a means through which the voices of some of Southern Africas social scientists can combine to be better heard. Sharp distinctions between bio~medical and so~ cia! scientific knowledge should not be drawn, and the knowledge of both must be combined. Biomedical factors must be familiar to social scientists, and in particular they must be aware that much of the social understanding of diseases is in fact contributed by medical scientists. South Africa, more broadly southern Africa, and even more broadly sub-Saharan Africa (SSA), with the largest number of HIV -infected people in the world, and with one of the fastest growing rates of prevalence and incidence, seems set to plunge on further into the depths of this pandemic, with catastrophic consequences. This crisis has so far been met by rather limited policy and programme responses, and with a disjointed strategy in developing appropriate research, whether bio-medical research or social science in nature. Of course, there has been much research carried out in South Africa, but for the most part this has been ad hoc or piecemeal, and has not been brought together within an overarching framework. It is the objective of this collection to endeavour to bring together important social science material related to HIV/AIDS within Southern Africa and to indicate on the one hand where this has begun to cumulate, and on the other hand where the more important gaps still lie.