Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women.

BACKGROUND: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies. METHODS: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014. RESULTS: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/µl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype. CONCLUSIONS: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.

Strengthening HIV services for pregnant women: an opportunity to reduce maternal mortality rates in Southern Africa/sub-Saharan Africa.

Reliable data from South Africa emanating from WHO recommendations for the Safe Motherhood programme underscores HIV/AIDS as the most common cause of maternal deaths. The strengthening of HIV services for pregnant women especially in countries with a high burden of HIV infection will reduce HIV-related and un-related maternal mortality rates. High-quality and complete data on maternal deaths is a critical foundation for reliably monitoring temporal trends in maternal deaths, and causes thereof, but needs substantial strengthening in many resource-constrained settings. HIV/AIDS is an increasing contributor to direct and indirect causes of maternal deaths in sub-Saharan Africa. A review of published data on maternal deaths and its association with HIV shows that reliable data come from the Confidential Enquiries into Maternal Deaths from South Africa, population-based surveys in sentinel populations, and facility-based data. Despite an increase in knowledge of the HIV status of pregnant women and the initiation of antiretroviral treatment, reversals in trends towards increased maternal deaths are not being observed. The strengthening of HIV services provides an opportunity to alter HIV epidemic trajectories and reduce maternal deaths.

Screening for 'window-period' acute HIV infection among pregnant women in rural South Africa.

OBJECTIVES: The aim of this study was to evaluate the HIV-1 RNA pooled nucleic acid amplification testing (NAAT) strategy to screen pregnant women in the 'window period' of acute HIV infection (AHI) in rural South Africa. METHODS: In 2007 and 2008, 750 consecutive pregnant women on their first antenatal care visit to a primary health care clinic were tested anonymously for HIV infection. HIV-1 RNA pooled NAAT was performed on HIV antibody-negative samples. All positive pools were tested individually and positive samples were classified as incident cases to calculate HIV incidence. RESULTS: The overall HIV prevalence was 37.3% [95% confidence interval (CI) 34.3­41.3]. Of the 467 HIV antibody-negative samples, four (0.9%) were HIV-1 RNA-positive. The mean viral load in the four samples was 386 260 HIV-1 RNA copies/mL (range 64 200­1 228130). The HIV incidence was 11.2%per year (95% CI 0.3­22.1) and all women with AHI were 21 years of age. CONCLUSIONS: Identifying AHI in pregnancy is important for health interventions to reduce perinatal and heterosexual transmission of HIV, and to estimate HIV incidence for epidemiological surveillance.

Expanding HIV surveillance to include TB patients in resource-limited settings with a generalized epidemic.

Screening of antenatal clinic attendees is central to monitoring the human immunodeficiency virus (HIV) epidemic. However, recent evidence suggests that declining fertility rates are affecting the reliability of antenatal clinic surveys as the epidemic matures. Population-based HIV surveys, while ideal, are resource-intensive, necessitating newer, cost-effective approaches. Unlinked anonymous testing for HIV in sputum of tuberculosis (TB) patients serves as reliable proxy for estimating the burden of symptomatic HIV disease and is a potential adjunct to current surveillance efforts. Unlinked anonymous testing for HIV surveillance in KwaZulu-Natal, South Africa, the epicentre of the global epidemic, is justified, as data from the largest urban TB referral clinic indicate that only 22% of TB patients uptake voluntary HIV testing.

Opportunities for treating sexually transmitted infections and reducing HIV risk in rural South Africa.

AIM: This paper is a report of a study to determine the aetiological distribution of sexually transmitted infections and prevalence of human immunodeficiency virus infection in selected primary health care clinic attendees. BACKGROUND: South Africa has a high prevalence of human immunodeficiency virus and other sexually transmitted infections. Sexually transmitted infections are managed syndromically in the public sector as part of the essential nurse-driven primary care services provided at no cost to the client. METHOD: This cross-sectional study was conducted in a rural community in South Africa between September and November 2002. A total of 277 consenting women were recruited. Vulvo-vaginal swabs were collected for screening for Neisseriae gonorrheae, Chlamydia trachomatis and Trichomonas vaginalis using DNA amplification methods and Gram stain with Nugent's score for the diagnosis of bacterial vaginosis. Seroprevalence of syphilis and human immunodeficiency virus infection were determined. FINDINGS: The overall prevalence of human immunodeficiency virus in the study was 43.7% (95% confidence interval 37.6-50.0) with the prevalence in family planning clinic attendees 45.5% (95% confidence interval 38.9-52.3) and antenatal clinic attendees 33.3% (95% confidence interval 19.6-50.3). The prevalence of sexually transmitted infections amongst both the antenatal clinic and family planning attendees accounted for at least 70% of cases. Fifty per cent of women had one recognized sexually transmitted infection with 17.9% of the family planning and 14.5% of the antenatal clinic attendees having infections from two recognized pathogens. All infections were asymptomatic. CONCLUSION: Nurse-driven antenatal and family planning services provide a useful opportunity for integrating reproductive health services, human immunodeficiency virus voluntary counselling and testing and treatment of sexually transmitted infections.

TB treatment outcomes following directly-observed treatment at an urban outpatient specialist TB facility in South Africa.

The treatment of 450 consecutive new patients with pulmonary TB was evaluated to determine outcome following directly-observed treatment. In all, 176 (39.1%) patients were cured, 23 (5.1%) completed treatment, 80 (17.8%) defaulted treatment, 24 (5.3%) died, 54 (12.0%) were lost to follow-up and 93 (20.7%) were transferred out. Increasing age was significant for death. Males were more likely to default and those with negative pretreatment sputum smears and those who were unemployed were more likely to be lost to follow-up. The overall treatment success rate remains low. Our data suggests that greater emphasis is needed to improve TB treatment success.

Breaking new ground--are changes in immunization services needed for the introduction of future HIV/AIDS vaccines and other new vaccines targeted at adolescents?

A safe, effective and accessible preventive vaccine is our best long-term hope for the control of the HIV/AIDS pandemic. Once the first generation of HIV vaccines are developed, many questions remain unanswered regarding their administration. For instance, which vaccines should be given to whom at what age and how many doses? We argue that pre- and early-adolescents will be one of the main target groups for future HIV vaccines, that is, before the age of exposure to the virus. Historically, immunization has mainly focused on infants. Indeed, vaccines have only occasionally been systematically targeted at adolescents, even in industrialized countries. Delivering vaccines to pre-adolescents and adolescents in developing countries would, to a great extent, be a new challenge. But it is not just HIV/AIDS vaccines that are coming down the pipeline. Herpes simplex type2 (HSV-2) and human papillomavirus (HPV) vaccines are also among the exciting candidate vaccines that may be the agents of change needed to encourage even the poorest countries to develop strategies for reaching adolescents with vaccines and other health services in the coming decade. Together, they may also provide the impetus for changing the paradigm for how vaccines are administered. Not only will more antigens be included in national immunization schedules, but the age of target groups will range much more widely than at present, encompassing older children, adolescents and young adults. While presenting major difficulties for delivery, these new ingredients also offer stimulating opportunities to completely rethink how vaccines are presented, administered and delivered. We predict that even the poorest countries will be looking to developing integrated, sustainable strategies for reaching pre-adolescents and adolescents with vaccines in the coming decade.

Microbicide research and development--where to?

PURPOSE: Against the backdrop of increasing numbers of HIV infections in women and the limitations of current safer sex messages, several calls have been made for the development of women-initiated methods of prevention as an essential component of the armamentarium to reduce women's vulnerability of acquiring infection with HIV. An effective microbicide is a critical survival tool in instances and situations where existing proven prevention strategies have failed to be adopted. METHOD: The results of published N-9 clinical trials in terms of anti-HIV activity, safety data, and anti-sexually transmitted infection (STI) activity are discussed. RESULTS: There is no evidence of efficacy against HIV in three clinical trials, there is scanty evidence for protection against STIs, and there is considerable evidence of dose-related adverse effects. CONCLUSION: During this time, a vast array of potential microbicides with differing modes of action have been discovered, and some have undergone preclinical and early clinical testing. Effort, time, and resources might be better spent on advancing preclinical and clinical testing of these other candidate microbicides.

Phase 1 trial of nonoxynol-9 film among sex workers in South Africa.

OBJECTIVES: To assess the acceptability and safety of a vaginal nonoxynol-9 film in a group of sex workers at a truck stop in South Africa. DESIGN: A randomized double-blinded crossover trial was conducted between April 1995 and July 1995. INTERVENTION: Seventy-two mg nonoxynol-9 film and an identical glycerine placebo film. METHODS: Following informed consent, each study participant was randomly assigned the designated pre-coded film for 1 month. The second month was a film-free washout period and the participants used the alternate film in the third month. Besides measuring behavioural and clinical outcomes, colposcopy examination for genital lesions, serology and microbiology investigations for sexually transmitted diseases and semi-quantitative PCR for vaginal HIV load estimates were performed. RESULTS: Twenty women participated in the study. The women reported, on average, 19 sexual encounters per week. Vaginal intercourse was protected 25% of the time by condoms. On average, 11 vaginal films, either nonoxynol-9 or placebos were inserted per week. There were no statistically significant differences between the two treatment groups for genital lesions (P = 0.29), reported side effects (P = 0.73), and viral load (P = 0.9). However, the proportions of clinically detected genital lesions (six out of eight versus two out of eight) and self-reported side-effects (five out of eight versus three out of eight) were higher in the nonoxynol-9 group when compared with the placebo group. Incident sexually transmitted diseases occurred more frequently in the placebo group. An increased viral load was associated with the development of a genital lesion (relative risk, 6.0; 95% confidence interval, 0.81-44.4). CONCLUSIONS: The 72 mg film formulation of nonoxynol-9 was an acceptable product for use in this population of sex workers. Although no statistically significant differences in adverse outcomes were detected, clinically there appeared to be an increase in minor lesions and self-reported side-effects with nonoxynol-9 and less protection against sexually transmitted diseases with the placebo. Furthermore, HIV shedding was correlated with the presence of incident vaginal or cervical lesions. This brings into question the potential narrow margin of safety for this product; additional Phase 2 studies are therefore required.

Informed consent for HIV testing in a South African hospital: is it truly informed and truly voluntary?

OBJECTIVE: The purpose of this study was to assess informed consent to human immunodeficiency virus (HIV) testing in a perinatal HIV transmission study in a major referral hospital serving a largely Black population in South Africa. METHODS: First-time antenatal clinic attenders who were randomly selected from those enrolled in the perinatal HIV study (n = 56) answered questionnaires before and after counseling. RESULTS: Knowledge of HIV transmission and prevention, high at the outset, was little improved after counseling. The acceptance rate for HIV testing was high. Despite assurances that participation was voluntary, 88% of the women said they felt compelled to participate in the study. CONCLUSIONS: Informed consent in this setting was truly informed but not truly voluntary.

Government responses to HIV/AIDS in Africa: what have we learnt?

While we should not lose sight of the development of vaccines and cures, more immediate priorities include the implementation of effective STD control. The syndromic management approach developed in Zimbabwe to overcome laboratory constraints is a cost-effective way of managing STD. Of urgency is the integration of STD services into primary health-care services, appropriate training of staff, adequate provision and control over drugs and condoms, and incorporation of traditional healers and community-based education on STD. A second area of priority is the strengthening of the interaction between prevention, care and support activities, which act in synergy. Effective prevention and care require easy access to testing facilities with pre- and post-test counselling, appropriate structures and services to provide affordable and sustained care and support to those found to be infected with HIV, provision of drugs for the treatment of opportunistic infections, and the creation of a social environment and a legislation which protect against any form of discrimination the rights of people living with HIV, their sexual partners and their families.

Unsustainability of a measles immunisation campaign--rise in measles incidence within 2 years of the campaign.

The 1990 national mass measles immunisation campaign resulted in a marked reduction in measles incidence in Natal/KwaZulu in the first 6 months after the campaign. Data from the measles ward admissions book at Clairwood Hospital were collated for the period 1 January 1989 to 31 May 1992 to assess the sustainability of the effects of the campaign. For the first 12 months after the campaign, measles admissions were consistently low. Thereafter, the number increased steadily, rising sharply to above pre-campaign levels 21 months after the campaign. The age distribution of measles patients indicated that the initial fall in the 10-12-month age group had been reversed in the second year after the campaign, suggesting that the high vaccination coverage achieved for this age group during the campaign had not been maintained. Measles admissions to Clairwood Hospital indicate that the effect of the measles immunisation campaign has not been sustained and that urgent action is required to avert a possible epidemic.

Seroprevalence of HIV infection in rural South Africa.

OBJECTIVES: To establish the prevalence of HIV infection in rural South Africa and to investigate demographic factors that influence this prevalence. DESIGN: An anonymous HIV seroprevalence survey was performed in conjunction with a population-based malaria surveillance programme. SETTING: The rural area of northern Natal/KwaZulu, South Africa. PARTICIPANTS: A total of 5023 black African participants were recruited by malaria surveillance agents during house-to-house visits; each house in an endemic malaria area is visited approximately once every 6 weeks. Participants included 4044 healthy and 979 febrile individuals (i.e., suspected of having malaria). MAIN OUTCOME MEASURES: HIV-1 and HIV-2 serological status, degree of mobility, age and sex. RESULTS: Sixty of the 5023 blood specimens were confirmed to be HIV-1-antibody-positive by Western blot, an overall prevalence of 1.2% (95% confidence interval, 0.9-1.5). None of the specimens was positive for HIV-2 antibodies. After adjusting for age, presence of fever and migrancy, women had a 3.2-fold higher prevalence of HIV-1 infection than men. HIV-1 infection was approximately three times more common among subjects who had changed their place of residence recently (2.9 versus 1.0%, P < 0.01). CONCLUSIONS: The prevalence of HIV-1 infection is higher among women than men resident in rural Natal/KwaZulu, South Africa. This is at least in part the result of oscillatory migration, particularly of men who work in urban areas but have families and homes in rural areas. Migration is associated with a higher prevalence of HIV-1 infection, suggesting that improving social conditions so that families are not separated and become settled in their communities is one way to help reduce the spread of HIV-1.

PIP: As part of a population-based malaria surveillance program in late 1990, surveillance agents took blood samples from 979 people who had had a fever within the last 2 weeks and from 4044 healthy people during regular house-to-house visits in rural northern Natal/KwaZulu, South Africa, to determine HIV seroprevalence and risk factors of HIV infection. 60 (1.2%) people were HIV-1 seropositive. No one had HIV-2 infection. Febrile people had a 30% higher sex-adjusted relative risk (RR) of HIV-1 infection than healthy individuals, but this increase was insignificant. Women were at greater risk of HIV-1 infection than men (1.6% vs. 0.4%; age-adjusted RR = 3.8). In fact, this risk still existed when the researchers controlled for fever (RR = 3.75) and migrancy (RR = 3.2). The fall in the RR for women from 3.8 to 3.2 when controlled for migrancy suggested an underrepresentation of migrant male workers in the study sample. 2.3% of the women in their childbearing years (15-44) were HIV-1 seropositive, indicating an increased likelihood of transmission of HIV-1 to newborns. The youngest person afflicted with HIV-1 was a 12-year-old female and the oldest was a 66-year-old woman. No 10-to-19-year-old males tested HIV-1 positive, while 1.7% of the 10-to-19-year-old females did, suggesting that the young females had sex with older men. This may have indicated teenage prostitution and sexual abuse. 2.9% of the people who changed their place of residence within the last year (migrancy) had HIV-1 infection. For women it was linked to a 2.4 times higher RR (age-adjusted) of HIV-1 infection. For men, the age-adjusted RR was even greater (7.3). Even though HIV-1 seroprevalence was about 45% greater in areas crossed by the main national road than it was in other areas (1.3% vs. 0.9%), the difference was not significant. Since migrants were a key source of HIV-1 infection, improvement in social conditions, allowing families to live together and to settle in their communities, may reduce HIV-1 transmission.

Teenagers seeking condoms at family planning services. Part I. A user's perspective.

The promotion of condom use is an essential part of any AIDS prevention programme. By distributing condoms and promoting their use, clinics that provide family planning services can play an important role in preventing the spread of AIDS. This study assesses the accessibility of condoms to teenagers at selected family planning services in Durban. Twelve randomly selected clinics in Durban were visited by each of 4 teenage fieldworkers. During these visits, the fieldworkers' experiences were recorded in detailed notes which were subsequently analysed for content. The fieldworkers experienced difficulty in locating a few of the clinics and some were embarrassed by security staff. The two female fieldworkers, in particular, were intimidated by their reception at the clinics and found resistance to their requests for condoms. On two occasions, supplies of condoms had run out. When condoms were available, they were distributed in a setting that lacked privacy. Information on how to use condoms, if offered at all, was supplied by way of pamphlets and information on AIDS was rarely offered. Overall, the experiences of the fieldworkers indicated that it was difficult for teenagers to obtain condoms from clinics providing family planning services in Durban. It is recommended that there be signs indicating the location of the clinics, and that privacy be ensured and adequate stocks of condoms maintained. Most importantly, clinic staff need to use every opportunity to discuss AIDS prevention with teenagers attending the clinic.