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Background and Objectives: The objective was to assess reliability of self-reported sexual histories among sexually transmitted disease clinic attendees who enrolled in a study in 1994.Goal Of This Study: Knowledge about the reliability of sexual data is important to decide whether these measures of sexual behavior can be used in epidemiologic studies of sexually transmitted diseases.Study Design: In 288 attendees, degree of agreement was assessed in responses to an identical set of sexual questions asked independently by a medical doctor and a public health nurse and in responses made by members of the same couple (n = 50) to a public health nurse.Results: In the test-retest comparison, high agreement was found for most questions: kappa-values and exact agreement ranged from 0.73 to 0.96 and 54% to 99%, respectively. Participants interviewed by the medical doctor reported significantly lower numbers of partners and a higher age at first intercourse. Stratified analyses showed variability in agreement across subgroups. Most consistent, women provided more reliable reports than men. In the comparison of couples, substantial agreement was found for the municipality where they met (88% agreement; kappa = 0.72) and contraceptive method (87% agreement; kappa = 0.60), but only moderate agreement was found for frequency of sexual intercourse (26% agreement; kappa = 0.50).Conclusion: The authors conclude that data on sexual behavior can be collected reliably among sexually transmitted disease clinic attendees, although reporting bias does occur. The frequency of sexual intercourse was not sufficiently reliable and should be interpreted as an estimate only. [ABSTRACT FROM AUTHOR]

Objective: Vaccine-induced CD8(+) T-cell responses in primates have been associated with a reduced simian immunodeficiency virus plasma viral load and enhanced T-cell responses, but cellular vaccines have shown limited success in human trials. We previously described HIV-specific T-cell responses in two groups of highly exposed, persistently seronegative Kenyan female sex workers, and a subset of these participants have subsequently acquired HIV. We examined the impact of pre-existing CD8(+) T-cell responses on post-acquisition outcomes., Design and Methods: HIV-specific CD8(+) T-cell responses had been examined in highly exposed, persistently seronegative participants from the Pumwani and Kibera cohorts, using a combination of virus-specific lysis, proliferation, interferon-gamma production, or all. Plasma viral load set point and HIV-specific T-cell proliferation and cytokine production were now examined post hoc by blinded investigators in the subset of participants who acquired HIV., Results: Pre-acquisition cellular immune assays and post-infection viral load were available for 46 participants, and HIV-specific CD8(+) T-cell responses had been detected in 25 of 46 (54%) participants. Pre-acquisition CD8(+) T-cell responses were associated with a lower post-acquisition HIV viral load set point in both cohorts (pooled analysis, 3.1 vs. 4.1 log(10) RNA copies/ml; P=0.0002) and with enhanced post-acquisition HIV-specific CD8(+) T-cell proliferation (3.8 vs. 1.0%, P=0.03), but with a trend to reduced post-acquisition CD8(+) T-cell interferon-gamma responses., Conclusion: HIV-specific CD8(+) T-cell responses prior to HIV acquisition were associated with a lower HIV viral load and an altered functional profile of post-acquisition CD8(+) T-cell responses.

Objectives: To examine the impact of an intensive HIV preventive intervention (IPI) among female sex workers (FSW) on community HIV transmission, as represented by HIV prevalence among young antenatal clinic (ANC) attenders in Karnataka state, south India., Methods: The IPI was initiated in 18 of the 27 districts in Karnataka in 2003, and was generally at scale by mid-2005, covering over 80% of the urban FSW population. We examined trends over time in HIV prevalence from annual HIV surveillance conducted among ANC attenders in Karnataka under the age of 25 years from 2003 to 2007, comparing the IPI with the other districts., Results: Overall, HIV prevalence among ANC attenders under 25 years of age declined from 1.40% to 0.77%. In a multivariate model, the decline in HIV prevalence in the IPI districts compared to the other districts was statistically significant (P = 0.01), with an adjusted annual odds ratio of 0.88 (95% CI 0.79-0.97). The decline in standardized HIV prevalence in the IPI districts over the period was 56%, compared to 5% in the non-IPI districts., Conclusions: Although this analysis is limited by lack of precise comparative data on intervention coverage and intensity, it supports the notion that scaled-up, intensive, targeted HIV preventive interventions among high-risk groups can have a measurable and relatively rapid impact on HIV transmission in the general population, particularly young sexually active populations as represented by ANC attenders. Such focused intervention programmes should be rapidly taken to scale in all HIV epidemics, and especially in concentrated epidemics such as in India.

Objective: A group of commercial sex workers in the Pumwani Sex Worker Cohort, established in 1985 in Nairobi, Kenya, remain HIV-1 uninfected despite heavy exposure to HIV-1 through active sex work. Previous studies showed that this resistance is associated with a strong CD4+ T-cell response, which suggested that human leukocyte antigen class II antigens are important in resistance/susceptibility to HIV-1 infection. DRB1 is the most polymorphic locus among class II genes and forms haplotypes with DRB3, DRB4 and DRB5. The aim of this study is to investigate the role of DRB alleles/haplotypes on resistance/susceptibility to HIV-1 infection., Design: In total, 1090 women enrolled in the Pumwani cohort were genotyped for DRB1, DRB3, DRB4 and DRB5 using a high-resolution sequence-based method. Allele/haplotype frequencies were compared between HIV-positive women and women who have remained HIV negative for more than 3 years despite frequent exposure., Methods: Human leukocyte antigen DRB genes were amplified, sequenced and genotyped using a two-step sequence-based method. Allele/haplotype frequencies were determined using PyPop32-0.6.0. Statistical analysis was conducted using SPSS 11.0 for Windows., Results: Three DRB1 alleles were associated with resistance: DRB1*010101 (P = 0.016; odd ratio (OR): 2.55; 95% confidence interval (CI): 1.16-5.61), DRB1*010201 (P = 0.019; OR: 1.86; 95% CI: 1.10-3.15), and DRB1*1102 (P = 0.025; OR: 1.72; 95% CI: 1.07-2.78). DRB1*030201 (P = 0.038; OR: 0.48; 95% CI: 0.23-0.98), DRB1*070101 (P = 0.035; OR: 0.54; 95% CI: 0.30-0.97), DRB1*1503 (P = 0.0004; OR: 0.34; 95% CI: 0.19-0.64), and DRB5*010101 (P = 0.001; OR: 0.37; 95% CI: 0.20-0.67) were associated with susceptibility. The haplotype DRB1*1102-DRB3*020201 was associated with HIV-1 resistance (P = 0.041; OR: 1.68; 95% CI: 1.02-2.78), whereas the haplotypes DRB1*070101-DRB4*01010101 (P = 0.041; OR: 0.52; 95% CI: 0.28-0.98) and DRB1*1503-DRB5*01010101 (P = 0.0002; OR: 0.30; 95% CI: 0.15-0.58) were associated with susceptibility. These associations with resistance/susceptibility to HIV-1 were independent of previously reported alleles HLA-DRB1*01 and HLA-A*2301., Conclusion: Our findings indicate that human leukocyte antigen DRB-specific CD4+ T-cell responses are an important factor in resistance/susceptibility to HIV-1 infection.

Objectives: To determine the association of DQ antigens with resistance and susceptibility to HIV-1., Design: Despite repeated exposure to HIV-1, a subset of women in the Pumwani Sex Worker cohort established in Nairobi, Kenya in 1985 have remained HIV-1 negative for at least 3 years and are classified as resistant. Differential susceptibility to HIV-1 infection is associated with HIV-1 specific CD4 and CD8 T cell responses. As human leukocyte antigen-DQ antigens present viral peptides to CD4 cells, we genotyped human leukocyte antigen -DQ alleles for 978 women enrolled in the cohort and performed cross-sectional and longitudinal analyses to identify associations of human leukocyte antigen -DQ with resistance/susceptibility to HIV-1., Methods: DQA1 and DQB1 were genotyped using taxonomy-based sequence analysis. SPSS 13.0 was used to determine associations of DQ alleles/haplotypes with HIV-1 resistance, susceptibility, and seroconversion rates., Results: Several DQB1 alleles and DQ haplotypes were associated with resistance to HIV-1 infection. These included DQB1*050301 (P = 0.055, Odds Ratio = 12.77, 95% Confidence Interval = 1.44-112), DQB1*0603 and DQB1*0609 (P = 0.037, Odds Ratio = 3.25, 95% Confidence Interval = 1.12-9.47), and DQA1*010201-DQB1*0603 (P = 0.044, Odds Ratio = 17.33, 95% Confidence Interval = 1.79-168). Conversely, DQB1*0602 (P = 0.048, Odds Ratio = 0.68, 95% Confidence Interval = 0.44-1.05) and DQA1*010201-DQB1*0602 (P = 0.039, Odds Ratio = 0.64, 95% Confidence Interval = 0.41-1.03) were overrepresented in the HIV-1 infected population. DQA1*0504-DQB1*0201, DQA1*010201-DQB1*0201, DQA1*0402-DQB1*0402 and DQA1*0402-DQB1*030101 genotypes were only found in HIV-1 positive subjects (Odds Ratio = 0.30-0.31, 95% Confidence Interval = 0.03-3.70), and these women seroconverted rapidly. The associations of these DQ alleles and haplotypes with resistance and susceptibility to HIV-1 were independent of the previously reported human leukocyte antigen-DRB*01, human leukocyte antigen A2/6802, and human leukocyte antigen-A*2301., Conclusion: The associations of DQ alleles and haplotypes with resistance and susceptibility to HIV-1 emphasize the importance of human leukocyte antigen-DQ and CD4 in anti-HIV-1 immunity.

Objectives: Female sex workers (FSWs) form a core group at high risk of both sexual HIV acquisition and secondary transmission. The magnitude of these risks may vary by sexual risk taking, partner HIV prevalence, host immune factors and genital co-infections. We examined temporal trends in HIV prevalence and per-act incidence, adjusted for behavioral and other variables, in FSWs from Nairobi, Kenya., Methods: An open cohort of FSWs followed since 1985. Behavioral and clinical data were collected six monthly from 1985 to 2005, and sexually transmitted infection (STI) diagnostics and HIV serology performed. A Cox proportional hazards model with time-dependent covariables was used to estimate infection risk as a function of calendar time., Results: HIV prevalence in new FSW enrollees peaked at 81% in 1986, and was consistently below 50% after 1997. Initially uninfected FSWs remained at high risk of acquiring HIV throughout the study period, but the rate of HIV acquisition during unprotected sex with a casual client declined by over four-fold. This reduction correlated closely with decreases in gonorrhea prevalence, and predated reductions in the Kenyan HIV population prevalence by over a decade., Conclusions: The per-act rate of HIV acquisition in high-risk Nairobi FSWs fell dramatically between 1985 and 2005. This decline may represent the impact of improved STI prevention/therapy, immunogenetic shifts in at-risk women, or changes in the proportion of HIV exposures occurring with clients who had acute HIV infection. Declining HIV incidence in high-risk cohorts may predict and/or be causally related to future reductions in population prevalence.

Background: Vitamin A is involved in normal immune function and the maintenance of mucosal integrity through complex effects on cellular differentiation., Objective: We sought to determine whether serum vitamin A levels were associated with altered susceptibility to primary infection with HIV-1 in men with high-risk sexual behaviour and genital ulcers who presented for treatment at an STD clinic in Nairobi, Kenya., Methods: HIV-1 seronegative men were prospectively followed. Vitamin A levels at study entry were compared among 38 men who HIV-1 seroconverted versus 94 controls who remained HIV seronegative., Results: Vitamin A deficiency (retinol less than 20 microg/dl) was very common and was present in 50% of HIV-1 seroconverters versus 76% of persistent seronegatives. Seroconversion was independently associated with a retinol level greater than 20 microg/dl (HR 2.43, 95% CI 1.25-4.70, P = 0.009), and a genital ulcer aetiology caused by Haemophilus ducreyi (HR 3.49, 95% CI 1.03-11.67, P = 0.04). Circumcision was independently associated with protection (HR 0.46, 95% CI 0.23-0.93, P = 0.03)., Conclusion: Vitamin A deficiency was not associated with an increased risk of HIV-1 infection among men with concurrent STD. A decreased risk of HIV-1 seroconversion was independently associated with lower retinol levels. The effects of vitamin A on macrophage and lymphoid cell differentiation may paradoxically increase mucosal susceptibility to HIV-1 in some vulnerable individuals, such as men with genital ulcers. Lack of circumcision and chancroid are confirmed as important co-factors for heterosexual HIV-1 transmission. The role of vitamin A in heterosexual HIV-1 transmission requires further study.

Objective: To identify factors affecting HIV-1 breastfeeding transmission., Design: Longitudinal observational cohort study., Methods: HIV-1 seropositive pregnant women and seronegative controls were enrolled at a maternity hospital in Nairobi. Women and their children were followed from birth, and data on HIV-1 transmission, breastfeeding, clinical illness, and growth were collected. Specimens for HIV-1 serology and/or polymerase chain reaction were obtained at birth, 2, 6, and 14 weeks, 6, 9, 12, and 18 months, and every 6 months thereafter. Children were classified as HIV-1 uninfected, perinatally, or postnatally infected. Potentially breastfeeding transmission related risk factors were compared between postnatally infected and uninfected children., Results: Among children born to seropositive or seroconverting mothers, 317 were uninfected, 51 infected perinatally and 42 infected postnatally. Identified risk factors for postnatal transmission were maternal nipple lesions (OR = 2.3, CI 95% 1.1-5.0), mastitis (OR = 2.7, CI 95% 1.1-6.7), maternal CD4 cell count < 400 mm3 (OR = 4.4, CI 95% 1.9-9.9), maternal seroconversion while breastfeeding (OR = 6.0, CI 95% 1.8-19.8), infant oral thrush at < 6 months of age (OR = 2.8, CI 95% 1.3-6.2) and breastfeeding longer than 15 months (OR = 2.4, CI 95% 1.2-5.1). All factors, except maternal seroconversion due to its rarity, were independently associated with an increased postnatal transmission risk by multivariate logistic regression analysis., Conclusion: In addition perinatal antiretroviral therapies, public health strategies should address: (i) prevention of maternal nipple lesions, mastitis and infant thrush; (ii) reduction of breastfeeding duration by all HIV-1-infected mothers; (iii) absolute avoidance of breastfeeding by those at high risk, and (iv) prevention of HIV-1 transmission to breastfeeding mothers.

Studies from Kenya have reported rapid clinical disease progression among HIV-infected professional sex workers. The reasons for this rapid decline are unknown. To better understand factors influencing the course of disease, HIV-1 disease progression was explored in terms of declines in CD4 counts. Two samples from Nairobi, Kenya, were studied, one from a cohort of female sex workers and another, as a comparison group, from mothers enrolled in an HIV-1 vertical-transmission study. A Markov model was used to analyze transitions between HIV-1 disease stages as defined by CD4 counts. It appears that sex workers experience a rapid decline in CD4 counts, consistent with earlier findings of rapid clinical disease progression among individuals in this group. The rate of decline in CD4 counts among the mothers appears to be lower. It is speculated that either intensive exposure to sexually transmitted pathogens or infection with several strains of HIV-1 may account for the rapid disease progression among female sex workers.

How best to advise mothers infected with human immunodeficiency virus type 1 (HIV-1) in developing countries regarding breastfeeding is an important issue that has generated considerable debate. Previous studies have addressed this problem by means of mathematical models, but without considering the issue of the duration of breastfeeding. A mathematical model was developed to compare the age-specific risks of mother-to-child HIV transmission versus the excess mortality due to not breastfeeding. In this model it is assumed that both the risk of mother-to-child transmission of HIV through breast milk and the relative risk of not breastfeeding do not vary with age. The model indicates that, in HIV-1-seropositive mothers, the decrease in child mortality afforded by breastfeeding may exceed the risk of mother-to-child HIV-1 transmission only during the first 3-7 months of life. Thereafter the risk of HIV-1 transmission probably exceeds the mortality benefit of breastfeeding. Experimental studies of counselling HIV-1-infected mothers to limit their duration of breastfeeding should be considered in the setting of developing countries.

Since 1985, a population of over 1,000 predominantly HIV-positive female prostitutes residing in a low-income area of Nairobi, has been enrolled in a sexually transmitted disease (STD)/HIV control programme. The major elements of the programme include the diagnosis and treatment of conventional STD, and the promotion of condom use to prevent the transmission of HIV and other sexually transmitted infections. Using estimates of numbers of HIV-seropositive prostitutes, numbers of sexual contacts, susceptibility of clients to HIV, HIV transmission efficiency, rates of condom use and the basic reproductive rate of HIV infection in Kenya, we estimate that the programme is responsible for preventing between 6,000 and 10,000 new cases of HIV infection per year among clients and contacts of clients. The total annual operating cost of the programme is approximately US$77,000 or between US$8.00 and US$12.00 for each case of HIV infection prevented. Programmes to reduce the transmission of HIV and other sexually transmitted infections which are targeted at high-frequency STD transmitters, such as prostitutes, can be effective and relatively inexpensive to undertake. More such programmes should be developed and evaluated in different settings.

The progression of HIV-related disease from infection to death is represented as a staged Markov model. Transitions between stages are considered reversible. The model is fitted to data from a cohort of African prostitutes by means of maximum likelihood. It appears that the progression to symptomatic disease (Centers for Disease Control stage IV) in this population is considerably more rapid than that reported from studies in Western countries.

Using logistic regression, we analyzed the predictive value of a number of entry variables with respect to the outcome variables delayed cerebral ischemia, rebleeding, and poor outcome (death or severe disability) in patients with aneurysmal subarachnoid hemorrhage. The entry variables were clinical condition on admission (grades on the Glasgow Coma Scale, Hunt and Hess system), the amount of subarachnoid and intraventricular blood and the presence of hydrocephalus on the admission computed tomogram, and antifibrinolytic treatment with tranexamic acid. We used data from a prospectively studied population of 176 patients admitted within 72 hours after subarachnoid hemorrhage. The risk of delayed cerebral ischemia was best predicted by the amount of subarachnoid blood, intraventricular blood, and antifibrinolytic treatment irrespective of clinical condition and hydrocephalus. The site of delayed cerebral ischemia was not related to the location of the subarachnoid hemorrhage. Antifibrinolytic treatment was the only entry variable (negatively) predicting the risk of rebleeding. Death or severe disability after 3 months was best predicted by the amount of subarachnoid blood and the initial clinical condition reflected by the grade on the Glasgow Coma Scale.