Joel P. Rakwar

Gender differences in HIV-1 diversity at time of infection

To develop an HIV-1 vaccine with global efficacy, it is important to identify and characterize the viruses that are transmitted, particularly to individuals living in areas of high incidence. Several studies have shown that virus from the blood of acutely infected adults was homogeneous, even when the virus population in the index case was genetically diverse. In contrast to those results with mainly male cohorts in America and Europe, in several cases a heterogeneous virus population has been found early in infection in women in Africa. Thus, we more closely compared the diversity of transmitted HIV-1 in men and women who became infected through heterosexual contact. We found that women from Kenya were often infected by multiple virus variants, whereas men from Kenya were not. Moreover, a heterogeneous virus was present in the women before their seroconversion, and in each woman it was derived from a single index case, indicating that diversity was most likely to be the result of transmission of multiple variants. Our data indicate that there are important differences in the transmitted virus populations in women and men, even when cohorts from the same geographic region who are infected with the same subtypes of HIV-1 are compared.

Effect of Circumcision on Incidence of Human Immunodeficiency Virus Type 1 and Other Sexually Transmitted Diseases: A Prospective Cohort Study of Trucking Company Employees in Kenya

To determine the effect of circumcision status on acquisition of human immunodeficiency virus (HIV) type 1 and other sexually transmitted diseases, a prospective cohort study of 746 HIV-1-seronegative trucking company employees was conducted in Mombasa, Kenya. During the course of follow-up, 43 men acquired HIV-1 antibodies, yielding an annual incidence of 3.0%. The annual incidences of genital ulcers and urethritis were 4.2% and 15.5%, respectively. In multivariate analysis, after controlling for demographic and behavioral variables, uncircumcised status was an independent risk factor for HIV-1 infection (hazard rate ratio [HRR=4.0; 95% confidence interval [CI], 1.9-8.3) and genital ulcer disease (HRR=2.5; 95% CI, 1.1-5.3). Circumcision status had no effect on the acquisition of urethral infections and genital warts. In this prospective cohort of trucking company employees, uncircumcised status was associated with increased risk of HIV-1 infection and genital ulcer disease, and these effects remained after controlling for potential confounders.

Cofactors for the acquisition of HIV-1 among heterosexual men: prospective cohort study of trucking company workers in Kenya.

OBJECTIVE To determine the prevalence, incidence, and correlates of HIV-1 infection in a cohort of east African trucking company employees. METHODS HIV-1-seronegative trucking company employees were enrolled in a prospective cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion, sexually transmitted diseases, and sexual behavior. RESULTS The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8%. Among 752 HIV-1-seronegative men who were followed, the HIV-1 annual seroincidence was 3.1%. In univariate analysis, HIV-1 acquisition was associated with age under 25 years, 10 years or less of sexual activity, occupation as a driver/drivers assistant, occupational travel for more than 14 days per month, religion other than Christian or Muslim, uncircumcised status, sex with a prostitute, sex with a girlfriend/casual partner, extramarital sex, and enrollment seropositivity to Treponema pallidum, Haemophilus ducreyi, and Herpes simplex virus type 2 (all P values < or = 0.05). Using multivariate analysis, HIV-1 acquisition was independently associated with 10 years or less of sexual activity (hazard rate ratio (HRR) 2.0, 95% confidence interval (CI) 1.0-4.3), occupation as a driver/drivers assistant (HRR 3.9, 95% CI 1.7-9.0), religion other than Christian or Muslim (HRR 6.1, 95% CI 1.4-25.7), uncircumcised status (HRR 2.3, 95% CI 1.0-5.0), and unprotected sex with a prostitute (HRR 2.8, 95% CI 1.1-7.0). CONCLUSIONS Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up. Risk factors for HIV-1 seroconversion included years of sexual activity, occupation, religion, uncircumcised status, and unprotected sex with a prostitute. This population is an appropriate target for HIV-1 prevention trials and behavioral interventions.

Decreased incidence of sexually transmitted diseases among trucking company workers in Kenya: results of a behavioural risk-reduction programme

Objective: To establish a cohort of high‐risk individuals suitable for HIV‐prevention trials, and to measure changes in sexual behaviour and sexually transmitted disease (STD) incidence after a behavioural intervention. Design: Prospective cohort study in trucking company depots in Mombasa, Kenya. Participants: A total of 556 male HIV‐seronegative employees of trucking companies. Interventions: HIV serological testing, individual counselling, condom promotion, STD diagnosis and management. Main outcome measures: Sexual risk behaviour and symptomatic STD incidence. Results: Using time‐trend modelling, significant declines in self‐reported high‐risk sexual behaviour were demonstrated during a 1‐year follow‐up. The percentage of men reporting any extramarital sex during the 3‐month period prior to a follow‐up visit decreased from 49% during the first quarter of follow‐up to 36% during the last quarter (P < 0.001). The decline in reported female sex worker contact was from 12% to 6% (P = 0.001). Approximately 30% of men reported consistent condom use during extramarital sex and this percentage remained unchanged during the study period. The incidence of STD declined from 34 per 100 person years (PY) during the first quarter to 10 per 100 PY during the last quarter (P = 0.001). Significant reductions in gonorrhoea (15 to five cases per 100 PY, P = 0.04), non‐gonococcal urethritis (10 to two cases per 100 PY, P = 0.05), and genital ulcer disease (nine to two cases per 100 PY, P = 0.02) were observed. Conclusions: Among truck company workers who participated in a cohort study in Mombasa, Kenya, there was a significant decrease in sex with high‐risk partners, but no change in condom use. The change in heterosexual risk behaviour was accompanied by a significant decrease in incidence of gonorrhoea, non‐gonococcal urethritis, and genital ulcer disease.

Female-to-Male Infectivity of HIV-1 among Circumcised and Uncircumcised Kenyan Men

BACKGROUND A lack of male circumcision has been associated with increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition in a number of studies, but questions remain as to whether confounding by behavioral practices explains these results. The objective of the present study was to model per-sex act probabilities of female-to-male HIV-1 transmission (i.e., infectivity) for circumcised and uncircumcised men, by use of detailed accounts of sexual behavior in a population with multiple partnerships. METHODS Data were collected as part of a prospective cohort study of HIV-1 acquisition among 745 Kenyan truck drivers. Sexual behavior with wives, casual partners, and prostitutes was recorded at quarterly follow-up visits. Published HIV-1 seroprevalence estimates among Kenyan women were used to model HIV-1 per-sex act transmission probabilities. RESULTS The overall probability of HIV-1 acquisition per sex act was 0.0063 (95% confidence interval, 0.0035-0.0091). Female-to-male infectivity was significantly higher for uncircumcised men than for circumcised men (0.0128 vs. 0.0051; P=.04). The effect of circumcision was robust in subgroup analyses and across a wide range of HIV-1 prevalence estimates for sex partners. CONCLUSIONS After accounting for sexual behavior, we found that uncircumcised men were at a >2-fold increased risk of acquiring HIV-1 per sex act, compared with circumcised men. Moreover, female-to-male infectivity of HIV-1 in the context of multiple partnerships may be considerably higher than that estimated from studies of HIV-1-serodiscordant couples. These results may explain the rapid spread of the HIV-1 epidemic in settings, found throughout much of Africa, in which multiple partnerships and a lack of male circumcision are common.

Correlates of human herpesvirus 8 seropositivity among heterosexual men in Kenya

Background: Several studies have suggested that sexual transmission of human herpesvirus 8 (HHV-8) occurs among homosexual men in developed countries. However, few studies have examined heterosexual HHV-8 transmission, especially among African populations in which HHV-8 is endemic. Objectives: To determine the seroprevalence and correlates of HHV-8 infection among heterosexual African men. Design: Cross-sectional study. Methods: Participants were 1061 men enrolled in a prospective cohort study of risk factors for HIV-1 acquisition among trucking company employees in Mombasa, Kenya. Stored frozen sera from the study baseline visit were tested for antibodies to HHV-8 by whole-virus lysate ELISA. Results: HHV-8 seroprevalence was 43%. In multivariate logistic regression analysis, HHV-8 infection was independently associated with older age [for men aged 30–39 years: odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1–2.0; for men aged ⩾ 40 years: OR, 1.7; 95% CI, 1.1–2.7, compared with men aged < 30 years], Christian religion (OR, 1.6; 95% CI, 1.2–2.1), being uncircumcised (OR, 1.5; 95% CI, 1.0–2.2), and ever having syphilis (OR, 2.2; 95% CI, 1.4–3.5). Ever having used condoms was associated with decreased likelihood of infection (OR, 0.7; 95% CI, 0.6–1.0). Seropositivity was not significantly related to other sexual behaviors characterized or to HIV-1 status. Conclusions: HHV-8 seropositivity is common in this population and increases with age, suggesting on-going transmission during adulthood. Infection was more common among men who were uncircumcised or who had ever had syphilis and was less common among those who had ever used condoms, suggesting that sexual factors may play a role in HHV-8 transmission. Prospective studies of HHV-8 acquisition in heterosexual African populations are needed to demonstrate whether safer sexual practices can reduce transmission.

Acceptability of HIV vaccine trials in high-risk heterosexual cohorts in Mombasa Kenya.

ObjectivesTo ascertain the level of acceptance of a prophylactic HIV vaccine trial in high-risk HIV-seronegative heterosexual cohorts of men, and women in Mombasa, Kenya, and to assess the anticipated effects of participation on risk behavior. MethodsStandardized questionnaire administered to a convenience sample of commercial sex workers, and trucking company employees enrolled in prospective cohort studies. ResultsNinety-six per cent of respondents believed that HIV was a major problem in Kenya, and 86% of men, and 94% of women perceived themselves at risk. One hundred per cent of women, and 84% of men expressed interest in participation in an HIV vaccine trial, after explanation of the experimental nature of the vaccine, double-blind placebo-controlled design, prolonged follow-up, and potential change in serostatus. Seventeen per cent of men, and 9% of women anticipated an increase in risk behavior as a result of participation. ConclusionThe majority of individuals in two high-risk cohorts were interested in participating in Phase III efficacy trials of HIV vaccines. A significant minority anticipated an increase in risk behavior, which emphasizes the need for intensive counseling, and education throughout a vaccine trial.

Healthcare-seeking behavior and sexual behavior of patients with sexually transmitted diseases in Nairobi, Kenya.

Background Sexualand health-seeking behaviors are important components of sexually transmitteddisease (STD)control. Goals Togenerate data for improved STD prevention and care, and to assess sexualbehavior and relevant health-seekingbehavior. StudyDesign A questionnaire to elicit social, demographic,healthcare-seeking, and sexual behavior information was administered to 471patients attending the referral clinic for STDs in Nairobi,Kenya. Results Alarge proportion of the patients had sought treatment in public and privatesectors before attending the clinic for STDs. Women waited longer than men toseek medical care. In addition, women more than men engaged in sex whilesymptomatic, mostly with their regular partner. Condoms were used rarelyduring illness. In their self-reports, 68% of the men admitted to havingextramarital affairs, and 30% to paying for sex, yet they blamed their wivesfor theirSTDs. Conclusion Healtheducation messages in Kenya need adaptation to improve health-seeking behaviorand safe sexpractices.

Urethral Infection in a Workplace Population of East African Men: Evaluation of Strategies for Screening and Management

Transport workers (n = 504) in Mombasa, Kenya, were screened for urethral infection by history, clinical examination, and laboratory testing of urethral swabs and first-catch urine specimens. The prevalence of Neisseria gonorrhoeae was 3.4%, Chlamydia trachomatis, 3.6%, and Trichomonas vaginalis, 6.0%; more than two-thirds of infections were asymptomatic. A complaint of urethral discharge, dysuria, or both was twice as sensitive as the sign of discharge on physical examination (34.5% vs. 15.5%) in identifying infection. A positive leukocyte esterase dipstick (LED) test on urine predicted infection with a sensitivity of 95.0% and a specificity of 59.3% in symptomatic men and with a sensitivity of 55.3% and a specificity of 82.8% in asymptomatic men. Demographic and behavioral factors were not independent predictors of infection. In resource-poor settings with high prevalences of urethral infection, an effective screening and management strategy would be to treat symptomatic men, as well as asymptomatic men with a positive LED test, for all three infections.

Studies of human immunodeficiency virus type 1 mucosal viral shedding and transmission in Kenya

If human immunodeficiency virus type 1 (HIV-1) vaccines are to be highly effective, it is essential to understand the virologic factors that contribute to HIV-1 transmission. It is likely that transmission is determined, in part, by the genotype or phenotype (or both) of infectious virus present in the index case, which in turn will influence the quantity of virus that may be exchanged during sexual contact. Transmission may also depend on the fitness of the virus for replication in the exposed individual, which may be influenced by whether a virus encounters a target cell that is susceptible to infection by that specific variant. Of interest, our data suggest that the complexity of the virus that is transmitted may be different in female and male sexual exposures.