Jo Ndinya-Achola

Male circumcision for HIV prevention in young men in Kisumu, Kenya: a randomised controlled trial

BACKGROUND Male circumcision could provide substantial protection against acquisition of HIV-1 infection. Our aim was to determine whether male circumcision had a protective effect against HIV infection, and to assess safety and changes in sexual behaviour related to this intervention. METHODS We did a randomised controlled trial of 2784 men aged 18-24 years in Kisumu, Kenya. Men were randomly assigned to an intervention group (circumcision; n=1391) or a control group (delayed circumcision, 1393), and assessed by HIV testing, medical examinations, and behavioural interviews during follow-ups at 1, 3, 6, 12, 18, and 24 months. HIV seroincidence was estimated in an intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, with the number NCT00059371. FINDINGS The trial was stopped early on December 12, 2006, after a third interim analysis reviewed by the data and safety monitoring board. The median length of follow-up was 24 months. Follow-up for HIV status was incomplete for 240 (8.6%) participants. 22 men in the intervention group and 47 in the control group had tested positive for HIV when the study was stopped. The 2-year HIV incidence was 2.1% (95% CI 1.2-3.0) in the circumcision group and 4.2% (3.0-5.4) in the control group (p=0.0065); the relative risk of HIV infection in circumcised men was 0.47 (0.28-0.78), which corresponds to a reduction in the risk of acquiring an HIV infection of 53% (22-72). Adjusting for non-adherence to treatment and excluding four men found to be seropositive at enrollment, the protective effect of circumcision was 60% (32-77). Adverse events related to the intervention (21 events in 1.5% of those circumcised) resolved quickly. No behavioural risk compensation after circumcision was observed. INTERPRETATION Male circumcision significantly reduces the risk of HIV acquisition in young men in Africa. Where appropriate, voluntary, safe, and affordable circumcision services should be integrated with other HIV preventive interventions and provided as expeditiously as possible.

Vaginal Lactobacilli, Microbial Flora, and Risk of Human Immunodeficiency Virus Type 1 and Sexually Transmitted Disease Acquisition

A prospective cohort study was conducted to examine the relationship between vaginal colonization with lactobacilli, bacterial vaginosis (BV), and acquisition of human immunodeficiency virus type 1 (HIV-1) and sexually transmitted diseases in a population of sex workers in Mombasa, Kenya. In total, 657 HIV-1-seronegative women were enrolled and followed at monthly intervals. At baseline, only 26% of women were colonized with Lactobacillus species. During follow-up, absence of vaginal lactobacilli on culture was associated with an increased risk of acquiring HIV-1 infection (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.2-3.5) and gonorrhea (HR, 1.7; 95% CI, 1.1-2.6), after controlling for other identified risk factors in separate multivariate models. Presence of abnormal vaginal flora on Grams stain was associated with increased risk of both HIV-1 acquisition (HR, 1.9; 95% CI, 1.1-3.1) and Trichomonas infection (HR, 1.8; 95% CI, 1.3-2.4). Treatment of BV and promotion of vaginal colonization with lactobacilli should be evaluated as potential interventions to reduce a womans risk of acquiring HIV-1, gonorrhea, and trichomoniasis.

Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men

To determine the frequency and risk factors for female to male sexual transmission of human immunodeficiency virus type 1 (HIV-1), a prospective study was carried out in 422 men who had acquired a sexually transmitted disease (STD) from a group of prostitutes with a prevalence of HIV-1 infection of 85%. The initial seroprevalence of HIV among the men was 12%. 24 of 293 (8.2%) initially seronegative men seroconverted to HIV-1. Newly acquired infection was independently associated with frequent prostitute contact (risk ratio 3.2, 95% confidence interval 1.2-8.1), with the acquisition of genital ulcer disease (risk ratio 4.7, 95% confidence interval 1.3-17.0), and with being uncircumcised (risk ratio 8.2, 95% confidence interval 3.0-23.0). 96% of documented seroconversions occurred in men with one or both of the latter two risk factors. In a subgroup of 73 seronegative men who reported a single prostitute sexual contact, the frequency of HIV-1 infection was 8.2% during 12 weeks of observation. No man without a genital ulcer seroconverted. A cumulative 43% of uncircumcised men who acquired an ulcer seroconverted to HIV-1 after a single sexual exposure. These data indicate an extremely high rate of female to male transmission of HIV-1 in the presence of STD and confirm a causal relation between lack of male circumcision, genital ulcer disease, and susceptibility to HIV-1 infection.

AIDS virus infection in Nairobi prostitutes: spread of the epidemic to East Africa

The acquired immunodeficiency syndrome (AIDS) is epidemic in Central Africa. To determine the prevalence of AIDS virus infection in East Africa, we studied 90 female prostitutes, 40 men treated at a clinic for sexually transmitted diseases, and 42 medical personnel in Nairobi, Kenya. Antibody to human T-cell lymphotropic virus Type III (HTLV-III) was detected in the serum of 66 percent of prostitutes of low socioeconomic status, 31 percent of prostitutes of higher socioeconomic status, 8 percent of the clinic patients, and 2 percent of the medical personnel. The presence of the antibody was associated with both immunologic and clinical abnormalities. The mean T-cell helper/suppressor ratio was 0.92 in seropositive prostitutes and 1.82 in seronegative prostitutes (P less than 0.0001). Generalized lymphadenopathy was present in 54 percent of seropositive prostitutes and 10 percent of seronegative prostitutes (P less than 0.0001). No constitutional symptoms, opportunistic infections, or cases of Kaposis sarcoma were present. Our results indicate that the epidemic of AIDS virus infection has, unfortunately, spread extensively among urban prostitutes in Nairobi, Kenya. Sexual exposure to men from Central Africa was significantly associated with HTLV-III antibody among prostitutes, suggesting transcontinental spread of the epidemic.

Infection with Trichomonas vaginalis Increases the Risk of HIV-1 Acquisition

We conducted a prospective study among women in Mombasa, Kenya, to determine whether Trichomonas vaginalis infection was associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) infection. At monthly follow-up visits, laboratory screening for HIV-1 and genital tract infections was conducted. Among 1335 HIV-1-seronegative women monitored for a median of 566 days, there were 806 incident T. vaginalis infections (23.6/100 person-years), and 265 women seroconverted to HIV-1 (7.7/100 person-years). Trichomoniasis was associated with a 1.52-fold (95% confidence interval, 1.04-2.24-fold) increased risk of HIV-1 acquisition after adjustment for potential confounding factors. Treatment and prevention of T. vaginalis infection could reduce HIV-1 risk in women.

Human immunodeficiency virus infection among men with sexually transmitted diseases. Experience from a center in Africa

Heterosexual transmission of the human immunodeficiency virus (HIV) appears to occur readily in Africa but less commonly in North America and Europe. We conducted a case-control study among men attending a clinic for sexually transmitted diseases in Nairobi to determine the prevalence of HIV infection and the risk factors involved. HIV antibody was detected in 11.2 percent of 340 men who enrolled in the study. Reports of nonvaginal heterosexual intercourse and homosexuality were notably rare. Recent injections and blood transfusions were not associated with HIV infection. Travel and frequent contact with prostitutes were associated with HIV seropositivity. Men who were uncircumcised were more likely to have HIV infection (odds ratio, 2.7; P = 0.003), as were those who reported a history of genital ulcers (odds ratio, 7.2; P less than 0.001). A current diagnosis of genital ulcers was also associated with HIV seropositivity (odds ratio, 2.0; P = 0.028). Multivariate analysis revealed an independent association of genital ulcers with HIV infection in both circumcised and uncircumcised men. Uncircumcised men were more frequently infected with HIV, regardless of a history of genital ulcers. Our study finds that genital ulcers and an intact foreskin are associated with HIV infection in men with a sexually transmitted disease. Genital ulcers may increase mens susceptibility to HIV, or they may increase the infectivity of women infected with HIV. The intact foreskin may operate to increase the susceptibility to HIV.

Genital ulceration as a risk factor for human immunodeficiency virus infection

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina

BACKGROUND Factors that influence shedding of HIV-1 infected cells in cervical and vaginal secretions may be important determinants of sexual and vertical transmission of the virus. We investigated whether hormonal contraceptive use, vitamin A deficiency, and other variables were risk factors for cervical and vaginal shedding of HIV-infected cells. METHODS Between December, 1994, and April, 1996, women who attended a municipal sexually transmitted diseases (STDs) clinic in Mombasa, Kenya, and had previously tested positive for HIV-1, were invited to take part in our cross-sectional study. Cervical and vaginal secretions from 318 women were evaluated for the presence of HIV-1 infected cells by PCR amplification of gag DNA sequences. FINDINGS HIV-1 infected cells were detected in 51% of endocervical and 14% of vaginal-swab specimens. Both cervical and vaginal shedding of HIV-1 infected cells were highly associated with CD4 lymphocyte depletion (p = 0.00001 and p = 0.003, respectively). After adjustment for CD4 count, cervical proviral shedding was significantly associated with use of depot medroxyprogesterone acetate (odds ratio 2.9, 95% CI 1.5-5.7), and with use of low-dose and high-dose oral contraceptive pills (3.8, 1.4-9.9 and 12.3, 1.5-101, respectively). Vitamin A deficiency was highly predictive of vaginal HIV-1 DNA shedding. After adjustment for CD4 count, severe vitamin A deficiency, moderate deficiency, and low normal vitamin A status were associated with 12.9, 8.0, and 4.9-fold increased odds of vaginal shedding, respectively. Gonococcal cervicitis (3.1, 1.1-9.8) and vaginal candidiasis (2.6, 1.2-5.4) were also correlated with significant increases in HIV-1 DNA detection, but Chlamydia trachomatis and Trichomonas vaginalis were not. INTERPRETATION Our study documents several novel correlates of HIV-1 shedding in cervical and vaginal secretions, most notably hormonal contraceptive use and vitamin A deficiency. These factors may be important determinants of sexual or vertical transmission of HIV-1 and are of public health importance because they are easily modified by simple interventions.

Correlates of Mother-to-Child Human Immunodeficiency Virus Type 1 (HIV-1) Transmission: Association with Maternal Plasma HIV-1 RNA Load, Genital HIV-1 DNA Shedding, and Breast Infections

To determine the effects of plasma, genital, and breast milk human immunodeficiency virus type 1 (HIV-1) and breast infections on perinatal HIV-1 transmission, a nested case-control study was conducted within a randomized clinical trial of breast-feeding and formula feeding among HIV-1-seropositive mothers in Nairobi, Kenya. In analyses comparing 92 infected infants with 187 infants who were uninfected at 2 years, maternal viral RNA levels >43,000 copies/mL (cohort median) were associated with a 4-fold increase in risk of transmission (95% confidence interval [CI], 2.2-7.2). Maternal cervical HIV-1 DNA (odds ratio [OR], 2.4; 95% CI, 1.3-4.4), vaginal HIV-1 DNA (OR, 2.3; 95% CI, 1.1-4.7), and cervical or vaginal ulcers (OR, 2.7; 95% CI, 1.2-5.8) were significantly associated with infant infection, independent of plasma virus load. Breast-feeding (OR, 1.7; 95% CI, 1.0-2.9) and mastitis (relative risk [RR], 3.9; 95% CI, 1.2-12.7) were associated with increased transmission overall, and mastitis (RR, 21.8; 95% CI, 2.3-211.0) and breast abscess (RR, 51.6; 95% CI, 4.7-571.0) were associated with late transmission (occurring >2 months postpartum). Use of methods that decrease infant exposure to HIV-1 in maternal genital secretions or breast milk may enhance currently recommended perinatal HIV-1 interventions.

Hormonal Contraception, Sexually Transmitted Diseases, and Risk of Heterosexual Transmission of Human Immunodeficiency Virus Type 1

To examine associations between method of contraception, sexually transmitted diseases (STDs), and incident human immunodeficiency virus type 1 (HIV-1) infection, a prospective observational cohort study was done among female sex workers attending a municipal STD clinic in Mombasa, Kenya. Demographic and behavioral factors significantly associated with HIV-1 infection included type of workplace, condom use, and parity. In multivariate models, vulvitis, genital ulcer disease, vaginal discharge, and Candida vaginitis were significantly associated with HIV-1 seroconversion. Women who used depo medroxyprogesterone acetate (DMPA) had an increased incidence of HIV-1 infection (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.4-3.4). In a multivariate model controlling for demographic and exposure variables and biologic covariates, the adjusted HR for HIV-1 infection among DMPA users was 2.0 (CI, 1.3-3.1). There was a trend for an association between use of high-dose oral contraceptive pills and HIV-1 acquisition (HR, 2.6; CI, 0.8-8.5).