Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers.

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.

Genital ulcer disease among STD clinic attenders in Nairobi: association with HIV-1 and circumcision status.

In previous studies, genital ulcers in men have been found to be associated with increased risk of HIV-1 seroconversion. To further explore this association male patients attending a sexually transmitted disease (STD) clinic in Nairobi for either urethritis (controls, n = 276) or a genital ulcer (cases, n = 607) were compared with respect to sexual behaviour, presence of HIV-1 antibody and circumcision status. Patients were followed to study risk factors for incident genital ulcers and HIV-1 seroconversion. At entry, being married was associated with higher prevalence of HIV-1 (OR = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.23). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. It is argued that the association between genital ulcers and HIV-1 infection may be more complex than ulcers simply being a risk factor for HIV-1 infection, and that HIV-1 infection may either increase the risk of acquiring a genital ulcer, or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

PIP: Male patients (mean age, 28 years) attending a sexually transmitted disease clinic in Nairobi, Kenya, for either urethritis (276 controls) or a genital ulcer (607 cases) were compared with respect to sexual behavior, presence of HIV-1 antibody, and circumcision status. Only 164 men were not circumcised. Circumcised men reported more life-time sex partners than uncircumcised men (19 vs. 10, p 0.01). Patients were followed up for 196 days to explore the risk factors for incident genital ulcers and HIV-1 seroconversion. On average, 2.66 follow-up visits per patient were recorded. 28 men seroconverted to HIV-1 during follow-up. 61% of the ulcer patients reported sex workers as the likely source of their infection, whereas 58% of the urethritis patients did so. Multiple logistic regression variables of marital status, age, and genital ulcer in the past were used to examine the relationship among these variables. Ulcer in the past was a significant predictor of a current ulcer (p 0.01) and higher age was significantly associated with HIV-1 seropositivity (p 0.01). At entry, being married was associated with higher prevalence of HIV-1 (odds ratio [OR] = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.3). 68 men acquired a new ulcer during follow-up. HIV-1 seropositivity at enrolment was significantly associated with genital ulcer reinfection (relative risk = 3.63 by Cox's regression). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. The association between genital ulcers and HIV-1 infection may be more complex than ulcers' simply being a risk factor for HIV-1 infection: either HIV-1 infection may increase the risk of acquiring a genital ulcer or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

Lesions of primary and secondary syphilis contain activated cytolytic T cells.

This study demonstrates that CD8+ cytotoxic lymphocytes (CTL) are found in both primary and secondary syphilis lesions. CD8+ T cells were detected by immunohistology, and mRNAs for granzyme B and perforin were detected by reverse transcription and PCR, suggesting that CD8+ cytotoxic lymphocytes are activated.

Primary and secondary syphilis lesions contain mRNA for Th1 cytokines.

Phagocytosis of Treponema pallidum by cytokine-activated macrophages aids bacterial clearance and lesion resolution in early syphilis. To investigate the cytokine profiles of cells infiltrating primary and secondary syphilis lesions, reverse transcription and polymerase chain reaction (RT-PCR) were used to detect cytokine mRNA in 13 lesion biopsies. Both primary and secondary lesions contained mRNA encoding interleukin (IL)-2, interferon-gamma (IFN-gamma), IL-12p40, and IL-10. In contrast to a lesion from a patient with recurrent herpes simplex virus type 2, no message for IL-4 could be detected in any of the syphilis lesions, and 10 of 13 had no mRNA for IL-5 or IL-13. These findings are consistent with a Th1-predominant local cellular response activating macrophages and support the hypothesis that IFN-gamma-activated macrophages are primary effectors in treponeme clearance.