Sungwal Rugpao

Hormonal contraception and the risk of HIV acquisition

Background:Combined oral contraceptives (COC) and depot-medroxyprogesterone acetate (DMPA) are among the most widely used family planning methods; their effect on HIV acquisition is not known. Objective:To evaluate the effect of COC and DMPA on HIV acquisition and any modifying effects of other sexually transmitted infections. Methods:This multicenter prospective cohort study enroled 6109 HIV-uninfected women, aged 18–35 years, from family planning clinics in Uganda, Zimbabwe and Thailand. Participants received HIV testing quarterly for 15–24 months. The risk of HIV acquisition with different contraceptive methods was assessed (excluding Thailand, where there were few HIV cases). Results:HIV infection occurred in 213 African participants (2.8/100 woman-years). Use of neither COC [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.69–1.42] nor DMPA (HR, 1.25; 95% CI, 0.89–1.78) was associated with risk of HIV acquisition overall, including among participants with cervical or vaginal infections. While absolute risk of HIV acquisition was higher among participants who were seropositive for herpes simplex virus 2 (HSV-2) than in those seronegative at enrolment, among the HSV-2-seronegative participants, both COC (HR, 2.85; 95% CI, 1.39–5.82) and DMPA (HR, 3.97; 95% CI, 1.98–8.00) users had an increased risk of HIV acquisition compared with the non-hormonal group. Conclusions:No association was found between hormonal contraceptive use and HIV acquisition overall. This is reassuring for women needing effective contraception in settings of high HIV prevalence. However, hormonal contraceptive users who were HSV-2 seronegative had an increased risk of HIV acquisition. Additional research is needed to confirm and explain this finding.

Epidemiologic and biologic characterization of a cohort of human immunodeficiency virus type 1 highly exposed, persistently seronegative female sex workers in northern Thailand

Characterization of persons highly exposed to human immunodeficiency virus (HIV)-1 who remain uninfected may help define protective immunity. Seventeen HIV-1-seronegative Thai female sex workers (CSWs) with epidemiologic evidence of exposure to HIV-1 were studied for humoral immune responses and phenotypic and genotypic analyses of HLA class I and CCR5 allelic profiles. Infected CSWs and low-risk HIV-1-seronegative Thai women were controls. Highly exposed, persistently seronegative (HEPS) CSWs did not differ from HIV-infected CSWs in HIV risks, condom use, or sexually transmitted diseases. Significant differences were seen in humoral immune responses: gp160-specific IgA responses were detected in cervicovaginal lavage fluids in 6 of 13 HEPS CSWs but 0 of 21 seronegative subjects. All women had wild-type CCR5. HEPS CSWs were more likely to have the HLA-B18 phenotype and genotype than were matched controls (corrected P=.018). Epidemiologic exposure to HIV-1 without apparent infection, an unusual distribution of HLA class I alleles, and HIV-1 gp160-specific IgA responses suggest a biologic basis for this phenomenon.

Protection against sexually transmitted diseases by granting sex workers in Thailand the choice of using the male or female condom: results from a randomized controlled trial.

Background:The male condom is the most effective barrier method available for protection against sexually transmitted diseases (STDs), including HIV infection. There is an urgent need to develop and evaluate other prevention methods, such as the female condom. This study estimated the additional protection against STDs offered to sex workers by giving them the option of using the female condom when clients refused to use a male condom. Methods:Sex establishments in four cities in Thailand were randomized into two study groups: one in which sex workers were instructed to use male condoms consistently (male condom group); and one in which sex workers had the option of using the female condom if clients refused or were not able to use male condoms (male/female condom group). Randomization was done by sex establishments, and not by individuals, to minimize sharing of female condoms across study groups. The proportion of unprotected sexual acts (defined as sexual acts in which condoms were not used, tore, or slipped in or out) and incidence rate of STDs (gonorrhoea, chlamydial infection, trichomoniasis and genital ulcer disease) were measured over a 24-week period and compared between the two study groups. Findings:Results are available from 34 sex establishments (249 women) in the male/female condom group, and 37 sex establishments (255 women) in the male condom group. Condom use was very high in both groups (97.9 and 97.3 % of all sexual acts, respectively, P > 0.05). Male condom use was lower in the male/female condom group when compared with the male condom group (88.2 and 97.5%, respectively, P < 0.001). However, this reduction in male condom use was counterbalanced by the use of female condoms in 12.0% of all sexual acts in the male/female condom group, contributing to a 17% reduction in the proportion of unprotected sexual acts in this group when compared to the male condom group (5.9 versus 7.1%, respectively, P = 0.16). Female condom use was sustained over the entire study period. There was also a 24% reduction in the weighted geometric mean incidence rate of STDs in the sex establishments of the male/female condom group compared to the male condom group (2.81 versus 3.69 per 100 person-weeks, P = 0.18). Interpretation:The replacement of male condoms by female condoms in a proportion of sexual acts in the male/female condom group suggests that some sex workers and/or their clients preferred using the female condom. This switch in barrier method was accompanied by non-significant reductions in the proportion of unprotected sexual acts and in the incidence rate of STDs in the women of the male/female condom group. Special attention should be paid to a potential risk of slippage of the female condom in inexperienced users.

Protective effect of depot-medroxyprogesterone acetate on surgically treated uterine leiomyomas: a multicentre case-control study

Objective To assess the protective effect of depot‐medroxyprogesterone acetate (DMPA) on uterine leiomyomas. DMPA has been widely used in Thailand for many years; uterine leiomyomas is the most common female tumour.

Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe

Background:An association has been demonstrated between herpes simplex type 2 (HSV-2) and HIV infection among men, but prospective studies in women have yielded mixed results. Objective:To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries. Design:Prospective cohort study. Methods:HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15–24 months among 4531 sexually active, HIV-uninfected women aged 18–35 years from Uganda and Zimbabwe. The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model, adjusted for covariates. Results:HSV-2 seroprevalence at enrollment was 52% in Uganda and 53% in Zimbabwe; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Uganda and Zimbabwe, respectively. In Uganda, the hazard ratio (HR) for HIV was 2.8 [95% confidence interval (CI), 1.5–5.3] among women with seroprevalent HSV-2 and 4.6 (95% CI, 1.6–13.1) among women with seroincident HSV-2, adjusted for confounding. In Zimbabwe, the HR for HIV was 4.4 (95% CI, 2.7–7.2) among women with seroprevalent HSV-2, and 8.6 (95% CI, 4.3–17.1) among women with seroincident HSV-2, adjusted for confounding. The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42% in Uganda and 65% in Zimbabwe. Conclusions:HSV-2 plays an important role in the acquisition of HIV among women. Efforts to implement known HSV-2 control measures, as well as identify additional measures to control HSV-2, are urgently needed to curb the spread of HIV.

phase 1 Trial of the Topical Microbicide Buffergel: Safety Results From Four International Sites

Aim: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high‐dose tolerance trial. Methods: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator (˜5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. Results: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman‐week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty‐two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. Conclusion: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.

Risk factors for HIV-1 transmission from HIV-seropositive male blood donors to their regular female partners in northern Thailand.

Objective:To describe risks for HIV transmission from male blood donors to their regular female sex partners in Chiang Mai, Thailand. Design:Cross-sectional study. Methods:From March 1992 through September 1995, 405 HIV-seropositive male blood donors (index cases) and their regular female partners were enrolled in the study. Women with risk factors for HIV infection other than sexual contact with the index male were excluded. Couples were interviewed and examined; specimens were collected for laboratory analysis. Results:Overall, 46% of the 405 women enrolled were HIV-positive. Ninety-eight per cent of male index cases had a history of sex with a female prostitute; 1.5% reported always using condoms with their regular partner. History of sexually transmitted disease (STD) and swollen inguinal lymph nodes in the female partner were associated with an increased risk of HIV infection in the female. History in the female of genital herpes [odds ratio (OR), 3.46; 95% confidence interval (CI), 1.50–8.78], gonorrhea or chlamydia infection (OR, 2.71; 95% CI, 1.39–5.53), and stable relationship of longer than 24 months (OR, 2.28; 95% CI, 1.02–5.09) were associated with an increased risk of HIV infection in the female. Consistent condom use in the past 2 years (OR, 0.10; 95% CI, 0.01–0.79) was associated with a decreased risk of HIV infection in the female. Conclusions:Married women in northern Thailand who appear otherwise to be at low risk for HIV infection may be exposed to this virus by their husbands. High rates of sex with commercial sex workers among men and low use of condoms within stable relationships may be important factors promoting the transmission of HIV in married couples. Programs to increase the regular use of condoms among married couples could be an important public health intervention to prevent transmission of HIV and other types of STD in northern Thailand.

In vivo identification of Langerhans and related dendritic cells infected with HIV-1 subtype E in vaginal mucosa of asymptomatic patients

In Thailand, the predominant HIV subtype is E, rather than Subtype B as in North America and Europe, and the predominant mode of transmission is heterosexual contact. Subtype E has the ability to replicate in vitro in Langerhans cells. We hypothesized that this cell type might constitute a reservoir for the HIV virus in vaginal mucosa of asymptomatic carriers. To examine this hypothesis, we compared vaginal tissue histology in HIV-1–seropositive cases with seronegative cases and determined the immunophenotype of HIV-1–infected cells, their numbers, and their distribution in vaginal mucosa. Vaginal biopsies were performed at four different sites from six asymptomatic HIV-1 Subtype E–infected persons and from six seronegative cases at necropsy and examined histologically. Immunophenotyping was performed using immunoperoxidase for Gag p24 HIV, CD3, CD20, CD68, CD1a, S-100 and p55 antigens and by double labeling, combining immunoperoxidase with alkaline phosphatase using pairs of the above antigens. Twenty of twenty-four vaginal biopsies (83.3%) from HIV-seropositive cases showed definite inflammation compared to five of twenty-four vaginal necropsies (20.8%) from HIV-seronegative cases. One third of HIV-seropositive biopsies (8/24) demonstrated p24-positive cells in the epithelium, whereas three-fourths (18/24) of the biopsies revealed p24-positive cells in the lamina propria. All seropositive patients showed positive cells in at least one biopsy, but not all biopsies contained positive cells. Infected cells were more frequently observed at sites of greater inflammation. The dendritic cell count in HIV-seropositive vaginal epithelium was significantly higher than that observed in the seronegative cases (P =.004). The majority of p24-positive cells in the vaginal epithelium were Langerhans cells (CD1a+/S-100+), whereas in the lamina propria, about half of p24-positive cells were Langerhans-related dendritic cells (p55+ and S-100+) and half were T lymphocytes. In conclusion, the increased propensity for heterosexual transmission of Subtype E may be related to vaginal inflammation, leading to the accumulation of Langerhans cells and related dendritic cells which, once infected with HIV, can act as a reservoir for further virus transmission.

Chronic inflammation with increased human immunodeficiency virus (HIV) RNA expression in the vaginal epithelium of HIV-infected Thai women

Thai residents have a greater risk of heterosexual transmission of human immunodeficiency virus (HIV) than do US residents. To analyze host factors associated with heterosexual transmission, vaginal epithelial biopsies from HIV-seropositive Thai and US women were evaluated for tissue virus load and histologic makeup. In all, 84% of Thai and 14% of US women exhibited a chronic inflammatory T cell infiltrate in the vaginal epithelium. In Thai tissue, the infiltrate was associated with elevated levels of HIV RNA in the epidermis. Uninfected Thai women also had vaginal epithelial inflammation. Inflammation did not correlate with sexually transmitted diseases or HIV disease stage. The higher rates and increased risk of heterosexual transmission in Thailand may be due to chronic inflammation at the site where the virus is transmitted, which leads to the accumulation of activated T cells. Such cells might act as targets for initial viral infection and subsequently as reservoirs that support efficient transmission.

Acceptability of the female condom among sex workers in Thailand: results from a prospective study.

Background The female condom may provide women with the first female-controlled barrier method that is effective against sexually transmitted diseases, including HIV infection. Goal This study evaluated the acceptability of the female condom among sex workers in Thailand. Study Design Data on use and acceptability of the female condom were collected using a structured questionnaire during an 8-week follow-up. Results Analyses included 148 women who were still in follow-up at week 8. Sex workers used, on average, 2.8 female condoms per week. The overall satisfaction rate with the female condom was 68%, although, among users, 31% had difficulties in device insertion, 37% had pain from the inner ring, and 22% reported itching sensations. The main reason for using the female condom in the future was its perceived safety, and the main reason for not using it would be the client’s refusal. Conclusion Two-thirds of the sex workers were satisfied with the female condom. Difficulties at insertion, discomfort during use, and clients’ attitude were potential obstacles to the use of the female condom in the future.