Acceptability of COL-1492, a vaginal gel, among sex workers in one Asian and three African cities.

OBJECTIVES: To evaluate the acceptability of COL-1492, a vaginal gel containing 52.5 mg nonoxynol-9, in an HIV prevention trial. METHODS: Sex workers participating in a phase II/III triple blind, randomised trial in Benin, Côte d'Ivoire, South Africa, and Thailand were interviewed on the gel's acceptability at monthly scheduled clinic visits. Safer sex counselling, male condoms, and study gels were given at each monthly visit; a gynaecological examination and HIV test were performed. Phase III interviews considered the participants' appreciation of the gel. On the first, second, and fifth follow up visits, the study volunteers completed more extensive questionnaires. RESULTS: Responses were similar between treatment arms. Women indicated not liking their gel in 1.8% of the visits; 98.1% of the women found the gel easy to apply; 30.1% said that it affected sexual intercourse. These effects were mostly improvements (92.6%) by facilitating intercourse (73.6%). Intercourse was more often affected in women reporting painful sexual intercourse (OR: 2.59 (95% CI 1.63 to 4.12)) and in older women. The latter effect differed among centres. CONCLUSION: Most participants found their assigned gel acceptable and the vast majority of reported effects on intercourse were favourable. The type of gel had no significant impact on the findings.

Cervicovaginal secretory antibodies to human immunodeficiency virus type 1 (HIV-1) that block viral transcytosis through tight epithelial barriers in highly exposed HIV-1-seronegative African women.

Antibodies to human immunodeficiency virus (HIV) of the IgA, IgG, and IgM isotypes and high levels of the HIV suppressive beta-chemokine RANTES (regulated on activation, normally T cell expressed and secreted) were found in the cervicovaginal secretions (CVSs) of 7.5% of 342 multiply and repeatedly exposed African HIV-seronegative female sex workers. The antibodies are part of a local compartmentalized secretory immune response to HIV, since they are present in vaginal fluids that are free of contaminating semen. Cervicovaginal antibodies showed a reproducible pattern of reactivity restricted to gp160 and p24. Locally produced anti-env antibodies exhibit reactivity toward the neutralizing ELDKWA epitope of gp41. Study results show that antibodies purified from CVSs block the transcytosis of cell-associated HIV through a tight epithelial monolayer in vitro. These findings suggest that genital resistance to HIV may involve HIV-specific cervicovaginal antibody responses in a minority of highly exposed HIV-seronegative women in association with other protecting factors, such as local production of HIV-suppressive chemokines.

Effect of interventions to control sexually transmitted disease on the incidence of HIV infection in female sex workers.

OBJECTIVE: To compare the seroincidence of HIV infection among female sex workers in Abidjan, Côte d'Ivoire before and during an intervention study to control sexually transmitted diseases (STD) and to study the effect of two STD diagnosis and treatment strategies on the prevalence of STD and on the seroincidence of HIV infection. METHOD: A screening facility for STD and HIV had been available since October 1992 for female sex workers. From June 1994, women who were HIV seronegative or HIV-2 positive during the screening could enroll in the intervention study in which participants reported once a month to a confidential clinic where they received health education, condoms and STD treatment if indicated. Women in the study were randomized either to a basic STD diagnosis and treatment strategy, which included a gynecologic examination when symptomatic, or to an intensive strategy that included a gynecologic examination regardless of symptoms. An outcome assessment every 6 months included a gynecologic examination, HIV serology and laboratory tests for STD. RESULTS: Of 542 women enrolled in the study, 225 (42%) had at least one outcome assessment. The HIV-1 seroincidence rate during the intervention study was significantly lower than before the study (6.5 versus 16.3 per 100 person-years; P = 0.02). During the study, the HIV-1 seroincidence rate was slightly lower in the intensive than in the basic strategy (5.3 versus 7.6 per 100 person-years; P = 0.5). CONCLUSION: National AIDS control programs should consider adopting as policy the type of integrated approach used in this intervention study for HIV prevention in female sex workers.

Challenges in the conduct of vaginal microbicide effectiveness trials in the developing world.

Conducting a phase III trial of a vaginal microbicide in a developing country poses several important and complex ethical challenges. As part of a process to bridge the gap between ethical theory and practice, we share our experiences in performing a phase III trial of Col 1492 (Advantage S) among female sex workers at four sites world-wide; Durban, Abidjan, Cotonou and Hat Yai. The ethical challenges included: (i) difficulties in obtaining informed consent. Participants were unable to grasp the concepts of a clinical trial for several weeks to months. In Cotonou, 30% of the women did not know the gel was tested for HIV prevention. Only 25% understood what a placebo was. In Durban, 70% of the women did not fully understand the study after 3 months; (ii) in sustaining the use of known HIV prevention strategies. Participants at the Durban site had difficulty in sustaining condom use due to financial and client preferences. Sex without condoms was worth more ($20) than sex with condoms ($10); (iii) in maintaining the confidentiality of the subject's HIV status. Novel approaches such as role plays and emphasis on other exclusion criteria were needed to maintain the confidentiality of women not included in the trial due to their HIV status; (iv) in providing care and support to the subjects who became infected with HIV during the trial. Women could only be offered routine sexually transmitted disease treatment and counselling. Anti-retrovirals were not offered. The successes and failures of the solutions attempted are described.

Cervicovaginal anti-HIV antibodies in HIV-seronegative female sex workers in Abidjan, Côte d'Ivoire.

OBJECTIVE: To detect anti-HIV antibodies in cervicovaginal secretions of HIV-seronegative female sex workers and to evaluate whether the presence of these antibodies is associated with increased sexual exposure. METHODS: A cross-sectional study was carried out at a confidential clinic for female sex workers in Abidjan, Côte d'Ivoire. The participants were 342 HIV-seronegative female sex workers in whom a cervicovaginal lavage was collected. The main outcome measures were the detection of antibodies to HIV-1 in cervicovaginal lavages using an in-house and a commercial (Seradyn Sentinel; Calypte Biomedical Corporation, Berkeley, California, USA) enzyme immunoassay; the detection of semen in cervicovaginal lavages; and the assessment of epidemiological and biological markers of sexual exposure to HIV. RESULTS: Cervicovaginal anti-HIV antibodies were detected in 7.3 and 29.8% of women using in-house enzyme-linked immunosorbent assay (ELISA) and Seradyn Sentinel respectively. All cervicovaginal secretions found to be positive by in-house ELISA were also positive by Seradyn Sentinel. In a minority of women, ranging from 2.9% by in-house ELISA to 12.3% by Seradyn Sentinel, the anti-HIV antibodies were present in vaginal fluids that did not contain semen. Sexual exposure to HIV was similar in women with anti-HIV antibodies in their semen-free cervicovaginal secretions compared with women without anti-HIV antibodies in their cervicovaginal secretions. CONCLUSIONS: Cervicovaginal HIV-specific antibodies were detected in a minority of sexually exposed HIV-seronegative female sex workers in Abidjan. The lack of association between increased sexual exposure to HIV and presence of cervicovaginal HIV-specific antibodies suggests that the production of genital HIV-specific antibodies in exposed seronegative women depends on the ability of individual women to mount specific mucosal immunity to HIV antigens, the determinants of which are currently unknown.

Evaluation of an HIV saliva test for the detection of HIV-1 and HIV-2 antibodies in high-risk populations in Abidjan, Côte d'Ivoire.

To evaluate saliva testing in a West African field situation where both HIV-1 and HIV-2 are present, a cross-sectional study was conducted among female sex workers (FSWs) and their stable male partners (SMPs) at a STD/HIV clinic in Abidjan, Côte d'Ivoire. Saliva samples were collected with the Omni-SAL device and tested for antibodies to HIV-1 or HIV-2 by GACELISA. The HIV seroprevalence was 71% among 468 FSWs and 61% among 31 SMPs. Salivary HIV antibodies were detected in all 227 HIV-1-seropositive, in all 6 HIV-2-seropositive and in 115 of 117 dually seroreactive participants, while no salivary HIV antibodies were detected in 148 of 149 seronegative participants. The sensitivity and specificity of the saliva test were 99.4% and 99.3% respectively, and the positive and negative predictive values were 99.7% and 98.7% respectively. In this West African field situation saliva testing has a high validity compared to serum testing. The Omni-SAL and GACELISA combination is an alternative strategy to serological testing because of its high sensitivity and specificity, the ease and safety of sample collection and its relatively low cost.

Evaluation of simple diagnostic algorithms for Neisseria gonorrhoeae and Chlamydia trachomatis cervical infections in female sex workers in Abidjan, Côte d'Ivoire.

OBJECTIVE: To generate simple algorithms for the diagnosis of cervical infection with Neisseria gonorrhoeae or Chlamydia trachomatis in female sex workers in Abidjan, Côte d'Ivoire and to evaluate their validity. METHODS: From October 1992 to the end of June 1993, female sex workers were interviewed and clinically examined at a confidential clinic. N gonorrhoeae was cultured on modified Thayer-Martin medium and C trachomatis was detected by polymerase chain reaction. The associations of gonococcal or chlamydial cervical infection with sociodemographic, behavioural, clinical, and biological factors were assessed and three algorithms were generated. The validity parameters of these diagnostic algorithms were calculated and compared to those of standard algorithms and mass treatment. RESULTS: Among 683 women, cervical infection was present in 239 (35%). The sensitivity an algorithm incorporating sociodemographic and behavioural factors and symptoms, of an algorithm incorporating clinical signs and simple laboratory tests, and of a combined algorithm was 83%, 86%, and 79% respectively while the specificity was 32%, 44%, and 54%, and the positive predictive value 40%, 46%, and 48% respectively. A standard algorithm incorporating only the symptom vaginal discharge, and a standard algorithm requiring both the symptom vaginal discharge and the presence of an endocervical mucopurulent discharge on examination had a sensitivity of 44% and 18%, a specificity of 75% and 95%, and a positive predictive value of 49% and 67% respectively. CONCLUSIONS: The algorithms generated in this study may be useful for the control of cervical infections in female sex workers in resource poor settings in the absence of rapid, inexpensive, and accurate laboratory tests for the diagnosis of cervical infections.

The associations between cervicovaginal HIV shedding, sexually transmitted diseases and immunosuppression in female sex workers in Abidjan, Côte d'Ivoire.

OBJECTIVE: To measure the frequency and associated factors of cervicovaginal HIV shedding and to determine the impact of sexually transmitted disease (STD) treatment on HIV shedding. DESIGN: Cross-sectional study with 1-week follow-up. SETTING: Confidential clinic for female sex workers in Abidjan, Côte d'Ivoire. PARTICIPANTS: A total of 1201 female sex workers. INTERVENTIONS: STD treatment based on clinical signs. MAIN OUTCOME MEASURES: HIV serostatus; cervicovaginal HIV shedding at enrollment and at 1-week follow-up; STD status at enrollment and at 1-week follow-up. RESULTS: Cervicovaginal shedding of HIV-1 in HIV-1-seropositive women was more frequent (96 out of 404, 24%) than shedding of HIV-2 in HIV-2-seropositive women [one out of 21, 5%; odds ratio (OR), 6.2; 95% confidence interval (CI), 1.0-261]. Among 609 HIV-1-seropositive or dually seroreactive women, HIV-1 shedding was significantly more frequent in immunosuppressed women [adjusted OR (AOR), 6.3; 95% CI, 3.4-11.9; and AOR, 2.9; 95% CI, 1.6-5.0 for CD4 < 14% and CD4 14-28%, respectively, versus CD4 > 28%], and in women with Neisseria gonorrhoeae (AOR, 1.9; 95% CI, 1.2-3.0), those with Chlamydia trachomatis (AOR, 2.5; 95% CI, 1.1-5.8), and with a cervical or vaginal ulcer (AOR, 3.9; 95% CI, 2.1-7.4). HIV-1 shedding decreased from 42 to 21% (P < 0.005) in women whose STD were cured. CONCLUSIONS: These data help to explain the difference in transmissibility between HIV-1 and HIV-2 and the increased infectiousness of HIV in the presence of immunosuppression and STD. In addition, they lend biological plausibility to arguments for making STD control an integral part of HIV prevention strategies in Africa.

Sexually transmitted diseases and human immunodeficiency virus infections in women attending an antenatal clinic in Abidjan, Côte d'Ivoire.

A cross-sectional survey was conducted among women attending an antenatal clinic in Abidjan to determine the prevalence of sexually transmitted diseases (STDs) and HIV infection, and to identify factors associated with the presence of gonococcal and/or chlamydial cervical infection. Among 546 women, 3.7% had a gonococcal infection and 5.5% had a chlamydial infection. The seroprevalence of syphilis and HIV was 1.1% and 16.2% respectively. Gonococcal and/or chlamydial cervical infection was associated with young age, the presence of endocervical mucopus and with more than 10 polymorphonuclear leucocytes per high power field in a vaginal smear. None of these associated factors had a large enough predictive value to allow its use as a diagnostic criterion. Sexually transmitted diseases are common in pregnant women in Abidjan. The development of rapid, inexpensive diagnostic tests for STD is a priority to improve the care of women attending antenatal clinics in the developing world.

Genital ulcers associated with human immunodeficiency virus-related immunosuppression in female sex workers in Abidjan, Ivory Coast.

A cross-sectional study among female sex workers in Abidjan was conducted to study the association between sexually transmitted diseases and human immunodeficiency virus (HIV) infection and HIV-related immunosuppression. Among 1209 women tested for HIV, 962 (80%) were seropositive. HIV infection was independently associated with a longer duration of sex work, a lower price for intercourse, being an immigrant, and having a positive Treponema pallidum hemagglutination test (P < .05). Genital ulcers (25% vs. 5%), genital warts (14% vs. 4%), Neisseria gonorrhoeae (32% vs. 16%), Trichomonas vaginalis (27% vs. 17%), and syphilis (27% vs. 17%) were more frequent (P < .05) in HIV-infected than -uninfected women. Among HIV-infected women, the proportions with a genital ulcer were 17%, 25%, and 36% for those with > 28%, 14%-28%, and < 14% CD4 cells, respectively (P < .001). This study suggests that genital ulcers are an opportunistic disease in female sex workers in Abidjan.

Dual seroreactivity to HIV-1 and HIV-2 in female sex workers in Abidjan, Côte d'Ivoire.

OBJECTIVE: To determine the absolute and proportional prevalence of dual seroreactivity to HIV-1 and HIV-2 in female sex workers in Abidjan, to determine risk determinants for this serologic profile, and to describe the associated clinical and immunological characteristics. DESIGN: Cross-sectional study. SETTING: Confidential clinic for female sex workers in Abidjan. PARTICIPANTS: Female sex workers. MAIN OUTCOME MEASURES: HIV serostatus, CD4+ counts, women with AIDS, behavioural and sociodemographic characteristics. RESULTS: Among 1209 women tested, the overall HIV seroprevalence was 80%, while the prevalence of dual seroreactivity was 30%. Dual seroreactivity accounted for 38% of all HIV infections. Compared with women reacting to HIV-1 only, dually seroreactive women were significantly more likely to have been in sex work for a longer period, to be aged > or = 20 years, and to charge less money for intercourse. No difference in mean CD4+ count was noted between women with dual seroreactivity (561 x 10(6)/l) and HIV-1-seropositive women (558 x 10(6)/l). CONCLUSIONS: Female sex workers in Abidjan had the highest absolute (30%) and proportional rate (38%) of dual seroreactivity yet described in any population. Increased sexual exposure is associated with an increased risk of dual seroreactivity. Although better molecular diagnostic techniques are required, a substantial proportion of female sex workers in Abidjan is likely to be infected with both HIV-1 and HIV-2.