Factors influencing SARS-CoV-2 infection rate in Belgian nursing home residents during the first wave of COVID-19 pandemic.

In April 2020, Belgium experienced high numbers of fatal COVID-19 cases among nursing home (NH) residents. In response, a mass testing campaign was organised testing all NH residents and staff. We analysed the data of Flemish NHs to identify institutional factors associated with increased SARS-CoV-2 infection rates among NH residents. Cross-sectional study was conducted between 8 April and 15 May 2020. Data collected included demographics, group category (i.e. staff or resident), symptom status and test result. We retrieved additional data: number of beds and staff, type of beds (level of dependency of residents) and ownership (public, private for profit/non-profit institutions). Risk factor analysis was performed using negative binomial regression. In total, 695 NHs were included, 282 (41%) had at least one resident tested positive. Higher infection rate among residents was associated with a higher fraction of RVT beds, generally occupied by more dependent residents (incidence rate ratio (IRR) 1.97; 95% CI 1.00-3.86) and higher staff infection rate (IRR 1.89; 95% CI 1.68-2.12). No relationship was found between other investigated NH characteristics and infection rate among residents. Staff-resident interactions are key in SARS-CoV-2 transmission dynamics. Vaccination, regular staff testing, assessment of infection prevention and control strategies in all NHs are needed to face future SARS-CoV-2 epidemics in these settings.

A venue-based HIV prevalence and behavioural study among men who have sex with men in Antwerp and Ghent, Flanders, Belgium, October 2009 to March 2010.

This venue-based, cross-sectional study reports on human immunodeficiency virus (HIV) prevalence and behaviour of 649 men who have sex with men (MSM) in Antwerp and Ghent, Flanders, Belgium, from October 2009 to March 2010. Using time-location sampling, we found that HIV prevalence in MSM who attended different types of venue ranged from a high of 14.5% (95% CI: 8.9­20.1; n=22 in cruising venues to 4.9% (95% CI: 1.9­7.9; n=10) in more general gay venues to 1.4% (95% CI: 0.0­3.6; n=3) at younger MSM venues. Of those who tested HIV positive (n=35, five were unaware of their HIV status or self-reported as being HIV negative. One in five respondents were of non-Belgian nationality. The results showed relatively high rates of testing for HIV (52.2%; 95 % CI: 47.8­56.2; n=288) and other sexually transmitted infections (STIs) (57.4%; 95% CI: 52.6­62.0; n=248) in the last 12 months. A majority of the men (n=233) used condoms consistently during their last anal sexual contact with a casual partner; however, HIV-positive men who were aware of their serostatus (n=30) reported less condom use with casual partners. This is the first such study in Belgium and the results constitute the evidence base for local, targeted interventions. Furthermore, our findings underscore the need for European cross-border cooperation to prevent HIV infection and other STIs among MSM.

Case series on acute HCV in HIV-negative men in regular clinical practice: a call for action.

BACKGROUND: The evidence that HIV treatment as prevention (TasP) and HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV transmission is overwhelming. But as PrEP and TasP can lead to increased sexual mixing between HIV positive and negative men who have sex with men (MSM), sexually transmitted infections such as acute hepatitis C (HCV), which were thought to be limited to HIV-infected MSM, could become more frequent in HIV uninfected MSM as well. The objective of this study was to describe a series of cases of sexually transmitted HCV infections in HIV-uninfected MSM in the Netherlands and Belgium. METHODS: Through the Dutch Acute HCV in HIV Study (a Dutch-Belgian prospective multicentre study on the treatment of acute HCV infection, NCT02600325) and the Be-PrEP-ared study (a PrEP project in Antwerp, EudraCT2015-000054-37) several acute HCV infections were detected in HIV-negative men. RESULTS: A newly acquired HCV infection was diagnosed in ten HIV-negative MSM. HCV was diagnosed at a sexually transmitted infection (STI) clinic (n = 2), by their general practitioner (n = 2), by their HIV physician (n = 1) or at a PrEP clinic (n = 5). Ten patients reported unprotected anal intercourse and four had a concomitant STI at the time of HCV diagnosis. Six patients reported using drugs during sex. CONCLUSIONS: Our observation calls for a larger nationwide epidemiological study on the prevalence, incidence and risk factors of HCV infection in HIV-uninfected MSM. In the changing landscape of TasP and PrEP, reliable and up-to-date epidemiological data on HCV among HIV-uninfected MSM are needed and will help in developing evidence-based testing policies.

Heterosexual transmission of HIV.

PIP: Recent developments concerning heterosexual transmission of HIV (review of 1988 literature only) suggest improved understanding of the pattern of spread and role of risk behaviors and biological cofactors in its transmission. 3 distinct patterns if HIV infection are known: heterosexual spread in sub-Saharan Africa and the Caribbean, spread primarily among homosexuals and injecting drug users in Europe, North American and much of Latin America and Australia, and both homosexual and heterosexual transmission in Asia, the Pacific, the Middle East and Eastern Europe, where prevalence is low. In Africa an estimated 80% of cases are acquired heterosexually. Important risk factors are number of sex partners, sex with prostitutes, being a prostitute, being a sex partner of an infected person, and having a history of other sexually transmitted diseases. Prevalence rates have risen rapidly in Zaire and Kenya. In Africa, acquisition of HIV is related to sexual activity only. In contrast, in the U.S., heterosexual cases make up only 4% of all cases, and in Europe only 6%. Data on types of sexual transmission of HIV are mounting, in aggregate suggestive of a marked heterogeneity in infectivity and possibly susceptibility between individuals. Among couples where the man is positive, in some places individuals appear to be highly infective, notably those from Kinshasa, Zaire and Haiti, while other series of discordant couples the receptive partner remained seronegative for several years. Transmission from women to men appears to be less efficient than from men to women, as has been observed with other STDs such as gonorrhea. Biological cofactors implicated in enhanced HIV transmission appear to be advanced CDC Stage IV AIDS disease, with low T-helper lymphocyte counts and high antigenemia; concomitant STDS, especially those with genital ulceration; lack of circumcision; oral contraceptive use; practice of anal intercourse; inconsistent or no use of condoms. Theoretical models for future heterosexual spread emphasize number of partners, use of condoms, and treatment of STDs.^ieng

The interrelationship of sexually transmitted diseases and HIV infection: implications for the control of both epidemics in Africa.

PIP: There is a high burden of sexually transmitted diseases (STDs) in many parts of Africa. As for HIV, the highest rates of STDs are found in urban men and women aged 15-35 years. STDs may be responsible for up to 17% of productive life years lost to disease in sub-Saharan urban populations. Despite this heavy burden of STDs, however, their diagnosis and treatment remain neglected by public health in most of the developing world. Many factors drive the epidemiology of STDs in Africa. The disproportionate number of men relative to women in many cities prompts many men in urban areas to have sex with a core group of prostitutes who facilitate the spread of STDs. In other cities, the frequent change of sex partners, economic factors, access to health services, lack of health education, health seeking behavior, and lack of political will play roles in the spread of STDs. Genital ulcer disease is also more frequent in Africa than in developed countries. The authors discuss the interactions between HIV and other STDs, the impact of HIV infection upon other STDs, the impact of the HIV/STD interactions upon the HIV and STD epidemics, and implications for STD and HIV control programs.^ieng

Advanced immunodeficiency as a risk factor for heterosexual transmission of HIV.

To define the rate of HIV infection and associated risk factors among heterosexual partners of HIV-infected individuals, 80 partners and 77 index cases were examined for clinical, behavioural and virological variables. The study population included 61 male and 16 female index cases, of whom 40 were European and 37 African. Multiple sexual partners in central Africa was the risk factor for HIV infection in 83%. The overall infection rate among the contact cases was 45%, 53% among female partners and 13% among male partners (P less than 0.001). Variables significantly associated with HIV infection in the partners included advanced clinical stage (AIDS-related complex or AIDS), a low concentration of T4 lymphocytes and African nationality of the index case, young age of the partner, and more than 50 instances of sexual contact with the index cases. In a logistic regression analysis, a low concentration of T4 lymphocytes, clinical stage ARC/AIDS and African nationality of the index case but not number of sexual contacts, remained as independent risk factors for HIV transmission. Our data indicate that there is a significant biological heterogeneity in sexual transmission of HIV and that advanced clinical stage and severe T cell depletion of the index case are major determinants of infectivity.

Safety of multiple daily applications of COL-1492, a nonoxynol-9 vaginal gel, among female sex workers. COL-1492 Phase II Study Group.

RATIONALE: COL-1492 is a nonoxynol-9 (N-9)-containing vaginal gel and may be a potential microbicide. As part of an effectiveness trial, an initial toxicity study was conducted. OBJECTIVES: The main objective of the reported study was the assessment of the toxicity of a 52.5 mg N-9 gel, COL-1492, when used a number of times each day by female sex workers. METHODS: This was a randomized, placebo-controlled triple-blinded trial among female sex workers. The participants were asked to use the product for each vaginal sexual act. At each monthly visit a gynaecological examination with sexually transmitted disease sampling and colposcopy was performed. Venous blood was drawn for syphilis and HIV serology. All women received intensive counselling on condom use. Male condoms and sexually transmitted disease treatment were given free of charge. RESULTS: Only blinded results on the colposcopic examinations are reported. The incidence of lesions with or without an epithelial disruption was low: 0.06 and 0.29, respectively, per 100 woman-days in group A; 0.09 and 0.26 respectively per 100 woman-days in group B. There was no significant difference between the two arms. CONCLUSION: The multiple daily use of COL-1492 by female sex workers did not show an increase of local toxicity over that of a placebo. Colposcopy was discontinued in the autumn of 1997 in accordance with a Data Safety Monitoring Board decision. In the currently ongoing effectiveness trial the assessment of the product's toxicity continues to be monitored by simple visual examination.

Phase 1 trial of nonoxynol-9 film among sex workers in South Africa.

OBJECTIVES: To assess the acceptability and safety of a vaginal nonoxynol-9 film in a group of sex workers at a truck stop in South Africa. DESIGN: A randomized double-blinded crossover trial was conducted between April 1995 and July 1995. INTERVENTION: Seventy-two mg nonoxynol-9 film and an identical glycerine placebo film. METHODS: Following informed consent, each study participant was randomly assigned the designated pre-coded film for 1 month. The second month was a film-free washout period and the participants used the alternate film in the third month. Besides measuring behavioural and clinical outcomes, colposcopy examination for genital lesions, serology and microbiology investigations for sexually transmitted diseases and semi-quantitative PCR for vaginal HIV load estimates were performed. RESULTS: Twenty women participated in the study. The women reported, on average, 19 sexual encounters per week. Vaginal intercourse was protected 25% of the time by condoms. On average, 11 vaginal films, either nonoxynol-9 or placebos were inserted per week. There were no statistically significant differences between the two treatment groups for genital lesions (P = 0.29), reported side effects (P = 0.73), and viral load (P = 0.9). However, the proportions of clinically detected genital lesions (six out of eight versus two out of eight) and self-reported side-effects (five out of eight versus three out of eight) were higher in the nonoxynol-9 group when compared with the placebo group. Incident sexually transmitted diseases occurred more frequently in the placebo group. An increased viral load was associated with the development of a genital lesion (relative risk, 6.0; 95% confidence interval, 0.81-44.4). CONCLUSIONS: The 72 mg film formulation of nonoxynol-9 was an acceptable product for use in this population of sex workers. Although no statistically significant differences in adverse outcomes were detected, clinically there appeared to be an increase in minor lesions and self-reported side-effects with nonoxynol-9 and less protection against sexually transmitted diseases with the placebo. Furthermore, HIV shedding was correlated with the presence of incident vaginal or cervical lesions. This brings into question the potential narrow margin of safety for this product; additional Phase 2 studies are therefore required.

AIDS in Africa: the first decade and challenges for the 1990s.

PIP: In less than a decade, AIDS has spread throughout Africa. The authors review what is known about the current situation of HIV infection in Africa, with emphasis upon sub-Saharan Africa, and identify questions and challenges for AIDS control and prevention in the 1990s. Well-conducted random cluster surveys have shown that in some urban centers as many as one adult in three is infected, but that in other countries less than 1% of the population is infected. There are many different HIV/AIDS epidemics interwoven across the continent, although the prevailing modes of HIV transmission are identical throughout Africa. Patterns of behavior vary widely across Africa. There are major differences between and even within African countries in the rate of spread of HIV, the level of presumed stabilized seroprevalence rate, the male-to-female ratio of AIDS cases and the number of people with HIV infection, the spread of the epidemic to rural areas, and the socioeconomic groups involved. Many different behavioral, biological, and social factors explain this heterogeneity. It remains clear, however, that AIDS is exacting a heavy toll upon many African populations. Even in a city as recently affected as Abidjan, AIDS has become the leading cause of death in adult men, and second only to deaths related to pregnancy and abortion in women. The vast majority of Africans infected with HIV remain deprived not only of any antiretroviral therapy, but also of treatment of many opportunistic infections and sometimes of the most basic care. Community support for AIDS patients is developing in a few areas with large numbers of cases.^ieng

Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study.

OBJECTIVES: The heterosexual spread of HIV-1 is occurring at different rates in different parts of the world. The transmission probability of HIV-1 per sexual contact is low, but may be greatly enhanced by several cofactors. Sexually transmitted diseases (STD), especially genital ulcers, may be such factors. So far, epidemiological evidence that other STD facilitate HIV-1 transmission is weak. The objective of this study was to determine whether treatable STD enhanced sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa, Zaire. METHODS: We conducted a nested case-control study of 431 initially HIV-1-negative women followed prospectively for a mean duration of 2 years (with monthly STD check-ups and 3-monthly HIV-1 serology). Cases (seroconverters, n = 68) were compared with controls (women who remained HIV-1-negative, n = 126) for incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition. RESULTS: The annual incidence of HIV-1 in this cohort was 9.8%. Seroconverters were younger than HIV-1-negative women (mean age, 24.6 versus 26.8 years; P = 0.04). During the period of HIV-1 acquisition, cases had a much higher incidence of gonorrhoea, chlamydial infection and trichomoniasis, and engaged in unprotected sex with clients and partners more frequently than controls. After controlling for sexual exposure by multivariate analysis, adjusted odds ratios for seroconversion were 4.8 [95% confidence interval (CI), 2.4-9.8] for gonorrhoea, 3.6 (95% CI, 1.4-9.1) for chlamydial infection and 1.9 (95% CI, 0.9-4.1) for trichomoniasis. Genital ulcers were more frequent in cases than controls, but much less common than other STD. CONCLUSION: Non-ulcerative STD were risk factors for sexual transmission of HIV-1 in women, after controlling for sexual exposure. Because of their high prevalence in some populations, non-ulcerative STD may represent a considerable population-attributable risk in the transmission of HIV-1 worldwide. The identification of treatable STD as risk factors for HIV-1 transmission offers an important additional strategy for the prevention of HIV/AIDS.

PIP: There is only a small probability that HIV-1 will be transmitted via any single sexual contact. The risk of transmission, however, during such an act may be greatly increased by the presence of ulcerative genital sexually transmitted disease (STD). Little evidence is published on whether infection with non-ulcerative STD facilitates the transmission of HIV-1. The authors therefore investigated whether treatable STD enhanced the sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa, Zaire. 431 initially HIV-1-seronegative women were followed prospectively in this nested case-control study for a mean duration of two years in monthly STD check-ups and three-monthly HIV-1 serology. The 68 women who seroconverted were compared against the 126 women who remained HIV-1-seronegative for the incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition. There was a 9.8% annual incidence of HIV-1 in this cohort of subjects. Seroconverters were of mean age 24.6 years compared to 26.8 years for the HIV-seronegative women. During the period of HIV-1 acquisition, cases had a much higher incidence of gonorrhea, chlamydial infection, and trichomoniasis, and engaged in unprotected sex with clients and partners more frequently than controls. After controlling for sexual exposure by multivariate analysis, adjusted odds ratio for seroconversion were 4.8 for gonorrhea, 3.6 for chlamydial infection, and 1.9 for trichomoniasis. Genital ulcers were more frequent in cases than controls, but much less common than other STD. These findings therefore suggest that non-ulcerative STDs were risk factors for the sexual transmission of HIV-1 in these women. Such STD may be a considerable population-attributable risk in the transmission of HIV-1 worldwide given the high prevalence of non-ulcerative STDs in some populations.

Evaluation of the WHO clinical case definition for AIDS in rural Zaire.

The clinical case definition for AIDS proposed by WHO for use in Africa was evaluated against HIV antibody status in 72 patients in rural Zaire. Twenty-one (29%) of the patients were antibody-positive. For diagnosing anti-HIV seropositivity, the case definition had a sensitivity of 52%, a specificity of 78%, a positive predictive value of 50% and a negative predictive value of 80%. Calculation of the positive predictive value at different levels of prevalence of HIV infection suggests that the case definition operates at maximum reliability in selected high-risk groups. Modifications to the case definition should be evaluated to try and improve its sensitivity and positive predictive value.

PIP: In many areas of Africa where AIDS is endemic, facilities for laboratory diagnosis are too limited to reliably diagnose opportunistic infections. Therefore, the World Health Organization defined a clinical case definition of AIDS in which 2 major signs and at least 1 minor sign must be present to diagnose AIDS. The major signs are: weight loss greater than 10%, diarrhea for more than 1 month, and prolonged fever for more than 1 month. The minor signs are: persistent cough for more than 1 month, generalized pruritic dermatitis, recurrent herpes zoster, oropharyngeal candidiasis, chronic disseminated herpes simplex, and generalized lymphadenopathy. (The presence of Kaposi's sarcoma or cryptococcal meningitis are sufficient by themselves for a diagnosis of AIDS.) 72 patients in 4 hospitals in Equateur Province of Zaire were used to test the reliability of the clinical case definition. 21 (29%) of the patients were HIV seropositive, and 22 (32%) fulfilled the clinical criteria. From these data the sensitivity of the case definition was 52%, specificity was 78%, positive predictive value was 50%, and negative predictive value was 80%. Since positive predictive value rises with prevalence and HIV infection is maximal in the 20-40 age group, restricting the case definition to this age group would increase its predictive value. Exclusion of patients with tuberculosis would reduce the number of false positive results.

The epidemiology of gonorrhoea, chlamydial infection and syphilis in four African cities.

OBJECTIVES: To compare the epidemiology of gonorrhoea, chlamydial infection and syphilis in four cities in sub-Saharan Africa; two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon). DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa. METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) Trichomonas vaginalis infection. Risk factor analyses were carried out for chlamydial infection and syphilis seroreactivity. RESULTS: The prevalence of gonorrhoea ranged between 0% in men in Kisumu and 2.7% in women in Yaoundé. Men and women in Yaoundé had the highest prevalence of chlamydial infection (5.9 and 9.4%, respectively). In the other cities, the prevalence of chlamydial infection ranged between 1.3% in women in Cotonou and 4.5% in women in Kisumu. In Ndola, the prevalence of syphilis seroreactivity was over 10% in both men and women; it was around 6% in Yaoundé, 3-4% in Kisumu, and 1-2% in Cotonou. Chlamydial infection was associated with rate of partner change for both men and women, and with young age for women. At the population level, the prevalence of chlamydial infection correlated well with reported rates of partner change. Positive syphilis serology was associated with rate of partner change and with HSV-2 infection. The latter association could be due to biological interaction between syphilis and HSV-2 or to residual confounding by sexual behaviour. At the population level, there was no correlation between prevalence of syphilis seroreactivity and reported rates of partner change. CONCLUSION: Differences in prevalence of chlamydial infection could be explained by differences in reported sexual behaviour, but the variations in prevalence of syphilis seroreactivity remained unexplained. More research is needed to better understand the epidemiology of sexually transmitted infections in Africa.

The epidemiology of trichomoniasis in women in four African cities.

OBJECTIVES: To describe the epidemiology of Trichomonas vaginalis infection and its association with HIV infection, in women in four African cities with different levels of HIV infection. DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa: two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low prevalence of HIV (Cotonou, Benin and Yaoundé, Cameroon). METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) T. vaginalis infection. Risk factor analyses were carried out for trichomoniasis for each city separately. Multivariate analysis, however, was only possible for Yaoundé, Kisumu and Ndola. RESULTS: The prevalence of trichomoniasis was significantly higher in the high HIV prevalence cities (29.3% in Kisumu and 34.3% in Ndola) than in Cotonou (3.2%) and Yaoundé (17.6%). Risk of trichomoniasis was increased in women who reported more lifetime sex partners. HIV infection was an independent risk factor for trichomonas infection in Yaoundé [adjusted odds ratio (OR) = 1.8, 95% confidence interval (CI) = 0.9-3.7] and Kisumu (adjusted OR = 1.7, 95% CI = 1.1-2.7), but not in Ndola. A striking finding was the high prevalence (40%) of trichomonas infection in women in Ndola who denied that they had ever had sex. CONCLUSION: Trichomoniasis may have played a role in the spread of HIV in sub-Saharan Africa and may be one of the factors explaining the differences in levels of HIV infection between different regions in Africa. The differences in prevalence of trichomoniasis between the four cities remain unexplained, but we lack data on the epidemiology of trichomoniasis in men. More research is required on the interaction between trichomoniasis and HIV infection, the epidemiology of trichomoniasis in men, and trichomonas infections in women who deny sexual activity.

HIV and other sexually transmitted diseases among female prostitutes in Kinshasa.

In 1988, 1233 prostitutes from different geographic areas of Kinshasa participated in a cross-sectional survey on HIV infection and other sexually transmitted diseases (STDs). Despite relatively good knowledge about AIDS and STDs, the reported preventive behaviour was poor. Only 12% of the women reported regular use of condoms, while greater than 50% of the women reported regular use of antibiotics and 38% reported doing nothing specific to prevent STDs. Thirty-five per cent of the women were HIV-positive compared with 27% in a similar survey in Kinshasa in 1986. The prevalence of other STDs was very high, ranging from 5% for genital ulcer disease (GUD) to 23% for gonococcal infection. HIV-positive women were older than HIV-negative women (26.9 versus 25.4 years; P less than 0.001), had a significantly lower level of reported condom use (9 versus 14%, P = 0.009), and reported more frequent use of antibiotics to prevent STDs (55 versus 42%, P = less than 0.001). The prevalence of syphilis, gonorrhoea, chlamydial infection and trichomoniasis was not higher in HIV-positive women compared with HIV-negative women. However, HIV-positive women had a higher prevalence of GUD (9 versus 3%, P less than 0.001), antibodies against Haemophilus ducreyi (82 versus 57%, P less than 0.001), antibodies against herpes simplex virus type 2 (96 versus 76%, P less than 0.001), condylomata accuminata (5 versus 1%, P = 0.003) and cytologic evidence of human papilloma virus on Papaniclaou cervical smear (11 versus 5%, P = 0.006). This study confirms the high incidence of HIV and other STDs among prostitutes in Africa.(ABSTRACT TRUNCATED AT 250 WORDS)

Safety evaluation of nonoxynol-9 gel in women at low risk of HIV infection.

OBJECTIVE: To determine the safety of a vaginal microbicide, COL-1492, containing 52.5 mg nonoxynol-9, applied once daily for 14 days among healthy volunteers. METHODS: A randomized, double-blind controlled trial with three arms, COL-1492 gel versus placebo gel versus no-treatment controls, was conducted. Outcomes of interest were reported genital symptoms, incidence of gynaecological signs, and incidence of genital lesions revealed by colposcopy. Participants were enrolled in four centres (Belgium, The Netherlands, and two in Thailand). RESULTS: A total of 534 women participated in the study: 179 used COL-1492, 178 used placebo, and 177 were no-treatment controls. Study visits were scheduled 1 week prior to enrollment (day -7), day 0 (enrollment), day 8 and day 14. The most frequently reported genital symptom was vaginal discharge in both the COL-1492 and placebo groups. This appeared to be related to leakage of the product out of the vagina. The incidence of lesions associated with epithelial disruption (ulcers and abrasions) was very low (< 2%) and there was no statistically significant difference between the three groups. Of the lesions observed by colposcopy that did not involve epithelial disruption, petechial haemorrhage was the most frequently detected, with an incidence of 20.1, 9.0 and 7.3% in the COL-1492, placebo and control groups, respectively. COL-1492 users had a higher incidence of erythema (8.4 versus 2% in the other groups). CONCLUSION: COL-1492 showed minimal toxicity when applied once daily. A Phase III trial to assess the product's effectiveness in HIV prevention is currently ongoing.

Preclinical studies on thiocarboxanilide UC-781 as a virucidal agent.

BACKGROUND: Thiocarboxanilide UC-781 is a highly potent and selective non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1, which also has virucidal properties. Recent studies have shown that UC-781 would seem an ideal candidate for application as a vaginal virucide. OBJECTIVE: To investigate the antiviral potency and stability of UC-781 in a lipophilic gel formulation. METHODS: UC-781 was formulated in replens gel at different concentrations and administered intravaginally to rabbits at 5% in replens gel for 10 days. UC-781 was also exposed to temperatures of 4, 37 and 50 degrees C, and to low pH (6.0, 4.3, 2.0 and 1.2). A number of microorganisms were exposed in culture to serial dilutions of UC-781. RESULTS: The drug was stable under low pH conditions and did not lose its antiviral potency upon 4 h exposure to pH 3.5 (the estimated vaginal pH). UC-781 can be easily formulated into a lipophilic gel (replens; up to 5%) and proved fully stable at 50 degrees C for 30 days. There was no effect on the growth of microorganisms (i.e., Candida and Lactobacillus strains) that are present in the vaginal flora. Neither systemic side-effects, nor local inflammation or damage of the vaginal mucosa or epithelium were observed in rabbits to which 5% UC-781 in replens gel had been administered. UC-781, formulated as 0.5, 0.2 and 0.05% replens gel, and UC-38, alpha-APA and zidovudine, formulated as 0.5 or 0.2% replens gel, were effective in protecting CEM cells in the very beginning against productive HIV-1 replication. This points to an efficient diffusion of the drugs from the lipophilic gel to the hydrophilic culture medium. However, subsequent subcultivations at a dilution rate of 1:10 every 3-4 days resulted in a rapid breakthrough of virus with all drugs except UC-781 in its 0.5 and 0.2% gel formulation. These cultures were fully protected against HIV-1 and remained completely cleared from virus for at least 10 subcultivations. CONCLUSIONS: The virus that emerged under 0.05% UC-781 remained highly sensitive to the NNRTI, including UC-781, in cell culture, suggesting a lack of resistance development under our experimental conditions.

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.

HIV-1 subtypes and the HIV epidemics in four cities in sub-Saharan Africa.

OBJECTIVE: To describe the distribution of HIV-1 subtypes in two cities with high HIV prevalence (Kisumu, Kenya and Ndola, Zambia) and two with relatively low prevalence (Cotonou, Benin and Yaoundé, Cameroon), and to examine whether the differences in prevalence of HIV infection could be due to the predominance within the infected populations of subtypes with differing efficiency of heterosexual transmission. METHODS: For around 100 randomly selected HIV-positive sera from the general population and 60 from sex workers in each city, the HIV-1 subtype was determined in the envfragment. For between 19 and 52 of the sera from the general population and 20-32 sera from sex workers, the subtype was also determined in the gag fragment. RESULTS: Over 70% of infections in Cotonou, Yaoundé and Kisumu were with subtype A (by env). However, around one-half of subtype A infections in Cotonou and Yaoundé were found to be the circulating recombinant form CRF02_AG when the gag fragment was also examined. A large number of different HIV strains were found in Yaoundé, including some belonging to group O. Over 20% of infections in Kisumu and around 10% in Yaoundé were with isolated intersubtype recombinant forms. All but a few infections in Ndola were with subtype C and no recombinants were found. CONCLUSIONS: The pattern of distribution of subtypes that we found does not suggest that differences in circulating subtypes play a major role in explaining the differences in prevalence of HIV-1 infection between the four cities. The emergence and spread of recombinants requires close surveillance to adapt testing strategies if needed, to inform vaccine development and to ascertain their role in the future spread of HIV.

The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

OBJECTIVES: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. DESIGN AND METHODS: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. RESULTS: HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. CONCLUSIONS: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

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.