Fernand Guédou

Lack of Effectiveness of Cellulose Sulfate Gel for the Prevention of Vaginal HIV Transmission

BACKGROUND Women make up more than 50% of adults living with human immunodeficiency virus (HIV) infection or the acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa. Thus, female-initiated HIV prevention methods are urgently needed. METHODS We performed a randomized, double-blind, placebo-controlled trial of cellulose sulfate, an HIV-entry inhibitor formulated as a vaginal gel, involving women at high risk for HIV infection at three African and two Indian sites. The primary end point was newly acquired infection with HIV type 1 or 2. The secondary end point was newly acquired gonococcal or chlamydial infection. The primary analysis was based on a log-rank test of no difference in the distribution of time to HIV infection, stratified according to site. RESULTS A total of 1398 women were enrolled and randomly assigned to receive cellulose sulfate gel (706 participants) or placebo (692 participants) and had follow-up HIV test data. There were 41 newly acquired HIV infections, 25 in the cellulose sulfate group and 16 in the placebo group, with an estimated hazard ratio of infection for the cellulose sulfate group of 1.61 (P=0.13). This result, which is not significant, is in contrast to the interim finding that led to the trial being stopped prematurely (hazard ratio, 2.02 [corrected]; P=0.05 [corrected]) and the suggestive result of a preplanned secondary (adherence-based) analysis (hazard ratio, 2.02; P=0.05). No significant effect of cellulose sulfate as compared with placebo was found on the risk of gonorrheal infection (hazard ratio, 1.10; 95% confidence interval [CI], 0.74 to 1.62) or chlamydial infection (hazard ratio, 0.71; 95% CI, 0.47 to 1.08). CONCLUSIONS Cellulose sulfate did not prevent HIV infection and may have increased the risk of HIV acquisition. (ClinicalTrials.gov number, NCT00153777; and Current Controlled Trials number, ISRCTN95638385.)

Chemokine expression patterns in the systemic and genital tract compartments are associated with HIV-1 infection in women from Benin.

IntroductionUnderstanding the genital mucosal immunity and the factors involved in linking innate to adaptive immunity is crucial for the design of efficient preventive strategies against human immunodeficiency virus (HIV)-1.MethodsLevels of both genital mucosal and blood chemokines were compared between 58 HIV-1-uninfected and 50 HIV-1-infected female commercial sex workers (CSWs) as well as 53 HIV-1-uninfected non-CSW control women at low risk for exposure, recruited in Cotonou, Benin.ResultsHIV-1-infected CSWs had significantly higher blood and genital levels of monocyte chemotactic protein (MCP-3/CCL7) and monokine induced by gamma interferon (MIG/CXCL9) compared with those in both the HIV-1-uninfected CSW and non-CSW groups. In the HIV-1-infected group, levels of MCP-3 and MIG were significantly higher in the genital mucosa than in the blood. However, the blood levels of macrophage inflammatory protein (MIP-1a/CCL3) and MIP-1b/CCL4 were higher in HIV-1-uninfected CSWs compared with those in the other groups.ConclusionIncreased production of chemokines in the genital tract may favour the recruitment of HIV-1 target cells causing a mucosal environment that promotes viral replication and dissemination, whereas higher expression of β-chemokines at the systemic level is associated with protection from HIV-1 infection.

Intermediate vaginal flora is associated with HIV prevalence as strongly as bacterial vaginosis in a cross-sectional study of participants screened for a randomised controlled trial

Objective The authors analysed data from female sex workers screened prior to participation in a microbicide trial to examine the association between prevalent vaginal flora abnormalities and HIV infection, with special emphasis on the role of the intermediate vaginal flora (IVF) in this association. Methods Data from the Kampala, Cotonou, Chennai and Mudhol/Jamkhandi sites were analysed. Participants were interviewed and provided blood for HIV and syphilis antibody testing, genital samples for the diagnosis of vaginal flora abnormalities (using Nugent score) and other reproductive tract infections. Log-binomial regression was used to estimate the HIV prevalence ratio (PR) in relation to IVF and bacterial vaginosis (BV). Results Among 1367 women, BV, IVF and HIV prevalences were 47.6% (95% CI=45.0% to 50.3%), 19.2% (95% CI=17.1% to 21.2%) and 27.0% (95% CI=24.6% to 29.3%), respectively. In multivariate analysis, adjusting for study site, age, years of education, occupation, female sterilisation, oral sex, past history of sexually transmitted infection, gonorrhoea and candidiasis, IVF was significantly associated with HIV infection with a PR similar to that of BV (adjusted PR=1.56 (95% CI=1.22 to 1.98) and 1.48 (95% CI=1.20 to 1.84), respectively). Conclusions Though the cross-sectional design of the study precludes directional interpretation of the findings, the data do suggest that IVF may be as important as BV in HIV acquisition. The authors recommend prospective research to better understand the association between IVF and HIV acquisition.

Behavioural and medical predictors of bacterial vaginosis recurrence among female sex workers: longitudinal analysis from a randomized controlled trial

BackgroundData on risk factors of recurrent bacterial vaginosis (RBV) are still scarce. We used data from female sex workers (FSW) participating in a randomized controlled microbicide trial to examine predictors of BV recurrence.MethodsTrial’s participants with at least an episode of BV which was treated and/or followed by a negative BV result and at least one subsequent visit offering BV testing were included in the analysis. Behavioural and medical data were collected monthly while laboratory testing for STI and genital tract infections were performed quarterly. The Andersen-Gill proportional hazards model was used to determine predictors of BV recurrence both in bivariate and multivariate analyses.Results440 women were included and the incidence rate for RBV was 20.8 recurrences/100 person-months (95% confidence interval (CI) =18.1–23.4). In the multivariate analysis controlling for the study site, recent vaginal cleansing as reported at baseline with adjusted hazard-ratio (aHR)=1.30, 95% CI = 1.02-1.64 increased the risk of BV recurrence, whereas consistent condom use (CCU) with the primary partner (aHR=0.68, 95% CI=0.49-0.93) and vaginal candidiasis (aHR=0.70, 95% CI=0.53-0.93), both treated as time-dependent variables, were associated with decreased risk of RBV.ConclusionThis study confirms the importance of counselling high-risk women with RBV about the adverse effects of vaginal cleansing and the protective effects of condom use with all types of partners for the prevention of sexually transmitted infections, including BV. More prospective studies on risk factors of BV recurrence are warranted.Trial registrationTrial registration: NCT00153777

Violence condom breakage and HIV infection among female sex workers in Benin West Africa.

Objective To examine the relationship between violence, condom breakage, and HIV prevalence among female sex workers (FSWs). Methods Data were obtained from the 2012 cross-sectional integrated biological and behavioral survey conducted in Benin. Multivariable log-binomial regression was used to estimate the adjusted prevalence ratios of HIV infection and condom breakage in relation to violence toward FSWs. A score was created to examine the relationship between the number of violence types reported and HIV infection. Results Among the 981 women who provided a blood sample, HIV prevalence was 20.4%. During the last month, 17.2%, 13.5%, and 33.5% of them had experienced physical, sexual, and psychological violence, respectively. In addition, 15.9% reported at least 1 condom breakage during the previous week. There was a significant association between all types of violence and HIV prevalence. The adjusted prevalence ratios of HIV were 1.45 (95% confidence interval [95% CI], 1.05–2.00), 1.42 (95% CI, 1.02–1.98), and 1.41 (95% CI, 1.08–1.41) among those who had ever experienced physical, sexual, and psychological violence, respectively. HIV prevalence increased with the violence score (P = 0.002, test for trend), and physical and sexual violence were independently associated with condom breakage (P = 0.010 and P = 0.003, respectively). Conclusions The results show that violence is associated with a higher HIV prevalence among FSWs and that condom breakage is a potential mediator for this association. Longitudinal studies designed to analyze this relationship and specific interventions integrated to current HIV prevention strategies are needed to reduce the burden of violence among FSWs.

Short Communication: Anti-HIV-1 Envelope Immunoglobulin Gs in Blood and Cervicovaginal Samples of Beninese Commercial Sex Workers

Characterization of the immune correlates of protection against HIV infection is crucial for the development of preventive strategies. This study examined HIV-1 envelope (Env) glycoproteins, specifically immunoglobulin G (IgG), in systemic and mucosal compartments of female Beninese commercial sex workers (CSWs). Samples of 23 HIV-1-positive and 20 highly exposed HIV-1-seronegative (HESN) CSWs were studied. HIV-1 Env-specific IgG detection in sera and cervicovaginal lavages (CVLs) from the study population was done by cell-based ELISA. The HIV neutralizing activity was evaluated with a neutralization assay. The HIV-1-specific antibody-dependent cellular cytotoxicity (ADCC) response of the cohort was measured with a FACS-based assay evaluating the ADCC-mediated elimination of gp120-coated target cells. No anti-HIV-1 Env-specific IgG neutralizing or ADCC activities were detected in samples from HESN CSWs. Samples from HIV-1-infected CSWs presented ADCC activity in both sera and CVLs. Anti-Env IgG from sera and CVLs from HIV-1-infected CSWs preferentially recognized Env in its CD4-bound conformation. HIV-1-infected CSWs have ADCC-mediating IgG that preferentially recognizes Env in its CD4-bound conformation at the mucosal site.

Intermediate vaginal flora and bacterial vaginosis are associated with the same factors: findings from an exploratory analysis among female sex workers in Africa and India

Objectives Several recent studies suggest that intermediate vaginal flora (IVF) is associated with similar adverse health outcomes as bacterial vaginosis (BV). Yet, it is still unknown if IVF and BV share the same correlates. We conducted a cross-sectional and exploratory analysis of data from women screened prior to enrolment in a microbicide trial to estimate BV and IVF prevalence and examine their respective correlates. Methods Participants were interviewed, examined and provided blood and genital samples for the diagnosis of IVF and BV (using Nugent score) and other reproductive tract infections. Polytomous logistic regressions were used in estimating respective ORs of IVF and BV, in relation to each potential risk factor. Results Among 1367 women, BV and IVF prevalences were 47.6% (95% CI 45.0% to 50.3%) and 19.2% (95% CI 17.1% to 21.2%), respectively. Multivariate polytomous analysis of IVF and BV showed that they were generally associated with the same factors. The respective adjusted ORs were for HIV 1.98 (95% CI 1.37 to 2.86) and 1.62 (95% CI 1.20 to 2.20) (p=0.2248), for gonorrhoea 1.25 (95% CI 0.64 to 2.4) and 2.01 (95% CI 1.19 to 3.49) (p=0.0906), for trichomoniasis 3.26 (95% CI 1.71 to 6.31) and 2.39 (95% CI 1.37 to 4.33) (p=0.2630), for candidiasis 0.52 (95% CI 0.36 to 0.75) and 0.59 (95% CI 0.44 to 0.78) (p=0.5288), and for hormonal contraception 0.65 (95% CI 0.40 to 1.04) and 0.62 (95% CI 0.43 to 0.90) (p=0.8819). In addition, the association between vaginal flora abnormalities and factors such as younger age, HIV, gonorrhoea trichomoniasis and candidiasis were modified by the study site (all p for interaction ≤0.05). Conclusions IVF has almost the same correlates as BV. The relationship between some factors and vaginal flora abnormalities may be site-specific.

Outreach strategies for the promotion of HIV testing and care: closing the gap between health services and female sex workers in Benin.

Background:Regular voluntary counseling and testing is a key component of the fight against HIV/AIDS. In Benin, the project SIDA-1/2/3 established to decrease HIV/sexually transmitted infection (STIs) among female sex workers (FSWs), implemented a multifaceted intervention, including outreach activities. The objective of this article was to present potential advantages and limitations of 3 categories of outreach interventions designed to increase the use of testing services among FSWs in Benin. Methods:This analysis is based on ethnographic fieldwork conducted in Benin from June to December 2012. Results:Sixty-six FSWs and 24 health care workers were interviewed. Their narratives revealed 3 main factors impeding the development of appropriate HIV testing behavior. These negative elements can be positioned along a continuum of health care behaviors, with each stage of this continuum presenting its own challenges: fear or lack of motivation to use testing services, inaccessibility of care when the decision to go has been made, and a perceived lack of quality in the care offered at the health care center. Many of these needs seem to be addressed in the outreach strategies tested. However, the study also exposed some potential barriers or limitations to the success of these strategies when applied in this specific context, due to social disruption, mobility, access to care, and hard to reach population. Conclusions:To increase the use of testing services, an outreach strategy based on community workers or peer educators, along with improved access to testing services, would be well adapted to this context and appreciated by both FSWs and health care workers.

Understanding the intention to undergo regular HIV testing among female sex workers in Benin: a key issue for entry into HIV care.

Background:HIV testing constitutes an entry point for HIV prevention and access to care. Although access to tests has increased in most low- and middle-income countries in recent years, regular HIV testing among high-risk populations remains a challenge. Understanding the determinants of regular HIV testing is the key to improving treatment-as-prevention programs and access to care. This study aimed to identify psychosocial factors associated with the intention to be HIV tested every 3 months among female sex workers (FSWs) in Benin. Methods:We developed an interview questionnaire based on the Theory of Planned Behavior and other theoretical variables. We interviewed 450 FSWs in their work place. Using Amos software, we applied structural equation modeling to identify the determinants of intention. Results:Previous testing was reported by 87% of FSWs, 40% of whom reported having been tested in the last 3 months. More than half of the FSWs (69%) showed a strong intention to be HIV tested during the next 3 months. The structural model indicates that 55% of the variance in intention is explained in descending order of importance (standardized coefficient weight, &bgr;) by perceived control, descriptive norms, control beliefs, habits, attitude, risk perception, and normative beliefs. Conclusions:This is the first theoretically based study identifying determinants of intention to undergo regular HIV testing among FSWs in sub-Saharan Africa. The results can inform development of interventions to maintain and increase regular HIV testing among FSWs, thus reinforcing primary prevention and supporting early access to care.

Highly-Exposed HIV-1 seronegative Female Commercial Sex Workers sustain in their genital mucosa increased frequencies of tolerogenic myeloid and regulatory T-cells

We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-α, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a “tolerogenic/regulatory” anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-α, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin. Endocervical myeloid HLA-DR+ cells from HESN CSWs expressed higher levels of IFN-α, TLR-7, IL-10 and HLA-G than those from both HIV-1-infected CSWs and HIV-1-uninfected non-CSWs. Further characterization of the endocervical myeloid HLA-DR+ cells in HESN CSWs revealed a population of “tolerogenic” CD103+ CD14+ CD11c+ myeloid cells expressing high levels of IFN-α and IL-10. Concomitantly, HESN CSWs had higher frequencies of endocervical regulatory CD4+ T-cells when compared to those from the two other groups of women. These novel findings provide strong evidence to support the implication of tolerogenic myeloid cells expressing high levels of antiviral molecules in shaping the genital mucosal immune response to prevent HIV infection.