Abdoulaye Ouedraogo

Herpes simplex virus and HIV-1: deciphering viral synergy

Recent proof-of-concept randomised controlled trials have shown a causal relation between herpes simplex virus (HSV) type 2 infection and HIV-1 replication in co-infected individuals. We explore the mechanisms that may operate to enhance reciprocal viral replication. Direct interactions could involve HIV-1-related immune deficiency, disruption of mucosal barrier by HSV infection/reactivation, HSV-induced mucosal cell recruitment, transactivation of HIV-1 replication by HSV proteins, and immune modulation by HSV decoys. Indirect interactions might coexist through disturbances of the vaginal flora during HSV shedding and systemic immune activation. In co-infected individuals, suppressive HSV treatment reduces HIV-1 genital and systemic excretion. This finding is a likely result of efficacious prevention of HSV2 reactivations, and perhaps of other herpesviruses. Strategies to control HSV2 and other herpesviruses deserve urgent attention and should become part of the HIV-1 prevention and care package.

Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial

Objective:To demonstrate a causal relationship between herpes simplex virus 2 (HSV-2) and increased genital HIV-1-RNA shedding in women on HAART. Design:A randomized, double-blind, placebo-controlled trial of herpes-suppressive therapy (valacyclovir 500 mg twice a day) in HIV-1/HSV-2-infected women taking HAART in Burkina Faso. Methods:Participants were followed for a total of 12 biweekly visits before and after randomization. The presence and frequency of genital and plasma HIV-1 RNA, and of genital HSV-2 were assessed using summary measures, adjusting for baseline values. Random effect linear regression models were used to assess the impact of treatment on genital and plasma viral loads among visits with detectable virus. Results:Sixty women were enrolled into the trial. Their median CD4 lymphocyte count was 228 cells/μl, and 83% had undetectable plasma HIV-1 RNA at baseline. Valacyclovir reduced the proportion of visits with detectable genital HSV-2 DNA [odds ratio (OR) 0.37, 95% confidence interval (CI) 0.13, 1.05], but had no significant impact on the frequency (OR 0.90, 95% CI 0.31, 2.62) or quantity (reduction of 0.33 log copies/ml, 95% CI −0.81, 0.16) of genital HIV-1 RNA. However, according to pre-defined secondary analyses restricted to women who shed HIV-1 at least once in the baseline phase, valacyclovir reduced both the proportion of visits with detectable HIV-1 shedding (OR 0.27, 95% CI 0.07, 0.99) and the quantity of genital HIV-1 RNA during these visits (−0.71 log10 copies/ml, 95% CI −1.27, −0.14). Conclusion:HSV-2 facilitates residual genital HIV-1 replication among dually infected women taking HAART despite HIV-1 suppression at the systemic level.

Association between bacterial vaginosis and Herpes simplex virus type-2 infection : implications for HIV acquisition studies

Objectives: Bacterial vaginosis (BV) and Herpes simplex virus type-2 (HSV-2) have been linked to an increased risk of HIV-1 acquisition. Recent research suggests an association between BV and HSV-2 acquisition, but the converse has not been studied. Here, we investigate whether an association exists between BV and HSV-2 infection Methods: We examined the determinants of BV occurrence in a cohort of female sex workers in Burkina Faso. Participants were followed every 3 months for diagnosis of genital infections and report of sexual behaviours. Factors associated with BV occurrence were assessed using generalised estimating equation models. Results: We enrolled 273 women (mean age, 28 years) and conducted 812 follow-up visits (mean 2.93 visit per woman). Baseline seroprevalence of HIV-1, HSV-2 and recent syphilis were 31.5%, 70.1% and 0.4%, respectively, while baseline prevalence of BV, Trichomonas vaginalis (TV) and Candida albicans were 20.5%, 3.3% and 2.5%, respectively. In multivariable analysis, HSV-2 (relative risk (RR) = 1.73, 95% CI 1.12 to 2.65), HIV-1 (RR = 1.76, 95% CI 1.30 to 2.40), TV (RR = 1.5, 95% CI 1.0 to 2.3), and having ⩾3 sexual partners in the preceding week (RR = 2.2, 95% CI 1.1 to 4.6) were independently associated with BV, while hormonal contraception showed a protective effect (RR = 0.11, 95% CI 0.02 to 0.70). Conclusions: HSV-2 infection was associated with BV occurrence in this population. As HSV-2 is strongly linked to HIV-1 acquisition, studies assessing the cofactor effect of BV on HIV acquisition should control for the presence of HSV-2. Further studies are required to investigate the relative effect of asymptomatic HSV-2 shedding and/or genital ulcerations on BV occurrence.

Spectrum of Commercial Sex Activity in Burkina Faso: Classification Model and Risk of Exposure to HIV

Objective: Before designing a sexually transmitted infection (STI)/HIV intervention study targeting female commercial sex workers in Bobo Dioulasso, Burkina Faso, we conducted a socioanthropologic survey to analyze the prostitution network in the city in 1998. According to social characteristics, women were classified in six different categories, including four groups of nonprofessional sex workers. The aim of the current study is to assess HIV exposure across this classification model. Methods: A total of 447 women belonging to the six categories were enrolled in the study. After collection of social and behavioral data by means of a questionnaire, each woman received a physical examination and a blood sample was taken for HIV serologic testing. Results: The category of “seaters” was the most often infected, with an HIV prevalence of 57% (58 of 101 women). Nonprofessional “sellers” and “bar waitresses” were more often infected than professional “roamers,” with an HIV prevalence of 37% (24 of 65 women), 40% (27 of 67 women), and 29% (27 of 92 women), respectively, despite a much lower number of clients per week (average of 2.6 clients, 3.3 clients, and 18.6 clients, respectively). Finally, “students” and “cabarets” (women making and selling local beer in huts) were infected with an HIV prevalence of 15% (9 of 62 women and 9 of 60 women, respectively), which remains higher than the prevalence measured recently in the general female population in the city (6.4%). Conclusion: Our results highlight the high level of vulnerability of nonprofessional sex workers, who need to be considered in the design of any program targeting this population for STI/HIV control purposes.

Long term virological, immunological and mortality outcomes in a cohort of HIV-infected female sex workers treated with highly active antiretroviral therapy in Africa

BackgroundConcerns have been raised that marginalised populations may not achieve adequate compliance to antiretroviral therapy. Our objective was to describe the long-term virological, immunological and mortality outcomes of providing highly active antiretroviral therapy (HAART) with strong adherence support to HIV-infected female sex workers (FSWs) in Burkina Faso and contrast outcomes with those obtained in a cohort of regular HIV-infected women.MethodsProspective study of FSWs and non-FSWs initiated on HAART between August 2004 and October 2007. Patients were followed monthly for drug adherence (interview and pill count), and at 6-monthly intervals for monitoring CD4 counts and HIV-1 plasma viral loads (PVLs) and clinical events.Results95 women, including 47 FSWs, were followed for a median of 32 months (interquartile range [IQR], 20-41). At HAART initiation, the median CD4 count was 147 cells/μl (IQR, 79-183) and 144 cells/μl (100-197), and the mean PVLs were 4.94 log10copies/ml (95% confidence interval [CI], 4.70-5.18) and 5.15 log10 copies/ml (4.97-5.33), in FSWs and non-FSWs, respectively. Four FSWs died during follow-up (mortality rate: 1.7 per 100 person-years) and none among other women. At 36 months, the median CD4 count increase was 230 cells/μl (IQR, 90-400) in FSWs vs. 284 cells/μl (193-420) in non-FSWs; PVL was undetectable in 81.8% (95% CI, 59.7-94.8) of FSWs vs. 100% (83.9-100) of non-FSWs; and high adherence to HAART (> 95% pills taken) was reported by 83.3% (95% CI, 67.2-93.6), 92.1% (95% CI, 78.6-98.3), and 100% (95% CI, 54.1-100) of FSWs at 6, 12, and 36 months after HAART initiation, respectively, with no statistical difference compared to the pattern observed among non-FSWs.ConclusionsClinical and biological benefits of HAART can be maintained over the long term among FSWs in Africa and could also lead to important public health benefits.

Is Sexually Transmitted Infection Management Among Sex Workers Still Able to Mitigate the Spread of HIV Infection in West Africa

Objective:To assess the role of sexually transmitted infection (STI) management to prevent HIV acquisition among sex workers in Burkina Faso. Design:Open cohort study of professional and nonprofessional sex workers with 3-month follow-up visits. Methods:Baseline and follow-up visits consisted of the administration of a behavioral questionnaire, education sessions on HIV and STIs, a medical examination, and laboratory testing for STI and HIV diagnosis. Results:Three hundred seventy-seven HIV-negative women were enrolled in the study. The cumulated HIV incidence was 3.2 per 100 person-years (Poisson 95% confidence interval: 1.9-4.9). Bacterial and parasitic STIs were low at baseline, whereas herpes simplex virus-2 (HSV-2) prevalence was 54.7%. By a Cox regression model, self-assessment of high HIV risk in the past, less than 5 clients per week, and no change of a steady partner were independently associated with HIV acquisition. Among STIs, only infection with HSV-2 tended to be associated with HIV acquisition (odds ratio = 2.45; P = 0.15). Overall, condom use increased during the study but to a lesser extent with steady partners. Conclusions:Bacterial and parasitic STIs are no longer a key determinant of HIV acquisition, given the current stage of the outbreak in Burkina Faso. Although efforts for STI control should be maintained, strategies should focus on nonprofessional sex workers, steady partners, and HSV-2 infection to tackle HIV transmission further in this high-risk group.

Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study

BackgroundHuman papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology.MethodsA prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrolment.ResultsGenital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/μL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ≤200 cells/μL. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts.ConclusionsGenital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population.

Viral load and physical status of human papillomavirus (HPV) 18 in cervical samples from female sex workers infected with HPV 18 in Burkina Faso.

Viral DNA load and physical status might be predictive of either high‐grade cervical lesions or disease progression among women infected by human papillomavirus (HPV) 16, but these virological markers have rarely been studied in HPV 18 infections. The relationships between HPV 18 DNA load, viral genome physical status and cervical squamous intraepithelial lesions were analyzed among female sex workers infected with HPV18 in Burkina Faso. HPV 18 E2 and E6 genes were quantitated by real‐time PCR. Among 21 women infected with HPV 18, 67% of whom were HIV‐1‐seropositive, 11 (52.4%) had a normal cytology, 8 (38.1%) had low‐grade squamous intraepithelial lesions, and 2 (9.5%) had high‐grade squamous intraepithelial lesions. Total viral load and integrated viral load were higher in women with squamous intraepithelial lesions than in women with normal cytology (P = 0.01 for both parameters). Total viral load and integrated viral load were higher in HIV‐1‐seropositive women than in those who were not infected with HIV (P = 0.01, and P, 0.01, respectively). Total viral load or integrated viral load >1,000 copies/ng of DNA were more frequent in women with squamous intraepithelial lesions than in women with normal cytology (7/10 vs. 1/11; P = 0.007) and in HIV‐1‐seropositive women (8/14 vs. 0/7 in HIV‐uninfected women; P = 0.02). Both HPV 18 DNA and integrated DNA loads might represent markers of cervical lesions. Prospective evaluations are needed to establish the value of these parameters to predict high‐grade lesion or lesion progression. J. Med. Virol. 81:1786–1791, 2009.

Design of epidemiological studies measuring genital and plasma HIV-1 outcomes: lessons from a randomised controlled trial.

Objective  HIV‐1 genital viral loads have not been extensively used as markers of HIV transmissibility. We set out to determine whether the variability of genital HIV‐1 RNA over time necessitates design adjustments in studies measuring genital shedding to account for this variability.