Nicolas Nagot

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.

Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso

Human papillomavirus (HPV) infection and cervical squamous intraepithelial lesions (SILs) were studied in 379 high-risk women. Human papillomavirus DNA was detected in 238 of 360 (66.1%) of the beta-globin-positive cervical samples, and 467 HPV isolates belonging to 35 types were identified. Multiple (2–7 types) HPV infections were observed in 52.9% of HPV-infected women. The most prevalent HPV types were HPV-52 (14.7%), HPV-35 (9.4%), HPV-58 (9.4%), HPV-51 (8.6%), HPV-16 (7.8%), HPV-31 (7.5%), HPV-53 (6.7%), and HPV-18 (6.4%). Human immunodeficiency virus type 1 (HIV-1) seroprevalence was 36.0%. Human papillomavirus prevalence was significantly higher in HIV-1-infected women (87 vs 54%, prevalence ratio (PR)=1.61, 95% confidence interval (CI): 1.4–1.8). High-risk HPV types (71 vs 40%, PR=1.79, 95% CI: 1.5–2.2), in particular HPV-16+18 (22 vs 9%, PR=2.35, 95% CI: 1.4–4.0), and multiple HPV infections (56 vs 23%, PR=2.45, 95% CI: 1.8–3.3) were more prevalent in HIV-1-infected women. High-grade SIL (HSIL) was identified in 3.8% of the women. Human immunodeficiency virus type 1 infection was strongly associated with presence of HSIL (adjusted odds ratio=17.0; 95% CI 2.2–134.1, P=0.007) after controlling for high-risk HPV infection and other risk factors for HSIL. Nine of 14 (63%) HSIL cases were associated with HPV-16 or HPV-18 infection, and might have been prevented by an effective HPV-16/18 vaccine.

Dried blood spot for hepatitis C virus serology and molecular testing

We investigated the performance of dried blood spots (DBS) in hepatitis C virus (HCV) diagnosis using modified commercial tests. Paired DBS and serum samples were collected from 200 patients: 100 patients with anti‐HCV antibodies (anti‐HCV), including 62 patients with detectable serum HCV RNA, and 100 patients without anti‐HCV. The DBS sample consisted of three drops of approximately 50 μL of whole blood applied to a paper card, which was then stored at −20°C within 48 hours of collection. Using the Ortho HCV 3.0 enzyme‐linked immunosorbent assay kit on DBS, we observed both a specificity and sensitivity of 99% in detecting anti‐HCV. HCV RNA was detected on DBS in 60/62 (97%) patients with detectable serum HCV RNA, which was then successfully quantified in 55 samples (89%) using the Cobas TaqMan HCV test. A good correlation was observed between the DBS HCV RNA concentration and the serum level (r2 = 0.95; P < 0.001). HCV genotyping was successfully performed on DBS samples, with a full concordance between the 14 paired DBS and serum samples (genotypes 1‐4). Conclusion: This study presents DBS as a reliable alternative to serum specimens for detecting anti‐HCV, quantifying HCV RNA and genotyping HCV. DBS may increase the opportunities for HCV testing and treatment follow‐up in hard‐to‐reach individuals. (HEPATOLOGY 2010.)

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.

Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells.

The recent Zika virus (ZIKV) epidemic has highlighted the poor knowledge on its physiopathology. Recent studies showed that ZIKV of the Asian lineage, responsible for this international outbreak, causes neuropathology in vitro and in vivo. However, two African lineages exist and the virus is currently found circulating in Africa. The original African strain was also suggested to be neurovirulent but its laboratory usage has been criticized due to its multiple passages. In this study, we compared the French Polynesian (Asian) ZIKV strain to an African strain isolated in Central African Republic and show a difference in infectivity and cellular response between both strains in human neural stem cells and astrocytes. Consistently, this African strain led to a higher infection rate and viral production, as well as stronger cell death and anti-viral response. Our results highlight the need to better characterize the physiopathology and predict neurological impairment associated with African ZIKV.

Review of STI and HIV epidemiological data from 1990 to 2001 in urban Burkina Faso: implications for STI and HIV control

Objectives: To better understand the sexually transmitted infection (STI)/HIV dynamics in an urban west African setting in order to adapt STI/HIV control efforts accordingly. Methods: Review of STI and HIV epidemiological studies performed over the past decade in Bobo-Dioulasso, the second city of Burkina Faso. Trends in STI prevalence among commercial sex workers and the general population were assessed over time through studies that used the same recruitment and laboratory diagnostic procedures. Variations in aetiologies of vaginal discharge, urethral discharge, and genital ulcers were also evaluated among patients consulting for genital infection complaints. Antenatal clinic based surveys provided data to assess HIV trend among the general population. Results: We observed an important decline of classic bacterial STI such as syphilis, Neisseria gonorrhoea, Chlamydia trachomatis, and Haemophilus ducrey infections in all study groups. Trichomoniasis also declined but to a lesser extent. HIV infection followed the same trend at the same time, with a significant decline in the 15–19 year age group of pregnant women, suggesting a possible decrease of HIV incidence. Although no evidence of a causal relation can be drawn from this review, adoption of safer sex behaviour, introduction of the syndromic management (SM) approach, or higher antibiotic use may have contributed to these changes. Conclusions: Classic bacterial STI declined over the past decade in parallel with a stabilisation of HIV infection. Variations in syndromes aetiology and sexual behaviours should be monitored as part of STI surveillance in order to improve STI syndromic management algorithms and to adapt HIV/STI prevention efforts.

HIV-1 Reservoirs in Breast Milk and Challenges to Elimination of Breast-Feeding Transmission of HIV-1

The breast milk of HIV-infected mothers contains reservoirs of HIV, even when they are successfully treated with antiretroviral therapy; new approaches to prophylactic therapy are needed to prevent HIV transmission to their infants through breast-feeding. The breast milk of HIV-infected mothers contains reservoirs of HIV, even when they are successfully treated with antiretroviral therapy; new approaches to prophylactic therapy are needed to prevent HIV transmission to their infants through breast-feeding. By compensating for the relative immaturity of the neonatal immune system, breast milk and breast-feeding prevent deaths in children. Nevertheless, transmission of HIV-1 through breast-feeding is responsible for more than half of new pediatric HIV infections. Recent studies of possible HIV-1 reservoirs in breast milk shed new light on features that influence HIV-1 transmission through breast-feeding. The particular characteristics of breast milk CD4+ T cells that distinguish them from circulating blood lymphocytes (high frequency of cell activation and expression of memory and mucosal homing markers) facilitate the establishment of HIV-1 replication. Breast milk also contains a plethora of factors with anti-infectious, immunomodulatory, or anti-inflammatory properties that can regulate both viral replication and infant susceptibility. In addition, CD8+ T lymphocytes, macrophages, and epithelial cells in breast milk can alter the dynamics of HIV-1 transmission. Even during efficient antiretroviral therapy, a residual stable, CD4+ T cell–associated reservoir of HIV-1 is persistently present in breast milk, a likely source of infection. Only prophylactic treatment in infants—ideally with a long-acting drug, administered for the entire duration of breast-feeding—is likely to protect HIV-exposed babies against all forms of HIV transmission from breast milk, including cell-to-cell viral transfer.

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.