Herpes Simplex Virus Type-2 Cervicovaginal Shedding Among Women Living With HIV-1 and Receiving Antiretroviral Therapy in Burkina Faso: An 8-Year Longitudinal Study.

BACKGROUND: The impact of antiretroviral therapy (ART) on herpes simplex virus type-2 (HSV-2) replication is unclear. The aim of this study was to assess factors associated with cervicovaginal HSV-2 DNA shedding and genital ulcer disease (GUD) in a cohort of women living with human immunodeficiency virus type-1 (HIV-1) in Burkina Faso. METHODS: Participants were screened for cervicovaginal HSV-2 DNA, GUD, cervicovaginal and systemic HIV-1 RNA, and reproductive tract infections every 3-6 months over 8 years. Associations with HSV-2 shedding and quantity were examined using random-effects logistic and linear regression, respectively. RESULTS: Of the 236 women with data on HSV-2 shedding, 151 took ART during the study period. Cervicovaginal HSV-2 DNA was detected in 42% of women (99 of 236) in 8.2% of visits (151 of 1848). ART was associated with a reduction in the odds of HSV-2 shedding, which declined for each year of ART use (odds ratio [OR], 0.74; 95% confidence interval [CI], .59-.92). In the multivariable model, the impact of ART was primarily associated with suppression of systemic HIV-1 RNA (adjusted OR, 0.32; 95% CI, .15-.67). A reduction in the odds of GUD was also observed during ART, mainly in those with HIV-1 suppression (adjusted OR, 0.53; 95% CI, .25-1.11). CONCLUSIONS: ART is strongly associated with a decrease in cervicovaginal HSV-2 shedding, and the impact was sustained over several years

Neisseria gonorrhoeae and Chlamydia trachomatis infection in HIV-1-infected women taking antiretroviral therapy: a prospective cohort study from Burkina Faso.

OBJECTIVES: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are common sexually transmitted infections (STI). We assessed the cumulative risk of NG and CT in a cohort of HIV-1-infected high-risk women taking antiretrovirals over 4 years in Burkina Faso. METHODS: Between March 2007 and February 2011, participants were followed every 3-6 months. At each visit, participants underwent a gynaecological examination with collection of cervical and vaginal swabs. Random-effects logistic regression models were used to analyse associations of NG and CT infection with behavioural and biological factors. RESULTS: 172 women had samples tested for NG and CT during the study period, in a total of 1135 visits. NG was detected in 6.4% of women (11/172, 95% CI 2.7 to 10.1) at a rate of 2.76 cases (95% CI 1.53 to 4.99) per 100 person-years. CT was detected in 1.7% (3/172, 95% CI 0 to 3.7) of women at a rate of 0.75 cases (95% CI 0.24 to 2.34) per 100 person-years. The majority of women were asymptomatic (9/14). In the multivariable model, the presence of NG or CT was associated with tobacco use (aOR=11.85, 95% CI 1.13 to 124.17), and concurrent genital HIV-1 RNA shedding (aOR=4.78, 95% CI 1.17 to 19.46). Higher levels of education (aOR=0.17, 95% CI 0.03 to 0.92), and age greater than 35 years (aOR=0.07, 95% CI 0.01 to 0.92) were associated with lower odds of infection. CONCLUSIONS: The risk of NG or CT infection remains low among high-risk women in Bobo-Dioulasso. This provides some evidence that antiretroviral use does not contribute to behavioural disinhibition. The asymptomatic nature of most infections underscores the need for regular screening and treatment of STIs in core groups

HIV risk and behaviour among part-time versus professional FSW: baseline report of an interventional cohort in Burkina Faso.

OBJECTIVE: To readjust HIV control programmes in Africa, we assessed the factors associated with high-risk behaviours and HIV infection among young female sex workers (FSW) in Burkina Faso. METHODS: We carried out a cross-sectional study from September 2009 to September 2010 in Ouagadougou, the capital city. FSW were categorised as professionals and part-time sex workers (PTSW). After a face-to-face questionnaire, blood and urine samples were collected for HIV, HSV-2, genital infections and pregnancy. High-risk behaviour was defined as a recent unprotected sex with either casual clients, regular clients or regular partners. RESULTS: We recruited 609 FSW including 188 (30.9%) professionals. Their median age was 21 years (IQR 19-23), and the prevalence of HIV was 10.3% among professionals and 6.5% among PTSW. Only 3 of 46 HIV-infected women were aware of their status. Overall, 277 (45.6%) women reported high-risk behaviours (41.2% among professionals and 47.5% among PTSW), which were driven mainly by non-systematic condom use with regular partners. In multivariable analysis, PTSW (adjusted OR (AOR)=1.89; 95% CI 1.27 to 2.82) and having a primary (AOR=1.75; 95% CI 1.15 to 2.67) or higher education level (AOR=1.80; 95% CI 1.13 to 2.89) remained associated with high-risk behaviours. HIV infection was associated with older age (AOR=1.44; 95% CI 1.22 to 1.71), with being married/cohabiting (AOR=2.70; 95% CI 1.21 to 6.04) and with Trichomonas vaginalis infection (AOR=9.63; 95% CI 2.93 to 31.59), while history of HIV testing was associated with a decreased risk (AOR=0.18; 95% CI 0.08 to 0.40). CONCLUSIONS: This study highlights the need for targeted interventions among young FSW focusing particularly on PTSW, sexual behaviours with regular partners and regular HIV testing

Potential impact of existing interventions and of antiretroviral use in female sex workers on transmission of HIV in Burkina Faso: a modeling study.

BACKGROUND: The impact and cost-effectiveness of antiretroviral treatment (ART) as prevention is likely to vary depending on the local context. Burkina Faso has a concentrated mature HIV epidemic where female sex workers (FSW) are thought to have driven HIV transmission. METHODS: A dynamic HIV transmission model was developed using data from the Yerelon FSW cohort in Bobo-Dioulasso and population surveys. Compared with current ART provision [status quo (SQ)], the model estimated the proportion of HIV infections averted or incremental life-years gained per additional person-year of ART over 20 years for ART targeting different subgroups or expanding eligibility to all HIV-infected individuals compared with SQ. RESULTS: Modeling suggests that condom use within commercial sex has averted 40% of past HIV infections. Continuing SQ averts 35%-47% of new infections over 20 years compared with no ART. Expanding ART eligibility to all HIV-infected individuals and increasing recruitment (80% per year) could avert a further 65% of new infections, whereas targeting full-time FSW or all FSWs achieved less impact but was more efficient in terms of life-years gained per 100 person-years of ART. Local HIV elimination is possible with expanded ART provision to FSWs but requires condom use within commercial sex to be maintained at high levels. CONCLUSIONS: Increasing FSW recruitment onto ART could be a highly efficient method for reducing HIV transmission in concentrated epidemic settings but should not be undertaken at the expense of existing interventions for FSWs. Specialized clinics providing multiple interventions for FSWs should be a fundamental component of prevention in concentrated epidemics

The cost of providing combined prevention and treatment services, including ART, to female sex workers in Burkina Faso.

BACKGROUND: Female Sex workers (FSW) are important in driving HIV transmission in West Africa. The Yerelon clinic in Burkina Faso has provided combined preventative and therapeutic services, including anti-retroviral therapy (ART), for FSWs since 1998, with evidence suggesting it has decreased HIV prevalence and incidence in this group. No data exists on the costs of such a combined prevention and treatment intervention for FSW. This study aims to determine the mean cost of service provision per patient year for FSWs attending the Yerelon clinic, and identifies differences in costs between patient groups. METHODS: Field-based retrospective cost analyses were undertaken using top-down and bottom-up costing approaches for 2010. Expenditure and service utilisation data was collated from primary sources. Patients were divided into groups according to full-time or occasional sex-work, HIV status and ART duration. Patient specific service use data was extracted. Costs were converted to 2012 US$. Sensitivity analyses considered removal of all research costs, different discount rates and use of different ART treatment regimens and follow-up schedules. RESULTS: Using the top-down costing approach, the mean annual cost of service provision for FSWs on or off ART was US$1098 and US$882, respectively. The cost for FSWs on ART reduced by 29$781, if all research-related costs were removed and national ART monitoring guidelines were followed. The bottom-up patient-level costing showed the cost of the service varied greatly across patient groups (US$505-US$1117), primarily due to large differences in the costs of different ART regimens. HIV-negative women had the lowest annual cost at US$505. CONCLUSION: Whilst FSWs may require specialised services to optimise their care and hence, the public health benefits, our study shows that the cost of ART provision within a combined prevention and treatment intervention setting is comparable to providing ART to other population groups in Africa

Maladie de Bowen à localisations multiples: présentation clinique et approche thérapeutique

The Bowen’s disease (MB), also known as squamous cell carcinoma in situ is a neoplastic skin disease that was clinically and histologically individualized by Darier in 1914. The isolated lesions in the majority of patients can be multiplied in 10 to 20% of cases. We report many locations which has posed problems of therapeutic choice. It is the case of a 35-year-old housewife, seen in consultation for red colored and squamous patches associated to pruritus and pain. On the skin, the examination found red colored and squamous patches, in projection, shaped rounded with a very slow evolution combining in a variable manner, rashes, scales, crusts and keratosis. Patches tended to grow progressively. The vulvar lesions were pigmented patches. In the mouth, we noted ulcers and a diffuse hypopigmentation with cheilitis, perlèche and odynophagia. The oncology checkup in search of another skin, mucosal and visceral cancer was done without any cancer found and the general condition was retained. The histopathology performed on two biopsies confirmed the diagnosis. Considering the spread of lesions and after a pretreatment evaluation, we put the patient under 5fluorouracil in cream on evening and under isotretinoin capsule with favorable evolution in the third week. The multiple sites of MB are rare but pose a management problem because of the evolutionary potential of each individual lesion in squamous cell carcinoma. The choice of treatment depends on the general condition of the patient, the expected efficacy of the treatment but also on its tolerance and cost

Improved Inhibitors Targeting the Thymidylate Kinase of Multidrug-Resistant Mycobacterium tuberculosis with Favorable Pharmacokinetics

This study aims to design improved inhibitors targeting the thymidylate kinase (TMK) of Mycobacterium tuberculosis (Mtb), the causative agent of infectious disease tuberculosis that is associated with high morbidity and mortality in developing countries. TMK is an essential enzyme for the synthesis of bacterial DNA. We have performed computer-aided molecular design of MtbTMK inhibitors by modification of the reference crystal structures of the lead micromolar inhibitor TKI1 1-(1-((4-(3-Chlorophenoxy)quinolin-2-yl)methyl)piperidin-4-yl)-5-methylpyrimidine-2,4(1H,3H)-dione bound to TMK of Mtb strain H37Rv (PDB entries: 5NRN and 5NR7) using the computational approach MM-PBSA. A QSAR model was prepared for a training set of 31 MtbTMK inhibitors with published inhibitory potencies (IC50exp) and showed a significant correlation between the calculated relative Gibbs free energies of the MtbTMK–TKIx complex formation and the observed potencies. This model was able to explain approximately 95% of the variation in the in vitro inhibition data and validated our molecular model of MtbTMK inhibition for the subsequent design of new TKI analogs. Furthermore, we have confirmed the predictive capacity of this complexation QSAR model by generating a 3D QSAR PH4 pharmacophore-based model. A satisfactory correlation was also obtained for the validation PH4 model of MtbTMK inhibition (R2 = 0.84). We have extended the hydrophobic m-chloro-phenoxyquinolin-2-yl group of TKI1 that can occupy the entry into the thymidine binding cleft of MtbTMK by alternative larger hydrophobic groups. Analysis of residue interactions at the enzyme binding site made it possible to select suitable building blocks to be used in the preparation of a virtual combinatorial library of 28,900 analogs of TKI1. Structural information derived from the complexation model and the PH4 pharmacophore guided the in silico screening of the library of analogs and led to the identification of new potential MtbTMK inhibitors that were predicted to be effective in the low nanomolar concentration range. The QSAR complexation model predicted an inhibitory concentration IC50pre of 9.5 nM for the best new virtual inhibitor candidate TKI 13_1, which represents a significant improvement in estimated inhibitory potency compared to TKI1. Finally, the stability of the MtbTMK–inhibitor complexes and the flexibility of the active conformation of the inhibitors were assessed by molecular dynamics for five top-ranking analogs. This computational study resulted in the discovery of new MtbTMK inhibitors with predicted enhanced inhibitory potencies, which also showed favorable predicted pharmacokinetic profiles