Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations in HIV-2 Integrase: A Phenotypic Analysis Using an Expanded Panel of Site-Directed Mutants.

BACKGROUND: Integrase inhibitors (INIs) are a key component of antiretroviral therapy for human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. Although INI resistance pathways are well-defined for HIV-1, mutations that emerge in HIV-2 in response to INIs are incompletely characterized. METHODS: We performed systematic searches of GenBank and HIV-2 drug resistance literature to identify treatment-associated mutations for phenotypic evaluation. We then constructed a library of 95 mutants of HIV-2ROD9 that contained single or multiple amino acid changes in the integrase protein. Each variant was tested for susceptibility to raltegravir and dolutegravir using a single-cycle indicator cell assay. RESULTS: We observed extensive cross-resistance between raltegravir and dolutegravir in HIV-2ROD9. HIV-2-specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterized, significantly increased the half maximum effective concentration (EC50) for raltegravir when introduced into 1 or more mutational backgrounds; mutations E92A/Q, T97A, and G140A/S conferred similar enhancements of dolutegravir resistance. HIV-2ROD9 variants encoding G118R alone, or insertions of residues SREGK or SREGR at position 231, were resistant to both INIs. CONCLUSIONS: Our analysis demonstrates the contributions of novel INI-associated mutations to raltegravir and dolutegravir resistance in HIV-2. These findings should help to improve algorithms for genotypic drug resistance testing in HIV-2-infected individuals.

HIV screening in men and women in Senegal: coverage and associated factors; analysis of the 2017 demographic and health survey.

BACKGROUND: Despite the adoption of the provider-initiated HIV testing strategy, the rate of HIV testing is still very low in sub-Saharan Africa. The aim of this study was to assess the factors associated with HIV testing among sexually active women and men in Senegal. Knowledge of HIV status is the gateway to antiretroviral treatment. METHODS: A secondary analysis of the 2017 Senegal Demographic and Health Survey (DHS) was performed, using data on sexually active women aged 15-49 and men aged 15-59. The outcome variable was the proportion of women and men who reported ever being tested for HIV in the last 12 months before the survey. Descriptive, bivariate, and multivariable logistic regression analyses were performed to identify the socio-demographic, HIV-knowledge, media exposure, and behavioral factors associated with HIV testing in Senegal. RESULTS: The study found that 61.1% (95%CI: 59.2-62.9) of women and 26.2% (95%CI: 24.2-28.3) of men were tested for HIV at the last 12 months. In multivariate analysis, among men the factors independently associated with being tested for HIV were: age groups 20-24 to 40-44 and age group 50-54; a higher level of education; being in the richest household wealth quintile; being married; knowing about the efficacy of HAART during pregnancy; having 2 or more lifetime sex partners and owning a mobile phone. Among women factors independently associated with HIV testing were: being in any age groups versus 15-19; a higher level of education; being in the richest household wealth quintile; being married; knowing about the efficacy of HAART during pregnancy; having any STI in last 12 months; fearing stigma; owning a mobile phone; and having any number of ANC visits, versus none. CONCLUSION: Although HIV remains a public health threat, HIV testing's prevalence is still low in Senegal, making it difficult to interrupt the transmission chain within the community and to reach the UNAIDS goal for 2020 of "90-90-90". Innovative community-based strategies are needed to address barriers and improve access to HIV testing in Senegal, particularly for men and for the youngest and poorest populations.

[Primary breast tuberculosis in a man: a case report]. / Tuberculose mammaire primitive chez un sujet de sexe masculin : à propos d'un cas.

The breast tuberculosis accounts for 0.06 to 0.1% of extra-pulmonary localizations. Frequent in women, it remains exceptional in men. We report a rare case of primary breast tuberculosis occurring in a male patient. A 33-years-old patient presented with a chronic and fistulized non-inflammatory-right breast swelling with an atrophic cutaneous ulceration. The thoracic CT was in favor of a right breast abscess with a thick wall. The patient had received non-specific antibiotics (amoxicillin-clavulanate and metronidazole) for 10 days coupled with a surgical drainage before consulting us for persisting symptoms. The culture of the pus was sterile, the GeneXpert and the search for acid-fast bacilli (AFB) both performed on the swab of the ulceration were negative. Histopathological analysis of the lesion was in favor of a granulomatous mastitis. Given the chronic and atrophic nature of the ulceration, the histological aspect of granulomatous mastitis and the persisting symptoms despite the non-specific antibiotic therapy, we made a presumptive diagnostic of breast tuberculosis. The evolution was favorable with oral anti-tuberculosis treatment.

[Factors associated with immunovirologic dissociation in HIV-1-infected patients under highly active antiretroviral therapy in the Ambulatory Treatment Center (ATC) in Dakar]. / Facteurs associés à la dissociation immunovirologique chez les patients infectés par le VIH-1 sous traitement antirétroviral hautement actif au Centre de Traitement Ambulatoire (CTA) de Dakar.

INTRODUCTION: The objective of this work is to evaluate the different factors associated with immunovirologic dissociation despite highly active and effective antiretroviral treatment. METHODS: We conducted a retrospective, cohort, descriptive and analytical study of the medical records of HIV-1 infected patients having received at least 12 months of antiretroviral therapy, followed in the ATC cohort from 2001 to 2011 and with undetectable viral load in the last 6 months. RESULTS: During this 10-year study period, the prevalence of IVD was 19.3%. Female sex was predominant, with a sex ratio of 1.9. Immunovirologic dissociation was more frequent in male patients (29.7% vs 14.1%) with a statistically significant difference (p = 0,00006). The average age was 44 years ± 10 years. A history of tuberculosis was found in about a third of the cases (31.4%). Immunovirologic dissociation was significantly more frequent in patients with a history of tuberculosis (p = 0.00005). Most patients (68%) had AIDS at WHO clinical stages 3 or 4. Patients with immunovirologic dissociation were more often in WHO clinical stages 3 and 4 (p = 0.0001). More than half of the cases (56.2%) were found to be malnourished and immunovirologic dissociation was prevalent in malnourished patients (p=0.005). The mean CD4+ T lymphocytes counts was 86.7± 83 cells / mm3. Immunovirologic dissociation was more frequent in patients with initial low CD4+ T lymphocyte counts and with a statistically significant difference (p = 0.00000). By multivariate analysis, only age greater than or equal to 43 years, CD4 initial counts < 100 c/mm3 and male sex were significantly associated with this immunovirologic dissociation. CONCLUSION: Our study assessed the main factors associated with immunovirologic dissociation. Other studies of this nature would also merit consideration in order to highlight the impact of this partial immune response on the emergence of opportunistic infections or the implementation of a specific tritherapy for the sole purpose of producing fully successful immune restoration.

[Prevalence of hepatitis B surface antigen and its associated factors in Senegalese military personnel sent on mission to Darfur]. / Prévalence de l'antigène de surface du virus de l'hépatite B et facteurs associés chez des militaires sénégalais envoyés en mission au Darfour.

INTRODUCTION: In Senegal, 85% of the adult population have been exposed to the hepatitis B virus and about 11% of them are chronic surface antigen (HBsAg) carriers. This infection is poorly documented among Senegalese Armed Forces. The aim of this study was to assess the prevalence of HBsAg in Senegalese military personnel on mission to Darfur (Sudan) and to identify its associated factors. METHODS: We conducted a cross-sectional study among Senegalese military personnel stationed in Darfur from 1 July 2014 to 31 July 2014. HBsAg test was performed on serum of participants using immunochromatographic method. The search for associated factors was carried out using multivariate logistic regression. RESULTS: Our study included 169 male military personnel. The average age was 36.6 ± 9.5 years. A history of familial chronic liver disease, blood exposure and sexual exposure were found in 12.4%, 24.9% and 45.6% of the study population respectively. HBsAg was found in 24 participants [14.2% (CI 95% = 8.9-19.5)]. After adjusting for potential confounding factors, age (OR = 0.9 CI 95% = 0.9-1.0), university level (OR = 9.5 CI 95% = 1.3 - 67 , 1>) and sexual exposure (OR = 3.3 <; CI 95% = 1.0 - 10.3) were independently associated with hepatitis B. CONCLUSION: Our study shows high prevalence of HBsAg and underlines the need for further evaluation of hepatitis B in this population.

[Occult hepatitis B reactivation in a patient with homozygous sickle cell disease: clinical case and literature review]. / Réactivation d'une hépatite B occulte chez un patient drépanocytaire homozygote: cas clinique et revue de la litérature.

Occult Hepatitis B corresponds to the presence of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) in serum and/or in liver of a patient despite HBsAg negativity. Clinically, it is usually asymptomatic. Its reactivation is rare and commonly occurs in immunosuppressed individuals. We report the case of a 21-year old patient from Senegal, with homozygous sickle cell disease, presenting with cholestatic jaundice. Laboratory tests showed reactivation of occult Hepatitis B. This study emphasizes the need to systematically investigate the presence of occult Hepatitis B in patients with sickle cell disease suffering from acute liver disease.