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Depression is highly prevalent in people living with HIV (PLHIV) worldwide. As mental health specialists are scarce in sub-Saharan Africa (SSA), the World Health Organization (WHO) encourages task-shifting. We aimed to evaluate the barriers that could compromise task-shifting in front-line health care workers (HCWs) who provide HIV integrated care in West Africa. We collected knowledge, attitudes and practices (KAP) information on symptoms, causes and management of depression in PLHIV in care in four clinics in Senegal and Côte d'Ivoire (N = 168). The main barriers that could compromise task-shifting came from poor knowledge, particularly on symptoms and causes. Knowledge was more limited in HCWs other than medical doctors (good answers < 70%). The access to a depression training was limited (32.7%) and was the main factor associated to poor knowledge on depression. Even when social distance and barriers to practice were low (70.8% and 69.6%, respectively), some barriers persisted. More than half of respondents considered that diagnosis and management needed to be performed by a specialist. To guarantee the success of task-shifting, in the perspective of integrated care, efforts are needed to improve the access to specific training on depression considering screening, management, but also perceptions and attitudes, as some barriers subsist. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID-19) has rapidly spread to all 7 continents. Due to yet unknown reasons, the African continent has remained relatively unaffected. We discuss the importance of mitigating pan-continental spread in light of the fragile healthcare systems. [ABSTRACT FROM AUTHOR]

Background: Non-communicable diseases, including hypertension (HTN), are increasingly recognized as important causes of morbidity and mortality among people living with HIV (PLHIV) in resource-limited settings. The goals of this study were to determine the prevalence of HTN among PLHIV in Senegal over time and to identify predictors of HTN among HIV-positive versus HIV-negative adults. Methods: We conducted a retrospective study using data from individuals enrolled in previous studies in Senegal from 1994–2015. Blood pressure (BP) measurements taken during study visits were used for analysis. HTN was defined as systolic BP≥140 or diastolic BP≥90. We used logistic regression to identify predictors of HTN. Results: We analyzed data from 2848 adults (1687 HIV-positive, 1161 HIV-negative). Among PLHIV, the prevalence of HTN increased from 11% during 1994–1999 to 22% during 2010–2015. Among HIV-negative individuals, the prevalence of HTN increased from 16% to 32%. Among both groups, the odds of HTN more than doubled from 1994–1999 to 2010–2015 (HIV-positive OR 2·4, 95% CI 1·1–5·0; HIV-negative OR 2·6, 95% CI 1·5–4·6). One quarter of all individuals with HTN had stage 2 HTN. The strongest risk factor for HTN was obesity (HIV-positive OR 3·2, 95% CI 1·7–5·8; p<0·01; HIV-negative OR 7·8, 95% CI 4·5–13·6; p<0·01). Male sex and age ≥50 were also predictive of HTN among both groups. Among HIV-positive subjects, WHO stage 1 or 2 disease was predictive of HTN and among HIV-negative subjects, having no formal education was predictive. Conclusion: Over the past 20 years, the prevalence of HTN has doubled among both HIV-positive and HIV-negative adults in Senegal. Our study indicates that there is an increasing need for the integration of chronic disease management into HIV programs in Senegal. Furthermore, our findings highlight the need for enhanced prevention, recognition, and management of non-communicable diseases, including hypertension and obesity, among both HIV-positive and HIV-negative individuals in Senegal. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Objectives: Efforts to control the COVID-19 pandemic have potentially compromised the availability and/or quality of HIV services. We aimed to assess the pandemic's impact on antiretroviral therapy (ART) initiation and HIV viral load (VL) monitoring in 3 West African countries. Methods: We used routinely collected data from 5 clinics contributing to the International epidemiologic Database to Evaluate AIDS collaboration in Burkina Faso, Côte d'Ivoire, and Nigeria. We included ART-naïve adults living with HIV initiating ART from January 1, 2018. We conducted regression discontinuity analysis to estimate changes in the number of ART initiations and VL measures per week, before and during the pandemic period in each country. Results: In clinics in Burkina Faso and Côte d'Ivoire, ART initiations per week remained constant throughout the studied periods (−0.24 points (p) of ART initiations/week 95% CI: −5.5 to 5.9, −0.9 p, 95% CI: −8.5 to 8.6, respectively), whereas in Nigeria's clinic, they decreased significantly (−6.3 p, 95% CI: −10.8 to −1.7) after the beginning of the pandemic. The volume of VL tests performed decreased significantly in all 3 countries (−17.0 p, 95% CI: −25.3 to −8.6 in Burkina Faso, −118.4 p, 95% CI: −171.1 to −65.8 in Côte d'Ivoire and −169.1 p, 95% CI: −282.6 to −55.6 in Nigeria). Conclusions: HIV clinics in two out of three countries in West Africa demonstrated resilience as they successfully maintained access to ART for ALWH despite the challenges imposed by the pandemic. However, VL monitoring was severely disrupted and did not return to prepandemic levels approximately 1 year after the beginning of the pandemic. Continued monitoring of the HIV care continuum in the postpandemic period is essential to mitigate potential enduring effects on ALWH's virological and clinical outcomes. [ABSTRACT FROM AUTHOR]

The activity of lenacapavir against human immunodeficiency virus type 1 (HIV-1) has been extensively evaluated in vitro, but comparable data for human immunodeficiency virus type 2 (HIV-2) are scarce. We determined the anti–HIV-2 activity of lenacapavir using single-cycle infections of MAGIC-5A cells and multicycle infections of a T-cell line. Lenacapavir exhibited low-nanomolar activity against HIV-2, but was 11- to 14-fold less potent against HIV-2 in comparison to HIV-1. Mutations in HIV-2 that confer resistance to other antiretrovirals did not confer cross-resistance to lenacapavir. Although lenacapavir-containing regimens might be considered for appropriate patients with HIV-2, more frequent viral load and/or CD4 testing may be needed to assess clinical response. [ABSTRACT FROM AUTHOR]

Background: Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. Methods: Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. Results: A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (β = 3.749), cost (β = -2.550), specificity (β = 1.134), and time-to-result (β = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. Conclusions: African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs. [ABSTRACT FROM AUTHOR]

GSK2838232 (GSK232) is a novel maturation inhibitor that blocks the proteolytic cleavage of HIV-1 Gag at the junction of capsid and spacer peptide 1 (CA/SP1), rendering newly-formed virions non-infectious. To our knowledge, GSK232 has not been tested against HIV-2, and there are limited data regarding the susceptibility of HIV-2 to other HIV-1 maturation inhibitors. To assess the potential utility of GSK232 as an option for HIV-2 treatment, we determined the activity of the compound against a panel of HIV-1, HIV-2, and SIV isolates in culture. GSK232 was highly active against HIV-1 isolates from group M subtypes A, B, C, D, F, and group O, with IC50 values ranging from 0.25–0.92 nM in spreading (multi-cycle) assays and 1.5–2.8 nM in a single cycle of infection. In contrast, HIV-2 isolates from groups A, B, and CRF01_AB, and SIV isolates SIVmac239, SIVmac251, and SIVagm.sab-2, were highly resistant to GSK232. To determine the role of CA/SP1 in the observed phenotypes, we constructed a mutant of HIV-2ROD9 in which the sequence of CA/SP1 was modified to match the corresponding sequence found in HIV-1. The resulting variant was fully susceptible to GSK232 in the single-cycle assay (IC50 = 1.8 nM). Collectively, our data indicate that the HIV-2 and SIV isolates tested in our study are intrinsically resistant to GSK232, and that the determinants of resistance map to CA/SP1. The molecular mechanism(s) responsible for the differential susceptibility of HIV-1 and HIV-2/SIV to GSK232 require further investigation. [ABSTRACT FROM AUTHOR]

Profiling of the antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in African populations is scarce. Here, we performed a detailed IgM and IgG epitope mapping study against 487 peptides covering SARS-CoV-2 wild-type structural proteins. A panel of 41 pre-pandemic and 82 COVID-19 RT-PCR confirmed sera from Madagascar and Senegal were used. We found that the main 36 immunodominant linear epitopes identified were (i) similar in both countries, (ii) distributed mainly in the Spike and the Nucleocapsid proteins, (iii) located outside the RBD and NTD regions where most of the reported SARS-CoV-2 variant mutations occur, and (iv) identical to those reported in European, North American, and Asian studies. Within the severe group, antibody levels were inversely correlated with the viral load. This first antibody epitope mapping study performed in patients from two African countries may be helpful to guide rational peptide-based diagnostic assays or vaccine development. [ABSTRACT FROM AUTHOR]

Depression is highly prevalent in people living with HIV (PLWH) and has negative consequences for daily life and care. We evaluated for the first time the acceptability, feasibility and benefits of group interpersonal therapy (IPT), combined with a task-shifting approach, to treat depression in PLWH in Senegal. PLWH with depression received group IPT following the World Health Organization protocol. Acceptability and feasibility criteria were defined from the literature data. The PHQ-9, the WHODAS, and the 12-item-stigma scale were used, pre- and post-treatment, including a 3-month follow-up, to assess depressive symptom severity, functioning and stigma, respectively. General linear mixed models were used to describe changes in outcomes over time. Of 69 participants, 60 completed group IPT. Refusal to enroll and dropout rates were 6.6 and 12.7%, respectively. Ninety-seven percent of participants attended at least seven out of eight sessions. Patients and facilitators endorsed group IPT, with willingness to recommend it. Depressive symptoms and disability improved drastically and sustainably. We showed that group IPT is well accepted and feasible in Senegal as treatment for depression in PLWH. Combined with a taskshifting approach, it can narrow the gap in mental health treatment. Implementation may be enhanced by refining patient identification procedures and increasing treatment accessibility. [ABSTRACT FROM AUTHOR]

Objective: Verbal fluency decline, observed both in aging and HIV infection, has been related to lower quality of life. This study aimed to evaluate the factors associated with categorical fluency in people living with HIV (PLHIV) aged ≥60 years living in West Africa. Methods: In this longitudinal study, PLHIV aged ≥60 years, on antiretroviral therapy (ART) for ≥6 months were included in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. Categorical fluency was evaluated with the Isaacs Set Test at 60 s at baseline and 2 years later. Factors associated with verbal fluency baseline performance and annual rates of changes were evaluated using multivariate linear regression models. Results: Ninety‐seven PLHIV were included with 41 of them (42%) having a 2‐year follow‐up visit. The median age was 64 (62–67), 45.4% were female, and 89.7% had an undetectable viral load. The median annual change in categorical fluency scores was −0.9 (IQR: −2.7 to 1.8). Low baseline categorical fluency performance and its decline were associated with older age and being a female. Low educational level was associated with low baseline categorical fluency performance but not with its decline. Categorical fluency decline was also associated with marital status and hypertension. Conclusions: Among older West African PLHIV, usual socio‐demographic variables and hypertension were the main factors associated with low categorical fluency performance and/or its decline. Interventions that focus on supporting cardiometabolic health are highly recommended to prevent cognitive disorders in PLHIV. [ABSTRACT FROM AUTHOR]

The prevalence of active hepatitis B among asymptomatic persons remains unclear in Africa. Of 1206 newly diagnosed persons in Senegal, 12.3% had significant fibrosis and 31.3% had hepatitis B virus (HBV) DNA levels >2000 IU/mL. Overall, 128 (12.9%) were eligible for antiviral therapy. Generalized HBV screening allowed the identification of a large population requiring HBV care. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is the first cause of liver cirrhosis and cancer in West Africa. Although the exposure to additional environmental and infectious risk factors may lead to the faster progression of liver disease, few large-scale studies have evaluated the determinants of HBV-related liver fibrosis in the region. We used transient elastography to evaluate the prevalence of liver fibrosis and assessed the association between HBV markers and significant liver fibrosis in a cohort of people living with HBV in Dakar, Senegal. The prevalence of significant liver fibrosis was 12.5% (95% confidence interval [CI] 9.6%–15.9%) among 471 people with HBV mono-infection (pwHBV) and 6.4% (95% CI 2.6%–12.7%) in 110 people with HIV/HBV co-infection (pwHIV/HBV) on tenofovir-containing antiretroviral therapy (p = 0.07). An HBV viral load > 2000 IU/mL was found in 133 (28.3%) pwHBV and 5 (4.7%) pwHIV/HBV, and was associated with significant liver fibrosis (adjusted odds ratio (aOR) 1.95, 95% CI 1.04–3.66). Male participants (aOR 4.32, 95% CI 2.01–8.96) and those with elevated ALT (aOR 4.32, 95% CI 2.01–8.96) were especially at risk of having significant liver fibrosis. Our study shows that people with an HBV viral load above 2000 IU/mL have a two-fold increase in the risk of liver fibrosis and may have to be considered for antiviral therapy, independent of other disease parameters. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The goals of this study were to assess retention on antiretroviral therapy (ART) and to identify predictors of loss to follow-up (LTFU) among people living with HIV (PLHIV) in Senegal. HIV-positive individuals presenting for initiation of ART in Dakar and Ziguinchor were enrolled and followed for 12 months. Data were collected using interviews, clinical evaluations, laboratory analyses, chart review, and active patient tracing. Of the 207 individuals enrolled, 70% were female, 32% had no formal education, and 28% were severely food insecure. At the end of the follow-up period, 58% were retained on ART, 15% were deceased, 4% had transferred care, 5% had migrated, and 16% were lost to follow-up. Enrollment in Ziguinchor (OR 2.71 [1.01-7.22]) and severe food insecurity (OR 2.55 [1.09-5.96]) were predictive of LTFU. Sex, age, CD4 count, BMI <18.5, country of birth, marital status, number of children, household size, education, consultation with traditional healers, transportation time, and transportation cost were not associated with LTFU. The strongest predictor of severe food insecurity was lack of formal education (OR 2.75 [1.30-5.80]). Addressing the upstream drivers of food insecurity and implementing strategies to enhance food security for PLHIV may be effective approaches to reduce LTFU and strengthen the HIV care cascade in the region. [ABSTRACT FROM AUTHOR]

Background: Although direct-acting antivirals (DAA) have become standard care for patients with chronic hepatitis C worldwide, there is no evidence for their value for money in sub-Saharan Africa. We assessed the cost-effectiveness of four sofosbuvir-based regimens recommended by the World Health Organization (WHO) in Cameroon, Côte d'Ivoire and Senegal.Methods: Using modelling, we simulated chronic hepatitis C progression with and without treatment in hypothetical cohorts of patients infected with the country's predominant genotypes (1, 2 and 4) and without other viral coinfections, history of liver complication or hepatocellular carcinoma. Using the status-quo 'no DAA treatment' as a comparator, we assessed four regimens: sofosbuvir-ribavirin, sofosbuvir-ledipasvir (both recommended in WHO 2016 guidelines and assessed in the TAC pilot trial conducted in Cameroon, Côte d'Ivoire and Senegal), sofosbuvir-daclatasvir and sofosbuvir-ledipasvir (two pangenotypic regimens recommended in WHO 2018 guidelines). DAA effectiveness, costs and utilities were mainly estimated using data from the TAC pilot trial. Secondary data from the literature was used to estimate disease progression probabilities with and without treatment. We considered two DAA pricing scenarios: S1) originator prices; S2) generic prices. Uncertainty was addressed using probabilistic and deterministic sensitivity analyses and cost-effectiveness acceptability curves.Results: With slightly higher effectiveness and significantly lower costs, sofosbuvir/velpatasvir was the preferred DAA regimen in S1 with incremental cost-effectiveness ratios (ICERs) ranging from US$526 to US$632/QALY. At the cost-effectiveness threshold (CET) of 0.5 times the 2017 country's per-capita gross domestic product (GDP), sofosbuvir/velpatasvir was only cost-effective in Senegal (probability > 95%). In S2 at generic prices, sofosbuvir/daclatasvir was the preferred regimen due to significantly lower costs. ICERs ranged from US$139 to US$216/QALY according to country i.e. a 95% probability of being cost-effective. Furthermore, this regimen was cost-effective (probability> 95%) for all CET higher than US$281/QALY, US$223/QALY and US$195/QALY in Cameroon, Côte d'Ivoire and Senegal, respectively, corresponding to 0.14 (Côte d'Ivoire and Senegal) and 0.2 (Cameroon) times the country's per-capita GDP.Conclusions: Generic sofosbuvir/daclatasvir is very cost-effective for treating chronic hepatitis C in sub-Saharan Africa. Large-scale use of generics and an increase in national and international funding for hepatitis C treatment must be priorities for the HCV elimination agenda. [ABSTRACT FROM AUTHOR]

Immune activation has been suggested to increase susceptibility to human immunodeficiency virus type 1 (HIV-1) transmission, while at the same time it could be deemed essential for mounting an effective antiviral immune response. In this study, we compared levels of T cell activation between exposed seronegative (ESN) partners in HIV-1 discordant couples and HIV-unexposed control subjects in Dakar, Senegal. ESN subjects showed lower levels of CD38 expression on CD4+ T cells than did control subjects. However, this was found to be associated with concurrent differences in the use of condoms: ESN subjects reported a higher degree of condom use than did control subjects, which correlated inversely with CD38 expression. In addition, we observed markedly higher levels of T cell activation in women compared with men, irrespective of sexual behavior. These findings question the relevance of low-level CD4+ T cell activation in resistance to HIV-1 infection and underscore the need to take gender and sexual behavior characteristics of high-risk populations into account when analyzing correlates of protective immunity. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the leading cause of liver cirrhosis and cancer in West Africa. Despite current recommendations, HBV is often not tested for in clinical routine in the region. We included all people living with HIV (PLWH) in care between March and July 2019 at Fann University Hospital in Dakar (Senegal) and proposed hepatitis B surface antigen (HBsAg) test to those never tested. All HBsAg‐positive underwent HIV and HBV viral load (VL) and liver stiffness measurement. We evaluated, using logistic regression, potential associations between patient characteristics and (a) HBV testing uptake; (b) HIV/HBV co‐infection among individual HBsAg tested. We determined the proportion of co‐infected who had HBV DNA >20 IU/ml on ART and sequenced HBV polymerase in those with HBV replication.of 1076 PLWH in care, 689 (64.0%) had never had an HBsAg test prior to our HBV testing intervention. Women and individuals >40 years old were less likely to have been previously tested. After HBV testing intervention,107/884 (12.1%) PLWH were HBsAg‐positive. Seven of 58 (12.1%) individuals newly diagnosed with HIV/HBV co‐infection had a detectable HBV VL, of whom five were HIV‐suppressed. Two patients on ART including 3TC and AZT as backbone showed the presence of the triple resistance mutation 180M/204I/80V. In this Senegalese urban HIV clinic, the majority of patients on ART had never been tested for HBV infection. One in ten co‐infected individuals had a detectable HBV VL despite HIV suppression, and 8% were not receiving a TDF‐containing regimen. [ABSTRACT FROM AUTHOR]

Background: Second-line treatment of HIV-2 in resource-limited settings (RLS) is complicated by a lack of controlled trial data, limited availability of HIV-2-active antiretroviral drugs, and inadequate access to drug resistance testing. We conducted an implementation trial of a dried blood spot- (DBS) based, drug resistance genotype-informed antiretroviral therapy (ART) switching algorithm for HIV-2-infected patients in Senegal.Methods: HIV-2-infected adults initiating or receiving ART through the Senegalese national AIDS program were invited to participate in this single-arm trial. DBS from participants with virologic failure (defined as viral load (VL) > 250 copies/mL after > 6 months on the current ART regimen) were shipped to Seattle for genotypic drug resistance testing. Participants with evidence of drug resistance in protease or reverse transcriptase were switched to new regimens according to a pre-specified algorithm. Participant clinical and immuno-virologic outcomes were assessed, as were implementation challenges.Results: We enrolled 152 participants. Ten were initiating ART. The remainder were ART-experienced, with 91.0% virologically suppressed (< 50 copies/mL). Problems with viral load testing capability resulted in obtaining VL results for only 227 of 613 (37.0%) participant-visits. Six of 115 participants (5.2%) with VL available after > 6 months on current ART regimen experienced virologic failure, with per-protocol genotypic testing attempted. One additional test was performed for a participant with a VL of 222 copies/mL. Genotypes from three participants showed no evidence of major drug resistance mutations, two showed nucleoside reverse transcriptase inhibitor (NRTI) resistance, one showed both NRTI and protease inhibitor resistance, and one test failed. No integrase inhibitor resistance was observed. Five of six successfully-tested participants switched to the correct regimen or received additional adherence counseling according to the algorithm; the sixth was lost to follow-up. Follow-up VL testing was available for two participants; both of these were virally suppressed (< 10 copies/mL). The trial was terminated early due to the COVID-19 pandemic (which prevented further VL and genotypic testing), planned rollout of dolutegravir-based 1st-line ART, and funding.Conclusions: The RESIST-2 trial demonstrated that a DBS-based genotypic test can be used to help inform second-line ART decisions as part of a programmatic algorithm in RLS, albeit with significant implementation challenges.Trial Registration: ClinicalTrials.gov NCT03394196 . Registered on January 9, 2018. [ABSTRACT FROM AUTHOR]

Background: Understanding the impact of food insecurity on HIV outcomes is critical for the development and implementation of effective, evidence-based interventions to address food insecurity and improve the HIV care cascade. We conducted a prospective, longitudinal study to determine the impact of food insecurity on HIV outcomes in Senegal, West Africa.Methods: HIV-infected individuals presenting for care and initiation of ART through the Senegalese National AIDS program in Dakar and Ziguinchor were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart review at enrollment, month 6, and month 12. Logistic regression was used to determine the association between food insecurity and HIV outcomes.Results: Among the 207 participants in this study, 70% were female and the median age was 37 years. The majority (69%) were food insecure at enrollment, 29% were severely food insecure, and 38% were undernourished. Nearly a third (32%) had no formal education, 23% practiced agriculture, and 40% owned livestock. The median daily food expenditure per person was $0.58. The median round trip transportation time to clinic was 90 min (IQR 30-240). The median cost of transportation to clinic was $1.74. At month 12, 69% were food insecure, 23% were severely food insecure, and 14% were undernourished. At month 12, 43% had not disclosed their HIV status; food insecurity was associated with non-disclosure of HIV-status due to fear of stigmatization and feelings of shame. Severe food insecurity was a strong predictor of loss to follow-up (OR 3.13 [1.08-9.06]) and persistent severe food insecurity was associated with virologic failure (OR 5.14 [1.01-26.29]) and poor adherence to ART 8.00 [1.11-57.57]. Poor nutritional status was associated with poor immunologic recovery (OR 4.24 [1.56-11.47]), virologic failure (OR 3.39 [1.13-10.21]), and death (OR 3.35 [1.40-8.03]).Conclusion: Severity and duration of food insecurity are important factors in understanding the relationship between food insecurity and HIV outcomes. Our findings highlight the importance of nutritional status, socioeconomic opportunity, and self-stigmatization in the complex pathway between food insecurity and HIV outcomes. Interdisciplinary, multisectoral efforts are needed to develop and implement effective interventions to address food insecurity among people living with HIV. [ABSTRACT FROM AUTHOR]

Background: In Sub‐Saharan Africa, chronic hepatitis C (CHC) is a major public health issue. We estimated the long‐term clinical benefits of treating CHC with sofosbuvir‐based regimens in Cameroon, Côte d'Ivoire and Senegal using Markov model combining data from the literature with estimates of direct‐acting antiviral (DAAs) effectiveness in West and Central Africa. Methods: Disease progression was simulated with and without treatment in fictive cohorts of patients "diagnosed" with CHC in Cameroon (n = 3224), Côte d'Ivoire (n = 9748) and Senegal (n = 6358). Lifetime treatment benefits were assessed using (a) life‐years saved (LYS); (b) life‐years (LY) avoided in compensated cirrhosis (CC), decompensated cirrhosis (DC) and hepatocellular carcinoma; and (c) comparison of the proportions of patients at each disease stage with and without treatment. Probabilistic and determinist sensitivity analyses were performed to address uncertainty. Results: Sofosbuvir‐based treatment would save [mean, 95% confidence intervals] 3.3 (2.5; 5.7) LY per patient in Cameroon, 2.7 (2.1; 4.8) in Côte d'Ivoire and 3.6 (2.8; 6.3) in Senegal. With treatment, approximately 6% (1%) of the patients still alive in each of the study countries would be in the CC (DC) health state 11 (15) years after CHC diagnosis, vs 15% (5%) without treatment. Scenario analysis showed earlier diagnosis and treatment initiation would dramatically improve LYS and morbidity. Conclusion: Sofosbuvir‐based treatment could significantly reduce CHC‐related mortality and help control CHC‐related liver disease progression in West and Central Africa. However, the goal of disease elimination necessitates a substantial decrease in DAAs prices, greater political commitment and increases in both national and external health expenditures. [ABSTRACT FROM AUTHOR]

Although physical function decline is common with aging, the burden of this impairment remains underestimated in patients living with HIV (PLHIV), particularly in the older people receiving antiretroviral treatment (ART) and living in sub-Saharan Africa (SSA). PLHIV aged ≥50 years old and on ART since ≥6 months were included (N = 333) from three clinics (two in Côte d'Ivoire, one in Senegal) participating in the International epidemiological Databases to Evaluate AIDS (IeDEA) West Africa collaboration. Physical function was measured using the Short Physical Performance Battery (SPPB), the unipodal balance test and self-reported questionnaires. Grip strength was also assessed. Logistic regression was used to identify the factors associated with SPPB performance specifically. Median age was 57 (54–61) years, 57.7% were female and 82.7% had an undetectable viral load. The mean SPPB score was 10.2 ±1.8. Almost 30% had low SPPB performance with the 5-sit-to-stand test being the most altered subtest (64%). PLHIV with low SPPB performance also had significantly low performance on the unipodal balance test (54.2%, p = 0.001) and low mean grip strength (but only in men (p = 0.005)). They also showed some difficulties in daily life activities (climbing stairs, walking one block, both p<0.0001). Age ≥60 years (adjusted OR (aOR) = 3.4; CI95% = 1.9–5.9,), being a female (aOR = 2.1; CI95% = 1.1–4.1), having an abdominal obesity (aOR = 2.1; CI95% = 1.2–4.0), a longer duration of HIV infection (aOR = 2.9; CI95% = 1.5–5.7), old Nucleoside reverse transcriptase inhibitors (NRTIs) (i.e., AZT: zidovudine, ddI: didanosine, DDC: zalcitabine, D4T: stavudine) in current ART (aOR = 2.0 CI95% = 1.1–3.7) were associated with low SPPB performance. As in western countries, physical function limitation is now part of the burden of HIV disease complications of older PLHIV living in West Africa, putting this population at risk for disability. How to screen those impairments and integrate their management in the standards of care should be investigated, and specific research on developing adapted daily physical activity program might be conducted. [ABSTRACT FROM AUTHOR]

Introduction: Excessive alcohol consumption leads to unfavourable outcomes in people living with HIV (PLHIV), including reduced adherence to antiretroviral therapy (ART) and engagement into care. However, there is limited information on alcohol consumption patterns among PLHIV in sub‐Saharan Africa. Methods: Using a cross‐sectional approach, the Alcohol Use Disorders Identification Test (AUDIT‐C) was administered to PLHIV attending HIV clinics in Côte d'Ivoire, Togo, Senegal and Zambia (2013 to 2015). Hazardous drinking was defined as an AUDIT‐C score ≥4 for men or ≥3 for women, and binge drinking as ≥6 drinks at least once per month. The prevalence of binge drinking was compared to estimates from the general population using data from the World Health Organization. Factors associated with binge drinking among persons declaring any alcohol use in the past year were assessed using a logistic regression model to estimate odds ratio (OR) and their corresponding 95% confidence intervals (CI). Results: Among 1824 PLHIV (median age 39 years, 62.8% female), the prevalence of hazardous alcohol use ranged from 0.9% in Senegal to 38.4% in Zambia. The prevalence of binge drinking ranged from 14.3% among drinkers in Senegal to 81.8% in Zambia, with higher estimates among PLHIV than in the general population. Male sex (OR 2.4, 95% CI 1.6 to 3.7), tobacco use (OR 1.7, 95% CI 1.0 to 2.9) and living in Zambia were associated with binge drinking. Conclusions: Alcohol consumption patterns varied widely across settings and binge drinking was more frequent in HIV‐positive individuals compared to the general population. Interventions to reduce excessive alcohol use are urgently needed to optimize adherence in the era of universal ART. [ABSTRACT FROM AUTHOR]

Background: Food insecurity can contribute to poor adherence to both tuberculosis treatment and HIV antiretroviral therapy (ART). Interventions that target food insecurity have the potential to increase treatment adherence, improve clinical outcomes, and decrease mortality. The goals of this study were to compare the feasibility, acceptability, and potential impact of implementing two different forms of nutrition support for HIV-TB co-infected adults in the Casamance region of Senegal. Methods: We conducted a randomized pilot implementation study among HIV-TB co-infected adults initiating treatment for TB (ClinicalTrials.gov Identifier: NCT03711721). Subjects received nutrition support in the form of a local food basket or Ready-to-Use Therapeutic Food (RUTF), distributed on a monthly basis for six months. Results: A total of 178 monthly study encounters were completed by 26 HIV-TB co-infected adults; 14 received food baskets and 12 received RUTF. For both the food basket and RUTF, 100% of subjects obtained the supplement at every study encounter, transferred the supplement from the clinic to their household, and consumed the supplement. The food basket had greater acceptability and was more likely to be shared with members of the household. Adherence to TB treatment and ART exceeded 95%, and all outcomes, including CD4 cell count, hemoglobin, nutritional status, and food security, improved over the study period. All subjects completed TB treatment and were smear negative at treatment completion. The total cost of the local food basket was approximately $0.68 per day versus $0.99 for the RUTF. Conclusion: The implementation of nutrition support for HIV-TB co-infected adults in Senegal is feasible and may provide an effective strategy to improve adherence, treatment completion, and clinical outcomes for less than 1 USD per day. Further studies to determine the impact of nutrition support among a larger population of HIV-TB co-infected individuals are indicated. [ABSTRACT FROM AUTHOR]

Introduction: HIV-2, endemic in West Africa, has a natural resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) which makes it difficult to treat it in developing countries. Methods: we conducted a descriptive, longitudinal, prospective study over the period November 2005-June 2017. Virologic failure has been defined as any viral load greater than 50 copies/ml after 6 months of ARV treatment administered twice. Assays for detecting drug-resistance mutations was performed in the protease-coding region and in the reverse transcriptasecoding region. Results: data from a total of 110 patients were collected. The patients had a median age of 46 years (ranging from 18 to 67) with a sex-ratio F/M of 2.54. At inclusion, viral load could be assessed in 44% of cases with a median of 935cp/ml (ranging from 17 to 144038). Antiretroviral regimen consisted of a combination of 2 NRTIs and 1IP in 94% of cases. The median follow-up was 1200 days (ranging from 1 to 3840); 94 then 76 patients completed their 12-month and 24-month assessments respectively. At 24-month follow-up, 39 patients had virologic failure, reflecting a prevalence of 39% estimated at 33% at 12-month follow-up and at 11% at 24-month follow-up; NRTIs resistance was observed in 45% of patients, IP resistance in 41% of patients while multi-NRTIs resistance and multi-IP resistance in 30% of patients. Conclusion: currently, there is an urgent need to make available the new therapeutic classes of ARV for second line ART for patients living with HIV-2 with therapeutic failure in resourcelimited settings. [ABSTRACT FROM AUTHOR]

Abdominal tuberculosis accounts for 3 to 5% of all visceral diseases. Despite the demonstrated effectiveness of anti-tuberculosis treatments, some cases of exacerbation of the initial clinical presentation have been described during the initiation of treatment. However, these reactions also known as "paradoxical" have been rarely reported in immunocompetent patients and much less in the case of bowel obstruction. We report a case of intestinal tuberculosis revealed by acute bowel obstruction during paradoxical reaction to anti-tuberculosis treatment. The study included a 26- year old immunocompetent patient with occlusive syndrome after a month of treatment for pleuropulmonary tuberculosis. Abdominal computed tomography (CT) showed small bowel obstruction. Laparotomy objectified intraperitoneal mass with multiple adhesions. Anatomo-pathological examination of the surgical specimen showed intestinal tuberculosis. Patient's outcome was favorable after the continuation of initial antituberculosis treatment. [ABSTRACT FROM AUTHOR]

Background There is an urgent need for safe and effective antiretroviral therapy (ART) for human immunodeficiency virus type 2 (HIV-2) infection. We undertook the first clinical trial of a single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2–infected individuals in Senegal, West Africa. Methods HIV-2–infected, ART-naive adults with World Health Organization stage 3–4 disease or CD4 count <750 cells/μL were eligible for this 48-week, open-label trial. We analyzed HIV-2 viral loads (VL), CD4 counts, clinical and adverse events, mortality, and loss to follow-up. Results We enrolled 30 subjects who initiated E/C/F/TDF. Twenty-nine subjects completed 48 weeks of follow-up. The majority were female (80%). There were no deaths, no new AIDS-associated clinical events, and 1 loss to follow-up. The median baseline CD4 count was 408 (range, 34–747) cells/μL, which increased by a median 161 (range, 27–547) cells/μL at week 48. Twenty-five subjects had baseline HIV-2 VL of <50 copies/mL of plasma. In those with detectable HIV-2 VL, the median was 41 (range, 10–6135) copies/mL. Using a modified intent-to-treat analysis (US Food and Drug Administration Snapshot method), 28 of 30 (93.3%; 95% confidence interval, 77.9%–99.2%) had viral suppression at 48 weeks. The 1 subject with virologic failure had multidrug-resistant HIV-2 (reverse transcriptase mutation: K65R; integrase mutations: G140S and Q148R) detected at week 48. There were 8 grade 3–4 adverse events; none were deemed study related. Adherence and acceptability were good. Conclusions Our data suggest that E/C/F/TDF, a once-daily, single-tablet-regimen, is safe, effective, and well tolerated. Our findings support the use of integrase inhibitor–based regimens for HIV-2 treatment. Clinical Trials Registration NCT02180438. [ABSTRACT FROM AUTHOR]

Objective: To examine how patient characteristics combined with ART eligibility expansions affect the initiation of antiretroviral therapy (ART) among eligible patients attending a referral center in Senegal from 1998 to 2015. Methods: This is a retrospective observational study carried out at the outpatient treatment Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on computerized medical records, gathered from 1998 to 2015, of ART-naïve patients over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable CD4 count)) in 1998–2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in 2011–2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014–2015. Four periods were defined according to ART eligibility expansions and Senegal’s HIV care history: 1998–2003 (P 1), 2004–2010 (P 2), 2011–2013 (P3), and 2014–2015 (P4). Patients were expected to participate financially in their treatment during the first period (P1). Results: A total of 3651 patient records were included. The median patient age was 40 years (IQR: 32–48). Women represented 56% of the population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had CD4 < 200 cells/mm3 at entry. This proportion reached 45% in 2014–2015. 2535 patients (69%) were eligible for therapy, including 1503 (41%) who started ART. The proportion of treated patients among those who were eligible at entry or later increased steadily from 25%, 47%, 75% to 82% in the four periods, respectively. The median time to treatment decreased from 5.6 months (IQR: 3–11) in P1 to 0.8 months (IQR: 0–2) in P4. Eligible patients with more advanced disease (CD4<200 cells/mm3 and/or clinical stage 3 or 4) were more likely to be ART initiated than those with CD4≥200 cells/mm3 and/or clinical stage 1 or 2 at each stage of ART eligibility expansion. Conclusion: ART eligibility expansions were marked by a sharp increase in the proportion of eligible patients initiating treatment. These results show that in terms of management, the target of "Test and Treat" can be easily reached but that HIV testing will remain a key element to improve treatment success, as illustrated by the high proportion of people with advanced stage of infection at the time of ART initiation. [ABSTRACT FROM AUTHOR]

An understanding of the factors contributing to food insecurity and malnutrition among people living with HIV (PLHIV) in Senegal is urgently needed in order to develop effective interventions. The goals of this study were to identify differences in the dimensions of food security among PLHIV in Dakar versus Ziguinchor, Senegal, to determine which of these dimensions are most predictive of severe food insecurity, and to identify factors associated with malnutrition. We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. Interviews were conducted with ninety-five food insecure, HIV-infected subjects. Daily household income and daily food expenditure per household member were the strongest predictors of severe food insecurity. The practice of agriculture, livestock ownership, nutritional status, and HIV outcomes were not predictive of severe food insecurity. CD4 count <350/mm3was the strongest predictor of malnutrition. Severe food insecurity, daily household income, daily food expenditure per household member, dietary diversity score, skipping meals, the practice of agriculture, livestock ownership, ART status, and adherence were not predictive of malnutrition. This is the first study to analyze the dimensions of food security among PLHIV in Senegal. We discovered important differences in food access, availability, stability, and utilization in Dakar versus Ziguinchor. We found that economic access was the strongest predictor of severe food insecurity and poorly controlled HIV was the strongest predictor of malnutrition. Our findings suggest that the interventions needed to address food insecurity differ from those necessary to target malnutrition, and that effective interventions may differ in Dakar versus Ziguinchor. Furthermore, this study highlights a need for a greater understanding of the relationship between HIV and malnutrition among individuals receiving ART in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background The Alere q HIV-1/2 Detect test (Alere Detect) is a rapid point-of-care (POC) nucleic acid test (NAT) that can detect and differentiate HIV-1 and HIV-2 in 25-μL whole blood or plasma samples. The Alere Detect test has been validated for early infant diagnosis of HIV-1 infection, and it is the only POC NAT device currently known to detect HIV-2, which is endemic in West Africa. Objectives To evaluate the sensitivity detecting HIV-2 RNA and the differential performance of the Alere Detect. Study design Plasma samples from non-HIV (n = 4), HIV-1 (n = 22), HIV-2 (n = 111; 29 Group A, 2 Group B) and HIV-1/HIV-2 dually-seropositive (n = 8) participants in Senegal and the United States and HIV-2 reference strains (3 Group A, 1 Group B) were tested by Alere Detect, Abbott RealTime HIV-1 and the University of Washington HIV-2 RNA quantitative (UW HIV-2) assays. Results The Alere Detect correctly differentiated between HIV-1 and HIV-2 in all 80 (100%) patient samples with detectable HIV RNA (n = 20 HIV-1, 60 HIV-2). The overall HIV-2 detection concordance between Alere Detect and the UW HIV-2 assay was 68% (54/80); the concordance improved to 100% (30/30) for samples with HIV-2 RNA >300copies/mL. Neither assay detected HIV-2 RNA in 31 of 111 HIV-2 seropositive samples. Conclusions The Alere Detect test is a novel device detecting HIV RNA in clinical samples, and differentiating HIV-1 and HIV-2 with a high level of specificity. It has the potential for use as a rapid HIV-2 NAT-based diagnosis tool in resource-limited settings and to confirm HIV-2 infection for the CDC 4th generation HIV-1/2 diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Background: Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA.Methods: A medical chart review was conducted in large urban HIV treatment centers in Côte d'Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen.Results: Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4-14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02-4.79) had a confirmed HCV infection.Conclusions: The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Late diagnosis of HIV infection can be fatal because it favors the appearance of opportunistic infections whose management requires the use of several molecules which can cause drug interactions. We report the case of a 45-year old female patient under heroin substitution treatment, using methadone and with HIV1 under antiretroviral treatment. This patient had nonspecific pulmonary appearance associated with dry nagging cough and progressive dyspnea evolving in a feverish context. Moreover, clinical examination showed left lower limb lymphedema with painless angiomatous nodules evolving over three years associated with plaques, angiomatous nodules occurred more recently at the level of the anterior face of the thorax. Sputum GeneXpert test allowed isolation of Mycobacterium tuberculosis. The diagnosis of pulmonary tuberculosis associated with Kaposi's sarcoma and immunosuppression caused by HIV was retained. [ABSTRACT FROM AUTHOR]

Background & Aims While universal screening of hepatitis B virus ( HBV) is recommended in high burden countries, little is known about the proportion of HBV-infected persons in need of antiviral therapy in these settings. Methods Prisoners in Senegal and Togo as well as female sex workers and men who have sex with men in Cote d'Ivoire were screened for HBV infection. All HBsAg-positive participants underwent transient elastography, alanine aminotransferase ( ALT) and HBV viral load ( VL) quantification. Individuals with cirrhosis or those aged >30 years with an HBV replication ≥20 000 IU/mL and elevated ALT were considered eligible for antiviral therapy. Results Of 1256 participants, 110 (8.8%) were HBsAg positive; their median age was 30 years [interquartile range: 25-33] and 96 (86.5%) were men. Three individuals (2.7%) had cirrhosis, while 28 (29.5%) of 94 participants with available measurements had an HBV VL ≥20 000 IU/mL. Overall, 11 (10.0%) subjects were considered eligible for immediate antiviral treatment (2.1% of participants in Dakar, 7.7% in Abidjan and 21.6% in Lome, P=.001) and 59 (53.4%) for close monitoring due to the presence of significant liver fibrosis, elevated ALT or significant HBV replication. Conclusions Among vulnerable populations in West Africa, a minority of HBV-infected individuals were eligible for immediate antiviral therapy. Prospective cohort studies are necessary to evaluate anti- HBV treatment eligibility facing the significant proportion of individuals with active chronic HBV infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Liver fibrosis is often the first stage of liver disease in people living with HIV (PLWHIV) in industrialized countries. However, little is known about liver fibrosis and its correlates among PLWHIV in sub-Saharan Africa. Methods: The study was undertaken in three HIV referral clinics in Côte d'Ivoire, Senegal and Togo. Enrolled PLWHIV underwent a non-invasive assessment of liver fibrosis combining liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase-to-platelet ratio index (APRI). Significant liver fibrosis was defined as LSM =7.1 kPa. Patients were screened for alcohol use (alcohol use disorder identification test (AUDIT)-C questionnaire), hepatitis B virus (HBV) antigen, hepatitis Delta virus (HDV) antibody and anti-hepatitis C (HCV) antibody. A logistic regression model was used to identify the factors associated with significant liver fibrosis. Results: A total of 807 PLWHIV were screened at a median age of 43 years (interquartile range (IQR): 36-50). Their median CD4 count was 393 cells/mm³ (IQR: 234-563) and 682 (84.5%) were on antiretroviral therapy (ART). The prevalence of significant fibrosis was 5.3% (3.8-6.7). Infections with HBV and HCV were identified in 74 (9.2%) and nine (1.1%) participants. Main factors associated with liver fibrosis were alcohol use (AUDIT-C >6): (odds ratio (OR) = 4.0, confidence interval (CI): 1.2-14.0), (Ref. AUDIT-C <4) and HBV infection (OR = 2.9, CI: 1.2-7.2). Of the 74 patients positively screened for HBV, 50.0% were on a tenofovir-based ART regimen. Overall, 10% of HIV/HBV coinfected patients were detected with a positive HDV antibody with a higher prevalence in patients with a significant liver fibrosis (43.0%) compared to others (6.3%) (p = 0.01). Conclusions: Considering the WHO recommendations to screen for HBV infection and treat co-infected patients with tenofovir-based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co-infected patients. [ABSTRACT FROM AUTHOR]

Background: In sub-Saharan Africa, antiretroviral therapy (ART) including drugs with potential toxicity such as Zidovudine (ZDV) are routinely prescribed. This study aimed at estimating the incidence of severe neutropenia and associated factors after ART initiation in five West African countries. Methods: A retrospective cohort analysis was conducted within the international epidemiologic database to evaluate AIDS (IeDEA) collaboration in West Africa. All HIV-infected adults, initiating ART between 2002 and 2014, with a baseline and at least one follow-up absolute neutrophil count (ANC) measurement were eligible. Incidence of severe neutropenia (ANC <750 cells/mm3) was estimated with 95% confidence interval (CI) according to age, gender, HIV clinic, hemoglobin, CD4 count, clinical stage, and ART duration. A Cox proportional hazard model was used to identify factors associated with severe neutropenia, expressed with their adjusted hazard ratios (aHR). Results: Between 2002 and 2014, 9,426 HIV-infected adults were enrolled. The crude incidence rate of a first severe neutropenia was 9.1 per 100 person-years (95% CI: 8.6–9.8). Factors associated with severe neutropenia were exposure to ZDV <6 months (aHR = 2.2; 95% CI: 1.8–2.6), ≥6–12 months (aHR = 2.1; 95% CI: 1.6–2.8) and ≥12 months (aHR = 1.6; 95% CI: 1.2–2.2) [Ref. no ZDV exposure], CD4 count <350 cells/mm3 (aHR = 1.3; 95% CI: 1.1–1.5) and advanced clinical stage at ART initiation (aHR = 1.2; 95% CI: 1.0–1.4). Conclusion: The incidence of severe neutropenia after ART initiation in West Africa is high and associated with ZDV exposure and advanced HIV disease. In this context, efforts are needed to scale-up access to less toxic first-line ART drugs and to promote early ART initiation. [ABSTRACT FROM AUTHOR]

Introduction: Liver fibrosis is often the first stage of liver disease in people living with HIV (PLWHIV) in industrialized countries. However, little is known about liver fibrosis and its correlates among PLWHIV in sub-Saharan Africa. Methods: The study was undertaken in three HIV referral clinics in Côte d'Ivoire, Senegal and Togo. Enrolled PLWHIV underwent a non-invasive assessment of liver fibrosis combining liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase-to-platelet ratio index (APRI). Significant liver fibrosis was defined as LSM ≥7.1 kPa. Patients were screened for alcohol use (alcohol use disorder identification test (AUDIT)-C questionnaire), hepatitis B virus (HBV) antigen, hepatitis Delta virus (HDV) antibody and anti-hepatitis C (HCV) antibody. A logistic regression model was used to identify the factors associated with significant liver fibrosis. Results: A total of 807 PLWHIV were screened at a median age of 43 years (interquartile range (IQR): 36-50). Their median CD4 count was 393 cells/mm³ (IQR: 234-563) and 682 (84.5%) were on antiretroviral therapy (ART). The prevalence of significant fibrosis was 5.3% (3.8-6.7). Infections with HBV and HCV were identified in 74 (9.2%) and nine (1.1%) participants. Main factors associated with liver fibrosis were alcohol use (AUDIT-C >6): (odds ratio (OR) = 4.0, confidence interval (CI): 1.2-14.0), (Ref. AUDIT-C <4) and HBV infection (OR = 2.9, CI: 1.2-7.2). Of the 74 patients positively screened for HBV, 50.0% were on a tenofovir-based ART regimen. Overall, 10% of HIV/HBV coinfected patients were detected with a positive HDV antibody with a higher prevalence in patients with a significant liver fibrosis (43.0%) compared to others (6.3%) (p = 0.01). Conclusions: Considering the WHO recommendations to screen for HBV infection and treat co-infected patients with tenofovir-based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co-infected patients. [ABSTRACT FROM AUTHOR]

Background The 2014 CDC 4th generation HIV screening algorithm includes an orthogonal immunoassay to confirm and discriminate HIV-1 and HIV-2 antibodies. Additional nucleic acid testing (NAT) is recommended to resolve indeterminate or undifferentiated HIV seroreactivity. HIV-2 NAT requires a second-line assay to detect HIV-2 total nucleic acid (TNA) in patients’ blood cells, as a third of untreated patients have undetectable plasma HIV-2 RNA. Objectives To validate a qualitative HIV-2 TNA assay using peripheral blood mononuclear cells (PBMC) from HIV-2–infected Senegalese study participants. Study design We evaluated the assay precision, sensitivity, specificity, and diagnostic performance of an HIV-2 TNA assay. Matched plasma and PBMC samples were collected from 25 HIV-1, 30 HIV-2, 8 HIV-1/-2 dual-seropositive and 25 HIV seronegative individuals. Diagnostic performance was evaluated by comparing the outcome of the TNA assay to the results obtained by the 4th generation HIV screening and confirmatory immunoassays. Results All PBMC from 30 HIV-2 seropositive participants tested positive for HIV-2 TNA including 23 patients with undetectable plasma RNA. Of the 30 matched plasma specimens, one was HIV non-reactive. Samples from 50 non-HIV-2 infected individuals were confirmed as non-reactive for HIV-2 Ab and negative for HIV-2 TNA. The agreement between HIV-2 TNA and the combined immunoassay results was 98.8% (79/80). Furthermore, HIV-2 TNA was detected in 7 of 8 PBMC specimens from HIV-1/HIV-2 dual-seropositive participants. Conclusions Our TNA assay detected HIV-2 DNA/RNA in PBMC from serologically HIV-2 reactive, HIV indeterminate or HIV undifferentiated individuals with undetectable plasma RNA, and is suitable for confirming HIV-2 infection in the HIV testing algorithm. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Prisoners represent a vulnerable population for blood-borne and sexually transmitted infections which can potentially lead to liver fibrosis and ultimately cirrhosis. However, little is known about the prevalence of liver fibrosis and associated risk factors among inmates in sub-Saharan Africa.Methods: Screening of liver fibrosis was undertaken in a randomly selected sample of male inmates incarcerated in Lome, Togo and in Dakar, Senegal using transient elastography. A liver stiffness measurement ≥9.5 KPa was retained to define the presence of a severe liver fibrosis. All included inmates were also screened for HIV, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection. Substances abuse including alcohol, tobacco and cannabis use were assessed during face-to-face interviews. Odds Ratio (OR) estimates were computed with their 95 % Confidence Interval (CI) to identify factors associated with severe liver fibrosis.Results: Overall, 680 inmates were included with a median age of 30 years [interquartile range: 24-35]. The prevalence of severe fibrosis was 3.1 % (4.9 % in Lome and 1.2 % in Dakar). Infections with HIV, HBV and HCV were identified in 2.6 %, 12.5 % and 0.5 % of inmates, respectively. Factors associated with a severe liver fibrosis were HIV infection (OR = 7.6; CI 1.8-32.1), HBV infection (OR = 4.8; CI 1.8-12.8), HCV infection (OR = 52.6; CI 4.1-673.8), use of traditional medicines (OR = 3.7; CI 1.4-10.1) and being incarcerated in Lome (OR = 3.3; CI 1.1-9.8) compared to Dakar.Conclusions: HIV infection and viral hepatitis infections were identified as important and independent determinants of severe liver fibrosis. While access to active antiviral therapies against HIV and viral hepatitis expands in Africa, adapted strategies for the monitoring of liver disease need to be explored, especially in vulnerable populations such as inmates. [ABSTRACT FROM AUTHOR]

Introduction: the aim of this study was to describe our experience with the use of GeneXpert and to evaluate its contribution to confirmation of the diagnosis of tuberculosis. Methods: descriptive, analytical and prospective study conducted from January 2013 to December 2013 Results: ninetyfour patients underwent GeneXpert test for tuberculosis detection in patient in whom there is a clinical suspicion. GeneXpert was positive in 62% of cases. The radiological images which were highly suggestive of tuberculosis were associated with positive GeneXpert in 25% of cases. AFB was performed in 55 patients and was positive in 9 cases (16%) GeneXpert was positive in 46 sputum-negative (54%) and in 89% of sputum-positive The prevalence of extrapulmonary tuberculosis was 34%. The positivity rate was variable depending on the type of sample. Two cases with rifampicine resistance were detected. Conclusion: GeneXpert was a great contribution to the diagnosis of pulmonary and extrapulmonary tuberculosis but bacilloscopy remains essential. [ABSTRACT FROM AUTHOR]

Background: Malnutrition and food insecurity are associated with increased mortality and poor clinical outcomes among people living with HIV/AIDS; however, the prevalence of malnutrition and food insecurity among people living with HIV/AIDS in Senegal, West Africa is unknown. The objective of this study was to determine the prevalence and severity of food insecurity and malnutrition among HIV-infected adults in Senegal, and to identify associations between food insecurity, malnutrition, and HIV outcomes. Methods: We conducted a cross-sectional study at outpatient clinics in Dakar and Ziguinchor, Senegal. Data were collected using participant interviews, anthropometry, the Household Food Insecurity Access Scale, the Individual Dietary Diversity Scale, and chart review. Results: One hundred and nine HIV-1 and/or HIV-2 participants were enrolled. The prevalence of food insecurity was 84.6% in Dakar and 89.5% in Ziguinchor. The prevalence of severe food insecurity was 59.6% in Dakar and 75.4% in Ziguinchor. The prevalence of malnutrition (BMI <18.5) was 19.2% in Dakar and 26.3% in Ziguinchor. Severe food insecurity was associated with missing clinic appointments (p = 0.01) and not taking antiretroviral therapy due to hunger (p = 0.02). Malnutrition was associated with lower CD4 cell counts (p = 0.01). Conclusions: Severe food insecurity and malnutrition are highly prevalent among HIV-infected adults in both Dakar and Ziguinchor, and are associated with poor HIV outcomes. Our findings warrant further studies to determine the root causes of malnutrition and food insecurity in Senegal, and the short- and long-term impacts of malnutrition and food insecurity on HIV care. Urgent interventions are needed to address the unacceptably high rates of malnutrition and food insecurity in this population. [ABSTRACT FROM AUTHOR]

Background: Dolutegravir recently became the third integrase strand transfer inhibitor (INSTI) approved for use in HIV-1-infected individuals. In contrast to the extensive dataset for HIV-1, in vitro studies and clinical reports of dolutegravir for HIV-2 are limited. To evaluate the potential role of dolutegravir in HIV-2 treatment, we compared the susceptibilities of wild-type and INSTI-resistant HIV-1 and HIV-2 strains to the drug using single-cycle assays, spreading infections of immortalized T cells, and site-directed mutagenesis. Findings: HIV-2 group A, HIV-2 group B, and HIV-1 isolates from INSTI-naïve individuals were comparably sensitive to dolutegravir in the single-cycle assay (mean EC50 values = 1.9, 2.6, and 1.3 nM, respectively). Integrase substitutions E92Q, Y143C, E92Q + Y143C, and Q148R conferred relatively low levels of resistance to dolutegravir in HIV-2ROD9 (2- to 6-fold), but Q148K, E92Q + N155H, T97A + N155H and G140S + Q148R resulted in moderate resistance (10- to 46-fold), and the combination of T97A + Y143C in HIV-2ROD9 conferred high-level resistance (>5000-fold). In contrast, HIV-1NL4-3 mutants E92Q + N155H, G140S + Q148R, and T97A + Y143C showed 2-fold, 4-fold, and no increase in EC50, respectively, relative to the parental strain. The resistance phenotypes for E92Q + N155H, and G140S + Q148R HIV-2ROD9 were also confirmed in spreading infections of CEM-ss cells. Conclusions: Our data support the use of dolutegravir in INSTI-naïve HIV-2 patients but suggest that, relative to HIV-1, a broader array of replacements in HIV-2 integrase may enable cross-resistance between dolutegravir and other INSTI. Clinical studies are needed to evaluate the efficacy of dolutegravir in HIV-2-infected individuals, including patients previously treated with raltegravir or elvitegravir [ABSTRACT FROM AUTHOR]

In March 2014, the World Health Organization declared an outbreak of Ebola virus disease in Guinea. In August 2014, a case caused by virus imported from Guinea occurred in Senegal, most likely resulting from nonsecure funerals and travel. Preparedness and surveillance in Senegal probably prevented secondary cases. [ABSTRACT FROM AUTHOR]

Killer immunoglobulin-like receptors (KIRs) regulate natural killer (NK) cells in a human leukocyte antigen (HLA)-dependent manner. KIR/HLA mismatched hematopoietic stem cell transplants induce alloreactive NK cells, which prevent leukemia relapse. Certain KIR/HLA combinations protect against HIV-1 infection, but the effect of KIR/HLA mismatches between sexual partners has never been investigated. In this study, we analyzed the effect of allogeneic KIR/HLA combinations on HIV-1 transmission in a West African population of HIV-1-discordant and concordant couples. HIV-1-discordant couples were characterized by recipient partners with homozygous KIR2DL2, and by a mismatched recipient partner KIR2DL 1/HLA-C2 with index partner HLA-C1/C1 combination expected to allow licensed missing self NK cell killing of index partners' cells. HIV-1-concordant couples on the other hand were characterized by KIR2DL3 homozygous recipient partners with HLA-C1/C2 bearing index partners, resulting in a matched KIR/HLA combination expected to inhibit NK cell killing. In vitro cocultures of healthy donor-derived NK cells and HIV-1 patient-derived CD4+ T cells confirmed the involvement of these allogeneic KIR/HLA combinations in NK cell-mediated CD4+ T-cell killing. Our data suggest that KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission and that this may be due to alloreactive NK cell killing of the HIV-1-infected partner's cells. (Blood.2013;121(7):1157-1164) [ABSTRACT FROM AUTHOR]

Background: A large number of HIV-1 infections in Africa occur in married couples. The predominant direction of intracouple transmission and the principal external origins of infection remain important issues of debate. Methods: We investigated HIV-1 transmission in 46 HIV-1 concordant positive couples from Dakar, Senegal. Intracouple transmission was confirmed by maximum-likelihood phylogenetic analysis and pairwise distance comparisons of HIV-1 env gp41 sequences from both partners. Standardized interview data were used to deduce the direction as well as the external sources of the intracouple transmissions. Results: Conservative molecular analyses showed linked viruses in 34 (74%) couples, unlinked viruses in 6 (13%) couples, and indeterminate results for 6 (13%) couples. The interview data corresponded completely with the molecular analyses: all linked couples reported internal transmission and all unlinked couples reported external sources of infection. The majority of linked couples (93%) reported the husband as internal source of infection. These husbands most frequently (82%) reported an occasional sexual relationship as external source of infection. Pairwise comparisons of the CD4 count, antiretroviral therapy status, and the proportion of gp41 ambiguous base pairs within transmission pairs correlated with the reported order of infection events. Conclusions: In this suburban Senegalese population, a majority of HIV-1 concordant couples showed linked HIV-1 transmission with the husband as likely index partner. Our data emphasize the risk of married women for acquiring HIV-1 as a result of the occasional sexual relationships of their husbands. [ABSTRACT FROM AUTHOR]

Background: HIV-1 replication depends on a delicate balance between cellular co-factors and antiviral restriction factors. Lens epithelium-derived growth factor (LEDGF/p75) benefits HIV, whereas apolipoprotein B mRNA-editing catalytic polypeptide-like 3G (APOBEC3G), tripartite motif 5alpha (TRIM5a), and tetherin exert anti-HIV activity. Expression levels of these proteins possibly contribute to HIV-1 resistance in HIV-1-exposed populations. Methodology/Principal Findings: We used real-time PCR and flow cytometry to study mRNA and protein levels respectively in PBMC and PBMC subsets. We observed significantly reduced LEDGF/p75 protein levels in CD4+ lymphocytes of HIV-1- exposed seronegative subjects relative to healthy controls, whereas we found no differences in APOBEC3G, TRIM5a, or tetherin expression. Untreated HIV-1-infected patients generally expressed higher mRNA and protein levels than healthy controls. Increased tetherin levels, in particular, correlated with markers of disease progression: directly with the viral load and T cell activation and inversely with the CD4 count. Conclusions/Significance: Our data suggest that reduced LEDGF/p75 levels may play a role in resistance to HIV-1 infection, while increased tetherin levels could be a marker of advanced HIV disease. Host factors that influence HIV-1 infection and disease could be important targets for new antiviral therapies. [ABSTRACT FROM AUTHOR]

To compare human immunodeficiency virus (HIV) type 1 disease progression in patients infected by the predominant strain circulating recombinant form (CRF) 02AG in western and west-central Africa and in patients infected by other strains, a prospective multicenter cohort study was conducted in Cameroon and Senegal. Among the 335 patients, a broad HIV-1 group M subtype diversity was observed in the envelope V3-V5 region, but strain CRF02AG predominated in both Cameroon and Senegal (61.2% and 62.9%, respectively; P < .8). Multivariate analyses showed no difference between patients infected by CRF02 strains and those infected by other strains in terms of survival (adjusted hazards ratio [HR], 1.16; 95% confidence interval [CI], 0.76-1.78; P = .5), clinical disease progression (HR, 0.79; 95% CI, 0.50-1.25; P = .3), or square root CD4 cell decline (regression coefficient, -0.01; 95% CI, -0.82 to 0.81; P = .9). This study suggests that the predominance of HIV-1 CRF02AG strain in western and west-central Africa should have no major clinical consequences. [ABSTRACT FROM AUTHOR]

Introduction: Despite prevention efforts, malaria remains a public health problem. Methodology: This was a prospective study conducted between October and December 2010 that aimed to describe the therapeutic route of adults presenting with severe malaria prior to being admitted to Fann Teaching Hospital in Dakar, Senegal. Results: A total of 90 patients were included. The majority of them had consulted a public or private health care facility (92%) prior to admission. First consultation occurred on average two days after the onset of the disease. Self-medication (67.4%) and traditional medicine (26.1%) were the main causes of delaying care. Conclusions: Early care and adequate management are needed to reduce malaria mortality. [ABSTRACT FROM AUTHOR]