Prevalence of therapeutic failure and evolution of biological factors amongst people living with HIV enrolled in antiretroviral therapy at the Ambulatory Treatment Center in Nouakchott, Mauritania.

GOAL: The goal of this study is to determine the prevalence of therapeutic failure and the evolution of the biological factors after 6 and 12 months of anti-retroviral treatment (ART) amongst human immunodefeciency virus (HIV) Patients receiving care through the Ambulatory Treatment Center in Nouakchott. METHODS: The study presents a descriptive and retrospective analysis of 479 patients enrolled in ART between January 2015 and January 2019, with focus on treatment failures and related biomarkers. The average age of the patients studied was 37 ± 12.94 years. The majority (52.8%) were males, of whom (52.6%) were married. RESULTS: The average body mass index (BMI) of the patients progressively increased after 6 and 12 months on ART. The average BMI increased from 20.3 ± 5.1 kg/m2 , before treatment, to 21.7 ± 5.0 kg/m2 and 22.7 ± 5.4 kg/m2 , after 6 and 12 months of treatment, respectively. Of the 479 patients, 97.3% were on 2 NRTIs + NNRTI. During the first 6 months of treatment, the clinical, immunological, and virological therapeutic failures were 0.6%, 34.10%, and 9%, respectively. After 6 and 12 months of ART, the TCD4, Hemoglobin, platelets, glycemia, creatinemia, and transaminase remained normal during the entire monitoring period. CONCLUSION: study demonstrated effective HIV treatment amongst the study patients. It showed clearance of virus and immune restoration can be attained after 6 and 12 months of ART. The number of patients who received the tests did decrease during the treatment period, which highlights the importance of adherence to patient management protocols, including clinical and biological monitoring.

Trends in Reported Sexual Behavior and Y-Chromosomal DNA Detection Among Female Sex Workers in the Senegal Preexposure Prophylaxis Demonstration Project.

BACKGROUND: Preexposure prophylaxis (PrEP) can reduce HIV acquisition among female sex workers (FSWs). However, changes in condomless sex frequency after PrEP initiation could reduce PrEP effectiveness when PrEP adherence is suboptimal as well as increase the risk of acquiring other sexually transmitted infections. Objective measures of condomless sex may be more accurate for determining changes in sexual behavior than self-reported measures. METHODS: We longitudinally measured self-reported condom use, number of clients, and presence of Y-chromosomal DNA (Yc-DNA) in vaginal swabs among 267 FSWs accessing PrEP at 4 clinics in Senegal between 2015 and 2016. We assessed trends in sexual behavior over time since PrEP initiation using generalized estimating equations and evaluated predictors of Yc-DNA detection. RESULTS: We found no increase in self-reported condomless sex with clients (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89-1.00), main partners (OR, 0.99; 95% CI, 0.96-1.02), or Yc-DNA detection (OR, 0.99; 95% CI, 0.90-1.08) over time since initiation. Y-chromosomal DNA was detected in 34 (22%) of 154 swabs tested and in 15 (26%) of 58 swabs from FSW reporting consistent condom use among both clients and main partners. Self-reported condom use with clients or main partners did not predict Yc-DNA detection. CONCLUSIONS: In a FSW PrEP demonstration project in Senegal, we found no evidence of risk compensation among FSWs on PrEP as measured by self-reported behavior or through Yc-DNA detection. Y-chromosomal DNA detection was frequently detected among FSWs reporting consistent condom use, highlighting limitations of self-reported sexual behavioral measures.

Dried blood spots for HIV-1 drug resistance genotyping in decentralized settings in Senegal.

The aim of this study was to evaluate the use for HIV-1 drug resistance testing dried blood spots collected in remote areas and sent under field conditions to a reference laboratory and also to document virological failure in patients with suspected treatment failure. Samples were collected from patients receiving first line ART at 11 hospital sites around country, kept at room temperature (<37°C) and sent within 15 days maximum to the reference laboratory. Viral nucleic acids were obtained by magnetic extraction with NucliSENS (bioMérieux, Marcy l'Etoile, France). Genotyping of HIV-1 pol gene was performed using the ANRS protocol. Drug resistance mutations were analyzed according to the Stanford University HIV database version 6.0.8. Two hundred thirty one HIV-infected adults' on HAART first line regimen composed study population. The median time on ART was 18 months (range 6-68). Regardless of the treatment duration, the overall rate of virological failure (VL ≥ 3 log10 cp/ml) was 23.8% (n = 55/231). HIV genotypes were obtained successfully in 94.5% (n = 52/55). Drug resistance mutation was found in 41/52 patients in virological failure, for 17.7% (n = 41/231) an overall rate of drug resistance mutations. M184V/I was the most frequent mutation occurring, followed by K103N. Phylogenetic analysis of the 52 genotyped viral isolates showed the predominance of CRF02_AG with 62% (n = 32/52). Use of a DBS specimen is suitable to assist national programs for monitoring in remote areas HIV drug resistance in resources limited-settings.

m-PIMA™ HIV1/2 VL: A suitable tool for HIV-1 and HIV-2 viral load quantification in West Africa.

Point-of-Care for HIV viral RNA quantification seems to be a complementary strategy to the existing conventional systems. This study evaluated the performance of the m-PIMA™ HIV1/2 Viral Load for the quantification of both HIV-1 and HIV-2 RNA viral load. A total of 555 HIV-1 and 90 HIV-2 samples previously tested by Abbott RealTime HIV-1 (Abbott, Chicago, USA) and Generic HIV-2® Charge virale (Biocentric, France) were tested using the m-PIMA™ HIV1/2 Viral Load at the HIV National Reference lab in Senegal. For HIV-1, Pearson correlation and Bland-Altman plots showed a coefficient r = 0.97 and a bias of -0.11 log10 copies/ml (95% confidence interval [CI]: -0.086 to -0.133 log10 copies/ml) for the m-PIMA™ HIV1/2 Viral Load, respectively. Sensitivity and specificity at 3 log10 copies/ml (threshold of virological failure) were 93.6% (95%[CI]: 91.5% to 95.6%) and 99.1% (95%[CI]: 98.3% to 99.9%), respectively. For HIV-2, a correlation of r = 0.95 was also noted with a bias of - 0.229 log10 copies/ml (95%[CI]: -0.161 to -0.297 log10 copies/ml). Sensitivity and specificity at 3 log10 copies/ml were 97.6% (95%[CI]: 94.3% to 100%) and 93.9% (95%[CI]: 88.9% to 98.8%), respectively. These results confirmed that m-PIMA™ HIV1/2 VL could be a good alternative for HIV-1 and HIV-2 viral load testing in decentralized settings in Senegal.

COVID-19 in 16 West African Countries: An Assessment of the Epidemiology and Genetic Diversity of SARS-CoV-2 after Four Epidemic Waves.

West Africa faced the COVID-19 pandemic in early March 2020 and, as of March 31, 2022, had more than 900,000 confirmed cases and more than 12,000 deaths. During this period, SARS-CoV-2 genomes evolved genetically, resulting in the emergence of distinct lineages. This review was conducted to provide the epidemiological profile of COVID-19, the mutational profile of SARS-CoV-2, and the dynamics of its lineages in the 16 west African countries by analyzing data from 33 studies and seven situation reports. For a more complete representation of the epidemiology and genetic diversity of SARS-CoV-2, we used reliable public data in addition to eligible studies. As of March 31, 2022, the 16 west African countries experienced four epidemic waves with variable intensities. Higher mortality was noted during the third wave with a case fatality rate (CFR) of 1.9%. After these four epidemic waves, Liberia recorded the highest CFR (4.0%), whereas Benin had the lowest CFR (0.6%). Through mutational analysis, a high genetic heterogeneity of the genomes was observed, with a predominance of mutations in the spike protein. From this high mutational rate, different lineages emerged. Our analysis of the evolutionary diversity allowed us to count 205 lineages circulating in west Africa. This study has provided a good representation of the mutational profile and the prevalence of SARS CoV-2 lineages beyond the knowledge of the global epidemiology of the 16 African countries.

Genomic Epidemiology of SARS-CoV-2 in Urban Settings in Senegal.

We used whole genome sequencing to identify and analyze mutations in SARS-CoV-2 in urban settings during the deadliest wave of the COVID-19 epidemic-from March to April 2021-in Senegal. Nasopharyngeal samples testing positive for SARS-CoV-2 were sequenced on the Illumina NovaSeq 6000 sequencing system using the COVIDSeq protocol. A total of 291 genotypable consensus genome sequences were obtained. Phylogenetic analyses grouped the genomes into 16 distinct PANGOLIN lineages. The major lineage was B.1.1.420, despite circulation of the Alpha variant of concern (VOC). A total of 1125 different SNPs, identified relative to the Wuhan reference genome, were detected. These included 13 SNPs in non-coding regions. An average density of 37.2 SNPs per 1000 nucleotides was found, with the highest density occurring in ORF10. This analysis allowed, for the first time, the detection of a Senegalese SARS-CoV-2 strain belonging to the P.1.14 (GR/20J, Gamma V3) sublineage of the Brazilian P.1 lineage (or Gamma VOC). Overall, our results highlight substantial SARS-CoV-2 diversification in Senegal during the study period.

Detection and quantitation of hepatitis B surface antigen (HBsAg) on dried blood spots: a solution for easy access for hepatitis B diagnosis and elimination in remote areas.

Hepatitis B virus (HBV) is generally endemic in resource-limited countries, which are characterized by a deficit of technical facilities that could delay diagnosis and treatment. To facilitate the accessibility to diagnostic and connection to treatment, evaluation, and promotion of alternatives and/or simplified strategies and inexpensive tools such as dried blood specimens need to be investigated and implemented. This study aimed to evaluate dried blood spots (DBS) for the detection and quantification of HBsAg. This study included 100 DBS from subjects tested positive for HBsAg, and 50 DBSs from subjects tested negative for HBsAg by the automate Architect i1000sr (Abbott Diagnostics, Ireland). Hepatitis B surface antigen detection was performed with determine HBsAg Alere® tests (Alere International Limited, Ireland) and Architect® HBsAg Qualitative II Assays (Abbott, Diagnostics, Ireland) after 15 and 30 days (D15, D30). For HBsAg-positive subjects, the quantification of HBsAg was performed at day zero (D0) from plasma and at D15 and D30 from the DBSs. At D15, the sensitivity and specificity were 96% and 100% for the Determine® tests and 100% and 100% for the Architect® tests, respectively. At D30, the sensitivity and specificity were 96% and 100% for the Determine® tests and 100% and 100% for the Architect® tests, respectively. For HBsAg quantification, the agreement rates were 96%, 96% and 100% between D0-D15, D0-D30 and D15-D30, respectively. This work showed that DBSs can be very useful for HBsAg detection and quantification and therefore in the management of HBV infection in resource-limited settings.

Validation of the point-of-care (POC) technologies Xpert HIV-1 Qual and m-PIMA HIV 1/2 detect for early diagnosis of HIV-1 and HIV-2 in Senegal.

Introduction: early infant diagnosis (EID) is crucial in the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) and is an essential component for the elimination of HIV. EID can be strengthened in resource-limited countries by the introduction and the roll out of real-time polymerase chain reaction (PCR) technologies via point-of-care (POC) devices which improves treatment in remote areas and reduces turnaround time for clinicians and patients to receive results and linkage to care. The objective of this study was to evaluate the performance of Xpert® HIV-1 Qual Assay (Cepheid) and m-PIMA™ HIV 1/2 Detect (ABBOTT) for EID of HIV-1 and HIV-2. Methods: the performance of the Xpert® HIV-1 qual device was evaluated with 192 samples including 100 dried blood spot (DBS) samples from the National Reference Laboratory biobank (71 negative and 29 positive samples) and an additional 92 whole blood samples collected from infants from neonatal departments. These infants from seven treatment centers in the Dakar region were born to mothers infected with HIV-1 (n=91), HIV-2 (n= 8) or HIV-1/2 (n=1). The m-PIMA™ HIV 1/2 detect assay was evaluated on whole blood samples (n=100) with 92 HIV-1 samples and 8 HIV-2 samples from children born to HIV-infected mothers. The Cobas AmpliPreP/Cobas TaqMan (CAP/CTM) platform from Roche Diagnostic Laboratories was used as a reference for HIV-1 diagnosis and the Generic HIV-2 Viral Load Assay (Biocentric) was used as a reference for HIV-2 diagnosis. Performance was evaluated by calculating sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa coefficient. Results: for HIV-1 detection on GeneXpert and m-PIMA, no discordance was found on the samples tested, i.e. a sensitivity of 100% (95% CI: 93.9-100%), a specificity of 100% (95% CI: 97.5-100%), a positive predictive value (PPV) of 100% (95% CI: 93.9-100%) and a negative predictive value (NPV) of 100% (95% CI: 97.5-100%). Agreement with Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) was 100% with a Kappa coefficient of 1 (p<0.001, 95% CI) for both techniques. Similarly, the comparison between m-PIMA and generic biocentric for the detection of HIV-2 on the 8 samples tested showed perfect agreement. Conclusion: these results confirm the excellent performance of the Xpert® HIV-1 qual and m-PIMA™ HIV1/2 detect tests for the detection of HIV-1 and HIV-2 and encourage the extension of POC tests to improve access to EID in Senegal.

Performance of Xpert HIV-1 viral load test in Senegal: a country of high circulation of CRF02_AG.

Introduction: the introduction of the point-of-care in HIV-1 viral load quantification appears to be a complementary strategy to the existing conventional system of the acceleration plan for the achievement of the three 90s in Senegal. The objective of this study was to evaluate the performance of the Xpert® HIV-1 viral load in the context of circulation of non-B, non-C subtypes. Methods: two hundred samples, were tested on Xpert® HIV-1 Viral Load using 1 ml of plasma in comparison to 600 µl on Abbott Real-time HIV-1 assay. The difference between viral load values was considered significant for Dlog <0.5 log copies/ml. Results: a good correlation (r=0.985) was noted and confirmed using passing-bablok regression (slope 1.048; 95% CI: 1.036 to 1.069) for 188 samples with samples. A mean difference of 0.0075 log10 copies/ml for a 95% confidence interval (CI) of 0.002 log10 copies/ml to 0.013 log10 copies/ml was obtained. Sensitivity and specificity were respectively 93.6% and 93.5% at the threshold of 1.6 log10 copies/ml and 100% and 99% at the threshold of 3.0 log10 copies/ml. Conclusion: these results show that Xpert® HIV-1 Viral Load has excellent performance. In Senegal, and can be used for HIV viral load monitoring.

Characterization of Bacteria on Aerosols From Dust Events in Dakar, Senegal, West Africa.

We identify bacteria types on collected dust samples in Dakar Senegal, a region that experiences frequent Saharan dust events. We use classical techniques to identify bacteria types from dust samples. Seventy-seven bacteria types are identified from samples collected by spatula and the QuickTake® 30 air sampling pump. The dominant groups in the first batch of 51 bacteria (collected via deposition) are Micrococcus (33.33%), Bacillus (13.73%), Kytococcus (11.76%), Pseudomonas (9.80%), and Burkholderia (7.84%) and dominants in the second batch of 26 bacteria (collected with aerosol sampling vacuum pump): Pseudomonas (38.61%), Burkholderia (26.92%), Micrococcus (11.54%), and Brucella spp (7.69%). These bacteria are found in earlier studies from desert sources and can potentially cause respiratory diseases to exposed populations. Future work will use molecular methods is necessary to search for additional pathogens, including viruses on dust aerosols.

Phylodynamic analysis of HIV-1 subtypes B, C and CRF 02_AG in Senegal.

Surveillance of HIV epidemics in key populations and in developing countries is often challenging due to sparse, incomplete, or low-quality data. Analysis of HIV sequence data can provide an alternative source of information about epidemic history, population structure, and transmission patterns. To understand HIV-1 dynamics and transmission patterns in Senegal, we carried out model-based phylodynamic analyses using the structured-coalescent approach using HIV-1 sequence data from three different subgroups: reproductive aged males and females from the adult Senegalese population and men who have sex with other men (MSM). We fitted these phylodynamic analyses to time-scaled phylogenetic trees individually for subtypes C and CRF 02_AG, and for the combined data for subtypes B, C and CRF 02_AG. In general, the combined analysis showed a decreasing proportion of effective number of infections among all reproductive aged adults relative to MSM. However, we observed a nearly time-invariant distribution for subtype CRF 02_AG and an increasing trend for subtype C on the proportion of effective number of infections. The population attributable fraction also differed between analyses: subtype CRF 02_AG showed little contribution from MSM, while for subtype C and combined analyses this contribution was much higher. Despite observed differences, results suggested that the combination of high assortativity among MSM and the unmet HIV prevention and treatment needs represent a significant component of the HIV epidemic in Senegal.

Human Papillomavirus infection in senegalese female sex workers.

OBJECTIVES: Several studies have documented the HPV genotypes in the Senegalese general population. The objective was to explore the HPV genotype distribution in Senegalese FSWs in order to assess the potential relevance of currently-available vaccines. METHODS: Vaginal swabs samples collected as part of the National Integrated Biological and Behavioral Survey in 14 regions throughout the country were randomly selected for HPV testing using bead-based multiplex genotyping (TS-MPG). RESULTS: Among the 436 FSW samples analyzed, the overall HPV prevalence was 79.8% (N = 348), with 70.1% (N = 244) cases presenting as multiple infections. High Risk HPV genotypes affecting at least 10% of FSWs included in order of decreasing frequency: 52, 16, 35, 51, 33, 31, 18, and 45. Sixty-seven (15.4%) FSWs were HIV positive and they were significantly more affected by HPV (94% vs 77%; p < 0.01) than seronegative FSWs as well as infections with multiple genotype. CONCLUSION: The present study indicates that FSW in Senegal experience a high burden of HPV infection with a high frequency of coinfection with HIV and multiple HPV genotypes. Public health interventions for this key population should include an earlier cervical dysplasia/cancer detection and preventative measures such as vaccination programs that must consider the HPV genotype distribution.

Quantitation of HIV-1 RNA in dried blood spots by the real-time NucliSENS EasyQ HIV-1 assay in Senegal.

Measurement of viral load in plasma remains the best marker for the follow-up of antiretroviral therapy. However, its use is limited in developing countries due to the lack of adequate facilities and equipment, and cryopreservation of plasma during storage and transportation. Practical and reliable methods adapted to field conditions for the collection, transportation and accurate measurement of HIV-1 viral load are needed for the optimum use of antiretroviral therapy in resource-limited countries. This study evaluated the use of dried blood spots (DBS) for the real-time quantitation of HIV-1 RNA levels with the NucliSENS EasyQ((R)) HIV-1 assay (bioMérieux, Lyon, France) under field conditions in Senegal (Africa). Dried blood spots and plasma from 41 patients living in suburban Dakar were used for determination of HIV-1 RNA concentrations and stability at 37 degrees C. Analysis was performed at the Dakar University Hospital laboratory. Extraction was done with the bioMérieux NucliSENS((R)) miniMAGtrade mark, and real-time detection was done with the bioMérieux NucliSENS((R)) EasyQ system. HIV-1 RNA concentrations in plasma were compared with concentrations in dried blood spots after 8 and 15 days at 37 degrees C. The study showed a strong concordance in RNA levels between plasma and dried blood spots, which appear to be very stable over time with no apparent degradation observed after 2 weeks at 37 degrees C (mean difference 0.065logIU/ml). These results suggest that the use of dried blood spots in combination with the NucliSENS EasyQ HIV-1 assay is well adapted for HIV-1 RNA level monitoring in centralized laboratories in developing countries.

Surveillance of transmitted HIV-1 antiretroviral drug resistance in the context of decentralized HIV care in Senegal and the Ebola outbreak in Guinea.

OBJECTIVES: Disruption in HIV care provision may enhance the development and spread of drug resistance due to inadequate antiretroviral therapy. This study thus determined the prevalence of HIV-1 transmitted drug resistance (TDR) in settings of decentralized therapy and care in Senegal and, the Ebola outbreak in Guinea. Antiretroviral-naïve patients were enrolled following a modified WHO TDR Threshold Survey method, implemented in Senegal (January-March 2015) and Guinea (August-September 2015). Plasma and dried blood spots specimens, respectively from Senegalese (n = 69) and Guinean (n = 50) patients, were collected for direct sequencing of HIV-1 pol genes. The Stanford Calibrated Population Resistance program v6.0 was used for Surveillance Drug Resistance Mutations (SDRMs). RESULTS: Genotyping was successful from 54/69 (78.2%) and 31/50 (62.0%) isolates. In Senegal, TDR prevalence was 0% (mean duration since HIV diagnosis 4.08 ± 3.53 years). In Guinea, two patients exhibited SDRMs M184V (NRTI), T215F (TAM) and, G190A (NNRTI), respectively. TDR prevalence at this second site, however, could not be ascertained because of low sample size. Phylogenetic inference confirmed CRF02_AG predominance in Senegal (62.96%) and Guinea (77.42%). TDR prevalence in Senegal remains extremely low suggesting improved control measures. Continuous surveillance in both settings is mandatory and, should be done closest to diagnosis/transmission time and with larger sample size.

Estimating the contribution of key populations towards the spread of HIV in Dakar, Senegal.

INTRODUCTION: Key populations including female sex workers (FSW) and men who have sex with men (MSM) bear a disproportionate burden of HIV. However, the role of focusing prevention efforts on these groups for reducing a country's HIV epidemic is debated. We estimate the extent to which HIV transmission among FSW and MSM contributes to overall HIV transmission in Dakar, Senegal, using a dynamic assessment of the population attributable fraction (PAF). METHODS: A dynamic transmission model of HIV among FSW, their clients, MSM and the lower-risk adult population was parameterized and calibrated within a Bayesian framework using setting-specific demographic, behavioural, HIV epidemiological and antiretroviral treatment (ART) coverage data for 1985 to 2015. We used the model to estimate the 10-year PAF of commercial sex between FSW and their clients, and sex between men, to overall HIV transmission (defined as the percentage of new infections prevented when these modes of transmission are removed). In addition, we estimated the prevention benefits associated with historical increases in condom use and ART uptake, and impact of further increases in prevention and treatment. RESULTS: The model projections suggest that unprotected sex between men contributed to 42% (2.5 to 97.5th percentile range 24 to 59%) of transmissions between 1995 and 2005, increasing to 64% (37 to 79%) from 2015 to 2025. The 10-year PAF of commercial sex is smaller, diminishing from 21% (7 to 39%) in 1995 to 14% (5 to 35%) in 2015. Without ART, 49% (32 to 71%) more HIV infections would have occurred since 2000, when ART was initiated, whereas without condom use since 1985, 67% (27 to 179%) more HIV infections would have occurred, and the overall HIV prevalence would have been 60% (29 to 211%) greater than what it is now. Further large decreases in HIV incidence (68%) can be achieved by scaling up ART in MSM to 74% coverage and reducing their susceptibility to HIV by two-thirds through any prevention modality. CONCLUSIONS: Unprotected sex between men may be an important contributor to HIV transmission in Dakar, due to suboptimal coverage of evidence-informed interventions. Although existing interventions have effectively reduced HIV transmission among adults, it is crucial that further strategies address the unmet need among MSM.

Poor efficacy and tolerability of stavudine, didanosine, and efavirenz-based regimen in treatment-naive patients in Senegal.

OBJECTIVE: To study the effectiveness and tolerance of an antiretroviral therapy (ART) regimen composed of the antiretroviral agents (ARVs) stavudine (d4T) plus didanosine (ddI) plus efavirenz (EFV) in patients with advanced HIV infection in Senegal. DESIGN AND METHODS: This was an open-label, single-arm, 18-month trial in treatment-naive patients. The primary virologic end point was the percentage of patients with plasma HIV RNA < 500 copies/mL at months 6 (M6), 12 (M12) and 18 (M18). The primary analysis was done as intent-to-treat. RESULTS: The staging of HIV disease, performed using the definitions of the US Centers for Disease Control and Prevention (CDC), was CDC stage B or C for all 40 recruited patients. At baseline, the mean CD4+ cell count was 133 +/- 92/mcL (+/- standard deviation [SD]; range 1-346), and 23% of patients had CD4+ cell counts below 50/mcL. The mean baseline plasma HIV RNA level was 5.5 +/- 0.4 log(10) copies/mL (+/- SD; range 4.6-5.9). The proportion of patients with plasma HIV-1 RNA below 500 copies/mL fell during the study from 73% (95% CI [56; 85]) at M6 to 56% (95% CI [41; 73]) at M12 and 43% (95% CI [27; 59]) at M18. Plasma HIV-RNA was below 50 copies/mL in 50% of study subjects (95% CI [31; 66]) at M6, 43% (95% CI [27; 59]) at M12, and 33% (95% CI [19; 49]) at M18. The mean increase in the CD4+ cell count was 105 +/- 125/mcL (n = 38) at M3 and 186 +/- 122/mcL (n = 21) at M18. Eight patients died, including 6 because of infectious complications. The last viral load (VL) value before death was < 500 copies/mL in all these patients except 1 nonadherent patient. Fifteen patients (37.5%) had peripheral neuropathy that was severe enough in 5 patients (12.5%) to require ddI and d4T discontinuation. CONCLUSION: Virologic efficacy combination therapy with d4T, ddI, and EFV was measured by the percentage of patients with plasma HIV RNA values below 500 copies/mL and 50 copies/mL; for both parameters, virologic efficacy decreased during the study period. This is explained by the high mortality rate (20%) and treatment modifications due to adverse events (13%). These data strengthen the recently revised World Health Organization (WHO) guidelines advocating initiation of highly active antiretroviral therapy (HAART) before profound CD4 lymphocyte depletion occurs and avoiding HAART regimens containing d4T and ddI because of treatment-limiting side effects.

Ending AIDS as a public health threat by 2030: Scientific Developments from the 2016 INTEREST Conference in Yaoundé, Cameroon.

The underpinning theme of the 2016 INTEREST Conference held in Yaoundé, Cameroon, 3-6 May 2016 was ending AIDS as a public health threat by 2030. Focused primarily on HIV treatment, pathogenesis and prevention research in resource-limited settings, the conference attracted 369 active delegates from 34 countries, of which 22 were in Africa. Presentations on treatment optimization, acquired drug resistance, care of children and adolescents, laboratory monitoring and diagnostics, implementation challenges, HIV prevention, key populations, vaccine and cure, hepatitis C, mHealth, financing the HIV response and emerging pathogens, were accompanied by oral, mini-oral and poster presentations. Spirited plenary debates on the UNAIDS 90-90-90 treatment cascade goal and on antiretroviral pre-exposure prophylaxis took place. Joep Lange career guidance sessions and grantspersonship sessions attracted early career researchers. At the closing ceremony, the Yaoundé Declaration called on African governments; UNAIDS; development, bilateral, and multilateral partners; and civil society to adopt urgent and sustained approaches to end HIV by 2030.

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

BACKGROUND: Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART). METHODS: We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per µL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (< 50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059. FINDINGS: Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p<0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause). INTERPRETATION: After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients. FUNDING: Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

HIV infection and sexually transmitted infections among men who have sex with men in Senegal.

BACKGROUND: No epidemiological study has been conducted on HIV and vulnerability to sexually transmitted diseases (STI) among men who have sex with men (MSM) in sub-Saharan Africa. METHOD: A survey including questionnaire, physical examination and detection of HIV and STI was carried out among 463 MSM, aged 18-52 years, recruited through the snowball technique in five urban sites throughout Senegal. RESULTS: A total of 21.5% of men were found to be infected with HIV [95% confidence interval (CI), 17.8-25.6]. Active syphilis, positive serology for herpes simplex virus (HSV)-2, and polymerase chain reaction detection in urine of Chlamydia and gonorrhea infections were recorded in 4.8, 22.3, 4.1 and 5.4% of participants, respectively. Most respondents reported sex with women (94.1%). In the month preceding the interview, 24% reported at least one unprotected insertive anal intercourse with a male partner, 20% at least one unprotected receptive anal intercourse, and 18% at least one unprotected intercourse with a female partner. Genital examination showed that 5% of participants had at least one clinical sign of STI. Factors associated with HIV infection were age group, the reporting of more than nine lifetime male partners [odds ratio (OR), 3.76; 95% CI, 1.61-8.79], being a waiter or bartender (OR, 3.33; 95% CI, 1.41-7.84), and living in Dakar (OR, 3.33; 95% CI, 1.07-3.43). CONCLUSION: Men who have sex with men in Senegal are highly infected with HIV and other STI. Intervention programs targeting this population are urgently needed, given their particular vulnerability and because infections are likely to disseminate into the general population given the high proportion of bisexual activity in this community.

Pitfalls of antiretroviral drug resistance genotyping of HIV-1 Group M and Group N from Cameroon by sequenced-based assays.

BACKGROUND: HIV-1 genotyping for antiretroviral drug resistance mutations (DRMs) were developed based basically on subtype B HIV-1 Group M, which represents only 10% of HIV strains worldwide. In sub-Saharan Africa, non-B subtypes HIV-1 largely predominate and HIV-1 genetic diversity could affect the performance of drug resistance genotyping assays. We compared prospectively the performance of the ViroSeq(®) and Trugene(®) genotyping assays to detect DRM in HIV-1-infected adult patients living in Douala, Cameroun. MATERIALS AND METHODS: DRM in protease (P) and reverse transcriptase (RT) genes were assessed in parallel using both ViroSeq(®) and Trugene(®) assays in plasma samples from 45 first-line antiretroviral treatment-experienced patients in Douala, Cameroon. RESULTS: Trugene HIV-1 Genotyping Assay(®) (Siemens Health Care Diagnostics, NY, USA) and ViroSeq HIV-1 Genotyping System(®)(Celera Diagnostics, CA, USA) assessed equivalently antiretroviral DRMs in P and RT genes from non-B HIV-1 Group M in 44 Cameroonian adults in virological failure; Trugene(®) was slightly more sensitive than ViroSeq(®) (100% vs. 91%). One patient infected by HIV-1 Group N was successfully amplified only by the Trugene HIV-1 Genotyping assay(®), while ViroSeq HIV-1 Genotyping System v2.0(®) assay could not. CONCLUSION: Results showed the higher performance of the Trugene(®) system to detected and amplify P and RT genes targeting DRM to the principal antiretroviral drugs used in sub-Saharan Africa. Discrepancies between the results of HIV viral load assays and molecular tests should alert clinicians and virologists to the possibility of infection by an atypical variant virus, especially in Central Africa where very broad HIV-1 genetic diversity exists.