Durability of the Efficacy and Safety of Dolutegravir-Based and Low-Dose Efavirenz-Based Regimens for the Initial Treatment of Human Immunodeficiency Virus Type 1 Infection in Cameroon: Week 192 Data of the NAMSAL-ANRS-12313 Study.

Background: A prospective study was extended to the new antiretroviral and monitoring strategies in HIV-infected adults in low-income countries (NAMSAL-ANRS)-12313 trial, a 96-week open-label, multicenter, randomized phase 3 trial comparing dolutegravir (DTG) 50 mg with efavirenz 400 mg (EFV400), both administered with tenofovir disoproxil fumarate and lamivudine (TDF/3TC) as first-line treatment for antiretroviral therapy (ART)-naive people living with human immunodeficiency virus type 1 (HIV). Noninferiority of DTG to EFV400 was demonstrated at 48-week and sustained at 96 weeks. Here, we present results at 192-week. Methods: Previous trial participants were reconsented and followed up on their initial randomization arm (1:1 DTG/TDF/3TC:EFV400/TDF/3TC). Assessments included changes in viral suppression, biological parameters, and new serious adverse events (SAEs). Results: Among the participants enrolled in the trial, 81% (499/613) were analyzed at week 192: 84% (261/310) on DTG/TDF/3TC and 78% (238/303) on EFV400/TDF/3TC. HIV RNA suppression was maintained in 69% (214/310) on DTG/TDF/3TC-based and 62% (187/303) on EFV400/TDF/3TC-based regimens (difference, 7.3% [95% confidence interval, -.20 to 14.83]; P = .057). Five (DTG/TDF/3TC = 2; EFV400/TDF/3TC = 3) new viral failures (World Health Organization definition) without related resistance DTG mutations and 24 new SAEs were observed (DTG/TDF/3TC = 13; EFV400/TDF/3TC = 11). Mean weight gain was +9.4 kg on DTG/TDF/3TC and +5.9 kg on EFV400/TDF/3TC. The percentage of participants with obesity increased from 6.9% to 27.7% on DTG/TDF/3TC (P < .0001) and from 8.3% to 16.7% on EFV400/TDF/3TC (P = .0033). Conclusions: Four-year follow-up of people with HIV on DTG- and EFV400-based regimens showed long-term efficacy and safety of both ARTs, markedly among participants on DTG/TDF/3TC with high baseline viral load. However, unexpected substantial weight gain over time was prominent among participants on DTG/TDF/3TC, which should be closely monitored. Clinical Trials Registration. NCT02777229.

Improvements in Patient-Reported Outcomes Following Initiation of Dolutegravir-Based or Low-Dose Efavirenz-Based First-Line Antiretroviral Therapy: A Four-Year Longitudinal Analysis in Cameroon (NAMSAL ANRS 12313 Trial).

BACKGROUND: We provide new and comprehensive evidence on the evolution of a wide range of patient-reported outcomes (PROs) in the NAMSAL ANRS 12313 trial in Cameroon (2016-2021)-the first randomized comparison of dolutegravir 50 mg (DTG) and low-dose efavirenz (ie, 400 mg; EFV400) in treatment-naive adults living with HIV-1 in sub-Saharan Africa. METHODS: We first described the evolution of PROs between baseline and week 192. Then, we used random-effects models to measure the effect of time since the initiation of antiretroviral therapy and the differential effect of DTG versus EFV400 on each PRO, adjusting for clinical, demographic, and socioeconomic factors, while accounting for unobserved heterogeneity and missing data. RESULTS: Among the 613 patients randomized (DTG arm, n = 310; EFV400 arm, n = 303), (1) physical and mental health-related quality of life improved by 13.3% and 6.8%, respectively, (2) the percentage of patients with depression, anxiety, and stress decreased from 23.3%, 23.0%, and 7.7% to 3.1%, 3.5%, and 0.4%, respectively, and (3) the mean number of HIV-related symptoms decreased from 7.2 to 3.0 ( P < 0.001). For most PROs, no significant difference was found between both arms, even when accounting for the effect of DTG on weight gain. Nevertheless, our results suggest smaller improvements in mental health outcomes in the DTG arm, with a 5 percentage point higher adjusted probability of having anxiety at week 192 ( P < 0.01). CONCLUSIONS: Although supporting the current World Health Organization guidelines recommending DTG-based and EFV400-based regimens as preferred and alternative first-line antiretroviral therapy, further studies should investigate medium-term mental health outcomes in patients on DTG. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02777229.

Large Diffusion of Severe Acute Respiratory Syndrome Coronavirus 2 After the Successive Epidemiological Waves, Including Omicron, in Guinea and Cameroon: Implications for Vaccine Strategies.

Background: We aimed to estimate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence among the general population in Conakry, Guinea and Yaounde, Cameroon after the coronavirus disease 2019 Omicron wave. Methods: We conducted population-based, age-stratified seroprevalence surveys in Conakry and Yaounde (May and June 2022). We collected demographic and epidemiologic information and dried blood spot samples that were tested for SARS-CoV-2 immunoglobulin G (IgG) antibodies using recombinant nucleocapsid and spike proteins with Luminex technology. Results: Samples were obtained from 1386 and 1425 participants in Guinea and Cameroon, respectively. The overall age-standardized SARS-CoV-2 IgG seroprevalence against spike and nucleocapsid proteins was 71.57% (95% confidence interval [CI], 67.48%-75.33%) in Guinea and 74.71% (95% CI, 71.99%-77.25%) in Cameroon. Seroprevalence increased significantly with age categories. Female participants were more likely than male participants to be seropositive. The seroprevalence in unvaccinated participants was 69.6% (95% CI, 65.5%-73.41%) in Guinea and 74.8% (95% CI, 72.04%-77.38%) in Cameroon. In multivariate analysis, only age, sex, and education were independently associated with seropositivity. Conclusions: These findings show a high community transmission after the different epidemiological waves including Omicron, especially among people aged >40 years. In addition, our results suggest that the spread of SARS-CoV-2 has been underestimated as a significant proportion of the population has already contracted the virus and that vaccine strategies should focus on vulnerable populations.

Viral load suppression in HIV-infected adolescents in cameroon: towards achieving the UNAIDS 95% viral suppression target.

BACKGROUND: Achieving the UNAIDS 95% sustained viral suppression (VS) rate requires considerable global efforts, particularly among adolescents living with HIV (ALHIV) who are often associated with high rates of virological failure (VF). In this study, we prospectively assessed the rate of VS, and the factors associated with VF in a cohort of adolescents followed up according to the WHO guidelines in Cameroon. METHODS: A cross-sectional study was carried out in 2021 among adolescents (aged 10-19 years) receiving ART in the national program in Cameroon. Socio-demographic and clinical data were collected using patients' medical files and a brief interview with the participant and/or his guardian. Thereafter, a first viral load test (VL1) was performed using the ABBOTT Platform. For adolescents with VL1 > 1000 copies/ml, adherence-enhancing interventions were routinely performed each month for 3 consecutive months, after which a second viral load (VL2) was measured. Adolescents with VL2 > 1000 copies/ml were considered in VF. RESULTS: Overall, 280 adolescents were enrolled, of whom 89.3% (250/280) acquired HIV infection via mother-to-child transmission. The median age was 16.0 (IQR: 13.0-18.0) years and the median duration on ART was 9.8 (IQR: 5.1-12.8) years. Females and males were almost equally represented, as 52.1% (146/280) were female, while 47.9% (134/280) were males (p = 0.47). The VS rate was 88.2% (CI: 83.8-91.7%) overall; 89.0% (CI: 82.0-93.1%) and 88.7% (CI: 81.2-93.0%) in females and males, respectively. Being on second or third-line ART, self-declared suboptimal adherence, and a history of past VF were independently associated with VF. CONCLUSION: The high rate of VS we report in this study is welcome in the era of the 95/95/95 UNAIDS goals, and indicates that improving treatment outcomes in this specific and fragile population that represent adolescents in Sub-Saharan Africa is achievable. TRIAL REGISTRATION: 20/10/2020 NCT04593979 ( https://clinicaltrials.gov/ct2/show/NCT04593979 ).

Rapid Increase of Community SARS-CoV-2 Seroprevalence during Second Wave of COVID-19, Yaoundé, Cameroon.

We conducted 2 independent population-based SARS-CoV-2 serosurveys in Yaoundé, Cameroon, during January 27-February 6 and April 24-May 19, 2021. Overall age-standardized SARS-CoV-2 IgG seroprevalence increased from 18.6% in the first survey to 51.3% in the second (p<0.001). This finding illustrates high community transmission during the second wave of COVID-19.

Research priorities for accelerating the achievement of three 95 HIV goals in Cameroon: a consensus statement from the Cameroon HIV Research Forum (CAM-HERO).

INTRODUCTION: the Treat-All remains the globally endorsed approach to attain the 95-95-95 targets and end the AIDS pandemic by 2030, but requires some country-level contextualization. In Cameroon, the specific research agenda to inform strategies for improving HIV policy was yet to be defined. METHODS: under the patronage of the Cameroon Ministry of health, researchers, policy makers, implementing partners, and clinicians from 13 institutions, used the Delphi method to arrive at a consensus of HIV research priorities. The process had five steps: 1) independent literature scan by 5 working groups; 2) review of the initial priority list; 3) appraisal of priorities list in a larger group; 4) refinement and consolidation by a consensus group; 5) rating of top research priorities. RESULTS: five research priorities and corresponding research approaches, resulted from the process. These include: 1) effectiveness, safety and active toxicity monitoring of new and old antiretrovirals; 2) outcomes of Antiretroviral Therapy (ART) with focus in children and adolescents; 3) impact of HIV and ART on aging and major chronic diseases; 4) ART dispensation models and impact on adherence and retention; 5) evaluations of HIV treatment and prevention programs. CONCLUSION: the research priorities resulted from a consensus amongst a multidisciplinary team and were based on current data about the pandemic and science to prevent, treat, and ultimately cure HIV. These priorities highlighted critical areas of investigation with potential relevance for the country, funders, and regulatory bodies.

Outcomes of the first meeting of the CAMEROON HIV RESEARCH FORUM (CAM-HERO).

Research is a vital component for the development of any country. In Cameroon, HIV Operational research is rapidly growing, however, it faces some intractable problems which can only be solved through an urgent, strategic, efficient, and collaborative approach involving key stakeholders. The Kribi meeting (09 and 10th December 2020) brought together under the auspices of the Ministry of Public Health leading HIV research organisations and connected HIV researchers and actors from different sectors. These actors disseminated and discussed recent research findings and worked out mechanisms to advance HIV research development, developed new ideas and identified priority research areas, with emphasis on translational research. The official launching and consolidation of Cam-HERO was a critical step and it is hoped that these synergistic efforts will catalyse attainment of the 95-95-95 goals in Cameroon.

Cost-Utility Analysis of a Dolutegravir-Based Versus Low-Dose Efavirenz-Based Regimen for the Initial Treatment of HIV-Infected Patients in Cameroon (NAMSAL ANRS 12313 Trial).

OBJECTIVES: Evidence comparing the economic and patient values of the World Health Organization's preferred (dolutegravir 50 mg [DTG]-based) and alternative (low-dose [400 mg] efavirenz [EFV400]-based) first-line antiretroviral regimens is limited. We compared patient-reported outcomes (PROs), costs, and the cost-utility of DTG- versus EFV400-based regimens in treatment-naive HIV-1 adults in the randomised NAMSAL ANRS 12313 trial in Yaoundé, Cameroon. METHODS: We used clinical data, PROs, and health resource use data collected in the trial's first 96 weeks (2016-2019). Quality-adjusted life-years (QALYs) were computed using utility scores obtained from the 12-item Short Form (SF-12) generic health scale. Other PROs included perceived symptoms, depression, anxiety, and stress. In the 96-week base-case analysis, we estimated the unadjusted and multivariate-adjusted (1) mean costs (in US$, 2016 values) and QALYs/patient, (2) incremental costs and QALYs/patient, and (3) net health benefit (NHB). Outcomes were extrapolated over 5 and 10 years. Uncertainty was assessed using the cost-effectiveness acceptability curve and scenario and cost-effective price threshold analyses. RESULTS: In the base-case analysis, the NHB (95% confidence interval) for the DTG-based regimen relative to the EFV400-based regimen was 0.056 (- 0.037 to 0.153), corresponding to an 88% probability of DTG being cost-effective. A 10% decrease in this regimen's price (from $5.2 to $4.7/month) would increase its cost-effectiveness probability to 95%. When extrapolating outcomes over 5 and 10 years, the DTG-based regimen had a 100% probability of being cost-effective for a large range of cost-effectiveness thresholds. CONCLUSIONS: At 2020 antiretroviral drug prices, a DTG-based first-line regimen should be preferred over an EFV400-based regimen in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02777229.

Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon.

BACKGROUND: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96. METHODS: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing. FINDINGS: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p<0·001). Virological failure (>1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p<0·001, and incidence of obesity, 22% in the dolutegravir group and 16% in the efavirenz 400 mg group, p=0·043). The incidence of new WHO HIV-related stage 3 and 4 events was similar in each group (12 [4%] in each group). The two groups had similar rates of serious adverse events (28 [9%] of 310 in the dolutegravir group and 21 [7%] of 303 in the efavirenz 400 mg group). 18 deaths were observed during the 96-week follow-up (eight in the dolutegravir group and ten in the efavirenz 400 mg group). INTERPRETATION: The non-inferior efficacy of the dolutegravir-based regimen and non-emergence of dolutegravir resistance at 96 weeks supports its use as a first-line regimen for antiretroviral-naive adults with HIV-1 infection. Viral load suppression was reached more quickly in the dolutegravir group and weight gain was significantly higher. FUNDING: UNITAID and the French National Agency for AIDS Research.

Adherence to ready-to-use food and acceptability of outpatient nutritional therapy in HIV-infected undernourished Senegalese adolescents: research-based recommendations for routine care.

BACKGROUND: Ready-to-use food (RUF) is increasingly used for nutritional therapy in HIV-infected individuals. However, practical guidance advising nutrition care to HIV-infected adolescents is lacking, so that little is known about the acceptability of such therapy in this vulnerable population. This study assesses the overall acceptability and perception of a RUF-based therapy and risk factors associated with sub-optimal RUF intake in HIV-infected undernourished adolescents in Senegal. METHODS: Participants 5 to 18 years of age with acute malnutrition were enrolled in 12 HIV clinics in Senegal. Participants were provided with imported RUF, according to WHO prescription weight- and age-bands (2009), until recovery or for a maximum of 9-12 months. Malnutrition and recovery were defined according to WHO growth standards. Adherence was assessed fortnightly by self-reported RUF intake over the period. Sub-optimal RUF intake was defined as when consumption of the RUF provision was < 50%. RUF therapy acceptability and perceptions were assessed using a structured questionnaire at week 2 and focus group discussions (FGDs) at the end of the study. Factors associated with sub-optimal RUF intake at week 2 were identified using a stepwise logistic regression model. RESULTS: We enrolled 173 participants, with a median age of 12.5 years (Interquartile range: 9.5-14.9), of whom 61% recovered from malnutrition within the study period. Median follow-up duration was 66 days (21-224). RUF consumption was stable, varying between 64 and 57% of the RUF provided, throughout the follow-up. At week 2, sub-optimal RUF intake was observed in 31% of participants. Dislike of the taste of RUF (aOR = 5.0, 95% CI: 2.0-12.3), HIV non-disclosure (5.1, 1.9-13.9) and food insecurity (2.8, 1.1-7.2) were the major risk factors associated with sub-optimal RUF intake at week 2. FGDs showed that the need to hide from others to avoid sharing and undesirable effects were other constraints on RUF feeding. CONCLUSIONS: This study revealed several factors reducing the acceptability and adherence to RUF therapy based on WHO guidelines in HIV-infected adolescents. Tailoring prescription guidance and empowering young patients in their care are crucial levers for improving the acceptability of RUF-based therapy in routine care. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03101852, 04/04/2017.

Improving the informed consent process among HIV-infected undisclosed minors participating in a biomedical research: insights from the multicentre nutritional SNACS study in Senegal.

OBJECTIVES: Providing research information in a manner accessible to minors participating in biomedical research is a major challenge. Guidance is dramatically lacking regarding best practices for seeking informed consent among undisclosed minors enrolled in HIV-related research. We implemented an improved informed consent process (IICP) and identified factors associated with understanding of the information presented to HIV-infected minors prior to their enrolment in a study. METHODS: We enrolled study participants attending 12 paediatric HIV clinics in Senegal. Children ≥7 years were provided with standardised research information using the IICP, which involves viewing a video and taking part in extended group discussions. Understanding was assessed by seven basic questions scored 1 or 2 points, with a maximum score of 11 points. A score of 9 or more points was defined as satisfactory understanding. Factors associated with understanding were identified using a stepwise logistic regression model. RESULTS: Overall, 112 children, with a median age of 12.9 years (IQR: 10.2-15.0), participated in the IICP, of whom 37% were HIV disclosed. 71% achieved a satisfactory understanding score and all gave consent to participate in the research. HIV-disclosed children were more likely to demonstrate satisfactory understanding than undisclosed children (aOR = 3.2, 95% CI: 1.1-9.6). Age, study setting and education level were not associated with satisfactory understanding. CONCLUSION: These findings provide practical guidance for the development of improved and friendly informed consent processes in research involving minors. The implementation of the paediatric HIV research agenda will require a standardised and operational definition of informed consent, integrating the issue of HIV disclosure.

OBJECTIFS: Fournir des informations sur la recherche d'une manière accessible aux mineurs participant à la recherche biomédicale est un défi majeur. Les guidances font cruellement défaut en ce qui concerne les meilleures pratiques pour obtenir le consentement éclairé des mineurs non dévoilés, inscrits dans des recherches sur le VIH. Nous avons mis en place un processus de consentement éclairé amélioré (PCEA) et identifié les facteurs associés à la compréhension des informations présentées aux mineurs infectés par le VIH avant leur inscription à une étude. MÉTHODES: Nous avons recruté des participants à l'étude dans 12 cliniques pédiatriques de traitement du VIH au Sénégal. Les enfants de 7 ans et plus ont reçu des informations de recherche standardisées à l'aide du PCEA, qui consiste à visionner une vidéo et à participer à des discussions de groupe prolongées. La compréhension a été évaluée par 7 questions de base notées 1 ou 2 points, avec un score maximum de 11 points. Un score de 9 points ou plus a été défini comme une compréhension satisfaisante. Les facteurs associés à la compréhension ont été identifiés à l'aide d'un modèle de régression logistique par étapes. RÉSULTATS: Au total, 112 enfants âgés de 12,9 ans en moyenne (IQR: 10,2-15,0) ont participé au PCEA, dont 37% avaient leur statut VIH dévoilé. 71% ont obtenu un score de compréhension satisfaisant et tous ont consenti à participer à la recherche. Les enfants avec un statut VIH dévoilé étaient plus susceptibles de démontrer une compréhension satisfaisante que ceux avec un statut non dévoilé (aOR: 3,2; IC95%: 1,1-9,6). L'âge, le cadre de l'étude et le niveau d'éducation n'étaient pas associés à une compréhension satisfaisante. CONCLUSION: Ces résultats fournissent des guidances pratiques pour la mise au point de processus de consentement éclairé améliorés et conviviaux dans la recherche impliquant des mineurs. La mise en œuvre du programme de recherche pédiatrique sur le VIH nécessitera une définition normalisée et opérationnelle du consentement éclairé, intégrant la question de la révélation du VIH.

Acceptability of Outpatient Ready-To-Use Food-Based Protocols in HIV-Infected Senegalese Children and Adolescents Within the MAGGSEN Cohort Study.

OBJECTIVES: To assess the acceptability of ready-to-use food (RUF)-based outpatient protocols in HIV-infected children and adolescents with severe acute malnutrition (SAM) and moderate acute malnutrition (MAM). METHODS: Plumpy Nut and Plumpy Sup were supplied every 2 weeks and prescribed by weight to SAM and MAM children, respectively. Forty-three children, 24 MAM and 19 SAM, were enrolled. Organoleptic appreciation, feeding modalities, and perceptions surrounding RUF were recorded at week 2. Sachets were counted to measure adherence throughout the study. RESULTS: Median age was 12.2 years (interquartile range: 9.3-14.8), and 91% were on antiretroviral treatment. Overall, 80%, 76%, 68%, and 68% of children initially rated RUF color, taste, smell, and mouth feeling as good. However, feelings of disgust, refusal to eat, fragmentation of intake, self-stigma, and sharing within the household were commonly reported. Eighteen MAM and 7 SAM experienced weight recovery. Recovery duration was 54 days (31-90) in MAM versus 114 days (69-151) in SAM children ( P = .02). Their rate of RUF consumption compared to amount prescribed was approximately 50% from week 2 to week 10. Nine failed to gain weight or consume RUF and were discontinued for clinical management, and 9 dropped out due to distance to the clinic. CONCLUSION: Initial RUF acceptability was satisfactory. More than half the children had successful weight recovery, although adherence to RUF prescription was suboptimal. However, further research is needed to propose therapeutic foods with improved palatability, alternative and simpler intervention design, and procedures for continuous and tailored psychosocial support in this vulnerable population. TRIAL REGISTRATION: NCT01771562 (Current Controlled Trials).