Low CD4 counts predict excessive weight gains during first-line treatment for HIV.

BACKGROUND: Weight gain is common after antiretroviral initiation, especially among females, those of black race and lower baseline CD4, although this may potentially be due to lower baseline weight. Use of tenofovir disoproxil fumarate or efavirenz can suppress weight gain. METHODS: Data were pooled from the ADVANCE (n = 1053), NAMSAL (n = 613) and WHRI001 (n = 536) trials investigating first-line regimen. Week 96 weight and body mass index (BMI) was stratified by baseline CD4. Multivariable models of weight change and incident obesity (BMI ≥30 kg/m2) were adjusted for baseline CD4, age, sex, tenofovir disoproxil fumarate, efavirenz, baseline BMI and trial. RESULTS: Participants across all treatment arms experienced weight gain from baseline to week 96, with baseline CD4 count, baseline HIV RNA, tenofovir alafenamide and dolutegravir use, and female sex significant predictors. Mean unadjusted weight change was highest with CD4 < 100 (+8.6 kg; SD = 8.2) and lowest with CD4 ≥ 350 (+3.0 kg; SD = 6.5). This weight gain in CD4 < 100 was highest for participants on tenofovir alafenamide-inclusive treatment, such that absolute weight at week 96 was highest in the CD4 < 100 group. Although not statistically significant, obesity rate (BMI ≥ 30 kg/m2) in those taking TAF/FTC + DTG with CD4 < 100 overtook that seen in CD4 ≥ 350, despite lower baseline obesity prevalence. The unadjusted findings were corroborated in multivariable longitudinal models. CONCLUSIONS: Participants with low CD4 may demonstrate significant 'overshoot' weight gain, in addition to 'return to health', with a trend towards increased risk of obesity when initiated on TAF/FTC + DTG. Use of tenofovir disoproxil fumarate and efavirenz were associated with smaller weight gains. Effective weight management strategies are needed, especially for individuals with low baseline CD4.

A detailed characterization of drug resistance during darunavir/ritonavir monotherapy highlights a high barrier to the emergence of resistance mutations in protease but identifies alternative pathways of resistance.

BACKGROUND: Maintenance monotherapy with ritonavir-boosted darunavir has yielded variable outcomes and is not recommended. Trial samples offer valuable opportunities for detailed studies. We analysed samples from a 48 week trial in Cameroon to obtain a detailed characterization of drug resistance. METHODS: Following failure of NNRTI-based therapy and virological suppression on PI-based therapy, participants were randomized to ritonavir-boosted darunavir (n = 81) or tenofovir disoproxil fumarate/lamivudine +ritonavir-boosted lopinavir (n = 39). At study entry, PBMC-derived HIV-1 DNA underwent bulk Protease and Reverse Transcriptase (RT) sequencing. At virological rebound (confirmed or last available HIV-1 RNA ≥ 60 copies/mL), plasma HIV-1 RNA underwent ultradeep Protease and RT sequencing and bulk Gag-Protease sequencing. The site-directed mutant T375A (p2/p7) was characterized phenotypically using a single-cycle assay. RESULTS: NRTI and NNRTI resistance-associated mutations (RAMs) were detected in 52/90 (57.8%) and 53/90 (58.9%) HIV-1 DNA samples, respectively. Prevalence in rebound HIV-1 RNA (ritonavir-boosted darunavir, n = 21; ritonavir-boosted lopinavir, n = 2) was 9/23 (39.1%) and 10/23 (43.5%), respectively, with most RAMs detected at frequencies ≥15%. The resistance patterns of paired HIV-1 DNA and RNA sequences were partially consistent. No darunavir RAMs were found. Among eight participants experiencing virological rebound on ritonavir-boosted darunavir (n = 12 samples), all had Gag mutations associated with PI exposure, including T375N, T375A (p2/p7), K436R (p7/p1) and substitutions in p17, p24, p2 and p6. T375A conferred 10-fold darunavir resistance and increased replication capacity. CONCLUSIONS: The study highlights the high resistance barrier of ritonavir-boosted darunavir while identifying alternative pathways of resistance through Gag substitutions. During virological suppression, resistance patterns in HIV-1 DNA reflect treatment history, but due to technical and biological considerations, cautious interpretation is warranted.

Research Ethics in Training Curricula of Cameroon Health Training Institutions: A Cross-Sectional Study.

Introduction The quality of protection for research participants in Africa is still marked by the lack of trained actors in this area. The study was conducted to assess the availability of health research ethics in the curricula of health-related sciences training institutions in Cameroon. Methods The study involved a cross-sectional analysis to describe the training curricula on research ethics in health training institutions in Cameroon. Data were collected using a structured questionnaire that was administered face to face to the heads of institutions in late 2020. Results Twenty-one health training institutions were identified, and 18 (85.71%) participated. Health research ethics courses were present in the curricula of 16 (88.88%) of the institutions. Lectures were either a standalone module or part of a module in 14 (77.78%) institutions. The three first topics covered in the courses were the fundamental principles of ethics, the role of the ethics committee in the protection of research participants, and respect for research participants. A total of 14 (77.78%) institutions declared ethical clearance mandatory before the implementation of students' thesis protocols. Eight (50.00%) training institutions declared having at least one qualified lecturer to deliver training in research ethics evaluation. The organization of the training of lecturers in delivering lectures on research ethics was declared to be the main assistance needed. Conclusions The delivery of research ethics education in Cameroon's healthcare institutions is still limited by the fact that it does not cover all eligible populations, is not standardized, and does not yet promote the practice of requiring all student protocols to undergo preethical review prior to implementation. These points should be taken into account by the authorities in charge.

Prevalence, Epidemiological, and Clinical Profile of Patients Coinfected with Human Immunodeficiency Virus and Tuberculosis in the Coronavirus Disease 2019 Context in Health Facilities in the East Region, Cameroon.

Background and Objective: Suspected cases of tuberculosis (TB) are identified for confirmation by bacteriological tests through clinical screening for TB in people living with human immunodeficiency virus (HIV) during routine visits or when antiretrovirals (ARVs) are dispensed. Our aim is to determine the prevalence and describe the epidemiological and clinical characteristics of HIV-TB coinfected patients in the coronavirus disease 2019 (COVID-19) setting in health facilities in the East Region of Cameroon. This study addresses knowledge gaps on HIV-TB coinfection during COVID-19, aiming to provide insights into the interaction and impact of HIV, TB, and COVID-19 on individuals' health. Methods: This was an observational study. It involved two retrospective cohorts of HIV-TB coinfected patients before and after the COVID-19 pandemic. We conducted manual reviews of the medical records and antiretroviral therapy (ART) and TB registers of 262 patients. These patients were coinfected with HIV and TB during the period from April 2019 to April 2021 in 11 health facilities in the East Cameroon health region. The sociodemographic and clinical characteristics of the cases were extracted from the consultation registers and entered into the KoBo Collect application, then analyzed using the Statistical Package for the Social Sciences (SPSS) software, version 25. Results: In this study of 262 HIV-TB coinfection cases, 60.3% occurred before COVID-19, and 39.7% during the pandemic. HIV-TB coinfection prevalence among HIV patients was 1%. Patients averaged 39.3 years in age, with a significant shift in sex ratios from 0.65 to 1.33 between pre-COVID-19 and COVID-19 cohorts. Education varied, with 45.8% having secondary education, 44.8% with primary, 2.4% having higher education, and 7.1% having none. Most (78.9%) had professional occupations, and 53.7% lived in rural areas. The majority were newly diagnosed (96.3% before COVID-19; 93.3% during COVID-19), with 3.7% relapses and 4.2% discontinuing treatment. Most had pulmonary TB (84.9%) and were aware of treatment duration (94.6%). About 65.4% experienced treatment-related adverse events. Regarding family support, 69.3% received help with medication. However, the concern was 80.6% did not adhere to anti-COVID-19 measures. Conclusion and Global Health Implications: Gender was significantly associated with compliance. Most patients were on treatment, but a small percentage had discontinued it. Patients need to be made aware of the importance of complying with anti-COVID-19 barrier measures to prevent a potential worsening of the health situation. Moreover, clinical and biological monitoring needs to be stepped up throughout the course of anti-TB treatment.

The Feasibility and Acceptability of Using Mobile Applications for HIV Testing, Prevention, and Treatment Among Adolescent Girls and Young Women in Cameroon: A Cross-Sectional Study.

ABSTRACT: Adolescent girls and young women (AGYW) are vulnerable populations to HIV/AIDS. We conducted a cross-sectional survey among 637 AGYW in Cameroon to study the feasibility and willingness to use mobile applications (apps) for HIV testing, prevention, and treatment. We found that phone ownership is high among AGYW, where 93.9% ( n = 598) of them (median age: 22 years, interquartile range: 21-24 years) had access to a smartphone, 49.5% ( n = 315) frequently searched for health information, and 48.9% ( n = 312) frequently used health-related apps. AGYW's willingness to use mobile apps for HIV testing, prevention, and treatment were 87.9% ( n = 560), 84.4% ( n = 538), and 84.9% ( n = 541), respectively. The high willingness to use apps was associated with older age, HIV testing, and searching for health information on a phone. Barriers to willingness included having no internet access, concerns about internet cost and privacy, and lack of consistent access to a smartphone.

Acceptability and Feasibility of the Plasma Separation Card for an Integrated Model of Care for HBV and HCV Screening Among People Attending HIV Clinics in Cameroon and Uganda.

BACKGROUND: Sub-Saharan African countries have a high burden of viral hepatitis and poor access to screening and care. The aim of this study was to evaluate the feasibility and acceptability of using the plasma separation card (PSC) for viral hepatitis B and C screening among people living with HIV (PLHIV) in Cameroon and Uganda. METHODS: This is a cross-sectional study carried out between 05/2021 and 03/2023 including 192 PLHIV in Cameroon (n = 104) and Uganda (n = 88). Basic sociodemographic variables and whole blood samples were collected. Adequate filling with blood of PSCs was used to determine feasibility together with participant responses to questions on acceptability. A logistic regression model was carried out to assess the relationship between PSC acceptability and factors of interest. RESULTS: 70% of participants reported PSC as an acceptable viral hepatitis screening tool, and it was significantly more accepted in Uganda than Cameroon (100% vs. 43.2%, p < 0.001). Similarly, 75% of PSCs had at least one spot sample filled and were viable for analysis, 99% were correctly filled in Uganda and 53.4% in Cameroon. Reported ease of method performance (aOR: 24.77 95% CI 2.97-206.42, p = 0.003) and reduced collection time (aOR: 3.73 95% CI 1.26-11.04, p = 0.017) were associated with greater odds of PSC acceptance. HBsAg + and anti-HCV + prevalence were 11.1% and 1.0%, respectively. CONCLUSIONS: In spite of country differences, overall, the PSC was reported as a feasible and acceptable viral hepatitis testing method. Acceptability and feasibility of the method must be explored in heterogeneous target communities and qualitative research to better understand country-specific barriers and facilitators should be carried out.

Feasibility, safety, efficacy and potential scaling-up of sofosbuvir-based HCV treatment in Central and West Africa: (TAC ANRS 12311 trial).

Access to Hepatis C treatment in Sub-Saharan Africa is a clinical, public health and ethical concern. The multi-country open-label trial TAC ANRS 12311 allowed assessing the feasibility, safety, efficacy of a specific care model of HCV treatment and retreatment in patients with hepatitis C in Sub Saharan Africa. Between November 2015 and March 2017, with follow-up until mid 2019, treatment-naïve patients with HCV without decompensated cirrhosis or liver cancer were recruited to receive 12 week-treatment with either sofosbuvir + ribavirin (HCV genotype 2) or sofosbuvir + ledipasvir (genotype 1 or 4) and retreatment with sofosbuvir + velpatasvir + voxilaprevir in case of virological failure. The primary outcome was sustained virological response at 12 weeks after end of treatment (SVR12). Secondary outcomes included treatment adherence, safety and SVR12 in patients who were retreated due to non-response to first-line treatment. The model of care relied on both viral load assessment and educational sessions to increase patient awareness, adherence and health literacy. The study recruited 120 participants, 36 HIV-co-infected, and 14 cirrhotic. Only one patient discontinued treatment because of return to home country. Neither death nor severe adverse event occurred. SVR12 was reached in 107 patients (89%): (90%) in genotype 1 or 2, and 88% in GT-4. All retreated patients (n = 13) reached SVR12. HCV treatment is highly acceptable, safe and effective under this model of care. Implementation research is now needed to scale up point-of-care HCV testing and SVR assessment, along with community involvement in patient education, to achieve HCV elimination in Sub-Saharan Africa.

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.

Problématique duDiagnostic du VIH en Afrique Subsaharienne: Résultats Erronés dans une Etude Pilote (NAMSAL) au Cameroun

Introduction.The NAMSAL therapeutic trial evaluated the non-inferiority of a first line treatment comprising Dolutegravir to another line comprising Efavirenz 400. The criteria for not taking part to the trial included infection with non-M HIV-1, untreated patients with HIV viral load <1000 copies/mL. The objective of this study was to explain why some treatment naïve patients had undetectable viral loads. Materials and methods. Out of 817 patients pre-included with HIV-1 infection and untreated, 204 were not included and the present study focused on 114 of these 204 patients not included in NAMSAL. HIV plasma viral load, serological status and the serotype were confirmed by RT-qPCR (Abbott), INNOLIA HIVI/II Score (Fujirebio), and by ELISA with synthetic peptides of thedifferent HIV-1&2 groups. Universal or specific PCR (M and O) were performed on the samples for molecular confirmation and characterization. Results. Amongthe 114 patients studied, 49 (43%) had a viral load < 1000 copies/mL and 65 (57%) had a viral load > 1000 copies/mL. When reported to the whole cohort of pre-included patients (n=817), 4/817 (0.5%) were group-O confirmed by molecular biology. Based on the PCR results, 14 out of 817 patients (1.7%) deemed to be HIV-1 positive were most likely uninfected. Conclusion. 1.7% of HIV-1 patients referred for inclusion in NAMSAL were not actually infected. Ongoing staff training and quality control of laboratories must be strengthened in Cameroon in view of the social and economic consequences of misdiagnosis.