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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 (nâ=â1053), NAMSAL (nâ=â613) and WHRI001 (nâ=â536) 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 CD4â<â100 (+8.6 kg; SDâ=â8.2) and lowest with CD4â≥â350 (+3.0 kg; SDâ=â6.5). This weight gain in CD4â<â100 was highest for participants on tenofovir alafenamide-inclusive treatment, such that absolute weight at week 96 was highest in the CD4â<â100 group. Although not statistically significant, obesity rate (BMIâ≥â30 kg/m2) in those taking TAF/FTCâ+âDTG with CD4â<â100 overtook that seen in CD4â≥â350, 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/FTCâ+âDTG. 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.
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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.
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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.
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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.
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Antivirais , Hepacivirus , Sofosbuvir , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , África Central , África Ocidental , Ácidos Aminoisobutíricos , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Benzimidazóis/uso terapêutico , Benzimidazóis/efeitos adversos , Benzopiranos , Carbamatos/uso terapêutico , Ciclopropanos/uso terapêutico , Ciclopropanos/efeitos adversos , Quimioterapia Combinada , Estudos de Viabilidade , Fluorenos/uso terapêutico , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Prolina/análogos & derivados , Prolina/uso terapêutico , Quinoxalinas , Ribavirina/uso terapêutico , Ribavirina/efeitos adversos , Sofosbuvir/uso terapêutico , Sofosbuvir/efeitos adversos , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Resposta Viral Sustentada , Resultado do TratamentoRESUMO
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.
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Estudos de Viabilidade , Infecções por HIV , Teste de HIV , Aplicativos Móveis , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Feminino , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Camarões , Adolescente , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Teste de HIV/métodos , Adulto , Smartphone , Inquéritos e Questionários , Programas de Rastreamento/métodosRESUMO
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.
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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.
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Fármacos Anti-HIV , Infecções por HIV , Inibidores da Protease de HIV , Humanos , Darunavir/farmacologia , Darunavir/uso terapêutico , Ritonavir/farmacologia , Ritonavir/uso terapêutico , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Lopinavir/farmacologia , Lopinavir/uso terapêutico , Peptídeo Hidrolases/uso terapêutico , Leucócitos Mononucleares , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacologia , Inibidores da Protease de HIV/uso terapêutico , Mutação , RNA/uso terapêutico , DNA/uso terapêutico , Resistência a Medicamentos , Carga ViralRESUMO
While the SARS-CoV-2 dynamic has been described globally, there is a lack of data from Sub-Saharan Africa. We herein report the dynamics of SARS-CoV-2 lineages from March 2020 to March 2022 in Cameroon. Of the 760 whole-genome sequences successfully generated by the national genomic surveillance network, 74% were viral sub-lineages of origin and non-variants of concern, 15% Delta, 6% Omicron, 3% Alpha and 2% Beta variants. The pandemic was driven by SARS-CoV-2 lineages of origin in wave 1 (16 weeks, 2.3% CFR), the Alpha and Beta variants in wave 2 (21 weeks, 1.6% CFR), Delta variants in wave 3 (11 weeks, 2.0% CFR), and omicron variants in wave 4 (8 weeks, 0.73% CFR), with a declining trend over time (p = 0.01208). Even though SARS-CoV-2 heterogeneity did not seemingly contribute to the breadth of transmission, the viral lineages of origin and especially the Delta variants appeared as drivers of COVID-19 severity in Cameroon.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Camarões/epidemiologia , COVID-19/epidemiologia , GenômicaRESUMO
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) 50â 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 +9.4â kg on DTG/TDF/3TC and +5.9â 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.
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Community-based organizations (CBOs) are one of the initiatives implemented in Cameroon to improve access to antiretroviral treatment and influence retention in treatment centers. Despite its importance in the decongestion of patients in health facilities, we do not have data to evaluate the overall impact of these organizations. We conducted a two-part observational study. The first part was a descriptive cross-sectional study, where we included patients screened and initiated on anti-retroviral treatment (ART) either by the approved Treatment center (ATC) of Yaoundé Central Hospital (YCH) or by any of our CBOs in 2020. Then, the second part was a retrospective cohort-type study including patients from the 2015 cohort followed up from 2018 to 2020 in order to assess viral load suppression. As regards the first "90", 7,234 screening tests were performed by CBOs in 2020 out of the 28,302 screening tests registered at the YCH, giving a contribution of 25.6%. From the 7,234 screening tests performed by CBOs, 314 people had an HIV-positive result and 230 (73.34%) were linked to ART through CBOs. From the 28,302 screening tests performed at YCH, 1,089 people had an HIV-positive test, and only 354 (32.50%) were linked to ART, giving a significant difference in the link to ART (P-value < 0.00). Concerning the 3rd ''90'', the viral load suppression rates were respectively in CBOs and at YCH of (95.12% vs 90.54%, RR= 0.51; P-value= 0.27 at 12 months); (95.96% vs 95.34%, relative risk (RR)= 0.85; P-value= 0.81 at 24 months); and (96.91% vs 94.15%, RR= 0.52; P-value = 0.24 at 36 months). In conclusion, we say that the follow-up of patients living with HIV in the community does not negatively affect the evolution of the disease as one might think.
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Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , Estudos Transversais , Estudos Retrospectivos , Camarões , HospitaisRESUMO
Introduction: an increasing number of persons living with HIV (PLHIV) are accessing antiretroviral therapy (ART) since the adoption of the universal test and treat (UTT) policy by Cameroon in 2016. We sought to evaluate the effectiveness of the UTT approach to keep this growing number of PLHIV on a lifelong treatment. Methods: a retrospective cohort analysis was conducted at the Nkongsamba Regional Hospital between 2002 and 2020, using routine data to compare the cumulative incidence of loss to follow-up (LTFU) and mortality between PLHIV initiated on ART under UTT guidelines and those initiated under the standard deferred approach. Chi-squared test was used to compare the risk of attrition between the guideline periods while multiple logistic regression modelling was used to adjust for confounders. Results: of 1627 PLHIV included for analysis, 756 (46.47%) were enrolled during the era of UTT with 545 (33.54%) initiated on ART on the same day of HIV diagnosis. The transition to the UTT era was associated with an overall reduction in the risk of LTFU by 73% (aOR = 0.27, 95%CI: 0.17 - 0.45). There was modest evidence that the odds of mortality had increased under the UTT policy by about 3-fold (aOR = 2.86, 95%CI: 0.91-8.94). Same-day initiation had no overall effect on LTFU or mortality. LTFU was lower among the same-day initiators in the first 24 months but increased thereafter above the rate among late initiators. Conclusion: overall ART programme implementation under the UTT has led to a significant decline in LTFU though mortality appeared to have increased. Ongoing efforts to keep patients on long-term treatment should be sustained while other innovative schemes are sought.
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Fármacos Anti-HIV , Infecções por HIV , Humanos , Estudos Retrospectivos , Fármacos Anti-HIV/uso terapêutico , Seguimentos , Camarões , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologiaRESUMO
Cryptococcal meningitis is the second most common cause of death in people living with HIV/AIDS, yet we have a limited understanding of how cryptococcal isolates change over the course of infection. Cryptococcal infections are environmentally acquired, and the genetic diversity of these infecting isolates can also be geographically linked. Here, we employ whole genome sequences for 372 clinical Cryptococcus isolates from 341 patients with HIV-associated cryptococcal meningitis obtained via a large clinical trial, across both Malawi and Cameroon, to enable population genetic comparisons of isolates between countries. We see that isolates from Cameroon are highly clonal, when compared to those from Malawi, with differential rates of disruptive variants in genes with roles in DNA binding and energy use. For a subset of patients (22) from Cameroon, we leverage longitudinal sampling, with samples taken at days 7 and 14 post-enrollment, to interrogate the genetic changes that arise over the course of infection, and the genetic diversity of isolates within patients. We see disruptive variants arising over the course of infection in several genes, including the phagocytosis-regulating transcription factor GAT204. In addition, in 13% of patients sampled longitudinally, we see evidence for mixed infections. This approach identifies geographically linked genetic variation, signatures of microevolution, and evidence for mixed infections across a clinical cohort of patients affected by cryptococcal meningitis in Central Africa.
Cryptococcal meningitis, caused by Cryptococcus, results in approximately half a million deaths per year globally. We compare clinical Cryptococcus samples from Cameroon and Malawi to explore the genetic diversity of these isolates. We find instances of mixed-strain infections and identify genetic variants arising in Cryptococcus over disease.
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Síndrome da Imunodeficiência Adquirida , Coinfecção , Cryptococcus neoformans , Cryptococcus , Infecções por HIV , Meningite Criptocócica , Humanos , Meningite Criptocócica/epidemiologia , Meningite Criptocócica/veterinária , Cryptococcus neoformans/genética , Cryptococcus/genética , Camarões/epidemiologia , Coinfecção/veterinária , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/veterinária , Variação Genética , Infecções por HIV/complicações , Infecções por HIV/veterináriaRESUMO
Introduction: The ADVANCE and NAMSAL trials evaluating antiretroviral drugs have both reported substantial levels of clinical obesity in participants. As one of the main risk factors for metabolic syndrome, growing rates of obesity may drive metabolic syndrome development. This study aims to evaluate the risk of metabolic syndrome in the ADVANCE and NAMSAL trials. Methods: The number of participants with metabolic syndrome was calculated at baseline and week 192 as central obesity and any of the following two factors: raised triglycerides, reduced HDL-cholesterol, raised blood pressure and raised fasting glucose. Differences between the treatment arms were calculated using the χ2 test. Results: Across all visits to week 192, treatment-emergent metabolic syndrome was 15% (TAF/FTC + DTG), 10% (TDF/FTC + DTG) and 7% (TDF/FTC/EFV) in ADVANCE. The results were significantly higher in the TAF/FTC + DTG arm compared to the TDF/FTC/EFV arm (p < 0.001), and the TDF/FTC + DTG vs. the TDF/FTC/EFV arms (p < 0.05) in all patients, and in females. In NAMSAL, the incidence of treatment-emergent metabolic syndrome at any time point was 14% (TDF/3TC + DTG) and 5% (TDF/3TC + EFV) (p < 0.001). This incidence was significantly greater in the TDF/3TC/DTG arm compared to the TDF/3TC/EFV arm in all patients (p < 0.001), and in males (p < 0.001). Conclusion: In this analysis, we highlight treatment-emergent metabolic syndrome associated with dolutegravir, likely driven by obesity. Clinicians initiating or monitoring patients on INSTI-based ART must counsel for lifestyle optimisation to prevent these effects.
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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.
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Fármacos Anti-HIV , Infecções por HIV , Adulto , Humanos , Infecções por HIV/tratamento farmacológico , Camarões , Qualidade de Vida , Oxazinas/uso terapêutico , Benzoxazinas/uso terapêutico , Antirretrovirais/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piridonas/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Fármacos Anti-HIV/uso terapêuticoRESUMO
Objective We aimed to compare the safety and efficacy of a doxycycline-based regimen against Cameroon National Standard Guidelines (hydroxychloroquine plus azithromycin) for the treatment of mild symptomatic COVID-19. Methods We conducted an open-label, randomized, non-inferiority trial in Cameroon comparing doxycycline 100 mg, twice daily for seven days versus hydroxychloroquine 400 mg daily for five days and azithromycin 500 mg at day 1 and 250 mg from day 2 through 5 in mild COVID-19 patients. Clinical recovery, biological parameters, and adverse events were assessed. The primary outcome was the proportion of clinical recovery on days 3, 10, and 30. Non-inferiority was determined by the clinical recovery rate between protocols with a 20-percentage points margin. Results One hundred and ninety-four participants underwent randomization and were treated either with doxycycline (n = 97) or hydroxychloroquine-azithromycin (n = 97). On day 3, 74/92 (80.4%) participants on doxycycline versus 77/95 (81.1%) on hydroxychloroquine-azithromycin-based protocols were asymptomatic (p = 0.91). On day 10, 88/92 (95.7%) participants on doxycycline versus 93/95 (97.9%) on hydroxychloroquine-azithromycin were asymptomatic (p = 0.44). On day 30, all participants were asymptomatic. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) polymerase chain reaction (PCR) test was negative on day 10 in 60/92 (65.2%) participants who were assigned to doxycycline and in 63/95 (66.3%) participants who were assigned to hydroxychloroquine-azithromycin. None of the participants were admitted for worsening of the disease after treatment initiation. Conclusion Doxycycline 100 mg twice daily for seven days proved to be safe and non-inferior in terms of efficacy when compared to hydroxychloroquine-azithromycin for preventing clinical worsening of mild symptomatic or asymptomatic COVID-19 and achieving virological suppression.
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BACKGROUND: Four decades into the HIV epidemic, CNS infection remains a leading cause of preventable HIV-related deaths in routine care. The Driving Reduced AIDS-associated Meningo-encephalitis Mortality (DREAMM) project aimed to develop, implement, and evaluate pragmatic implementation interventions and strategies to reduce mortality from HIV-related CNS infection. METHODS: DREAMM took place in five public hospitals in Cameroon, Malawi, and Tanzania. The main intervention was a stepwise algorithm for HIV-related CNS infections including bedside rapid diagnostic testing and implementation of WHO cryptococcal meningitis guidelines. A health system strengthening approach for hospitals was adopted to deliver quality care through a co-designed education programme, optimised clinical and laboratory pathways, and communities of practice. DREAMM was led and driven by local leadership and divided into three phases: observation (including situational analyses of routine care), training, and implementation. Consecutive adults (aged ≥18 years) living with HIV presenting with a first episode of suspected CNS infection were eligible for recruitment. The primary endpoint was the comparison of 2-week all-cause mortality between observation and implementation phases. This study completed follow-up in September, 2021. The project was registered on ClinicalTrials.gov, NCT03226379. FINDINGS: From November, 2016 to April, 2019, 139 eligible participants were enrolled in the observation phase. From Jan 9, 2018, to March 25, 2021, 362 participants were enrolled into the implementation phase. 216 (76%) of 286 participants had advanced HIV disease (209 participants had missing CD4 cell count), and 340 (69%) of 494 participants had exposure to antiretroviral therapy (ART; one participant had missing ART data). In the implementation phase 269 (76%) of 356 participants had a probable CNS infection, 203 (76%) of whom received a confirmed microbiological or radiological diagnosis of CNS infection using existing diagnostic tests and medicines. 63 (49%) of 129 participants died at 2 weeks in the observation phase compared with 63 (24%) of 266 in the implementation phase; and all-cause mortality was lower in the implementation phase when adjusted for site, sex, age, ART exposure (adjusted risk difference -23%, 95% CI -33 to -13; p<0·001). At 10 weeks, 71 (55%) died in the observation phase compared with 103 (39%) in the implementation phase (-13%, -24 to -3; p=0·01). INTERPRETATION: DREAMM substantially reduced mortality from HIV-associated CNS infection in resource-limited settings in Africa. DREAMM scale-up is urgently required to reduce deaths in public hospitals and help meet Sustainable Development Goals. FUNDING: European and Developing Countries Clinical Trials Partnership, French Agency for Research on AIDS and Viral Hepatitis. TRANSLATIONS: For the French and Portuguese translations of the abstract see Supplementary Materials section.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Meningite Criptocócica , Adolescente , Adulto , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/diagnóstico , Malaui , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/epidemiologia , Tanzânia/epidemiologia , Estudos Controlados Antes e DepoisRESUMO
The seroprevalence to orthoebolaviruses was studied in 9594 bats (5972 frugivorous and 3622 insectivorous) from Cameroon, the Democratic Republic of Congo (DRC) and Guinea, with a Luminex-based serological assay including recombinant antigens of four orthoebolavirus species. Seroprevalence is expressed as a range according to different cut-off calculations. Between 6.1% and 18.9% bat samples reacted with at least one orthoebolavirus antigen; the highest reactivity was seen with Glycoprotein (GP) antigens. Seroprevalence varied per species and was higher in frugivorous than insectivorous bats; 9.1-27.5% versus 1.3-4.6%, respectively. Seroprevalence in male (13.5%) and female (14.4%) bats was only slightly different and was higher in adults (14.9%) versus juveniles (9.4%) (p < 0.001). Moreover, seroprevalence was highest in subadults (45.4%) when compared to mature adults (19.2%), (p < 0.001). Our data suggest orthoebolavirus circulation is highest in young bats. More long-term studies are needed to identify birthing pulses for the different bat species in diverse geographic regions and to increase the chances of detecting viral RNA in order to document the genetic diversity of filoviruses in bats and their pathogenic potential for humans. Frugivorous bats seem more likely to be reservoirs of orthoebolaviruses, but the role of insectivorous bats has also to be further examined.
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OBJECTIVES: Antibiotic resistance (AR) is a global health issue with multidimensional repercussions. There is a paucity of data regarding the molecular epidemiology of multidrug-resistant Enterobacterales (MDR-E) and extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE) in Africa, especially among people living with HIV (PLHIV). This study aimed at determining the prevalence, risk factors, phenotypic and genotypic profiles of MDR-E and ESBL-PE isolated from PLHIV in Yaoundé, Cameroon. METHODS: In total, samples were collected from 185 PLHIV during a three-month period (April-June 2021) at the Yaoundé Central Hospital. Stool samples and rectal swabs were collected and cultured on MacConkey agar. The API 20E kit was used for the phenotypic identification of the isolates, whereas antibiotic susceptibility testing was performed using the Kirby-Bauer disk diffusion method. The ß-lactamase genes and genotypic relatedness were studied by PCR and ERIC-PCR, respectively. RESULTS: The prevalence of MDR-E among PLHIV was 81%, of which 39% were ESBL-PE. A high level of resistance to fosfomycin (89%), chloramphenicol (63%), and gentamicin (56%) was observed. Escherichia coli was the predominant MDR non-ESBL-PE (80.8%) and MDR ESBL-PE (73.77%). The principal ß-lactamases genes in MDR non-ESBL and MDR ESBL-PE were blaTEM (62.90%) and blaCTX-M (40.86%), respectively. Genetic fingerprinting revealed high genetic relatedness among E. coli isolates. CONCLUSION: This study shows a high prevalence of MDR-E and ESBL-PE in the gut of PLHIV in Yaoundé, with blaTEM and blaCTX-M being the most prevalent. It demonstrates the need to strengthen real-time surveillance of these resistant bacteria in order to improve management of infection among PLHIV.
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Escherichia coli , Infecções por HIV , Humanos , Escherichia coli/genética , Camarões/epidemiologia , beta-Lactamases/genética , Fezes/microbiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologiaRESUMO
OBJECTIVE: To investigate the relation between interleukin-6 concentration and oxidative status of HIV infected patients with or at risk of Kaposi's disease in Yaoundé. METHODS: We conducted a two-months cross-sectional study on 87 consenting HIV infected patients followed at the Day Hospital of the Yaoundé Central Hospital. Serum/plasma obtained after centrifugation of blood collected in dry/EDTA tubes was used for the determination of Human Herpes Virus-8 antigen (HHV-8) and Interleukin-6 (IL-6) by the ELISA technique, and that of oxidative stress markers: Malondialdehyde (MDA) reduced Glutathione (GSH) and total antioxidant capacity by spectrophotometry. RESULTS: Subjects belonging to the [40-50[year-old age group were mainly represented in our study population with 43.7%. The average age was 44.6 ± 10.4 years with extremes ranging from 26 to 72 years. The sex ratio was 0.24. Our population was mainly represented by people infected with HIV type I (90.8%) and 3.4% had developed clinical signs of Kaposi's disease. The prevalence of the HHV-8 antigen was 57.5%. Immune and oxidative parameters did not vary with age, sex and therapeutic line. We noted a significant increase in IL-6 concentrations in patients positive to the HHV-8 antigen for IL-6 concentrations < 37 (P = 0.005; CI= [0.40; 0.59]. MDA and GSH concentrations increased significantly with the HHV-8 infection (P < 0.0001; CI= [0.40; 0.59] and P < 0.0001; CI= [13.30;21.45], respectively). Total antioxidant capacity (FRAP) decreased significantly with HHV-8 infection (P = 0.004; CI= [-69.18; -13.78]). We noted a significant increase in MDA concentrations in patients taking their ARVs irregularly, (P < 0.0001). CONCLUSION: Our study showed a weak positive correlation between IL-6 and MDA, a strong negative correlation between FRAP and MDA and a strong positive correlation between MDA and GSH highlighting the association of these few markers of oxidative stress and Il-6 to the risk of Kaposi's disease.