HIV-2 remains a neglected component of the global HIV epidemic, predominantly affecting west Africa but also present in Europe and other regions through historical and migratory links. Although generally characterised by lower transmissibility and slower disease progression than HIV-1, HIV-2 poses distinct diagnostic, therapeutic, and programmatic challenges. Research, implementation, and advocacy efforts aimed at reducing HIV-2 infection must account for the limitations of available typing tools, the restricted access to validated viral load assays, the virus' intrinsic resistance to certain antiretroviral drug classes, and the gaps in retention in care that hinder progress towards global treatment targets. Strengthening collaborative research, improving diagnostic capacity, and integrating HIV-2 into broader HIV policy frameworks are essential to optimise patient outcomes and to advance the global HIV response.
INTRODUCTION:Increasing evidence suggests that dolutegravir (DTG), endorsed by the WHO since 2018 for first-line antiretroviral therapy (ART), is associated with significant weight gain and potentially also with cardiometabolic disorders. In an effort to expand therapeutic options for people living with HIV (PLHIV), the EvaLuating the non-inferiority of DORAvirine vs DOlutegravir trial aims to compare the virologic efficacy of doravirine (DOR) and DTG-based regimens and to assess their safety, including a focus on cardiometabolic effects. METHODS AND ANALYSIS:This is an international, phase III, multicentre, open-label, non-inferiority, randomised trial that will enrol 610 ART-naïve PLHIV (HIV RNA≥1000 copies/mL at screening) across six countries (Brazil, Cameroon, France, Côte d'Ivoire, Mozambique and Thailand) spanning four continents. Key inclusion criteria include age ≥18 years, confirmed HIV-1 infection with plasma RNA levels ≥1000 copies/mL, indication for ART initiation and no prior ART exposure. Participants will be randomised in a 1:1 ratio to receive either DOR 100 mg once daily in combination with tenofovir disoproxil fumarate (TDF) (300 mg daily) plus lamivudine (3TC) (300 mg daily) or DTG (50 mg daily) in combination with TDF (300 mg once daily) plus either emtricitabine (FTC) (200 mg daily) or 3TC (300 mg daily). Randomisation will be stratified by screening HIV-1 RNA load (≤100 000 or >100 000 copies/mL) and by country. The primary outcome is virological efficacy, defined as the proportion of participants achieving HIV-1 RNA <50 copies/mL at week 48 on the assigned treatment (FDA Snapshot algorithm). Secondary outcomes include cardiometabolic safety endpoints (ie, weight gain, insulin resistance, hypertension, diabetes, waist and hip circumferences, waist-to-hip ratio, fasting glycaemia, insulin and fasting serum lipids), along with mental health, quality of life, virological and immunological parameters. Final data collection is expected by July 2028. ETHICS AND DISSEMINATION:Primary outcome results (week 48) are expected in early 2028. The project was submitted to and approved by national ethics committees and pharmaceutical regulatory authorities in all participating countries: Brazil (CEP INI FIOCRUZ (21.040-900)/CEP HGNI (26.030-380)); Cameroon (CNERSH (2024/09/1717/CE/CNERSH/SP)/Ministry of Public Health (D30-1464/AAR/MINSANTE/SG/DROS/CRC); Côte d'Ivoire: (CNESVS (0018224/MSHPCMU/CNESVS-km)/AIRP (1329/AIRP/DISMP/Om/kbaag); France (CTIS CPP/ANSM (2023-508626-10-00)); Mozambique (CNBS (20/CNBS/25)/ANARME (4635/380/ANARME)); Thailand: (IHRP (08/1944)/Thai FDA: ongoing on 19 January 2026). The trial received authorisation from the French National Commission for Data Protection and Liberties (CNIL) under approval number 924 302. Written informed consent is obtained from all participants prior to any study-specific procedures and trial enrolment, in accordance with the Declaration of Helsinki and applicable national regulations. Study findings will be disseminated through publication in peer-reviewed journals and presentations at national and international scientific conferences. Results will also be communicated to policymakers, healthcare professionals, community stakeholders and study participants through appropriate dissemination activities, including policy briefs, stakeholder meetings and lay summaries on dedicated and easily accessible platforms. TRIAL REGISTRATION NUMBERS:NCT06203132; EU-CT, 2023-508626-10-00.
Abstract Metrological variations strongly influence malaria transmission by affecting mosquito breeding and survival. Côte d'Ivoire, located within a tropical climate zone, is particularly vulnerable to metrological variations that can alter disease patterns. This study aimed to assess the relationship between meteorological variations of temperature, precipitation, relative humidity and malaria incidence in Côte d'Ivoire from 2021 to 2023. This was a retrospective ecological time‐series study that used data from the National Malaria Control Program (NMCP) and meteorological data from SODEXAM. Monthly data was analyzed by ecological zones and age groups. Pearson's correlation and multiple linear regression models were used to examine associations between metrological variation factors and malaria incidence. Malaria incidence peaked during the rainy season (May–August) across all regions, with children under five representing 39% of total cases. Precipitation and relative humidity were positively and significantly correlated with malaria incidence (r = 0.583–0.698, p < 0.05), while temperature showed a significant negative correlation (r = −0.539 to −0.600, p < 0.05). Interaction analysis revealed that the effect of precipitation and humidity was strongest in the northern zone, where malaria transmission risk increased significantly (β = 22.51, p = 0.01). Malaria transmission in Côte d'Ivoire is strongly associated with metrological variability, particularly rainfall and humidity. Elevated precipitation and humidity increase malaria morbidity, whereas high temperatures above 28°C suppress transmission. Integrating meteorological surveillance into malaria early warning systems can improve prediction and control strategies, especially among vulnerable populations such as children under five.
Objectives:Bacterial meningitis remains a major public health problem in Niger. Despite vaccination campaigns, the disease persists and continues to cause high morbidity and mortality in the pediatric population. This study aimed to describe the epidemiologic and evolutionary characteristics of bacterial meningitis in children in two tertiary hospitals in Niamey. Methods:This was a retrospective, descriptive, and analytical cross-sectional study conducted over a 22-month period (2023-2024). The study population included all children aged 0-59 months hospitalized for suspected or confirmed bacterial meningitis. Data were collected exhaustively from patient records. Variables associated with mortality in bivariate analysis were included in a multivariable logistic regression model. The Pearson chi-squared test at a significance level of 5% was used to determine factors associated with death by multivariate analysis. Results:Of a total of 220 suspected cases of meningitis, 105 (47.7%) were confirmed. The mean age was 24.2 ± 16.9 months, with a male-to-female ratio of 1.5. Fever (98.2%) and seizures (74.1%) were the main reasons for consultation. Neisseria meningitidis was the predominant pathogen (80.9% of cultures), with a majority of serogroup W135 identified by polymerase chain reaction (60%). The overall case fatality rate was alarming, reaching 50.9%, and 6.4% of survivors had sequelae. The main risk factors for death were age ≤24 months (odds ratio [OR] = 2.81), short duration of corticosteroid therapy (OR = 11.48), and antibiotic monotherapy. Conclusion:Pediatric bacterial meningitis in Niamey is characterized by high mortality and the predominance of N. meningitidis. These results call for an urgent review of national treatment protocols, the strengthening of diagnostic capacities, and the accelerated introduction of multivalent conjugate vaccines to cover emerging serogroups.
Dengue fever can progress to severe organ dysfunction, known as the expanded dengue syndrome. Among its atypical complications, acute myocarditis is rare, underdiagnosed, and potentially fatal. We report a series of four young male patients admitted to Treichville University Hospital (Abidjan, Côte d’Ivoire) illustrating the diverse spectrum of dengue-related myocarditis. Presentations ranged from acute heart failure to high-grade atrioventricular block requiring temporary transvenous pacing, occurring during different phases of dengue illness While elevated high-sensitivity troponin was a consistent warning sign, 3-Tesla cardiac magnetic resonance (CMR) imaging definitively confirmed myocardial inflammation via localized edema and subepicardial late gadolinium enhancement. This series highlights the need for a high index of suspicion during dengue outbreaks, where management demands a careful balance between fluid resuscitation and myocardial strain.
Background Extrapulmonary tuberculosis (EPTB) is a leading cause of death among people living with HIV (PLHIV) in sub-Saharan Africa, yet site-specific mortality patterns and risk factors remain poorly characterised. We aimed to describe EPTB localisations and assess mortality rates and determinants of death among HIV-infected adults with EPTB in Abidjan, Côte d’Ivoire. Methods We conducted a retrospective cohort study including all HIV-infected adults (≥ 18 years) treated for presumptive or confirmed EPTB at the Infectious and Tropical Diseases Department of Treichville University Hospital between January 1, 2010, and March 31, 2019. Data were extracted from medical records. Survival was estimated using Kaplan–Meier methods. Risk factors for death were identified using a stratified Cox proportional hazards model. Results Of 2,046 TB/HIV co-infected patients, 1,240 (60.6%) had EPTB. The most frequent localisations were lymph nodes (32.0%), miliary tuberculosis (23.6%), and tuberculous meningitis (TBM, 16.4%). Overall mortality was 38% (470/1,240), reaching 58% for TBM, 49% for serous membrane TB, and 43% for miliary TB. Most deaths occurred within the first 60 days of anti-tuberculosis treatment. In multivariable analysis, independent risk factors for death were TBM (adjusted hazard ratio [aHR] 2.20; 95% confidence interval [CI] 1.28–3.74) and serous membrane TB (aHR 1.77; 95% CI 1.02–3.09). Miliary TB showed a trend toward increased mortality (aHR 1.66; 95% CI 0.98–2.82). Protective factors included cotrimoxazole prophylaxis (aHR 0.65; 95% CI 0.53–0.80) and a CD4 count ≥ 100 cells/mm³ (aHR 0.26; 95% CI 0.18–0.36). Conclusions EPTB is frequent and highly lethal among HIV-infected patients in Côte d’Ivoire, particularly TBM and serous membrane TB. The first two months of treatment are a critical period for survival. Cotrimoxazole prophylaxis and preserved CD4 counts are strongly protective. These findings support earlier HIV diagnosis, prompt ART initiation, and strengthened diagnostic algorithms for disseminated EPTB in resource-limited settings.
RÉSUMÉIntroduction. La pan-résistance bactérienne, définie par une résistance à toutes les classes d'antibiotiques disponibles, représente une menace croissante dans les pays à ressources limitées, où les options thérapeutiques sont déjà restreintes. En Afrique subsaharienne, les données sur ces infections sont rares. Cette étude rapporte notre expérience dans la prise en charge des infections à bactéries pan-résistantes documentées au Service des Maladies Infectieuses (SMIT) d'Abidjan entre mars 2020 et février 2022. Méthodes. Nous avons mené une étude observationnelle rétrospective descriptive incluant tous les patients hospitalisés au SMIT chez qui une bactérie pan-résistante (résistance à tous les antibiotiques testés) avait été isolée. Les données ont été extraites des dossiers médicaux et des registres de laboratoire. La colistine n'étant pas testée en routine, la sensibilité à cette molécule n'a pas été évaluée. Résultats. Sept cas ont été diagnostiqués (âge médian : 58 ans ; extrêmes : 48-82 ans ; sex-ratio H/F : 1,3). Klebsiella pneumoniae était le germe prédominant (5/7), suivi de Pseudomonas aeruginosa (1/7) et Acinetobacter baumannii (1/7). Les facteurs de risque étaient : hospitalisation récente (6/7), antibiothérapie récente (6/7), dispositifs invasifs (3/7), infection VIH (2/7). Une co-infection par SARS-CoV-2 était présente chez 5 patients. Le délai médian d'obtention de l'antibiogramme était de 6 jours (extrêmes : 4-8 jours). L'antibiothérapie initiale probabiliste (pipéracilline-tazobactam + gentamicine ou imipénème + amikacine) était en échec à 48 heures chez tous les patients, justifiant un traitement de seconde intention par colistine (5/7) ou imipénème (2/7). Malgré ce réajustement, l'évolution était constamment fatale, tous les patients décédant dans un tableau de choc septique, avec une durée médiane d'hospitalisation de 10 jours (extrêmes : 3-29 jours). Conclusion. Les infections à bactéries pan-résistantes au SMIT d'Abidjan étaient associées à une léthalité de 100 %, dans un contexte de co-infection SARS-CoV-2 fréquent et de retards diagnostiques (délai médian de 6 jours). Le renforcement de la surveillance microbiologique, la réduction du délai d'obtention des antibiogrammes et la mise à disposition de nouveaux antibiotiques (dont la colistine) sont des priorités pour améliorer le pronostic.ABSTRACT Introduction. Pan-drug resistance, defined as resistance to all available antibiotic classes, is a growing threat in resource-limited settings where therapeutic options are already constrained. In sub-Saharan Africa, data on these infections are scarce. This study reports our experience in managing documented pan-drug-resistant bacterial infections at the Infectious Diseases Department (SMIT) of Abidjan between March 2020 and February 2022. Methods. We conducted a retrospective observational descriptive study including all hospitalized patients at SMIT in whom a pan-drug-resistant bacterium (resistant to all tested antibiotics) was isolated. Data were extracted from medical records and laboratory registries. Since colistin was not routinely tested, susceptibility to this molecule was not assessed. Results. Seven cases were diagnosed (median age: 58 years; range: 48-82 years; male/female ratio: 1.3). Klebsiella pneumoniae was the predominant pathogen (5/7), followed by Pseudomonas aeruginosa (1/7) and Acinetobacter baumannii (1/7). Risk factors included: recent hospitalization (6/7), recent antibiotic therapy (6/7), invasive devices (3/7), and HIV infection (2/7). SARS-CoV-2 co-infection was present in 5 patients. The median time to antibiogram availability was 6 days (range: 4-8 days). Initial empirical antibiotic therapy (piperacillin-tazobactam + gentamicin or imipenem + amikacin) failed at 48 hours in all patients, requiring second-line treatment with colistin (5/7) or imipenem (2/7). Despite this adjustment, outcome was uniformly fatal, with all patients dying from septic shock, with a median hospitalization duration of 10 days (range: 3-29 days). Conclusion. Pan-drug-resistant bacterial infections at the SMIT Abidjan were associated with 100% mortality, in a context of frequent SARS-CoV-2 co-infection and diagnostic delays (median time of 6 days). Strengthening microbiological surveillance, reducing time to antibiogram availability, and providing access to new antibiotics (including colistin) are priorities to improve prognosis.
Objectives:Several epidemic outbreaks have affected the Zinder region. These include diseases targeted by the expanded immunization program and other emerging diseases. This study aimed to analyze these epidemics. Methods:This is documentary research of the epidemics of meningitis, measles, cholera, COVID-19, and diphtheria, which occurred in the Zinder region from 2015 to 2023, as well as their determinants. The data collection is made from the linear list of notifiable diseases of the Regional Directorate of Health and Public Hygiene of Zinder, associated with literature review on the determinants of the appearance of these epidemics. Results:The number of meningitis cases has gradually increased in Zinder from 2019 to 2024. A total of 5019 cases were registered during these epidemics, with a mortality rate of 6.31%. Five measles epidemics have been recorded since 2015. A total of 13,887 cases were notified during these epidemics, with a mortality rate of 0.30%. Three cholera epidemics occurred: in 2021, in 2022, and in 2024. During these epidemics, 884 cases were recorded, with 24 deaths or a lethality of 2.71%. The COVID-19 epidemic occurred in 2020, with 364 cases, including 17 deaths, i.e. a mortality rate of 4.67%. Since 2022, the region has been facing a diphtheria epidemic. A total of 3310 cases has been reported, with 173 deaths. The causes of these epidemics are multifaceted; they involve the decline in vaccination coverage, migration, insecurity, the COVID-19 pandemic, and climate change. Conclusions:The impact of epidemics on the health of the population and the socio-economic development of regions implies a greater mastery of the root causes mentioned in this study.
Background Tuberculosis is a severe disease, not only due to its lethality but also to a significant morbidity occurring in people living with HIV (PLWH). If factors associated to mortality, severe morbidity and unsuccessful treatment related to the host are well identified in PLWH, there is scarce knowledge on factors related to the disease itself such as bacillary load, extent of lung involvement and disease dissemination to other organs. We sought to assess whether tuberculosis-related factors were associated with key patient outcomes in PLWH using data from an international clinical trial. Methods We conducted a secondary analysis of the ANRS 12300 Reflate TB2 international phase III open-label randomized trial that assessed different antiretroviral regimens in PLWH treated for tuberculosis. We evaluated whether bacillary load (smear positivity grade), extent of lung involvement (cavitation on chest x-ray) and disease dissemination (urine LAM positivity) were associated with mortality using Cox proportional hazard models and to severe morbidity and unsuccessful tuberculosis treatment using logistic regressions. Results Of 457 participants included in this study, 90 (20.4%) had grade 2 + or 3 + smear positivity, 39 (10.8%) had cavitation on chest X-ray, and 147 (32.2%) had a positive urinary LAM. Overall, 19 (4.2%) participants died, 113 (24.7%) presented severe morbidity, and 33 (7.2%) had unsuccessful tuberculosis treatment. Factors that remained independently associated with mortality were cavitation on chest x-ray (aHR = 7.92, 95% CI, 1.74–35.94, p = .0073) and LAM positivity (aHR = 5.53, 95% CI, 1.09–28.06, p = .0389). The only factor that remained significantly associated with severe morbidity was LAM positivity (aOR = 2.04, 95% CI, 1.06–3.92, p = .0323). No factor remained significantly associated with unsuccessful tuberculosis treatment. Conclusions In PLWH with tuberculosis enrolled in a trial, tuberculosis disease characteristics related to disease severity were cavitation on chest x-ray and urine LAM positivity. Early identification of these factors could help improve the management of PLWH with tuberculosis and improve their survival.
BACKGROUND:In Africa, for people with HIV on a dolutegravir-based regimen with a viral load of more than 1000 copies per mL despite enhanced adherence counselling, the appropriate course of action is uncertain. We aimed to evaluate the predicted effects of alternative antiretroviral regimen switching options in this population, including consideration of cost-effectiveness. METHODS:We used an existing individual-based model to simulate risk and experience of HIV in 100 000 adults alive between 1989 and 2076. Using sampling of parameter values, we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in eastern, central, southern, and western Africa. For each setting-scenario, we predicted the outcomes from the three alternative policies for people with sustained viral load non-suppression on a dolutegravir-containing regimen from 2026: a switch to a protease inhibitor-based regimen (switch policy), a switch to a protease inhibitor-based regimen only if HIV drug resistance testing beforehand shows integrase inhibitor resistance (resistance test policy), and no switch with no HIV drug resistance test (no switch policy). We considered predicted outcomes over 10-year and 50-year periods from 2026, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted. Ritonavir-boosted darunavir costs $210 per year, and dolutegravir less than $20. We assumed a cost of HIV drug resistance testing of $200 and considered variations around this. For comparing policies, we calculated net DALYs, which account for the health consequences of differences in costs and provide a measure of the impact of a policy on overall population burden of disease. FINDINGS:Across setting-scenarios, there was a mean of 14 480 deaths per year (95% CI 13 750-15 210) over 50 years with a mean annual discounted cost of $103·2 million (95·8-106·5) with the switch policy in the context of having scaled to a setting with an adult population of 10 million in 2024. Compared with the switch policy, the no switch policy was predicted to lead to an overall increased number of DALYs incurred (mean 4400 per year, 95% CI 3200-5500), although it resulted in the lowest overall cost, with a difference in annual discounted costs of $5·1 million (95% CI 4·6-5·6) lower than the switch policy. The resistance test policy led to a similar risk of death and DALYs to the switch policy at a lower overall cost (difference in annual discounted costs $3·5 million per year, 95% CI 3·1-3·9), leading to 6900 (95% CI 5500-8200) fewer net DALYs per year. Net DALYs for the resistance test versus no switch policies were similar (-1000 net DALYs, 95% CI 400 to -2300). The incremental cost-effectiveness ratio when comparing the resistance test policy with the no switch policy was $376 per DALY averted; the switch policy was dominated. INTERPRETATION:Introduction of HIV drug resistance testing for people with sustained viral load non-suppression on dolutegravir-based antiretroviral therapy is likely to be cost-effective. We suggest that exploratory planning for increased access and scale-up of high-quality, low-cost drug resistance testing for the region is undertaken. FUNDING:Gates Foundation as part of the HIV Modelling Consortium.
Objectives:Cryptococcal meningitis (CM) is a common cause of meningitis in patients with AIDS in sub-Saharan Africa, with a mortality rate of over 50% at 10 weeks. The preferred treatment in resource-limited countries without access to amphotericin B or 5-fluorocytosine is high-dose fluconazole (FCZ). However, survival and factors associated with mortality after completion of FCZ-based treatment are not well known. To assess the outcomes at 24 months of patients with HIV with CM who have completed the initial FCZ treatment. Methods:Retrospective cohort study of adult patients with HIV with CM on oral FCZ 1200 mg/day induction, having completed 10 weeks of specific treatment between January 2012 and December 2016. The survival probability (not lost to follow-up or death) at 24 months was determined and the risk factors associated with death were identified using the Cox proportional hazard model. Results:Thirty-one (31) patients were enrolled from a total of 82. The median age was 42 years (38-44). Overall, 58% of the patients were female (n = 18) and 50% (14/28) were antiretroviral therapy experienced. The following outcomes were observed after 24 months of follow-up: 13 patients (41.9%) were lost to follow-up, 12 (38.7%) were still alive, 6 (19.3%) died, and 5 (16.1%) relapsed. The mortality rate was reduced by 77% where the clusters of differentiation 4 count was less than 100 cells/mm3, with adjustments for length of hospitalization and history of morbidities. Conclusions:Long-term survival among patients with HIV with CM was poor. Interventions to strengthen linkage to HIV treatment and care and continuation of secondary fluconazole prophylaxis are critical.
OBJECTIVES:Since 2022, the Zinder region has been facing an epidemic of diphtheria. The objective of this study was to investigate the epidemiological and virulence characteristics of the diphtheria epidemic in the Zinder region. METHODS:This was a cross-sectional study conducted from 2022 to 2024 in the Zinder region. All suspected cases of diphtheria were included. A sequencing was carried out on one of the Corynebacterium diphtheriae strains responsible for the epidemic. RESULT:A total of 3196 suspected cases of diphtheria were reported in the Zinder region between 2022 and 2024. The age group from 5 to 14 years is the most represented, with 46.41%. The health district of Matamaye is the most concerned, declaring 34.39% of cases. Genomic analyses revealed a toxinogenic Corynebacterium diphtheriae strain QA1672, which belongs to ST-975. Regarding antibiotic resistance, only the sul1 gene, which encodes sulfonamide resistance, was detected. CONCLUSION:The diphtheria epidemic in the Zinder region illustrates the consequences of insufficient vaccination coverage. It is necessary to put access to the quality of actual vaccination coverage to control this epidemic phenomenon.
BackgroundFemale sex workers (FSWs) are at high risk of contracting STIs, in particular in Sub-Saharan Africa. The implementation of oral HIV pre-exposure prophylaxis provided an opportunity to draw attention to the sexual health needs of FSWs. Innovative strategies to screen for and reduce the burden of STIs is thus a priority. This study describes STI screening among FSWs enrolled in the PRINCESSE project in Côte d’Ivoire.MethodsThe PRINCESSE project (2019–2023) was an interventional cohort of FSWs ≥18 years, evaluating a comprehensive, community-based sexual and reproductive health care package, including the management of STIs, offered through mobile clinics operating on prostitution sites in San Pedro area. HIV testing and syndromic STI testing were offered at baseline and every 3 months. Biological testing of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was offered annually. Clinical forms included sociodemographic, behavioral and sex-work-related characteristics. We describe baseline characteristics, coverage of clinical examination, and vaginal, anal swab collection. Social, behavioral and sex work-related factors associated with an STI syndromic diagnosis were explored. A multivariable logistic regression model was used to identify factors associated with diagnosing a symptomatic STI.Results489 FSWs were included in the PRINCESSE cohort. Median age was 29 years (24–35 years), 28.6% had had sex without a condom in the last 7 days. The prevalence of HIV at baseline was 10.5%. Only one case of HIV seroconversion was observed during the project. The most frequent symptom was ano-vaginal discharge (19.1%). The prevalence of STI based on clinical symptoms was 26.6%. The proportion of vaginal swab samples for which the PCR result was positive was 8.0% for CT and 4.0% for NG. Only age remained significantly associated with diagnosing a symptomatic STI in the multivariable analysis.ConclusionThis study revealed a high prevalence of HIV and STIs, similar to national estimates among FSWs enrolled in a sexual health cohort. Screening for these generically asymptomatic bacterial STIs must be combined with the syndromic approach used in key populations, especially with the introduction of new PrEP programs, to reduce the exposure of individuals in these populations to STIs.
BACKGROUND:People living with HIV-2 are mainly found in West Africa and their identification and treatment have been impaired by diagnostic challenges and availability of effective antiretroviral treatment (ART). With the roll out of first line dolutegravir (DTG)-based regimen, the situation may have improved, emphasizing the need for data on long-term treatment outcomes and advanced HIV disease among ART-experienced people living with HIV-2. METHOD:A prospective cohort was initiated in 2012 in Côte d'Ivoire and Burkina Faso. All adult patients from Côte d'Ivoire with an undetectable viral load, were included and followed up. HIV-2 viral load and CD4 counts were done during the routine follow-up visits and a detailed clinical assessment was done during the last follow up visit of the year 2018 corresponding to the censor date of the cohort. Outcomes were described as follow: in care (known alive and present during the last ART follow up visit), loss to follow-up (absent for more than 90 days and not reported dead), and dead (reported dead with a date of event). Advanced HIV disease followed WHO definition and virologic failure was define as viral load > 50 copies/mm3. The Kaplan-Meier curve was used to estimate mortality and Loss to follow-up probability. RESULTS:Among the 108 HIV-2 patients in virologic success in 2012, 95 agreed to participate and were enrolled in the "success cohort". Their median age was 53 [47-60] years and all of them were receiving boosted-lopinavir-based ART regimen. Of the 95 participants, 65 (68.4%) remained in care, 20 (21.1%) were loss to follow-up and 10 (10.5%) were reported dead. The survival analysis retrieved a decreasing probability of remaining alive and in care over the time, moving from 90% to 80.7% and to 73.0% after 24, 48 and 72 months respectively. Overall, 36 (37.9%) patients presented with advanced HIV disease at their last visit, higher among those dead/ loss to follow-up compared to those remaining in care (60.0% vs 27.7%; p-0.003). CONCLUSION:High advanced HIV disease rate was found in HIV-2 patients, six years after an initial virologic success. This emphasizes the need to enable the one-stop-shop model that allow an early management of opportunistic infections while integrating non-communicable diseases services in HIV-2 care.
Observational studies suggest a reduction in fatal or severe COVID-19 disease with the use of ACE2 inhibitors and statins. We implemented a randomized controlled tree-arm open label trial evaluating the benefits of adding telmisartan (TLM) or atorvastatin (ATV) to lopinavir boosted ritonavir (LPVr) on the SARS-CoV-2 nasopharyngeal viral load in patients with mild / moderate COVID-19 infection in C & ocirc;te d'Ivoire. RT-PCR positive COVID-19 patients >= 18 years, with general or respiratory symptoms for less than 7 days were randomized (1:1:1) to receive LPVr (400 mg/100 mg twice daily), LPVr + TLM (10 mg once daily) or LPVr + ATV (20 mg once daily) for 10 days. The primary endpoint was viro-inflammatory success defined as a composite variable at day 11: Ct >= 40 and C-reactive protein < 27 mg/L. We randomized 294 patients: 96 to LPVr, 100 to LPVr + TLM, 98 to LPVr + ATV arms. Baseline characteristics were well balanced between arms. In the primary analysis (missing = failure), 46% patients in the LPVr arm reached viro-inflammatory success at day 11 vs 43% in the LPVr + TLM arm (p = 0.69) and 43% in the LPVr + ATV arm (p = 0.68). The median time from baseline to resolution of COVID-19 related symptoms was not different between arms. Nine patients were hospitalized: 2 in the LPVr arm, 5 in the LPVr + TLM arm and 2 in the LPVr + ATV arm and 4 patients died. Among adults with mild to moderate COVID-19 infection, the addition of telmisartan or atorvastatin, to the standard LPVr treatment is not associated with a better virological or clinical outcome.
BACKGROUND:Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches. METHODS:This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per μL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants. FINDINGS:Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group. INTERPRETATION:The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen. FUNDING:ANRS MIE.
Objectives Detailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world’s leading cause of liver disease. We sought to develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes.Methods We developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, ‘e’ antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA<300 copies/mL to >106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC).Results Model-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29–2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06–1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies.Conclusions We simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management.