Do tests devised to detect recent HIV-1 infection provide reliable estimates of incidence in Africa?

International audienceThe objective of this study was to assess the performance of 4 biologic tests designed to detect recent HIV-1 infections in estimating incidence in West Africa (BED, Vironostika, Avidity, and IDE-V3). These tests were assessed on a panel of 135 samples from 79 HIV-1-positive regular blood donors from Abidjan, C?d'Ivoire, whose date of seroconversion was known (Agence Nationale de Recherches sur le SIDA et les H?tites Virales 1220 cohort). The 135 samples included 26 from recently infected patients (180 days), and 15 from patients with clinical AIDS. The performance of each assay in estimating HIV incidence was assessed through simulations. The modified commercial assays gave the best results for sensitivity (100% for both), and the IDE-V3 technique gave the best result for specificity (96.3%). In a context like Abidjan, with a 10% HIV-1 prevalence associated with a 1% annual incidence, the estimated test-specific annual incidence rates would be 1.2% (IDE-V3), 5.5% (Vironostika), 6.2% (BED), and 11.2% (Avidity). Most of the specimens falsely classified as incident cases were from patients infected for >180 days but <1 year. The authors conclude that none of the 4 methods could currently be used to estimate HIV-1 incidence routinely in C?d'Ivoire but that further adaptations might enhance their accuracy

HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST).

INTRODUCTION HIV drug resistance poses a challenge to the United Nation's goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was endorsed by the WHO in 2019 for first-line, second-line and third-line antiretroviral therapy (ART). This multiplicity of roles of dolutegravir in ART may facilitate the emergence of dolutegravir resistance. METHODS AND ANALYSIS Nested within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST is a multicentre study of adults and adolescents living with HIV in sub-Saharan Africa, Asia, and South and Central America who experienced virological failure on dolutegravir-based ART. At the time of virological failure, whole blood will be collected and processed to prepare plasma or dried blood spots. Laboratories in Durban, Mexico City and Bangkok will perform genotyping. Analyses will focus on (1) individuals who experienced virological failure on dolutegravir and (2) those who started or switched to such a regimen and were at risk of virological failure. For population (1), the outcome will be any InSTI drug resistance mutations, and for population (2) virological failure is defined as a viral load >1000 copies/mL. Phenotypic testing will focus on non-B subtype viruses with major InSTI resistance mutations. Bayesian evolutionary models will explore and predict treatment failure genotypes. The study will have intermediate statistical power to detect differences in resistance mutation prevalence between major HIV-1 subtypes; ample power to identify risk factors for virological failure and limited power for analysing factors associated with individual InSTI drug resistance mutations. ETHICS AND DISSEMINATION The research protocol was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, South Africa and the Ethics Committee of the Canton of Bern, Switzerland. All sites participate in International epidemiology Databases to Evaluate AIDS and have obtained ethics approval from their local ethics committee to collect additional data. TRIAL REGISTRATION NUMBER NCT06285110

Impact of Drug Stock-Outs on Death and Retention to Care among HIV-Infected Patients on Combination Antiretroviral Therapy in Abidjan, Côte d'Ivoire

To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d'Ivoire.We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16).cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs

PLoS One

Introduction Evidence on childbearing desire and reproductive behaviors in women living with HIV on antiretroviral therapy (ART) is scarce, particularly in West Africa. We investigated the prevalence and associated factors of childbearing desire in HIV-infected women in care in Abidjan, Côte d’Ivoire and explored whether such desires were translated into behaviors related to contraceptive use and communication with health personnel. Methods A cross-sectional survey was conducted in two HIV-care facilities in Abidjan, Côte d’Ivoire in 2015. Eligible women were non-pregnant, non-menopausal, aged 18–49 years and diagnosed as HIV-infected. The outcomes were childbearing desire, prevalence of modern contraceptive use, unmet needs for family planning and intention of the last pregnancy since HIV diagnosis. Women wishing to conceive immediately were asked whether they had discussed their desire with HIV healthcare workers. Logistic regression models were used to assess the associations between the outcomes and women’s characteristics. Results Of 1,631 women, 80% declared having childbearing desire. No association was found between women’s childbearing desire and ART status or its duration. In multivariate models, younger age, being in a stable relationship and having no or only one child were significantly associated with increased childbearing desire. Of the women wishing to conceive immediately (n = 713), only 43% reported having had fertility-related dialogue with healthcare provider. Among sexually active women wanting to avoid or delay pregnancy (n = 650), unmet needs for family planning was 40%. Regarding the last pregnancy since HIV diagnosis, one in three women reported not having wanted a baby at that time. Conclusions Pregnancy desire in women living with HIV in Abidjan was extremely high. Integration of safe conception strategies as well as improvement of contraceptive uptake among women in need of family planning are of utmost importance to ensure optimal conception and to avoid transmission of HIV to the male partner or to the forthcoming child

Achieving consistency in measures of HIV-1 viral suppression across countries:derivation of an adjustment based on international antiretroviral treatment cohort data

INTRODUCTION: The third of the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is to achieve a 90% rate of viral suppression (HIV viral load <1000 HIV-1 RNA copies/ml) in patients on antiretroviral treatment (ART) by 2020. However, some countries use different thresholds when reporting viral suppression, and there is thus a need for an adjustment to standardize estimates to the <1000 threshold. We aim to propose such an adjustment, to support consistent monitoring of progress towards the "third 90" target. METHODS: We considered three possible distributions for viral loads in ART patients: Weibull, Pareto and reverse Weibull (imposing an upper limit but no lower limit on the log scale). The models were fitted to data on viral load distributions in ART patients in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration (representing seven global regions) and the ART Cohort Collaboration (representing Europe), using separate random effects models for adults and children. The models were validated using data from the World Health Organization (WHO) HIV drug resistance report and the Brazilian national ART programme. RESULTS: Models were calibrated using 921,157 adult and 37,431 paediatric viral load measurements, over 2010-2019. The Pareto and reverse Weibull models provided the best fits to the data, but for all models, the "shape" parameters for the viral load distributions differed significantly between regions. The Weibull model performed best in the validation against the WHO drug resistance survey data, while the Pareto model produced uncertainty ranges that were too narrow, relative to the validation data. Based on these analyses, we recommend using the reverse Weibull model. For example, if a country reports an 80% rate of viral suppression at <200 copies/ml, this model estimates the proportion virally suppressed at <1000 copies/ml is 88.3% (0.80(0.56) ), with uncertainty range 85.5-90.6% (0.80(0.70) -0.80(0.44) ). CONCLUSIONS: Estimates of viral suppression can change substantially depending on the threshold used in defining viral suppression. It is, therefore, important that viral suppression rates are standardized to the same threshold for the purpose of assessing progress towards UNAIDS targets. We have proposed a simple adjustment that allows this, and this has been incorporated into UNAIDS modelling software

Metabolic causes of liver disease among adults living with HIV from low- and middle-income countries: a cross-sectional study.

INTRODUCTION Liver disease is a leading cause of morbidity and mortality among persons living with HIV (PLHIV). While chronic viral hepatitis has been extensively studied in low- and middle-income countries (LMICs), there is limited information about the burden of metabolic disorders on liver disease in PLHIV. METHODS We conducted a cross-sectional analysis of baseline data collected between October 2020 and July 2022 from the IeDEA-Sentinel Research Network, a prospective cohort enrolling PLHIV ≥40 years on antiretroviral treatment (ART) for ≥6 months from eight clinics in Asia, Americas, and central, East, southern and West Africa. Clinical assessments, laboratory testing on fasting blood samples and liver stiffness measurement (LSM)/controlled attenuation parameter (CAP) by vibration-controlled transient elastography were performed. Multivariable logistic regression models assessed factors associated with liver fibrosis (LSM ≥7.1 kPa) and steatosis (CAP ≥248 dB/m). Population attributable fraction (PAF) of each variable associated with significant liver fibrosis was estimated using Levin's formula. RESULTS Overall, 2120 PLHIV (56% female, median age 50 [interquartile range: 45-56] years) were included. The prevalence of obesity was 19%, 12% had type 2 diabetes mellitus (T2DM), 29% had hypertension and 53% had dyslipidaemia. The overall prevalence of liver fibrosis and steatosis was 7.6% (95% confidence interval [CI] 6.1-8.4) and 28.4% (95% CI 26.5-30.7), respectively, with regional variability. Male sex at birth (odds ratio [OR] 1.62, CI 1.10-2.40), overweight/obesity (OR = 2.50, 95% CI 1.69-3.75), T2DM (OR 2.26, 95% CI 1.46-3.47) and prolonged exposure to didanosine (OR 3.13, 95% CI 1.46-6.49) were associated with liver fibrosis. Overweight/obesity and T2DM accounted for 42% and 11% of the PAF for liver fibrosis, while HBsAg and anti-HCV accounted for 3% and 1%, respectively. Factors associated with steatosis included overweight/obesity (OR 4.25, 95% CI 3.29-5.51), T2DM (OR 2.06, 95% CI 1.47-2.88), prolonged exposure to stavudine (OR 1.69, 95% CI 1.27-2.26) and dyslipidaemia (OR 1.68, 95% CI 1.31-2.16). CONCLUSIONS Metabolic disorders were significant risk factors for liver disease among PLHIV in LMICs. Early recognition of metabolic disorders risk factors might be helpful to guide clinical and lifestyle interventions. Further prospective studies are needed to determine the causative natures of these findings

Differences in HIV Natural History among African and Non-African Seroconverters in Europe and Seroconverters in Sub-Saharan Africa

Introduction It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. Methods We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. Results Of 1,959 (913 non-Africans, 302 Europeans - African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15–29 year old woman was 607 (588–627) (non-African European), 469 (442–497) (European - African origin) and 570 (551–589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228–289), 155 (110–200), and 199 (174–224) cells/µL (p<0.01). Discussion Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations

Ten-year attrition and antiretroviral therapy response among HIV-positive adults: a sex-based cohort analysis from eight West African countries

INTRODUCTION: Sex differences have already been reported in sub-Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow-up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults. METHODS: We used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no-follow-up and 10-year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively. RESULTS: A total of 71,283 patients (65.8% women) contributed to 310,007 person-years of follow-up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10-year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow-up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10-year attrition throughout the 10-year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow-up, whereas men failed to reach it even at the end of the 10-year follow-up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%). CONCLUSIONS: In West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex-adapted are needed for patients in care to monitor attrition, detect early high-risk groups so that they can stay in care with a durably controlled infection

Interest of a cohort of adult subjects with HIV infection estimated date in Sub-Saharan

L’infection par le VIH est caractérisée en l’absence d’intervention par une évolution progressive vers un état d’immunodépression favorisant la survenue d’affections opportunistes et entrainant le décès. La connaissance de l’évolution spontanée de l’infection par le VIH repose sur les données observationnelles issues des cohortes. La meilleure façon d’aborder l’histoire naturelle de cette infection est de l’étudier à partir de la date de séroconversion, ce qui ne peut se faire que dans les cohortes dites incidentes. Ces cohortes incidentes font appel à des structures parfois lourdes et des procédures rigoureuses que l’on peut plus aisément mettre en place dans les pays à ressources élevées. Les cohortes de personnes à date estimée de séroconversion permettent d’identifier les facteurs de risque de la transmission, d’étudier l’évolution de l’infection, d’étudier l’évolution de ses marqueurs et ses déterminants en minimisant le biais de sélection inhérent aux études prévalentes. L’évolution naturelle concerne la période qui s’écoule entre la date d’infection et le décès pour les patients qui n’ont pas bénéficié de prescription du traitement antirétroviral. Cette période s’arrête à la date de prescription des antirétroviraux pour ceux qui en bénéficient.La cohorte ANRS 1220 Primo-CI de personnes à date estimée de séroconversion pour le VIH-1 a été mise en place en juin 1997 sur le site de l'ANRS d'Abidjan en Côte d'Ivoire, au Centre national de transfusion sanguine (CNTS), avec la coordination de l'INSERM U330/593/897-ISPED de Bordeaux. C’est l’une des rares cohortes de séroconverteurs pour le VIH-1 dans le contexte des pays à faibles ressources et l’unique en Afrique de l’ouest. Dans cette cohorte de patients dépistés parmi les donneurs de sang effectuant plus de deux dons de sang par an, les données cliniques et biologiques ont été recueillies régulièrement pour tous les patients, tous les six mois depuis leur inclusion dans la cohorte.Les principaux apports de la cohorte Primo-CI dans la lutte contre le VIH en Côte d’Ivoire, ont consisté à recueillir des informations sur les facteurs de risque d’infection par le VIH pour aider à améliorer la sélection des donneurs de sang. La cohorte Primo-CI a permis d’améliorer également les capacités de la structure de prise en charge qui a servi de centre de recrutement et de prise en charge des patients de la cohorte. Cette cohorte a contribué à la mise en place d’un cadre d’échanges réguliers entre les médecins chargés de la sélection des dons de sang et l’équipe de la cohorte Primo-CI.Nos données ont fourni des estimations de la probabilité d'atteindre les critères d'initiation des antirétroviraux depuis le premier contact dans une population de séroconverteurs récents pour le VIH en Afrique de l’ouest et de la probabilité de survenue des événements morbides au cours du temps.L'ADN intracellulaire du VIH-1 était la variable la plus fortement associée à la progression de la maladie, indépendamment des autres variables explicatives. Il était suivi des lymphocytes CD4 avec une association plus faible. La charge virale plasmatique VIH-1 était faiblement associée à la progression de la maladie et ce après la prise en compte de l'ADN.La cohorte ANRS 1220 Primo-CI a participé à plusieurs travaux de collaborations portant sur les seuils d’éligibilité aux antirétroviraux, la comparaison de la baisse des lymphocytes CD4 avec des patients européens, la morbidité et la mortalité liées au SIDA et le rôle prédictif de l'ADN intracellulaire du VIH-1. Elle a également contribué à la réalisation de travaux scientifiques en virologie et immunologie qui ne portent pas sur l’objectif principal de ce travail.In the absence of any intervention, HIV infection is characterized by a gradual evolution towards a state of immunosuppression favoring the occurrence of opportunistic infections and causing death. The natural history of HIV infection is usually documented based on data from observational cohorts. But the best way to address the natural history of this infection is to observe subjects from the date of their seroconversion (within an “incident” cohort). However these incident cohorts often involve heavy structures and complex procedures that are more easily set-up in high-resources countries.Cohorts of individuals with estimated date of seroconversion can identify risk factors for HIV transmission, study the evolution of the infection, and study the evolution of its markers and determinants by minimizing the selection bias inherent in prevalent studies. The natural history of HIV is defined by the period between the date of infection and either the date of death for patients who were not prescribed antiretroviral therapy or the date of antiretroviral therapy prescription for others.The ANRS 1220 Primo-CI Cohort of people with a known date of HIV-1 seroconversion was launched in June 1997 in the site of the ANRS Abidjan in Côte d'Ivoire, National Blood Transfusion Centre (CNTS), with the coordination of U330/593/897-ISPED INSERM Bordeaux. This is one of the few adult cohorts of HIV-1 seroconverters in the context of low-resource countries and the only one in West Africa. Within this cohort of patients recruited among blood donors performing more than two blood donations per year, the clinical and laboratory data were collected routinely every six months from their inclusion.One of the main contributions of the Primo-CI cohort in the fight against HIV in Côte d’Ivoire was the collection of information on the risk factors for HIV infection. It helped to improve the selection of blood donors. It also helped to improve the capacity of the health structure where the cohort patients were recruited and followed-up.This cohort has contributed to establish a system for regular exchanges between physicians responsible for the selection of blood donations and the team of the Primo-CI cohort. Our data have provided estimates of the probability of reaching the criteria for initiating antiretroviral drugs from the first contact and the probability of occurrence of morbid events over time, in a population of recent HIV seroconverters in West Africa.The HIV-1 intracellular DNA was the variable most strongly associated with disease progression, independently of other variables. It was followed by lower CD4. Plasma viral load HIV-1 was poorly associated with disease progression after taking into account the HIV-1 intracellular DNA.Finally, the ANRS 1220 Primo-CI cohort participated in several collaborative studies regarding the threshold of eligibility for antiretroviral drugs, the comparison of the decrease in CD4 lymphocytes with European patients, morbidity and mortality related to AIDS and the predictive role of HIV-1 intracellular DNA. It also contributed to scientific studies in virology and immunology that do not concern the main objective of this work