Factors associated with verbal fluency in older adults living with HIV in West Africa: A longitudinal study.

OBJECTIVE: Verbal fluency decline, observed both in aging and HIV infection, has been related to lower quality of life. This study aimed to evaluate the factors associated with categorical fluency in people living with HIV (PLHIV) aged ≥60 years living in West Africa. METHODS: In this longitudinal study, PLHIV aged ≥60 years, on antiretroviral therapy (ART) for ≥6 months were included in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. Categorical fluency was evaluated with the Isaacs Set Test at 60 s at baseline and 2 years later. Factors associated with verbal fluency baseline performance and annual rates of changes were evaluated using multivariate linear regression models. RESULTS: Ninety-seven PLHIV were included with 41 of them (42%) having a 2-year follow-up visit. The median age was 64 (62-67), 45.4% were female, and 89.7% had an undetectable viral load. The median annual change in categorical fluency scores was -0.9 (IQR: -2.7 to 1.8). Low baseline categorical fluency performance and its decline were associated with older age and being a female. Low educational level was associated with low baseline categorical fluency performance but not with its decline. Categorical fluency decline was also associated with marital status and hypertension. CONCLUSIONS: Among older West African PLHIV, usual socio-demographic variables and hypertension were the main factors associated with low categorical fluency performance and/or its decline. Interventions that focus on supporting cardiometabolic health are highly recommended to prevent cognitive disorders in PLHIV.

Tobacco, alcohol, cannabis, and illicit drug use and their association with CD4/CD8 cell count ratio in people with controlled HIV: a cross-sectional study (ANRS CO3 AQUIVIH-NA-QuAliV).

BACKGROUND: To evaluate drug use (alcohol, tobacco, cannabis and other drugs) and its association with mean CD4/CD8 T cell count ratio, a marker of chronic inflammation, in virally suppressed people living with HIV-1 (PLWH) in Nouvelle Aquitaine, France. METHODS: A multi-centric, cross-sectional analysis was conducted in 2018-19 in the QuAliV study-ANRS CO3 AQUIVIH-NA cohort. Tobacco, alcohol, cannabis, and other drug use (poppers, cocaine, amphetamines, synthetic cathinones, GHB/GBL) were self-reported. CD4 and CD8 T cell counts and viral load measures, ± 2 years of self-report, and other characteristics were abstracted from medical records. Univariable and multivariable linear regression models, adjusted for age, sex, HIV risk group, time since HIV diagnosis, and other drug use were fit for each drug and most recent CD4/CD8 ratio. RESULTS: 660 PLWH, aged 54.7 ± 11.2, were included. 47.7% [315/660] had a CD4/CD8 ratio of < 1. Their mean CD4/CD8 ratio was 1.1 ± 0.6. 35% smoked; ~ 40% were considered to be hazardous drinkers or have alcohol use disorder; 19.9% used cannabis and 11.9% other drugs. Chemsex-associated drug users' CD4/CD8 ratio was on average 0.226 (95% confidence interval [95% CI] - 0.383, - 0.070) lower than that of non-users in univariable analysis (p = 0.005) and 0.165 lower [95% CI - 0.343, 0.012] in multivariable analysis (p = 0.068). CONCLUSIONS: Mean differences in CD4/CD8 ratio were not significantly different in tobacco, alcohol and cannabis users compared to non-users. However, Chemsex-associated drug users may represent a population at risk of chronic inflammation, the specific determinants of which merit further investigation. TRIAL REGISTRATION NUMBER: NCT03296202.

Barriers to early diagnosis of cervical cancer: a mixed-method study in Côte d'Ivoire, West Africa.

BACKGROUND: Cervical cancer, a major public health problem in many developing countries, is usually associated with a poor survival related to an advanced disease at diagnosis. In Côte d'Ivoire and other developing countries with high cervical cancer prevalence, little is known about factors associated with advanced cervical cancer stages in a context of limited access to screening services. METHODS: From May to July 2019, we conducted a cross-sectional study using a mixed, quantitative and qualitative method. Information on socio-demographic and history of the disease was extracted from a rapid case ascertainement study performed by the cancer registry of Côte d'Ivoire that enrolled all women diagnosed with cervical cancer between July 2018 and June 2019. In-depth semi-structured interviews were conducted among a subset of these women (12 women) and six healthcare providers to further capture barriers to early cervical cancer diagnosis. Factors associated with an advanced stage III, IV (according to FIGO classification) were estimated by a logistic regression model. Qualitative data were analyzed using a thematic analysis technique guided by the treatment pathway model and triangulated with quantitative data. RESULTS: In total, 95 women with cervical cancer [median age = 51 (IQR 42-59)] years, were included. Among them, 18.9% were living with HIV and only 9.5% were covered by a health insurance. The majority (71.5%) were diagnosed with advanced cervical cancer. Being HIV-uninfected (aOR = 5.4; [1.6-17.8], p = 0.006) and being uninsured (aOR = 13.1; [2.0-85.5], p = 0.007) were independently associated with advanced cervical cancer in multivariable analysis. Qualitative data raised additional factors potentially related to advanced cervical cancer stages at diagnosis, including the lack of patient information on cervical cancer by healthcare providers and inadequate national awareness and screening campaigns. CONCLUSION: In a context of challenges in access to systematic cervical cancer screening in Côte d'Ivoire, access to health insurance or integrated healthcare program appear to be key determinants of early diagnosis of cervical cancer.

Eliminating postnatal HIV transmission in high incidence areas: need for complementary biomedical interventions.

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies.

Early HIV treatment and survival over six years of observation in the ANRS 12249 Treatment as Prevention Trial.

OBJECTIVES: Population-based universal test and treat (UTT) trials have shown an impact on population-level virological suppression. We followed the ANRS 12249 TasP trial population for 6 years to determine whether the intervention had longer-term survival benefits. METHODS: The TasP trial was a cluster-randomized trial in South Africa from 2012 to 2016. All households were offered 6-monthly home-based HIV testing. Immediate antiretroviral therapy (ART) was offered through trial clinics to all people living with HIV (PLHIV) in intervention clusters and according to national guidelines in control clusters. After the trial, individuals attending the trial clinics were transferred to the public ART programme. Deaths were ascertained through annual demographic surveillance. Random-effects Poisson regression was used to estimate the effect of trial arm on mortality among (i) all PLHIV; (ii) PLHIV aware of their status and not on ART at trial entry; and (iii) PHLIV who started ART during the trial. RESULTS: Mortality rates among PLHIV were 9.3/1000 and 10.4/1000 person-years in the control and intervention arms, respectively. There was no evidence that the intervention decreased mortality among all PLHIV [adjusted rate ratio (aRR) = 1.10, 95% confidence interval (CI) = 0.85-1.43, p = 0.46] or among PLHIV who were aware of their status but not on ART. Among individuals who initiated ART, the intervention decreased mortality during the trial (aRR = 0.49, 95% CI = 0.28-0.85, p = 0.01), but not after the trial ended. CONCLUSIONS: The 'treat all' strategy reduced mortality among individuals who started ART but not among all PLHIV. To achieve maximum benefit of immediate ART, barriers to ART uptake and retention in care need to be addressed.

In utero exposure to antiretroviral drugs and pregnancy outcomes: Analysis of the French ANRS pharmacovigilance database.

AIMS: In 2018, 1.07 million pregnant women received antiretroviral drugs, raising whether this affects pregnancy outcomes. We assessed the adverse pregnancy outcomes associated with prenatal antiretroviral drug exposure, notified to the French ANRS pharmacovigilance system. METHODS: An exhaustive case report series has been performed using the ANRS pharmacovigilance database. All ANRS-sponsored HIV clinical research studies using antiretroviral drugs either in pregnant women or women of childbearing age were eligible from 2004 to 2019. We analysed the following pregnancy outcomes: abortion, ectopic pregnancy, stillbirth, prematurity (<37 weeks of gestational age), low birth weight (<2500 g) and congenital abnormalities. A logistic regression was performed to assess the odds ratio (OR) for each outcome separately (if occurrence >50) compared to the outcome observed when exposed to non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based regimen as the reference. RESULTS: Among the 34 studies selected, 918 deliveries occurred, of whom 88% had pregnancy outcomes documented. Pregnant women were mainly exposed to PI (n = 387, 48.6%), NNRTI (n = 331, 41.5%) and INI-based combinations (n = 40, 5.0%, 18 on dolutegravir). Compared to NNRTI-based combinations, there was no significant association observed with exposure to other antiretroviral combination for spontaneous abortion, prematurity or low birth weight, except an increased risk of low birth weight in new-born exposed to exclusive nucleoside-reverse-transcriptase-inhibitor (NRTI) combinations (n = 4; OR 7.50 [1.49-37.83]). CONCLUSIONS: Our study, mainly based on protease inhibitor (PI) and NNRTI-based regimens, is overall reassuring on the risk of adverse pregnancy outcomes, except for NRTI which should be interpreted cautiously (small number, indication bias). In this study, the number of integrase inhibitor (INI)-based combinations was too low to draw any conclusions.

Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus.

BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. CONCLUSIONS: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.

Chronic viral hepatitis, HIV infection and Non-Hodgkin lymphomas in West Africa, a case-control study.

Non-Hodgkin lymphomas (NHL) are underestimated causes of cancer in West Africa where chronic viral hepatitis and HIV are endemic. While the association with HIV infection has already been characterized, limited information is available on the association between chronic viral hepatitis and NHL in sub-Saharan Africa. A case-control study was conducted in referral hospitals of Abidjan (Cote d'Ivoire) and Dakar (Senegal). Cases of NHL were matched with controls on age, gender and participating site. The diagnosis of NHL relied on local pathological examination completed with immunohistochemistry. HIV, HBV and HCV serology tests were systematically performed. A conditional logistic regression model estimated the associations by the Odds Ratio (OR) with their 95% confidence interval (CI). A total of 117 NHL cases (Abidjan n = 97, Dakar n = 20) and their 234 matched controls were enrolled. Cases were predominantly men (68.4%) and had a median age of 50 years (IQR 37-57). While Diffuse Large B-cell lymphoma were the most reported morphological type (n = 35) among mature B-cell NHL, the proportion mature T-cell NHL (30%) was high. The prevalence figures of HBV, HCV and HIV infection were 12.8%, 7.7% and 14.5%, respectively among cases of NHL. In multivariate analysis, HBV, HCV and HIV were independently associated with NHL with OR of 2.23 (CI 1.05-4.75), 4.82 (CI 1.52-15.29) and 3.32 (CI 1.54-7.16), respectively. Chronic viral hepatitis B and C were significantly associated with NHL in West Africa. Timely preventive measures against HBV infection and access to curative anti-HCV treatment might prevent a significant number of NHL.

Human papilloma viruses infection among adolescent females perinatally infected with HIV in Côte d'Ivoire.

BACKGROUND: Cervical cancer prevention strategies recommend human papilloma virus (HPV) vaccination for female adolescents prior to their sexual debut. While HIV is a major risk factor for HPV infection in women of childbearing age, its prevalence among HIV-infected adolescent female is mostly unknown. This study aimed to describe the HPV prevalence and correlates among perinatally HIV-infected adolescent females prior to HPV immunisation. METHODS: A cross-sectional survey was conducted from January to June 2016, in the four major paediatric HIV clinics of Abidjan, Côte d'Ivoire. All HIV-infected females aged 11-16 years were approached to participate in the study. A questionnaire assessing sexual behaviours and genital hygiene practices was administered to participants completed with a systematic vaginal swab collection. HPV genotyping was performed using the Anyplex II HPV28 Detection (Seegene). A logistic regression analysis was performed to identify factors associated with the presence of HPV infection. HPV immunisation was proposed free of charge to all participants. RESULTS: A total of 250 participants were included, with a median age of 13 years (IQR 11-14). Among them, 237 (94.8%) were on antiretroviral treatment with a median CD4 count of 660 (IQR 439-914) cells/mm3. The overall prevalence of at least one HPV was 3.6% (95% CI 1.6 to 6.7) and the prevalence of at least one carcinogenic HPV was 2.8% (95% CI 0.7 to 4.8). Vaginal cleansing was reported by 75 (30%) of participants, with a median age at initiation of 12 years (IQR 10-13). Sexual activity was self-reported by 12 (4.8%) participants with a median age at sexual debut of 11 years (IQR 10-14). HPV infection was associated with vaginal cleansing (adjusted OR=7.0 (95% CI 1.4 to 31.6)). CONCLUSION: The reported low prevalence of carcinogenic HPV infections supports the appropriateness of HPV immunisation in this population. The reported association between cleansing practices and HPV infection deserves further prospective longitudinal studies.

Early ART Initiation Improves HIV Status Disclosure and Social Support in People Living with HIV, Linked to Care Within a Universal Test and Treat Program in Rural South Africa (ANRS 12249 TasP Trial).

We investigated the effect of early antiretroviral treatment (ART) initiation on HIV status disclosure and social support in a cluster-randomized, treatment-as-prevention (TasP) trial in rural South Africa. Individuals identified HIV-positive after home-based testing were referred to trial clinics where they were invited to initiate ART immediately irrespective of CD4 count (intervention arm) or following national guidelines (control arm). We used Poisson mixed effects models to assess the independent effects of (a) time since baseline clinical visit, (b) trial arm, and (c) ART initiation on HIV disclosure (n = 182) and social support (n = 152) among participants with a CD4 count > 500 cells/mm3 at baseline. Disclosure and social support significantly improved over follow-up in both arms. Disclosure was higher (incidence rate ratio [95% confidence interval]: 1.24 [1.04; 1.48]), and social support increased faster (1.22 [1.02; 1.46]) in the intervention arm than in the control arm. ART initiation improved both disclosure and social support (1.50 [1.28; 1.75] and 1.34 [1.12; 1.61], respectively), a stronger effect being seen in the intervention arm for social support (1.50 [1.12; 2.01]). Besides clinical benefits, early ART initiation may also improve psychosocial outcomes. This should further encourage countries to implement universal test-and-treat strategies.

Barriers influencing task-shifting for the management of depression in people living with HIV: a study from West Africa IeDEA cohort collaboration.

Depression is highly prevalent in people living with HIV (PLHIV) worldwide. As mental health specialists are scarce in sub-Saharan Africa (SSA), the World Health Organization (WHO) encourages task-shifting. We aimed to evaluate the barriers that could compromise task-shifting in front-line health care workers (HCWs) who provide HIV integrated care in West Africa. We collected knowledge, attitudes and practices (KAP) information on symptoms, causes and management of depression in PLHIV in care in four clinics in Senegal and Côte d'Ivoire (N = 168). The main barriers that could compromise task-shifting came from poor knowledge, particularly on symptoms and causes. Knowledge was more limited in HCWs other than medical doctors (good answers < 70%). The access to a depression training was limited (32.7%) and was the main factor associated to poor knowledge on depression. Even when social distance and barriers to practice were low (70.8% and 69.6%, respectively), some barriers persisted. More than half of respondents considered that diagnosis and management needed to be performed by a specialist. To guarantee the success of task-shifting, in the perspective of integrated care, efforts are needed to improve the access to specific training on depression considering screening, management, but also perceptions and attitudes, as some barriers subsist.

Human Immunodeficiency Virus/Hepatitis C Virus (HCV) Co-infected Patients With Cirrhosis Are No Longer at Higher Risk for Hepatocellular Carcinoma or End-Stage Liver Disease as Compared to HCV Mono-infected Patients.

It is widely accepted that human immunodeficiency virus (HIV) infection is a risk factor for increased severity of hepatitis C virus (HCV) liver disease. However, owing to better efficacy and safety of combination antiretroviral therapy (cART), and increased access to HCV therapy, whether this condition remains true is still unknown. Overall, 1,253 HCV mono-infected patients and 175 HIV/HCV co-infected patients with cirrhosis, included in two prospective French national cohorts (ANRS CO12 CirVir and CO13 HEPAVIH), were studied. Cirrhosis was compensated (Child-Pugh A), without past history of complication, and assessed on liver biopsy. Incidences of liver decompensation (LD), hepatocellular carcinoma (HCC), and death according to HIV status were calculated by a Fine-Gray model adjusted for age. Propensity score matching was also performed to minimize confounding by baseline characteristics. At baseline, HIV/HCV patients were younger (47.5 vs. 56.0 years; P < 0.001), more frequently males (77.1% vs. 62.3%; P < 0.001), and had at baseline and at end of follow-up similar rates of HCV eradication than HCV mono-infected patients. A total of 80.4% of HIV/HCV patients had an undetectable HIV viral load. After adjustment for age, 5-year cumulative incidences of HCC and decompensation were similar in HIV/HCV and HCV patients (8.5% vs. 13.2%, P = 0.12 and 12.8% vs. 15.6%, P = 0.40, respectively). Overall mortality adjusted for age was higher in HIV/HCV co-infected patients (subhazard ratio [SHR] = 1.88; 95% confidence interval [CI], 1.15-3.06; P = 0.011). Factors associated with LD and HCC were age, absence of sustained virological response, and severity of cirrhosis, but not HIV status. Using a propensity score matching 95 patients of each group according to baseline features, similar results were observed. Conclusion: In HCV-infected patients with cirrhosis, HIV co-infection was no longer associated with higher risks of HCC and hepatic decompensation. Increased mortality, however, persisted, attributed to extrahepatic conditions.

PMTCT care cascade and factors associated with attrition in the first four years after Option B+ implementation in Mozambique.

OBJECTIVE: To evaluate the effectiveness of the prevention of mother-to-child transmission (PMTCT) Option B+ programme in two provinces with high human immunodeficiency virus (HIV) burden in Mozambique over the first four years of programme implementation. METHODS: We assessed the PMTCT cascade in antenatal care (ANC) from July 2013 to December 2017 using facility-level data and performed a retrospective cohort analysis with patient-level data. We compared the 12-month antiretroviral therapy (ART) retention rates between women with HIV infection who initiated ART under Option B+ ('B+ pregnant') and those who initiated ART for their own health ('own health'). RESULTS: A total of 916 280 pregnant women enrolled in ANC. The proportion of women with a documented HIV status increased from 93% in 2013 to 96% in 2017. The proportion of those tested HIV-positive decreased from 8% to 6% while that of those HIV-positive on ART increased from 42% to 95%. Of the 44 377 HIV-positive women included in the analysis, 35% were lost to care. 'B+ pregnant' women initiating ART in 2015 were less likely to have no follow-up (NFU) compared with 'own health' women starting ART during the same period (adjusted odds ratio: 0.77, 95% confidence interval [CI]: 0.64-0.94, P = 0.01). There was no statistical difference between the two groups during the other years in which ART was initiated. Of those returning for care after their first visit (N = 39 801), the 'B+ pregnant' women showed a higher risk of non-retention than the other group (adjusted hazard ratio: 1.14, 95% CI: 1.03-1.25) when ART was initiated in 2013. The risk decreased during the subsequent years, with no difference observed between the groups. CONCLUSION: PMTCT Option B+ programme scale-up has yielded positive results, including the maintenance of high HIV testing and ART initiation rates in ANC. Challenges still remain, however, in improving immediate engagement in care and long-term retention. Seeking alternative service delivery models to support existing health systems and prevent defaulters is required to achieve the UNAIDS 95-95-95 targets for PMTCT in Mozambique.

OBJECTIF: Evaluer l'efficacité du programme de la prévention de la transmission mère-enfant (PTME) Option B+ dans deux provinces avec une charge élevée du virus de l' immunodéficience humaine (VIH) au Mozambique, au cours des quatre premières années de la mise en œuvre du programme. MÉTHODES: Nous avons évalué la cascade PTME dans les soins des cliniques prénatales (SCP) de juillet 2013 à décembre 2017 à l'aide de données à l'échelle de l'établissement et avons effectué une analyse de cohorte rétrospective avec des données à l'échelle du patient. Nous avons comparé les taux de rétention à 12 mois de la thérapie antirétrovirale (ART) entre les femmes infectées par le VIH qui ont commencé l'ART dans le cadre de l'option B+ (''enceintes B+'') et celles qui ont commencé l'ART pour leur propre santé (''propre santé''). RÉSULTATS: Au total, 916.280 femmes enceintes ont été inscrites dans les SCP. La proportion de femmes avec un statut VIH documenté est passée de 93% en 2013 à 96% en 2017. La proportion de celles testées positives pour le VIH est passée de 8% à 6% tandis que celle des femmes positives au VIH sous ART est passée de 42% à 95%. Sur les 44.377 femmes séropositives incluses dans l'analyse, 35% ont été perdues au cours des soins. Les femmes ''enceintes B+'' qui ont commencé l'ART en 2015 étaient moins susceptibles de ne pas avoir de suivi (NFU) que les femmes ''propre santé'' ayant commencé l'ART au cours de la même période (rapport de cotes ajusté: 0,77 ; intervalle de confiance à 95% [IC]: 0,64-0,94 ; P = 0,01). Il n'y avait aucune différence statistique entre les deux groupes durant les autres années au cours desquelles l'ART a été initiée. Parmi celles retournant pour des soins après leur première visite (N = 39.801), les femmes ''enceintes B+'' présentaient un risque plus élevé de non-rétention que l'autre groupe (rapport de risque ajusté: 1,14 ; IC95%: 1,03-1,25) lorsque l'ART a été initiée en 2013. Le risque diminuait au cours des années suivantes, sans différence observée entre les groupes. CONCLUSION: Le déploiement du programme PTME Option B+ a donné des résultats positifs, notamment le maintien de taux élevés de dépistage du VIH et d'initiation de l'ART dans les SCP. Il reste cependant des défis à relever pour améliorer l'engagement immédiat dans les soins et la rétention à long terme. La recherche de modèles de prestation de services alternatifs pour soutenir les systèmes de santé existants et prévenir les défaillances est nécessaire pour atteindre les objectifs de l'ONUSIDA 95-95-95 pour la PTME au Mozambique.

Assessing the psychometric properties of the French WHOQOL-HIV BREF within the ANRS CO3 Aquitaine Cohort's QuAliV ancillary study.

BACKGROUND: Antiretroviral therapy has prolonged the lives of those with human immunodeficiency virus (HIV), but the effects of chronic infection on their health-related quality of life (HRQoL) remain a concern. Numerous instruments have been developed to measure HRQoL, yet evidence of their cross-cultural equivalence and continued applicability is limited. We adapted the WHOQOL-HIV BREF to French and assessed its psychometric properties in a sample of community-dwelling adults living with HIV who were mostly virally suppressed. METHODS: We conducted a cross-sectional study within the ANRS CO3 Aquitaine cohort from July 2018 to May 2019. Five hundred eighty-six participants were consecutively enrolled at their HIV-consultations and completed either a web-based (n = 406) or paper self-administered assessment (n = 180). The means and standard deviations for items and domains were computed and the presence of floor and ceiling effects assessed. We evaluated internal consistency by calculating Cronbach's alpha coefficients per domain. We assessed construct validity by performing a Confirmatory Factor Analysis (CFA). Concurrent, convergent and discriminant validity were assessed with Pearson's correlations and known-group validity was assessed according to CD4 cell count, viral load, Centers for Disease Control and Prevention clinical categories for HIV, and hospitalization of more than 48 h within 2 years of the most recent consultation using one-way analysis of variance and independent t-tests. RESULTS: Five hundred eighty-six PLWH were included in this analysis. Their median age was 55; 73% were male; 85% were of French descent; 99% were on ART and 93% were virally suppressed. We found floor effects for one and ceiling effects for 11 items. Four of the six domains showed good internal consistency (α range: 0.63-0.79). CFA showed that the WHOQOL-HIV BREF's six-domain structure produced an acceptable fit (SRMR = 0.059; CFI = 0.834; RMSEA = 0.07; 90% CI: 0.06-0.08). It showed good concurrent, convergent and discriminant validity. There was some evidence of known-group validity. The personal beliefs domain had the highest score (15.04 ± 3.35) and the psychological health domain had the lowest (13.70 ± 2.78). CONCLUSIONS: The French WHOQOL-HIV BREF has acceptable measurement properties. Its broad conceptualisation of HRQoL, going beyond physical and mental health, may be of particular value in our older, treatment-experienced and virally suppressed population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03296202 (Archived by WebCite at http://www.webcitation.org/6zgOBArps ).

Prevalence and factors associated with severe depressive symptoms in older west African people living with HIV.

BACKGROUND: Depression is one of the most common psychiatric disorders in people living with HIV (PLHIV). Depression has a negative impact on both mental and physical health and is mainly associated with suboptimal HIV treatment outcomes. To encourage successful aging and the achievement of the 3 × 90 objectives in older PLHIV, the psychological domain must not be neglected. In this context and as data are scarce in West Africa, this study aimed to evaluate the prevalence and the factors associated with severe depressive symptoms in older PLHIV living in this region of the world. METHODS: Data from PLHIV aged ≥50 years and on ART since ≥6 months were collected in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. The severity of depressive symptoms was measured using the Center for Epidemiological Studies Depression scale (CES-D), and associated factors were identified using logistic regressions. RESULTS: The median age of the 334 PLHIV included in the study was 56.7 (53.5-61.1), 57.8% were female, and 87.1% had an undetectable viral load. The prevalence of severe depressive symptoms was 17.9% [95% Confidence Interval (95% CI): 13.8-22.0]. PLHIV with severe depressive symptoms were more likely to be unemployed (adjusted Odd Ratio (aOR) = 2.8; 95% CI: 1.4-5.7), and to be current or former tobacco smokers (aOR = 2.6; 95% CI: 1.3-5.4) but were less likely to be overweight or obese (aOR = 0.4; 95% CI: 0.2-0.8). CONCLUSIONS: The prevalence of severe depressive symptoms is high among older PLHIV living in West Africa. Unemployed PLHIV and tobacco smokers should be seen as vulnerable and in need of additional support. Further studies are needed to describe in more details the reality of the aging experience for PLHIV living in SSA. The integration of screening and management of depression in the standard of care of PLHIV is crucial.

Measuring retention in care for HIV-positive pregnant women in Prevention of Mother-to-Child Transmission of HIV (PMTCT) option B+ programs: the Mozambique experience.

BACKGROUND: Failure to retain HIV-positive pregnant women on antiretroviral therapy (ART) leads to increased mortality for the mother and her child. This study evaluated different retention measures for women's engagement along the continuum of care for prevention of mother-to-child transmission (PMTCT) option B+ services in Mozambique. METHODS: We compared 'point' retention (patient's presence in care 12-month post-ART initiation or any time thereafter) with the following definitions: alive and in care 12 month post-ART initiation (Ministry of Health; MOH); attendance at a health facility up to 15-month post-ART initiation (World Health Organization; WHO); alive and in treatment at 1-, 2-, 3-, 6-, 9-, and 12-month post-ART initiation (Inter-Agency Task Team; IATT); and alive and in care 12-month post-ART initiation with ≥75% appointment adherence during follow-up (i.e. 'appointment adherence' retention) or with ≥75% of appointments met on time during follow-up (i.e. 'on-time adherence' retention). Kaplan-Meier survival curves were produced to assess variability in retention rates. We used 'on-time adherence' retention as our reference to estimate sensitivity, specificity, and proportion of misclassified patients. RESULTS: Considering the 'point' retention definition, 16,840 HIV-positive pregnant women enrolled in option B+ PMTCT services were identified as 'retained in care' 12-month post-ART initiation. Of these, 60.3% (95% CI 59.6-61.1), 84.8% (95% CI 84.2-85.3), and 16.4% (95% CI 15.8-17.0) were classified as 'retained in care' using MOH, WHO, and IATT definitions, respectively, and 1.2% (95% CI 1.0-1.4) were classified as 'retained in care' using the '≥75% on-time adherence' definition. All definitions provided specificity rates of ≥98%. The sensitivity rates were 3.0% with 78% of patients misclassified according to the WHO definition and 4.3% with 54% of patients misclassified according to the MOH definition. The 'point' retention definition misclassified 97.6% of patients. Using IATT and 'appointment adherence' retention definitions, sensitivity rates (9.0 and 11.7%, respectively) were also low; however, the proportion of misclassified patients was smaller (15.9 and 18.3%, respectively). CONCLUSION: More stringent definitions indicated lower retention rates for PMTCT programs. Policy makers and program managers should include attendance at follow-up visits when measuring retention in care to better guide planning, scale-up, and monitoring of interventions.

Impact of Next-generation Sequencing Defined Human Immunodeficiency Virus Pretreatment Drug Resistance on Virological Outcomes in the ANRS 12249 Treatment-as-Prevention Trial.

BACKGROUND: Previous studies in human immunodeficiency virus (HIV)-positive individuals on thymidine analogue backbone antiretroviral therapy (ART) with either nevirapine or efavirenz have suggested poorer virological outcomes in the presence of pretreatment drug resistance (PDR). We assessed the impact of PDR on virological suppression (VS; <50 copies/mL) in individuals prescribed primarily tenofovir/emtricitabine/efavirenz in rural KwaZulu-Natal within a treatment-as-prevention trial. METHODS: Among 1557 HIV-positive individuals who reported no prior ART at study entry and provided plasma samples, 1328 individuals with entry viral load (VL) >1000 copies/mL had next-generation sequencing (NGS) of the HIV pol gene with MiSeq technology. Results were obtained for 1148 individuals, and the presence of PDR was assessed at 5% and 20% detection thresholds. Virological outcome was assessed using Cox regression in 837 of 920 ART initiators with at least 1 follow-up VL after ART initiation. RESULTS: PDR prevalence was 9.5% (109/1148) and 12.8% (147/1148) at 20% and 5% thresholds, respectively. After a median of 1.36 years (interquartile range, 0.91-2.13), mostly on fixed-dose combination tenofovir/emtricitabine/efavirenz, presence of both nonnucleoside reverse transcriptase inhibitor (NNRTI)/nucleoside reverse transcriptase inhibitor PDR vs no PDR was associated with longer time to VS (adjusted hazard ratio [aHR], 0.32; 95% confidence interval [CI], 0.12-0.86), while there was no difference between those with only NNRTI PDR vs no PDR (aHR, 1.05; 95% CI, 0.82-1.34) at the 5% threshold. Similar differences were observed for mutations detected at the 20% threshold, although without statistical significance. CONCLUSIONS: NGS uncovered a high prevalence of PDR among participants enrolled in trial clinics in rural KwaZulu-Natal. Dual-class PDR to a mainly tenofovir/emtricitabine/efavirenz regimen was associated with poorer VS. However, there was no impact of NNRTI PDR alone. CLINICAL TRIALS TEGISTRATION: NCT01509508; South African National Clinical Trials Register: DOH-27-0512-3974.

Incidence of hepatocellular carcinoma in HIV/HBV-coinfected patients on tenofovir therapy: Relevance for screening strategies.

BACKGROUND & AIMS: Robust data on hepatocellular carcinoma (HCC) incidence among HIV/hepatitis B virus (HBV)-coinfected individuals on antiretroviral therapy (ART) are needed to inform HCC screening strategies. We aimed to evaluate the incidence and risk factors of HCC among HIV/HBV-coinfected individuals on tenofovir disoproxil fumarate (TDF)-containing ART in a large multi-cohort study. METHODS: We included all HIV-infected adults with a positive hepatitis B surface antigen test followed in 4 prospective European cohorts. The primary outcome was the occurrence of HCC. Demographic and clinical information was retrieved from routinely collected data, and liver cirrhosis was defined according to results from liver biopsy or non-invasive measurements. Multivariable Poisson regression was used to assess HCC risk factors. RESULTS: A total of 3,625 HIV/HBV-coinfected patients were included, of whom 72% had started TDF-containing ART. Over 32,673 patient-years (py), 60 individuals (1.7%) developed an HCC. The incidence of HCC remained stable over time among individuals on TDF, whereas it increased steadily among those not on TDF. Among individuals on TDF, the incidence of HCC was 5.9 per 1,000 py (95% CI 3.60-9.10) in cirrhotics and 1.17 per 1,000 py (0.56-2.14) among non-cirrhotics. Age at initiation of TDF (adjusted incidence rate ratio per 10-year increase: 2.2, 95% CI 1.6-3.0) and the presence of liver cirrhosis (4.5, 2.3-8.9) were predictors of HCC. Among non-cirrhotic individuals, the incidence of HCC was only above the commonly used screening threshold of 2 cases per 1,000 py in patients aged >45 years old at TDF initiation. CONCLUSIONS: Whereas the incidence of HCC was high in cirrhotic HIV/HBV-coinfected individuals, it remained below the HCC screening threshold in patients without cirrhosis who started TDF aged <46 years old. LAY SUMMARY: We investigated the incidence of hepatocellular carcinoma in HIV/hepatitis B virus-coinfected individuals from a large multi-cohort study in Europe. Over 32,673 patient-years, 60 individuals (1.7%) developed hepatocellular carcinoma. The incidence of hepatocellular carcinoma remained low in patients without cirrhosis, who started on tenofovir disoproxil fumarate when aged <46 years old.

Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART.

Objectives: The WHO recently recommended the use of a new first-line ART containing dolutegravir. We investigated the efficacy of NRTI backbones (tenofovir or abacavir with a cytosine analogue) in low- and middle-income countries where there is significant prior exposure to antiretrovirals and drug resistance to NRTIs. Methods: Within the treatment-as-prevention study in South Africa, we selected participants with available next-generation sequencing (NGS) data for the HIV-1 pol gene at trial entry; they were either ART initiators (n = 1193) or already established on ART (n = 94). NGS of the HIV-1 pol gene was carried out using MiSeq technology; reverse transcriptase drug resistance mutations (DRMs) were detected at 5% (DRM5%) and 20% (DRM20%) for all 1287 participants. Genotypic susceptibility was assessed using the Stanford HIVDB resistance interpretation algorithm. Results: NRTI DRM20% and DRM5% were detected among 5/1193 (0.4%) and 9/1193 (0.8%) of ART initiators, respectively. There was tenofovir exposure in 73/94 (77.7%) of those established on ART, with full susceptibility to abacavir in 57/94 (60.6%) and 56/94 (59.6%) for DRM20% and DRM5%, respectively, while 67/94 (71.3%) and 64/94 (68.1%) were fully susceptible to tenofovir, respectively. The differences between tenofovir and abacavir were not statistically significant at the 20% or 5% variant level (P = 0.16 and 0.29, respectively). NGS detection of variants at the 5% level increased detection of K65R in both naive and treated groups. One of 607 integrase sequences carried a DRM20% (Q148R). Conclusions: Dolutegravir with a cytosine analogue plus tenofovir or abacavir appears to have similar efficacy in South Africans naive to ART. NGS should be considered in HIV drug resistance surveillance.

Contribution of Maternal Antiretroviral Therapy and Breastfeeding to 24-Month Survival in Human Immunodeficiency Virus-Exposed Uninfected Children: An Individual Pooled Analysis of African and Asian Studies.

Background: Human immunodeficiency virus (HIV)-infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on ART may improve survival, although this has not been reliably quantified. Methods: Individual data on 19 219 HEU children from 21 PMTCT trials/cohorts undertaken from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" were used to estimate the relative contribution of risk factors to overall mortality. Results: Cumulative incidence of death was 5.5% (95% confidence interval, 5.1-5.9) by age 24 months. Low birth weight (LBW <2500 g, adjusted hazard ratio (aHR, 2.9), no breastfeeding (aHR, 2.5), and maternal death (aHR, 11.1) were significantly associated with increased mortality. Maternal ART (aHR, 0.5) was significantly associated with lower mortality. At the population level, LBW accounted for 16.2% of 24-month mortality, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; combined, these factors explained 63.6% of deaths by age 24 months. Conclusions: Survival of HEU children could be substantially improved if public health practices provided all HIV-infected mothers with ART and supported optimal infant feeding and care for LBW neonates.