Epidaure Market-Effectiveness and transferability of a school-based intervention to improve healthy and sustainable food choices by schoolchildren: Protocol of a randomized controlled trial and qualitative study.

CONTEXT: At least 40% of cancers are linked to environmental or behavioral factors, and dietary behavior appears to be a major lever. Epidaure Market is a prevention initiative developed using a method for co-constructing health promotion initiatives and prevention programs that stratifies evidence from the scientific literature and combines it with experiential knowledge (DEVA, TPB, BCT). It promotes a sustainable diet (i.e., healthy, ecological and ethical nutrition) among 5th and 4th grade students during the crucial period of adolescence, when these behaviors are often far from the recommendations. METHOD: The protocol implemented was carried out in 72 middle school classes in the Montpellier and Dijon academies. The intervention included teaching sessions and a virtual supermarket game, integrated into the school curriculum and delivered by science teachers. Effectiveness is tested in a cluster randomized controlled trial with 3 evaluation times (pre- and post-intervention and 1 follow-up). The study also includes an implementation assessment, with process analysis and implementation elements, as well as a transferability assessment based on key functions (FIC model and Astaire grid). EXPECTED OUTCOMES: The study is still underway within the school. The primary expected outcome is a positive influence on the motives underlying food choices to move towards a sustainable diet. Secondary expectations involve changes in variables such as self-efficacy and perceived social norms, as well as an increase in knowledge about healthy eating. We also expect the qualitative approaches to provide information on the deployment process in the new territories. DISCUSSION: The study aims not only to demonstrate the effectiveness of Epidaure Market, but also to identify the optimal conditions for its nationwide implementation in France's middle schools. Ultimately, the initiative aims to help reduce the incidence of cancer by promoting healthier eating habits among teenagers.

Corrigendum to 'Defining a Dichotomous Indicator for Population-Level Assessment of Dietary Diversity Among Pregnant Adolescent Girls and Women: ' [Curr. Dev. Nutr. 8 (2024) 102053].

[This corrects the article DOI: 10.1016/j.cdnut.2023.102053.].

Prevalence of pretreatment HIV resistance to integrase inhibitors in West African and Southeast Asian countries.

OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. MATERIALS AND METHODS: Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. RESULTS: We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. CONCLUSIONS: Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class.

Defining a Dichotomous Indicator for Population-Level Assessment of Dietary Diversity Among Pregnant Adolescent Girls and Women: A Secondary Analysis of Quantitative 24-h Recalls from Rural Settings in Bangladesh, Burkina Faso, India, and Nepal.

Background: The Minimum Dietary Diversity for Women of Reproductive Age (MDD-W) indicator was validated as a proxy of micronutrient adequacy among nonpregnant women in low- and middle-income countries (LMICs). At that time, indeed, there was insufficient data to validate the indicator among pregnant women, who face higher micronutrient requirements. Objective: This study aimed to validate a minimum food group consumption threshold, out of the 10 food groups used to construct MDD-W, to be used as a population-level indicator of higher micronutrient adequacy among pregnant women aged 15-49 y in LMICs. Methods: We used secondary quantitative 24-h recall data from 6 surveys in 4 LMICs (Bangladesh, Burkina Faso, India, and Nepal, total n = 4909). We computed the 10-food group Women's Dietary Diversity Score (WDDS-10) and calculated the mean probability of adequacy (MPA) of 11 micronutrients. Linear regression models were fitted to assess the associations between WDDS-10 and MPA. Sensitivity, specificity, and proportion of individuals correctly classified were used to assess the performance of MDD-W in predicting an MPA of >0.60. Results: In the pooled sample, median values (interquartile range) of WDDS-10 and MPA were 3 (1) and 0.20 (0.34), respectively, whereas the proportion of pregnant women with an MPA of >0.60 was 9.6%. The WDDS-10 was significantly positively associated with MPA in each survey. Although the acceptable food group consumption threshold varied between 4 and 6 food groups across surveys, the threshold of 5 showed the highest performance in the pooled sample with good sensitivity (62%), very good specificity (81%), and percentage of correctly classified individuals (79%). Conclusions: The WDDS-10 is a good predictor of dietary micronutrient adequacy among pregnant women aged 15-49 y in LMICs. Moreover, the threshold of 5 or more food groups for the MDD-W indicator may be extended to all women of reproductive age, regardless of their physiologic status.

Urban nutrition situation in the slums of three cities in Asia during the COVID-19 pandemic.

Urban-poor households are disproportionately food insecure. The Status and Determinants of Food Insecurity and Undernutrition in Poor Urban Settings (SDFU) cross-sectional surveys were conducted in 2020-2021 to assess the impacts of COVID-19 on food security and diet quality among urban poor women of reproductive age (WRA) and children under 5 (CU5) in Jakarta, Quezon City, and Yangon. Data, collected on food insecurity and child and maternal diet quality using Computer Assisted Telephone Interviewing (CATI), were compared with prepandemic surveys. Prevalence for food insecurity and diet quality indicators were computed. Eight in 10 households in all three cities reported reduced incomes, with 6 in 10 worried about food the previous year. Over 10% of households in all cities substituted nutrient-dense (ND) foods with cheaper alternatives; yet less than 50% of children 6-59 months ate sugar-sweetened beverages or sweet and savoury snacks. Compared with baseline, women's minimum dietary diversity (MDD) in the three cities was significantly lower (up to 30% lower in Yangon and Jakarta), while the prevalence of children (6-23 months) meeting MDD was lower by 17.4%-42.5% in all cities. MDD was attained by >40% of children (24-59 months) in Yangon and Jakarta but only 12.6% in Quezon City. To improve food security and diet quality, multi-sectoral interventions are needed, including distributing ND foods and cash assistance to vulnerable households with CU5 and WRA and delivering targeted nutrition training to encourage appropriate complementary feeding practices and purchasing and consumption of ND foods.

Exploring the magnitude and drivers of the double burden of malnutrition at maternal and dyad levels in peri-urban Peru: A cross-sectional study of low-income mothers, infants and young children.

Multiple forms of malnutrition coexist in Peru, especially in peri-urban areas and poor households. We investigated the magnitude of, and the contribution of, dietary and socio-demographic factors to the double burden of malnutrition (DBM) at maternal (i.e., maternal overweight/obesity with anaemia) and dyad (i.e., maternal overweight/obesity with child anaemia) levels. A cross-sectional survey was conducted among low-income mother-child (6-23 months) dyads (n = 244) from peri-urban communities in Peru. Dietary clusters and the minimum dietary diversity score (MDD) were generated for mothers and infants, respectively. A composite indicator using the maternal dietary clusters and the MDD was created to relate to dyad level DBM. Two dietary clusters were found: (i) the 'high variety (i.e., animal-source foods, fruit and vegetables), high sugary foods/beverages' (cluster 1) and (ii) the 'high potato, low fruit and vegetables, low red meat' (cluster 2). DBM prevalence among mothers and dyads was 19.9% and 36.3%, respectively. Logistic regression analyses revealed that the only socio-demographic factor positively associated with maternal DBM was maternal age (aOR/5 years: 1.35 [1.07, 1.71]). Mothers belonging to diet cluster 1 were less likely to experience the DBM (aOR = 0.52 [0.26, 1.03]), although CIs straddled the null. Socio-demographic factors positively associated with dyad level DBM included maternal age (aOR/5 years: 1.41 [1.15, 1.73]), and having ≥ two children under 5 years (aOR = 2.44 [1.23, 4.84]). Diet was not associated with dyad-level DBM. Double-duty actions that tackle the DBM are needed given that one-third of dyads and a fifth of mothers had concurrent overweight/obesity and anaemia.

Prevention of mother-to-child transmission of HIV at the second immunization visit: a cross-sectional study, Burkina Faso.

Objective: To evaluate the performance of the cascade of activities for prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) at the second immunization visit in Burkina Faso. Methods: In a cross-sectional study, we recruited mothers attending the second immunization visit for their infant in 20 health centres of Bobo-Dioulasso city, Burkina Faso over 12 months (2019-2020). We administered a short questionnaire to 14 176 mothers and performed HIV serological tests on mothers who had not been tested in the last 3 months. All mothers were asked about their attendance for antenatal care and HIV rapid testing. HIV-infected mothers were also asked about the timing of their HIV diagnosis, antiretroviral therapy, pre-exposure prophylaxis initiation at birth and infant diagnosis of HIV. Findings: Of 14 136 respondents, 13 738 (97.2%) had at least one HIV serological test in their lifetime. Of 13 078 mothers who were never tested or were HIV-negative, 12 454 (95.2%) were tested during or after their last pregnancy. Among HIV-infected mothers already aware of their status, 110/111 (99.1%) women were on antiretroviral therapy. Among HIV-exposed infants, 84/101 (83.2%) babies received 6 weeks of antiretroviral prophylaxis at birth and 58/110 (52.7%) had a blood sample collected for early infant diagnosis. Only two mothers received their child's test results at the time of the second immunization visit. Four mothers were newly diagnosed as HIV-positive during the study. Conclusion: Collecting data at the second immunization visit, a visit rarely missed by mothers, could be useful for identifying gaps in the PMTCT cascade in settings where mothers are difficult to reach, such as in low-income countries with intermediate or low HIV prevalence.

APOL1 Renal Risk Variants and Kidney Function in HIV-1-Infected People From Sub-Saharan Africa.

Introduction: APOL1 G1 and G2 alleles have been associated with kidney-related outcomes in people living with HIV (PLHIV) of Black African origin. No APOL1-related kidney risk data have yet been reported in PLHIV in West Africa, where high APOL1 allele frequencies have been observed. Methods: We collected clinical data from PLHIV followed in Burkina Faso (N = 413) and in the ANRS-12169/2LADY trial (Cameroon, Senegal, Burkina Faso, N = 369). APOL1 G1 and G2 risk variants were genotyped using TaqMan assays, and APOL1 high-risk (HR) genotype was defined by the carriage of 2 risk alleles. Results: In West Africa (Burkina Faso and Senegal), the G1 and G2 allele frequencies were 13.3% and 10.7%, respectively. In Cameroon (Central Africa), G1 and G2 frequencies were 8.7% and 8.9%, respectively. APOL1 HR prevalence was 4.9% in West Africa and 3.4% in Cameroon. We found no direct association between APOL1 HR and estimated glomerular filtration rate (eGFR) change over time. Nevertheless, among the 2LADY cohort participants, those with both APOL1 HR and high baseline viral load had a faster eGFR progression (ß = -3.9[-7.7 to -0.1] ml/min per 1.73 m2 per year, P < 0.05) than those with low-risk (LR) genotype and low viral load. Conclusion: Overall, the APOL1 risk allele frequencies in PLHIV were higher in the West African countries than in Cameroon, but much lower than previously reported in some Nigeria ethnic groups, which strongly advocates for further investigation in the African continent. This study suggested that the virological status could modulate the APOL1 impact on kidney function, hence reinforcing the need for early therapeutic interventions.

Diet and food insecurity among mothers, infants, and young children in Peru before and during COVID-19: A panel survey.

The COVID-19 pandemic may impact diet and nutrition through increased household food insecurity, lack of access to health services, and poorer quality diets. The primary aim of this study is to assess the impact of the pandemic on dietary outcomes of mothers and their infants and young children (IYC) in low-income urban areas of Peru. We conducted a panel study, with one survey prepandemic (n = 244) and one survey 9 months after the onset of COVID-19 (n = 254). We assessed breastfeeding and complementary feeding indicators and maternal dietary diversity in both surveys. During COVID-19, we assessed household food insecurity experience and economic impacts of the pandemic on livelihoods; receipt of financial or food assistance, and uptake of health services. Almost all respondents (98.0%) reported adverse economic impacts due to the pandemic and 46.9% of households were at risk of moderate or severe household food insecurity. The proportion of households receiving government food assistance nearly doubled between the two surveys (36.5%-59.5%). Dietary indicators, however, did not worsen in mothers or IYC. Positive changes included an increase in exclusive breastfeeding <6 months (24.2%-39.0%, p < 0.008) and a decrease in sweet food consumption by IYC (33.1%-18.1%, p = 0.001) and mothers (34.0%-14.6%, p < 0.001). The prevalence of sugar-sweetened beverage consumption remained high in both mothers (97%) and IYC (78%). In sum, we found dietary indicators had not significantly worsened 9 months into the COVID-19 pandemic. However, several indicators remain suboptimal and should be targeted in future interventions.

Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.

Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction. At week-50, telomere shortening was observed among 44.3% of CHEU, irrespective of the prophylactic treatment. Furthermore, this telomere shortening was neither associated with poor growth indicators nor neuropsychological outcomes at year-6, except for motor abilities (MABC test n = 127, ß = -3.61, 95%CI: -7.08, -0.14; p = 0.04). Safety data on telomere shortening for infant HIV prophylaxis are scarce. Its association with reduced motor abilities deserves further attention among CHEU but also HIV-infected children receiving ARV treatment.

Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso.

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols.

Community intervention for child tuberculosis active contact investigation and management: study protocol for a parallel cluster randomized controlled trial.

BACKGROUND: There are major gaps in the management of pediatric tuberculosis (TB) contact investigation for rapid identification of active tuberculosis and initiation of preventive therapy. This study aims to evaluate the impact of a community-based intervention as compared to facility-based model for the management of children in contact with bacteriologically confirmed pulmonary TB adults in low-resource high-burden settings. METHODS/DESIGN: This multicenter parallel open-label cluster randomized controlled trial is composed of three phases: I, baseline phase in which retrospective data are collected, quality of data recording in facility registers is checked, and expected acceptability and feasibility of the intervention is assessed; II, intervention phase with enrolment of index cases and contact cases in either facility- or community-based models; and III, explanatory phase including endpoint data analysis, cost-effectiveness analysis, and post-intervention acceptability assessment by healthcare providers and beneficiaries. The study uses both quantitative and qualitative analysis methods. The community-based intervention includes identification and screening of all household contacts, referral of contacts with TB-suggestive symptoms to the facility for investigation, and household initiation of preventive therapy with follow-up of eligible child contacts by community healthcare workers, i.e., all young (< 5 years) child contacts or older (5-14 years) child contacts living with HIV, and with no evidence of TB disease. Twenty clusters representing TB diagnostic and treatment facilities with their catchment areas are randomized in a 1:1 ratio to either the community-based intervention arm or the facility-based standard of care arm in Cameroon and Uganda. Randomization was stratified by country and constrained on the number of index cases per cluster. The primary endpoint is the proportion of eligible child contacts who initiate and complete the preventive therapy. The sample size is of 1500 child contacts to identify a 10% difference between the arms with the assumption that 60% of children will complete the preventive therapy in the standard of care arm. DISCUSSION: This study will provide evidence of the impact of a community-based intervention on household child contact screening and management of TB preventive therapy in order to improve care and prevention of childhood TB in low-resource high-burden settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03832023 . Registered on 6 February 2019.

Deep sequencing analysis of M184V/I mutation at the switch and at the time of virological failure of boosted protease inhibitor plus lamivudine or boosted protease inhibitor maintenance strategy (substudy of the ANRS-MOBIDIP trial).

BACKGROUND: The ANRS12286/MOBIDIP trial showed that boosted protease inhibitor (bPI) plus lamivudine dual therapy was superior to bPI monotherapy as maintenance treatment in subjects with a history of M184V mutation. OBJECTIVES: We aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF). METHODS: Ultra-deep sequencing (UDS) was performed on proviral HIV-DNA at inclusion among 265 patients enrolled in the ANRS 12026/MOBIDIP trial, and on plasma from 31 patients experiencing VF. The proportion of M184V/I variants was described and the association between the M184V/I mutation at 1% of threshold and VF was explored with logistic regression models. RESULTS: M184V and I mutations were detected in HIV-DNA for 173/252 (69%) and 31/252 (12%) of participants, respectively. Longer duration of first-line treatment, higher plasma viral load at first-line treatment failure and higher baseline HIV-DNA load were associated with the archived M184V. M184I mutation was always associated with a STOP codon, suggesting defective virus. The 48 week estimated probability of remaining free from VF was comparable with or without the M184V/I mutation for dual therapy. At failure, M184V and major PI mutations were detected in 1/17 and 5/15 patients in the bPI arm and in 2/2 and 0/3 in the bPI+lamivudine arm, respectively. CONCLUSIONS: Using UDS evidenced that archiving of M184V in HIV-DNA is heterogeneous despite past historical M184V in 96% of cases. The antiviral efficacy of lamivudine-based dual therapy regimens is mainly due to the residual lamivudine activity.

Health Outcomes at School Age among Children Who Are HIV-Exposed but Uninfected with Detected Mitochondrial DNA Depletion at One Year.

Infant antiretroviral (ARV) prophylaxis given to children who are human immunodeficiency virus (HIV)-exposed but uninfected (CHEU) to prevent HIV transmission through breastfeeding previously proved its efficacy in the fight against the pediatric epidemic. However, few studies have investigated the short- and long-term safety of prophylactic regimens. We previously reported a decrease of mitochondrial DNA (mtDNA) content among CHEU who received one year of lamivudine (3TC) or lopinavir-boosted ritonavir (LPV/r) as infant prophylaxis. We aimed to describe mtDNA content at six years of age among these CHEU, including those for whom we identified mtDNA depletion at week 50 (decrease superior or equal to 50% from baseline), and to compare the two prophylactic drugs. We also addressed the association between mtDNA depletion at week 50 with growth, clinical, and neuropsychological outcomes at year 6. Quantitative PCR was used to measure mtDNA content in whole blood of CHEU seven days after birth, at week 50, and at year 6. Among CHEU with identified mtDNA depletion at week 50 (n = 17), only one had a persistent mtDNA content decrease at year 6. No difference between prophylactic drugs was observed. mtDNA depletion was not associated with growth, clinical, or neuropsychological outcomes at year 6. This study brought reassuring data concerning the safety of infant 3TC or LPV/r prophylaxis.

Evaluating family physicians' willingness to prescribe PrEP.

INTRODUCTION: We assessed family physicians' (FP) willingness to integrate PrEP into their clinical practice in Montpellier and its surroundings. METHOD: We aimed to randomly assess 92 FPs. RESULTS: Ninety-six FPs were interviewed from May to December 2018: 78% (95% CI [69; 86]) were willing to integrate PrEP, 65% to be trained, and 52% to be the first providers. Of the 65 (6%) with some knowledge of PrEP, 21 were not aware of targeted populations and 39 never talked about PrEP with their patients. Nearly all FPs declared HIV prevention as part of their job and felt at ease talking about sexuality. Considering HIV prevention as part of their job was associated with increased likelihood to integrate PrEP into their practice (P=0.015). CONCLUSIONS: Most FPs were willing to integrate and be trained on PrEP. Lack of PrEP prescription seemed related to a lack of knowledge.

Hepatitis B testing, treatment, and virologic suppression in HIV-infected patients in Cameroon (ANRS 12288 EVOLCAM).

BACKGROUND: Hepatitis B is a major concern in Africa, especially in HIV-infected patients. Unfortunately, access to hepatitis B virus (HBV) testing and adequate treatment remains a challenge in the continent. We investigated HBV testing, treatment, and virologic suppression in HIV-infected patients followed up as part of Cameroon's national antiretroviral programme. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in 19 hospitals in the Centre and Littoral regions in Cameroon. The proportions of patients tested for hepatitis B surface antigen (HBsAg) prior to the study were compared among all study hospitals using the Chi-square test. The association of individual and hospital-related characteristics with HBV testing and virologic suppression was assessed using multilevel logistic regression models. RESULTS: Of 1706 patients (women 74%, median age 42 years, median time on ART 3.9 years), 302 (17.7%) had been tested for HBsAg prior to the study. The proportion of HBV-tested patients ranged from 0.8 to 72.5% according to the individual hospital (p < 0.001). HBV testing was lower in women (adjusted odds ratio [aOR] 0.64, 95% confidence interval [CI] 0.46-0.89, p = 0.010) and higher in patients who initiated ART in 2010 or later (aOR 1.66, 95% CI 1.23-2.27, p < 0.001). Of 159 HBsAg-positive patients at the time of the study (9.3%), only 97 (61.0%) received Tenofovir + Lamivudine (or Emtricitabine). Of 157 coinfected patients, 114 (72.6%) had a HBV viral load < 10 IU/mL. HBV suppression was higher in patients with a HIV viral load < 300 copies/mL (aOR 3.46, 95% CI 1.48-8.09, p = 0.004) and lower in patients with increased ALT level (aOR 0.86 per 10 IU/mL increase, 95% CI 0.75-0.97, p = 0.019). CONCLUSIONS: A substantial proportion of HIV/HBV coinfected patients were at higher risk of liver disease progression. Improving the management of HBV infection in the routine healthcare setting in Africa is urgently required in order to achieve the 2030 elimination targets. Micro-elimination of HBV infection in people living with HIV could be an easier and cost-effective component than more widely scaling up HBV policies.

Multimorbidity in Elderly Persons According to the Year of Diagnosis of Human Immunodeficiency Virus Infection: A Cross-sectional Dat'AIDS Cohort Study.

BACKGROUND: We assessed prevalence of multimorbidity (MM) according to year of human immunodeficiency virus (HIV) diagnosis in elderly people living with HIV (PLWH). METHODS: This was a cross-sectional study of MM in PLWH aged ≥70 years from the Dat'AIDS French multicenter cohort. MM was defined as at least 3 coexistent morbidities of high blood pressure, diabetes mellitus, osteoporosis, non-AIDS cancer, chronic renal failure, cardiovascular and cerebrovascular disease, obesity, undernutrition, or hypercholesterolemia. Logistic regression models evaluated the association between MM and calendar periods of HIV diagnosis (1983-1996, 1997-2006, and 2007-2018). The secondary analysis evaluated MM as a continuous outcome, and a sensitivity analysis excluded PLWH with nadir CD4 count <200 cells/µL. RESULTS: Between January 2017 and September 2018, 2476 PLWH were included. Median age was 73 years, 75% were men, median CD4 count was 578 cells/µL, and 94% had controlled viremia. MM prevalence was 71%. HBP and hypercholesterolemia were the most prevalent comorbidities. After adjustment for age, gender, smoking status, hepatitis C and hepatitis B virus coinfection, group of exposure, nadir CD4 count, CD4:CD8 ratio, and last CD4 level, calendar period of diagnosis was not associated with MM (P = .169). MM was associated with older age, CD4/CD8 ratio <0.8, and nadir CD4 count <200 cells/µL. Similar results were found with secondary and sensitivity analyses. CONCLUSIONS: MM prevalence was high and increased with age, low CD4/CD8 ratio, and nadir CD4 count <200 cells/µL but was not associated with calendar periods of HIV diagnosis. Known duration of HIV diagnosis does not seem to be a criterion for selecting elderly PLWH at risk of MM.

Lopinavir-Ritonavir Impairs Adrenal Function in Infants.

BACKGROUND: Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. METHODS: Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. RESULTS: At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. CONCLUSIONS: Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. CLINICAL TRIALS REGISTRATION: NCT00640263.

Increased Prevalence of Neurocognitive Impairment in Aging People Living With Human Immunodeficiency Virus: The ANRS EP58 HAND 55-70 Study.

BACKGROUND: There are limited data on the comparative prevalence of neurocognitive impairment (NCI) in aging people living with human immunodeficiency virus (PLHIV) and people not living with HIV. METHODS: This was a cross-sectional study of PLHIV randomly matched by age (±4 years), gender, and education with 5 HIV-uninfected individuals from the CONSTANCES cohort. PLHIV were fluent in French and sequentially included during routine outpatient visits if aged 55-70 years, with HIV viral load <50 copies/mL, and lymphocyte T-CD4 level ≥200 cells/µL in the past 24 and 12 months, respectively. The primary outcome was NCI as defined by the Frascati criteria. Multivariate normative comparison (MNC) and -1.5 standard deviations in ≥2 neurocognitive domains were secondary outcomes of NCI. RESULTS: Two hundred PLHIV were matched with 1000 controls. Median age was 62 years, and 85% were men. In PLHIV, the median T-CD4 lymphocyte level was 650 cells/µL, and median nadir T-CD4 lymphocyte level was 176 cells/µL. NCI was found in 71 (35.5%) PLHIV and in 242 (24.2%) controls (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.25, 2.41). After adjusting for confounders, HIV remained significantly associated with NCI (OR, 1.50; 95% CI, 1.04, 2.16). Adjusted results were similar with NCI defined by MNC (ORMNC, 2.95; 95% CI, 1.13, 3.50) or -1.5 SD (OR-1.5, 2.24; 95% CI, 1.39, 3.62). CONCLUSIONS: In this matched study of aging individuals, HIV was significantly associated with an increased risk of NCI after adjusting for major confounders. Results were confirmed with more stringent NCI classifications. CLINICAL TRIALS REGISTRATION: NCT02592174.