Association between mental disorders with detectable viral load and poor adherence to antiretroviral therapy among adolescents infected with Human Immunodeficiency Virus on follow-up at Chantal Biya Foundation, Cameroon.

INTRODUCTION: Perinatally HIV-Infected Adolescents (HIVIA) are more likely to have mental health problems than their uninfected peers. In resource-limited settings, mental health disorders are rarely taken into account in the care offered to HIVIA and have an impact on their routine follow-up. The objective of this study was to assess the baseline socio-demographic factors and mental health conditions associated with detectable viral load or poor ART adherence in HIVIA on ART followed at the Mother and Child Centre of the Chantal Biya Foundation in Yaoundé (CME-FCB), Cameroon. METHODS: A cross-sectional study was conducted in HIVIA aged 10 to 19 years, followed at CME-FCB during the period from December 2021 to March 2022. Sociodemographic, clinical, and mental characteristics were collected using a structured questionnaire administered face-to-face by trained healthcare providers. The primary outcome was viral load ≥ 40 copies/mL in HIVIA on ART for at least six months. The secondary outcome was poor ART adherence, defined as ≥ 1 missed dose of antiretroviral therapy within the last past three days. The main exposure variables were mental health disorders, including the level of anxiety, depression and low self-esteem. RESULTS: In total, 302 adolescents were interviewed, 159 (52.7 %) were girls and median age was 15.2 years (IQR: 12.0-17.5). Having missed at least 1 dose of ART drugs during the last 3 days before screening concerned 53 (35.0 %) cases. Of the 247 adolescents with an available viral load (VL) in the last 12 months prior to screening, 33 (26.7 %) had a VL ≥ 40 copies/mL. Among participating adolescents, 29.1 % presented with high or very high anxiety, 26.5 % with severe depression, 36.4 % with history of suicidal ideation, and 20.5 % low self-esteem. Low self-esteem was strongly associated with a higher risk of poor ART adherence (adjusted odds ratio(aOR) (95 % confidence interval (95 %CI)): 2.2 (1.1-4.3); p = 0.022). Living with the father (aOR (95 %CI): 0.6 (0.3-1.1); p = 0.085) or in a household with a televisor (aOR (95 %CI): 0.5 (0.2-1.1); p = 0.069) were slightly associated with a lower risk of poor adherence to ART. Having both parents alive (aOR (95 %CI): 0.4 (0.2-0.9); p = 0.031) or receiving ART with efavirenz or dolutegravir (aOR (95 %CI): 0.5 (0.2-0.9); p = 0.047) was strongly associated with a lower likelihood of having a detectable VL. Moreover, detectable viral load was slightly less frequent in adolescents whose household was equipped with a television (p = 0.084) or who were completely disclosed for HIV status (p = 0.070). CONCLUSION: This study found that co-morbid low self-esteem had higher odds of poor ART adherence in HIVIA. Moreover, both poor ART adherence, and detectable viral load were associated with impaired life conditions in HIVIA.

Étude qualitative sur le vécu de l'annonce du statut VIH aux adolescents en Côte d'Ivoire.

INTRODUCTION: This qualitative study explores the experience of HIV-disclosure among adolescents living with HIV acquired during the perinatal period, followed in pediatric HIV care structures in Abidjan, Côte d’Ivoire. PURPOSE OF RESEARCH: Thirty adolescents and young adults living with HIV, ages 13 to 21, participated in a semi-structured interview about the conditions and consequences of the disclosure and asked for recommendations they would give. The interviews were analyzed using a thematic analysis procedure. RESULTS: We identified three types of illness and coping trajectories related to the HIV-disclosure : the trajectory of acceptance without prior crisis, the trajectory including a crisis before the HIV-disclosure, and the trajectory of crisis occurring after the disclosure. All three trajectories are impacted by the family context and the modalities of medical care. The results of the study show the importance of preparing the HIV-disclosure while including family members in an appropriate setting and confirm the importance of post-announcement follow-up. Peers appear to be an important resource for these young people, especially when they are adolescents living with HIV themselves and involved in the health care plan. CONCLUSIONS: This study contributes to the development of intervention strategies to improve the future of adolescents living with HIV, adapted to the local context of Ivory Coast.

Community Health Workers. Reinforcement of an Outreach Strategy in Rural Areas Aimed at Improving the Integration of HIV, Tuberculosis and Malaria Prevention, Screening and Care Into the Health Systems. "Proxy-Santé" Study.

Background: In Côte d'Ivoire, the health system remains poorly accessible and inefficient, particularly in rural areas. Malaria, tuberculosis and HIV remain a major concern. Tasks shifting to Community Health Workers (CHWs) in rural areas has been proposed in terms of responses and has shown encouraging results with some limitations. Objective is therefore to develop and implement, in a health district, at the level of a neighborhood, a sub-prefecture, two villages and two camps, innovative strategies aimed at improving the integration of HIV, malaria and tuberculosis prevention and care into the health system at the community level through CHWs. Methods: Introduce innovations to be integrated into the national system: (i) Selection and strengthening of the capacities of CHWs to provide care for the three diseases through home visits [Information Education and Counseling/Communication for Behavior Change (IEC/CBC)], simple malaria screening and management, referral of suspected tuberculosis cases and Directly Observed Treatment, short-course (DOTS), screening, prophylaxis and distribution of antiretrovirals (ARVs) to HIV-infected patients; (ii) monthly animation of village health committees by target groups (women of childbearing age, children under 5 years old, young adolescents); (iii) use of an application and tablets for data collection. Discussion: This innovative project integrates new activities such as ARV distribution by CHWs, management of pre-exposure prophylaxis in rural areas and electronic data capture by communities. Several lessons can be learned on the relevance of the role and activities to be carried out by these CHWs in the fight against these three diseases.

Tuberculosis Diagnosis in HIV-Infected Children: Comparison of the 2012 and 2015 Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease.

BACKGROUND: There is no gold standard for tuberculosis diagnosis in children. Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children were proposed by international experts in 2012 and updated in 2015. We aimed to compare the 2012 and 2015 Clinical Case Definitions in HIV-infected children with suspected tuberculosis. METHODS: We enrolled HIV-infected children with suspected tuberculosis in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS [Agence Nationale de Recherches sur le SIDA et les hépatites virales] 12229 PAANTHER [Pediatric Asian African Network for Tuberculosis and HIV Research] 01 Study). We classified children using the 2012 and 2015 Case Definitions considering as tuberculosis cases those with confirmed tuberculosis and those with probable and unconfirmed tuberculosis in the 2012 and the 2015 classifications, respectively. We assessed agreement between both classifications. RESULTS: Of 438 children enrolled, 197 (45.0%) children were classified as tuberculosis (45 confirmed, 152 probable) using the 2012 Case Definition and 251 (57.3%) were classified as tuberculosis (55 confirmed, 196 unconfirmed) using the 2015 classification. Inter-classification agreement for tuberculosis diagnosis was 364/438, 83.1%, with a kappa statistic of 0.667 (95% confidence interval 0.598-0.736). Of 152 children with probable tuberculosis (2012), 142 (93.4%) were considered as tuberculosis by the 2015 version and 10 (6.6%) as unlikely tuberculosis including 9 with spontaneous clinical improvement. Of 132 possible tuberculosis (2012), 58 (43.9%) were reclassified as tuberculosis (2015). CONCLUSIONS: Agreement between the 2 versions of the Case Definition was substantial but more children were considered as tuberculosis using the 2015 version. Spontaneous symptom resolution reinforces both confidence in the "unlikely" category as being children without tuberculosis and the importance of the clinician's treatment decision in the study.

Contribution and Acceptability of Bacteriological Collection Tools in the Diagnosis of Tuberculosis in Children Infected with HIV.

OBJECTIVE: The objective of this study is to evaluate the feasibility and tolerability of new bacteriological samples to diagnose tuberculosis (TB) in HIV-infected children. METHOD AND PATIENTS: HIV1-infected children with suspicion of TB in Universitary Hospital Sourô Sanon (Burkina Faso) were included in a prospective cohort study. Children underwent three gastric aspirates (GA) if aged <4 years; two GA, one string test (ST) if aged 4-9 years and three sputum, one ST if aged 10-13 years. All children underwent one nasopharyngeal aspirate (NPA) and one stool sample. To assess feasibility and tolerability of procedures, adverse events were identified and pain was rated on different scales. Samples were tested by microscopy, culture, GeneXpert® (Xpert®). RESULTS: Sixty-three patients were included. Mean age was 8.92 years, 52.38% were females. Ninety-five GA, 67 sputum, 62 NPA, 60 stool and 55 ST had been performed. During sampling, the main adverse events were cough at 68/95 GA and 48/62 NPA; sneeze at 50/95 GA and 38/62 NPA and vomiting at 4/55 ST. On the behavioral scale, the average pain score during collection was 6.38/10 for GA; 7.70/10 for NPA and 1.03/10 for ST. Of the 31 cases of TB, bacteriological confirmation was made in 12 patients. CONCLUSION: ST, stool is well-tolerated alternatives specimens for diagnosing TB in children. NPA has a poor feasibility and tolerability in children.

Long-term outcomes of early initiated antiretroviral therapy in sub-Saharan children: a Cameroonian cohort study (ANRS-12140 Pediacam study, 2008-2013, Cameroon).

BACKGROUND: In most studies, the virological response is assessed during the first two years of antiretroviral treatment initiated in HIV-infected infants. However, early initiation of antiretroviral therapy exposes infants to very long-lasting treatment. Moreover, maintaining viral suppression in children is difficult. We aimed to assess the virologic response and mortality in HIV-infected children after five years of early initiated antiretroviral treatment (ART) and identify factors associated with virologic success in Cameroon. METHODS: In the ANRS-12140 Pediacam cohort study, 2008-2013, Cameroon, we included all the 149 children who were still alive after two years of early ART. Virologic response was assessed after 5 years of treatment. The probability of maintaining virologic success between two and five years of ART was estimated using Kaplan-Meier curve. The immune status and mortality were also studied at five years after ART initiation. Factors associated with a viral load < 400 copies/mL in children still alive at five years of ART were studied using logistic regressions. RESULTS: The viral load after five years of early ART was suppressed in 66.8% (60.1-73.5) of the 144 children still alive and in care. Among the children with viral suppression after two years of ART, the probability of maintaining viral suppression after five years of ART was 64.0% (54.0-74.0). The only factor associated with viral suppression after five years of ART was achievement of confirmed virological success within the first two years of ART (OR = 2.7 (1.1-6.8); p = 0.033). CONCLUSIONS: The probability of maintaining viral suppression between two and five years of early initiated ART which was quite low highlights the difficulty of parents to administer drugs daily to their children in sub-Saharan Africa. It also stressed the importance of initial viral suppression for achieving and maintaining virologic success in the long-term. Further studies should focus on identifying strategies that would enhance better retention in care and improved adherence to treatment within the first two years of ART early initiated in Sub-Saharan HIV-infected children.

Understanding Long-term Evolution and Predictors of Sequelae of Ebola Virus Disease Survivors in Guinea: A 48-Month Prospective, Longitudinal Cohort Study (PostEboGui).

BACKGROUND: Longitudinal analyses are needed to better understand long-term Ebola virus disease (EVD) sequelae. We aimed to estimate the prevalence, incidence, and duration of sequelae and to identify risk factors associated with symptom occurrence among EVD survivors in Guinea. METHODS: We followed 802 EVD survivors over 48 months and recorded clinical symptoms with their start/end dates. Prevalence, incidence, and duration of sequelae were calculated. Risk factors associated with symptom occurrence were assessed using an extended Cox model for recurrent events. RESULTS: Overall, the prevalence and incidence of all symptoms decreased significantly over time, but sequelae remained present 48 months after Ebola treatment center discharge with a prevalence of 30.68% (95% confidence interval [CI] 21.40-39.96) for abdominal, 30.55% (95% CI 20.68-40.41) for neurologic, 5.80% (95% CI 1.96-9.65) for musculoskeletal, and 4.24% (95% CI 2.26-6.23) for ocular sequelae. Half of all patients (50.70%; 95% CI 47.26-54.14) complained of general symptoms 2 years' postdischarge and 25.35% (95% CI 23.63-27.07) 4 years' post-discharge. Hemorrhage (hazard ratio [HR], 2.70; P = .007), neurologic (HR 2.63; P = .021), and general symptoms (HR 0.34; P = .003) in the EVD acute phase were significantly associated with the further occurrence of ocular sequelae, whereas hemorrhage (HR 1.91; P = .046) and abdominal (HR 2.21; P = .033) symptoms were significantly associated with musculoskeletal sequelae. CONCLUSIONS: Our findings provide new insight into the long-term clinical complications of EVD and their significant association with symptoms in the acute phase, thus reinforcing the importance of regular, long-term follow-up for EVD survivors.

Temporal evolution of the humoral antibody response after Ebola virus disease in Guinea: a 60-month observational prospective cohort study.

BACKGROUND: Insufficient long-term data are available on antibody kinetics in survivors of Ebola virus disease (EVD). Likewise, few studies, with very small sample sizes, have investigated cross-reactions between Ebolavirus spp. In this study, we aimed to assess the humoral antibody response and its determinants in survivors of EVD and assess cross-reactivity of antibodies between diverse Ebolavirus spp. METHODS: In this observational, prospective cohort study, we collected blood samples from patients from three recruitment sites in Guinea included in the Postebogui study, and we assessed IgG antibody binding to recombinant glycoprotein, nucleoprotein, and 40-kDa viral protein (VP40) of Zaire (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) Ebolaviruses. Participants from the PostEbogui study, from whom we had at least one blood sample that could be tested for the presence of antibodies, were eligible for this analysis. Patients in the PostEbogui study were assessed clinically at inclusion, 1 month and 3 months later, and subsequently every 6 months for up to 60 months after discharge from the Ebola treatment centre. We explored predictors of glycoprotein, nucleoprotein, and VP40 antibody concentrations through a linear mixed model. A logistic mixed model was done to estimate the probability of seropositivity and associated determinants. We assessed cross-reactivity by use of hierarchical cluster analysis. FINDINGS: Of the 802 patients included in the Postebogui study, 687 were included in our analyses. 310 (45%) patients were men and 377 (55%) were women, with an overall median age at the time of the first blood sample of 27·3 years (IQR 19·5-38·2). We observed an overall significant decrease over time of EBOV antibodies, with antibodies against nucleoproteins decreasing more rapidly. At 60 months after discharge from the Ebola treatment centre, the probability of having antibodies against glycoproteins was 76·2% (95% CI 67·2-83·3), against nucleoproteins was 59·4% (46·3-71·3), and against VP40 was 60·9% (51·4-69·8). Persistence of EBOV RNA in semen was associated with higher concentrations of IgG antibodies against nucleoprotein EBOV antigens. Individually, we observed in some survivors an antibody wax-and-wane pattern. The proportion of cross-reactions was highest between glycoproteins from Kissidougou and Mayinga EBOV strains (94·5%, 95% CI 92·5-96·1), followed by EBOV VP40 and BDBV VP40 (88·3%, 85·7-90·6), and EBOV VP40 and SUDV VP40 (83·3%, 80·3-86·1). INTERPRETATION: The probability for survivors of EVD to have antibodies against one or more EBOV antigens remained high, although approximately 25% of survivors had undetectable antibodies, which could have implications, such as a possible decreasing population immunity, for future Ebola outbreaks in the same region. FUNDING: Reacting-Institut National de la Santé et de la Recherche Médicale, Institut de Recherche pour le Developpement, and Montpellier Université d'Excellence.

A Treatment-Decision Score for HIV-Infected Children With Suspected Tuberculosis.

BACKGROUND: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis. METHODS: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony. RESULTS: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis. CONCLUSIONS: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits.

High level of treatment failure and drug resistance to first-line antiretroviral therapies among HIV-infected children receiving decentralized care in Senegal.

BACKGROUND: In Senegal in 2015, an estimated 4800 children were living with HIV, with 1200 receiving ARV treatment, of whom half had follow-up care in decentralized sites outside Dakar. However, until now no studies have determined the efficacy of pediatric treatment in decentralized settings, even though the emergence of viral resistance, particularly among children in Africa, is a well-known phenomenon. This study aimed to assess the virological status of HIV-infected children in all decentralized facilities to help improve access to quality care. METHODS: A cross-sectional epidemiological and virological study was conducted in all of Senegal's regions, except Dakar, between March and June 2015 and sought to include all HIV-infected children and adolescents (0-19 years), treated or not with ARVs. Socio-demographic and clinical data and a blood sample on blotting paper were collected for children from treatment sites. Samples were routed on public transportation, assisted by a network of community health workers. A viral load (VL) assay was performed for each child, followed by genotyping when it exceeded 1000 copies/mL (3 log10). RESULTS: Of the 851 identified children, 666 (78%) were enrolled in the study. Half of the children were girls, and the average age was 8 years (6 months-19 years). Most of the children (96.7%) were infected with HIV-1, and 90% were treated with ART, primarily with AZT + 3TC + NVP/EFV therapeutic regimen. The median duration of time on ART was 21 months (1-129). VL was measured for 2% of children before this study. Almost two-thirds (64%) of the children are experiencing virological failure. Among them, there was resistance to at least one drug for 86.5% of cases. Also, 25% children presented resistance to one drug and 40% to two out of three. For nearly one-third of the children presenting resistance, none of the three drugs of the treatment was active. Factors associated with virological failure were male sex, follow-up by a generalist rather than a specialist, and treatment interruptions. CONCLUSIONS: We observed a high level of virological failure and a high percentage of viral resistance among children receiving health care in decentralized facilities in Senegal.

Prevalence of infection among asymptomatic and paucisymptomatic contact persons exposed to Ebola virus in Guinea: a retrospective, cross-sectional observational study.

BACKGROUND: The prevalence of Ebola virus infection among people who have been in contact with patients with Ebola virus disease remains unclear, but is essential to understand the dynamics of transmission. This study aimed to identify risk factors for seropositivity and to estimate the prevalence of Ebola virus infection in unvaccinated contact persons. METHODS: In this retrospective, cross-sectional observational study, we recruited individuals between May 12, 2016, and Sept 8, 2017, who had been in physical contact with a patient with Ebola virus disease, from four medical centres in Guinea (Conakry, Macenta, N'zérékoré, and Forécariah). Contact persons had to be 7 years or older and not diagnosed with Ebola virus disease. Participants were selected through the Postebogui survivors' cohort. We collected self-reported information on exposure and occurrence of symptoms after exposure using a questionnaire, and tested antibody response against glycoprotein, nucleoprotein, and 40-kDa viral protein of Zaire Ebola virus by taking a blood sample. The prevalence of Ebola virus infection was estimated with a latent class model. FINDINGS: 1721 contact persons were interviewed and given blood tests, 331 of whom reported a history of vaccination so were excluded, resulting in a study population of 1390. Symptoms were reported by 216 (16%) contact persons. The median age of participants was 26 years (range 7-88) and 682 (49%) were male. Seropositivity was identified in 18 (8·33%, 95% CI 5·01-12·80) of 216 paucisymptomatic contact persons and 39 (3·32%, 5·01-12·80) of 1174 (2-4) asymptomatic individuals (p=0·0021). Seropositivity increased with participation in burial rituals (adjusted odds ratio [aOR] 2·30, 95% CI 1·21-4·17; p=0·0079) and exposure to blood or vomit (aOR 2·15, 1·23-3·91; p=0·0090). Frequency of Ebola virus infection varied from 3·06% (95% CI 1·84-5·05) in asymptomatic contact persons who did not participate in burial rituals to 5·98% (2·81-8·18) in those who did, and from 7·17% (3·94-9·09) in paucisymptomatic contact persons who did not participate in burial rituals to 17·16% (12·42-22·31) among those who did. INTERPRETATION: This study provides a new assessment of the prevalence of Ebola virus infection among contact persons according to exposure, provides evidence for the occurrence of paucisymptomatic cases, and reinforces the importance of closely monitoring at-risk contact persons. FUNDING: Institut National de la Santé et de la Recherche Médicale, Reacting, the French Ebola Task Force, Institut de Recherche pour le Développement, and Montpellier University Of Excellence-University of Montpellier.

Isolation of Nontuberculous Mycobacteria in Southeast Asian and African Human Immunodeficiency Virus-infected Children With Suspected Tuberculosis.

We enrolled 427 human immunodeficiency virus-infected children (median age, 7.3 years), 59.2% severely immunodeficient, with suspected tuberculosis in Southeast Asian and African settings. Nontuberculous mycobacteria were isolated in 46 children (10.8%); 45.7% of isolates were Mycobacterium avium complex. Southeast Asian origin, age 5-9 years, and severe immunodeficiency were independently associated with nontuberculous mycobacteria isolation. CLINICAL TRIALS REGISTRATION: NCT01331811.

Low prevalence of lipodystrophy in HIV-infected Senegalese children on long-term antiretroviral treatment: the ANRS 12279 MAGGSEN Pediatric Cohort Study.

BACKGROUND: The long-term benefits of antiretroviral treatment (ART) are associated with metabolic complications, especially lipodystrophy, which has been well described among HIV-infected adults and children on ART in developed settings. Specifically, stavudine, and to a lesser extent zidovudine and protease inhibitors (PI), have been consistently implicated in the development of lipodystrophy. In 2006, following advice from the WHO, Senegal began phasing out stavudine from first-line ART. The objectives of this cross-sectional analysis are to assess and identify risk factors affecting the prevalence of lipodystrophy in Senegalese children and adolescents on long-term ART participating in a cohort study. METHODS: Lipodystrophy was clinically assessed in two- to 18-year-old children on ART for at least six months and with no concurrent severe acute malnutrition. Risk factors for lipodystrophy were identified using stepwise multivariable logistic regression. Explanatory variables included clinical and personal data, immunovirologic status, and therapeutic history. RESULTS: Overall, 254 children were assessed for lipodystrophy. The median age was 10.9 years (IQR: 8.1-14.2) and the median duration on ART was 54 months (32-84). Only 18% had been previously treated with stavudine, with a median treatment duration of 8 months (5-25). Ongoing treatment included 76% of children receiving zidovudine (median duration of 48 months (26-74)) and 27% receiving PI (lopinavir/ritonavir; median duration of 49 months (23-59)). Mild signs of lipodystrophy were observed in 33 children (13%): 28 with lipoatrophy, 4 with lipohypertrophy and one with combined type. Boys were more likely to present with lipoatrophy than girls (aOR: 4.3, 95% CI: 1.6-11.7). Children previously treated with stavudine for ≥1 year had a greater risk for lipoatrophy than those never exposed (3.8, 1.0-14.0), although the association was weak. There was no association between lipodystrophy and age or current or cumulative treatment with lopinavir/ritonavir or zidovudine. CONCLUSIONS: We report low prevalence of mild lipodystrophy in children and adolescents on long-term ART receiving a stavudine-sparing regimen. These findings are reassuring for clinicians in low-income settings where zidovudine is massively prescribed and lopinavir/ritonavir is the only widely available PI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01771562 (registration date: 01/18/2013).

Virologic Response to Early Antiretroviral Therapy in HIV-infected Infants: Evaluation After 2 Years of Treatment in the Pediacam Study, Cameroon.

INTRODUCTION: Little is known about virologic responses to early antiretroviral therapy (ART) in HIV-infected infants in resource-limited settings. We estimated the probability of achieving viral suppression within 2 years of ART initiation and investigated the factors associated with success. METHODS: We analyzed all 190 infants from the Cameroon Pediacam who initiated ART by 12 months of age. The main outcome measure was viral suppression (<1000 copies/mL) on at least 1 occasion; the other outcome measures considered were viral suppression (<400 copies/mL) on at least 1 occasion and confirmed viral suppression (both thresholds) on 2 consecutive occasions. We used competing-risks regression for a time-to-event analysis to estimate the cumulative incidence of outcomes and univariate and multivariate models to identify risk factors. RESULTS: During the first 24 months of ART, 20.0% (38) of the infants died, giving a mortality rate of 11.9 deaths per 100 infant-years (95% confidence interval: 8.1-15.7). The probability of achieving a viral load below 1000 or 400 copies/mL was 80.0% (69.0-81.0) and 78.0% (66.0-79.0), respectively. The probability of virologic suppression (with these 2 thresholds) on 2 consecutive occasions was 67.0% (56.0-70.0) and 60.0% (49.0-64.0), respectively. Virologic success was associated with not having missed any doses of treatment before the visit, but not with socioeconomic and living conditions. CONCLUSION: Many early treated children failed to achieve virologic suppression, likely due to a combination of adherence difficulties, drug dosing and viral resistance, which highlights the need for routine viral load monitoring. The high infant mortality despite early ART initiation needs to be addressed in sub-Saharan countries.

Mortality and its determinants in antiretroviral treatment-naive HIV-infected children with suspected tuberculosis: an observational cohort study.

BACKGROUND: Tuberculosis is a major cause of morbidity and mortality in HIV-infected children, but is difficult to diagnose. We studied mortality and its determinants in antiretroviral treatment (ART)-naive HIV-infected children presenting with suspected tuberculosis. METHODS: In this observational cohort study, HIV-infected children aged 13 years or younger with suspected tuberculosis were followed up for 6 months as part of the ANRS 12229 PAANTHER 01 cohort in eight hospitals in four countries (Burkina Faso, Cambodia, Cameroon, and Vietnam). Children started ART and antituberculosis treatment at the clinician's discretion and were retrospectively classified into one of three groups by tuberculosis documentation: confirmed by culture or Xpert MTB/RIF, unconfirmed, and unlikely. We assessed mortality and associated factors using Kaplan-Meier methods and Cox proportional hazard models. The ANRS 12229 PAANTHER 01 study is registered at ClinicalTrials.gov, number NCT01331811. FINDINGS: 266 (61%) of 438 children enrolled in the study between April 27, 2011, and May 31, 2014, were ART-naive and included in the analysis (40 had confirmed tuberculosis, 119 unconfirmed tuberculosis, and 107 unlikely tuberculosis). 112·5 person-years of follow-up were available. 154 children (58%) started antituberculosis treatment and 212 (80%) started ART. 50 children (19%) died. Mortality by 6 months was higher in children with confirmed tuberculosis (14 deaths; 2 month survival probability 65·0% [95% CI 50·2-79·8]) compared with unconfirmed tuberculosis (19 deaths; 83·5% [76·8-90·3]) and unlikely tuberculosis (17 deaths; 83·5% [76·3-90·7]; log-rank p=0·0141) and was lower in children with confirmed or unconfirmed tuberculosis who started antituberculosis treatment (p<0·0001 for both). In a multivariate analysis, ART started during the first month of follow-up (hazard ratio 0·08; 95% CI 0·01-0·67), confirmed tuberculosis (6·33; 2·15-18·64), young age (5·90; 2·02-17·19), CD4 less than 10% (2·63; 1·25-5·53), miliary features (4·08; 1·56-10·66), and elevated serum transaminases (4·40; 1·82-10·65) were all independently associated with mortality. INTERPRETATION: In our cohort, mortality was high in the first 6 months after suspicion of tuberculosis in ART-naive children. ART should be started early, particularly in children with factors associated with high mortality. Documented or empirical tuberculosis treatment decision should be accelerated to reduce mortality and allow early ART initiation. FUNDING: ANRS and Fondation Total.

Stunting among children under 3 years of age in Côte d'Ivoire: spatial and temporal variations between 1994 and 2011.

OBJECTIVE: To investigate spatial heterogeneity of stunting prevalence among children in Côte d'Ivoire and examine changes in stunting between 1994 and 2011, to assess the impact of the 2002-2011 civil war that led to temporary partitioning of the country. DESIGN: Data from 1994, 1998 and 2011 Côte d'Ivoire Demographic and Health Surveys (DHS) were analysed using a geostatistical approach taking into account spatial autocorrelation. Stunting data were interpolated using ordinary kriging; spatial clusters with high and low stunting prevalence were identified using Kulldorff spatial scan statistics. Multilevel multivariable logistic regression was then carried out, with year of survey as the main independent variable and an interaction term for time by geographic zone (Abidjan, South, North). SETTING: Côte d'Ivoire, West Africa. SUBJECTS: Children aged 0-35 months included in three DHS (n 6709). RESULTS: Overall stunting prevalence was 30·7, 28·7 and 27·8 % in 1994, 1998 and 2011, respectively (P=0·32). Clusters with high prevalence were found in 1994 (in the West region, P<0·001) and 1998 (in the West and North-West regions, P<0·01 and P=0·01, respectively), but not in 2011. Abidjan was included in a cluster with low prevalence in all surveys (P<0·05). Risk of stunting did not change between 1994 and 2011 at national level (adjusted OR; 95 % CI: 1·39; 0·72, 2·64), but decreased in the South (0·74; 0·58, 0·94) and increased from 1998 to 2011 in Abidjan (1·96; 1·06, 3·64). CONCLUSIONS: In Côte d'Ivoire, significant changes in stunting prevalence were observed at the sub-national level between 1994 and 2011.

Dynamics of Ebola RNA Persistence in Semen: A Report From the Postebogui Cohort in Guinea.

This study modeled the presence of Ebola virus RNA in the semen of male Ebola survivors participating in the Postebogui study in Guinea. The median time of reverse-transcription polymerase chain reaction negativity was 46.4 days after symptom onset (95% confidence interval, 11-82.6). The results emphasize the importance of the World Health Organization recommendations for survivors' management.

Risk Factors for Growth Retardation in HIV-infected Senegalese Children on Antiretroviral Treatment: The ANRS 12279 MAGGSEN Pediatric Cohort Study.

OBJECTIVES: To describe prevalence and risk factors for wasting and stunting among HIV-infected children with a median duration of 3 years of antiretroviral therapy (ART) at the time of their enrollment in the cohort study. METHODS: Wasting and stunting at ART initiation and enrollment were defined as weight-for-height/body mass index-for-age Z scores < -2 and height-for-age Z scores < -2, respectively. Logistic regression was used to assess risk factors for wasting and stunting. Main predictive factors were age at enrollment, nutritional status and age (< or ≥5 years) at ART initiation and ART duration (< or ≥3 years on first-line, or ≥3 years including a switch to second-line ART). RESULTS: Two hundred forty-four children 2-16 years of age were enrolled. Overall, wasting and stunting prevalence dropped off consistently in children 2-10 years of age, between ART initiation and enrollment, while it remained at high levels, 52% and 42%, respectively, in children 10-16 years of age. Risk factors for wasting at enrollment were ART duration of ≥3 years including a switch to second-line [adjusted odds ratio (aOR): 3.9, 95% confidence interval (CI): 1.7-8.9] and wasting at ART initiation (aOR: 2.7, 95% CI: 1.4-5.2). The risk factor for stunting at enrollment was stunting at ART initiation (aOR: 11.6, 95% CI: 5.4-25.0), independent of ART duration. CONCLUSIONS: Malnutrition at the time of ART initiation was the main predictor of malnutrition at enrollment among HIV-infected children on ART. Longer duration on ART had no overall protective effect on wasting and stunting. Growth and virologic monitoring are of utmost importance in the comprehensive care of children with HIV infection.

Multidisciplinary assessment of post-Ebola sequelae in Guinea (Postebogui): an observational cohort study.

BACKGROUND: The high number of survivors from the 2013-16 west African outbreak of Ebola virus disease (EVD) has raised several new issues: long-term clinical complications, psychosocial consequences, risks of EVD reactivation, and secondary transmission due to viral persistence in body fluids. We aimed to assess long-term clinical, psychosocial, and viral outcomes in EVD survivors in Guinea. METHODS: In this multidisciplinary observational cohort study, we recruited patients aged 1 year or more in four sites in Guinea (Donka National Hospital, Conakry; Macenta Prefectoral Hospital, Macenta; N'zérékoré Regional Hospital, N'zérékoré; and Forécariah Prefectoral Hospital, Forécariah) following discharge from any Ebola treatment centre in Guinea. Eligible patients had had laboratory-confirmed EVD and had then been declared clear of the virus in the blood. All consenting patients were included, with no exclusion criteria. Trained clinicians assessed patients at enrolment to the cohort, recording clinical symptoms and signs of depression. We did routine blood examinations and examined viral persistence in body fluids using RT-PCR. We did psychological evaluations using questionnaires developed for different age groups. Follow-up is planned to 2 years, and here we present findings at enrolment. FINDINGS: Between March 23, 2015, and July 11, 2016, we recruited 802 patients, of whom 360 (45%) were male, 442 (55%) were female; 158 (20%) were younger than 18 years. The median age was 28·4 years (range 1·0-79·9, IQR 19·4-39·8). The median delay after discharge was 350 days (IQR 223-491). The most frequent symptoms were general symptoms (324 [40%] patients), musculoskeletal pain (303 [38%]), headache (278 [35%]), depression (124 [17%] of 713 responses), abdominal pain (178 [22%]), and ocular disorders (142 [18%]). More adults than children had at least one clinical symptom (505 [78%] vs 101 [64%], p<0·0003), ocular complications (124 [19%] vs 18 [11%], p=0·0200), or musculoskeletal symptoms (274 [43%] vs 29 [18%], p<0·0001). A positive RT-PCR in semen was found in ten (5%) of 188 men, at a maximum of 548 days after disease onset. 204 (26%) of 793 patients reported stigmatisation. Ocular complications were more frequent at enrolment than at discharge (142 [18%] vs 61 [8%] patients). INTERPRETATION: Post-EVD symptoms can remain long after recovery and long-term viral persistence in semen is confirmed. The results justify calls for regular check-ups of survivors at least 18 months after recovery. FUNDING: INSERM/Reacting, the French Ebola Task Force, and Institut de Recherche pour le Développement.