HIV and hepatitis B, C co-infection and correlates of HIV infection among men who have sex with men in Rwanda, 2021: a respondent-driven sampling, cross-sectional study.

BACKGROUND: Men who have sex with men (MSM) are a key population group disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. In Rwanda, the HIV epidemic remains a significant public health concern, and understanding the burden of HIV and hepatitis B and C coinfections among MSM is crucial for designing effective prevention and control strategies. This study aims to determine the prevalence of HIV, hepatitis B, and hepatitis C infections among MSM in Rwanda and identify correlates associated with HIV infection within this population. METHODS: We used respondent-driven sampling (RDS) to recruit participants between November and December 2021. A face-to-face, structured questionnaire was administered. Testing for HIV infection followed the national algorithm using two rapid tests: Alere Combo and STAT PAK as the first and second screening tests, respectively. Hepatitis B surface antigen (HBsAg) and anti-HCV tests were performed. All statistics were adjusted for RDS design, and a multivariable logistic regression model was constructed to identify factors associated with HIV infection. RESULTS: The prevalence of HIV among MSM was 6·9% (95% CI: 5·5-8·6), and among HIV-positive MSM, 12·9% (95% CI: 5·5-27·3) were recently infected. The prevalence of hepatitis B and C was 4·2% (95% CI: 3·0-5·7) and 0·7% (95% CI: 0·4-1·2), respectively. HIV and hepatitis B virus coinfection was 0·5% (95% CI: 0·2-1·1), whereas HIV and hepatitis C coinfection was 0·1% (95% CI: 0·0-0·5), and no coinfection for all three viruses was observed. MSM groups with an increased risk of HIV infection included those who ever suffered violence or abuse because of having sex with other men (AOR: 3·42; 95% CI: 1·87-6·25), those who refused to answer the question asking about 'ever been paid money, goods, or services for sex' (AOR: 10·4; 95% CI: 3·30-32·84), and those not consistently using condoms (AOR: 3·15; 95% CI: 1·31-7·60). CONCLUSION: The findings suggest more targeted prevention and treatment approaches and underscore the importance of addressing structural and behavioral factors contributing to HIV vulnerability, setting interventions to reduce violence and abuse against MSM, promoting safe and consensual sexual practices, and expanding access to HIV prevention tools such as condoms and preexposure prophylaxis (PrEP).

Neurodevelopment outcomes in infants born to women with Zika virus infection during pregnancy in Mexico.

BACKGROUND: Few studies have assessed neurodevelopmental outcomes in normocephalic infants born to women with Zika virus (ZIKV) infection during pregnancy in Mexico. We sought to evaluate ZIKV exposed infants in Yucatan, Mexico, with performance-based and eye-gaze measures of neurodevelopment, removing observer bias. METHODS: We enrolled 60 infants about 6-month old born to women with PCR + test for ZIKV during pregnancy. Infants were normocephalic and asymptomatic. Sixty infants born to women without a history of ZIKV infection were included as comparison. Children were assessed with the Mullen scales of early learning (MSEL), a test with scales in motor, language, and overall cognitive skills development, and the Fagan test of infant intelligence (FTII) using automated eye-tracking instrumentation to evaluate infant visual preference of human faces, where longer gaze lengths to unfamiliar (i.e., new) faces are expected. RESULTS: All MSEL subscale scores, except expressive language, were significantly lower among ZIKV exposed children compared to controls, including the overall standard composite (80 ± 10 vs. 87 ± 7.4, respectively; p < 0.001). FTII eye-tracking measures of fixation and gaze length were in the expected direction, with longer times recorded among infants in the control group (i.e., higher attention), but none reached statistical significance. In adjusted linear regressions, the FTII high novelty score (expected preference for a novel face) predicted fine motor (ß = 3.61, p = 0.04) and receptive language (ß = 2.55, p = 0.03) scores. CONCLUSIONS: Nonmicrocephalic children born to women with ZIKV during pregnancy in Mexico merit early neurodevelopmental evaluation to allow for appropriate interventions and clinical follow-up. It is possible that long-term monitoring of cognitive deficits may need to be established for a proportion of affected cases.

Association between caregiver depression symptoms and child executive functioning. Results from an observational study carried out in four sub-Saharan countries.

Depressive symptoms among HIV-positive (HIV+) women may negatively impact their health and possibly that of their young children through risk of compromised caregiving. We evaluated how depression symptoms in predominantly (97%) female caregivers relate to neurodevelopmental outcomes in their HIV affected children. Data come from the IMPAACT P1104s Study, an observational cohort across six sites in four countries: Zimbabwe, South Africa, Uganda and Malawi. Participants (n = 611) were 5-11-year-old children with HIV (HIV), HIV exposed uninfected (HEU), or HIV unexposed uninfected (HUU). Primary caregivers were assessed for depression with the Hopkins Symptom Checklist (HSCL) and children with Behavior Rating Inventory for Executive Function (BRIEF) parent-report, Kauffman Assessment Battery for Children II (KABC), Bruininks-Oseretsky Test of Motor Proficiency 2nd Ed. (BOT-2), Test of Variables of Attention (TOVA), Multiple Indicators Cluster Survey, Child Disability and Development scales (MICS-4). Caregivers with higher depression scores (>1.75 mean HSCL score) reported more executive function problems in their children, regardless of HIV status. All executive function scores were significantly (p < 0.001) associated with depressive symptomatology at baseline and across time. Caregiver depressive symptomatology was not associated with other assessed neurocognitive outcomes. These results highlight the potential impact of caregiver depression on child behavioral outcomes.

Depression Symptom Trajectories Among Mothers Living with HIV in Rural Uganda.

The aim was to identify latent class trajectories of depression symptoms among HIV+ women in Uganda. Depression was assessed at four time points using the Hopkins Symptom Checklist among 288 women caring for a child 2-5 years old. Mixture modeling was used to estimate the number and nature of classes defined by trajectories of depressive symptoms over time. Maternal and child characteristics were explored as predictors of class. Three trajectories of symptoms of depression were identified; (1) stable-low, (2) moderate-subclinical, and (3) chronic-high. About 8% of women reported moderately or highly elevated symptoms at the first assessment and consistently onward (i.e. chronically). Higher anxiety levels, less social support, more functionality problems, and more executive behavior problems in children predicted membership in the moderate-subclinical and chronic-high classes. Identifying patterns of depression trajectories can help target intervention efforts for women who are likely to experience the most chronic and impairing symptomatology.

Prevalence and factors associated to disclosure of same-sex practices to family members and health care workers among men who have sex with men in Togo.

Disclosure of same-sex practices is associated with improved access to health services and better health outcomes. Our aim was to estimate the prevalence of same-sex practice disclosure to family members and health care workers (HCW) in two cities in Togo. 683 MSM ≥18 years of age were surveyed using respondent driven sampling (RDS) for a cross-sectional survey using a structured questionnaire in Lomé (354 (51.8%)) and Kara (n = 329 (48.2%)). Median age was lower in Lomé than in Kara. A significantly higher proportion of MSM in Lomé (RDSa: 37.0%; 95% CI: 29.7, 44.3) than in Kara (RDSa: 8.0%; 95% CI: 4.7, 11.3) told a HCW that they have sex with men. Disclosure to a family member was associated with female gender, living with HIV, difficulties accessing health services, and blackmail. Disclosure to a HCW was associated with living with HIV, and physical abuse. MSM had decreased odds of disclosure to a HCW if they were living in Kara, reported female gender or intersex, or if had difficulties accessing health services. These data highlight the positive health outcomes associated with disclosure contextualized by the complex environments in which disclosure of same-sex practices takes place.

Using a social ecological framework to characterize the correlates of HIV among men who have sex with men in Lomé, Togo.

In the mixed and concentrated HIV epidemics of West Africa, the relative disproportionate burden of HIV among men who have sex with men (MSM) compared to other reproductive-age men is higher than that observed in Southern and Eastern Africa. Our aim is to describe the correlates of HIV infection among MSM living in Lomé, Togo, using the Modified Social Ecological Model (MSEM). A total of 354 MSM ≥18 years of age were recruited using respondent driven sampling (RDS) for a cross-sectional survey in Lomé, Togo. Participants completed a structured questionnaire and were tested for HIV and syphilis. Statistical analyses included RDS-weighted proportions, bootstrapped confidence intervals (CI), and logistic regression models. Mean age of participants was 22 years; 71.5% were between 18 and 24 years. RDS-weighted HIV prevalence was 9.2% (95% CI=5.4-13.2). In RDS-adjusted (RDSa) bivariate analysis, HIV infection was associated with disclosure of sexual orientation to a family member, discriminatory remarks made by family members, forced sex, ever being blackmailed because of being MSM, community and social stigma and discrimination, and health service stigma and discrimination. In the multivariable model, HIV infection was associated with being 25 years or older (RDSa adjusted OR (aOR)=4.3, 95% CI=1.5-12.2), and having sex with a man before age 18 (RDSa aOR=0.3, 95% CI=0.1-0.9). HIV prevalence was more than seven times higher than that estimated among adults aged 15-49 living in Togo. Using the MSEM, network, community, and policy-level factors were associated with HIV infection among MSM in Lomé, Togo. Through the use of this flexible risk framework, a structured assessment of the multiple levels of HIV risk was characterized, highlighting the need for evidence-based and human-rights affirming combination HIV prevention and treatment programs that address these various risk levels for MSM in Lomé.

CNS Impact of Perinatal HIV Infection and Early Treatment: the Need for Behavioral Rehabilitative Interventions Along with Medical Treatment and Care.

There is growing concern that although the more severe forms of HIV-associated neurologic deficits are reduced following highly active anti-retroviral therapy (HAART), mild to moderate cognitive disorders may persist for years after HAART initiation and this may occur despite complete plasma viral suppression. According to the UNAIDS 2014 report, there were 3.2 million children living with HIV around the world at the end of 2013 and 91 % of these resided in sub-Saharan Africa. In the same year, only 24 % of children who needed antiretroviral treatment (ART) received it and 190,000 children died of AIDS-related illnesses. We propose that behavioral interventions are needed in combination with medical treatment and care in order to fully address the needs of children and adolescents in Africa living with HIV. In early childhood, caregiver training programs to enhance the developmental milieu of the child with HIV can enhance their cognitive and social development and that such interventions are both feasible and well-accepted by the local population. For school-age children, computerized cognitive rehabilitation training can be an entertaining and engaging way to improve attention, working memory, and problem solving skills for children with HIV. Further dissemination and implementation science work is needed for arriving at cost-effective strategies for scaling up such behavioral interventions in African resource-constrained settings, given that the vast majority of HIV-affected children and youth worldwide presently live in sub-Saharan Africa.

Malaria illness mediated by anaemia lessens cognitive development in younger Ugandan children.

BACKGROUND: Asymptomatic falciparum malaria is associated with poorer cognitive performance in African schoolchildren and intermittent preventive treatment of malaria improves cognitive outcomes. However, the developmental benefits of chemoprevention in early childhood are unknown. Early child development was evaluated as a major outcome in an open-label, randomized, clinical trial of anti-malarial chemoprevention in an area of intense, year-round transmission in Uganda. METHODS: Infants were randomized to one of four treatment arms: no chemoprevention, daily trimethoprim-sulfamethoxazole, monthly sulfadoxine-pyrimethamine, or monthly dihydroartemisinin-piperaquine (DP), to be given between enrollment (4-6 mos) and 24 months of age. Number of malaria episodes, anaemia (Hb < 10) and neurodevelopment [Mullen Scales of Early Learning (MSEL)] were assessed at 2 years (N = 469) and at 3 years of age (N = 453); at enrollment 70 % were HIV-unexposed uninfected (HUU) and 30 % were HIV-exposed uninfected (HEU). RESULTS: DP was highly protective against malaria and anaemia, although trial arm was not associated with MSEL outcomes. Across all treatment arms, episodes of malarial illness were negatively predictive of MSEL cognitive performance both at 2 and 3 years of age (P = 0.02). This relationship was mediated by episodes of anaemia. This regression model was stronger for the HEU than for the HUU cohort. Compared to HUU, HEU was significantly poorer on MSEL receptive language development irrespective of malaria and anaemia (P = 0.01). CONCLUSIONS: Malaria with anaemia and HIV exposure are significant risk factors for poor early childhood neurodevelopment in malaria-endemic areas in rural Africa. Because of this, comprehensive and cost/effective intervention is needed for malaria prevention in very young children in these settings.

Socio-demographic correlates of depression and anxiety among female caregivers living with HIV in rural Uganda.

Women living with HIV are at increased risk for psychosocial distress, especially among social and economically disadvantaged women living in rural areas. Little is known about how social support and wealth impacts the mental health of women caring for young children in low- and middle-income countries. The purpose of this paper was to assess demographic, socio-economic, and social support correlates of depression and anxiety in HIV-infected+ female caregivers living in rural Uganda. Depression and anxiety were assessed using the Hopkins Symptom Checklist (HSCL-25), two-domains of social support (family and community) were measured with the adapted Multidimensional Scale for Perceived Social Support, and wealth was measured using a checklist of material possessions and housing quality among 288 women. Multivariable linear regression models assessed the association of depression and anxiety with demographic and social predictors. Sixty-one percent of women reported clinically significant symptoms of depression or anxiety using the standard HSCL-25 cut-off of >1.75. Lower wealth (p = .01) and family support (p = .01) were significantly associated with more depressive symptoms, with greater family support being more protective of depression in the highest wealth group (top 20%) compared to the lowest. More anxiety symptoms were associated with lower wealth (p = .001), lower family support (p = .02), and higher community support (p = .003). Economic and social support factors are important predictors of caregiver mental health in the face of HIV disease in rural Uganda. Findings suggest that interventions should consider ways to increase economic opportunities and strengthen family support for HIV+ caregivers.

Caregivers' depressive symptoms and parent-report of child executive function among young children in Uganda.

Maternal mental health (particularly depression) may influence how they report on their child's behavior. Few research studies have focused on Sub-Saharan countries where pediatric HIV concentrates and impacts child neuropsychological development and caregiver mental health. We investigated the associations between caregivers' depressive symptoms and neuropsychological outcomes in HIV-infected (n=118) and HIV-exposed (n=164) Ugandan children aged 2-5 years. We compared performance-based tests of development (Mullen Scales of Early Learning, Color Object Association Test), to a caregiver report of executive function (Behavior Rating Inventory of Executive Function, BRIEF). Caregivers were assessed with Hopkins Symptom Checklist-25 depression subscale. The associations between all BRIEF indices and caregiver's depression symptoms were differential according to child's HIV status. Caregivers with greater depressive symptoms reported their HIV-infected children as having more behavioral problems related to executive functioning. Assessment of behavior of HIV-infected children should incorporate a variety of sources of information and screening of caregiver mental health.

Cross-sectional assessments of participants' characteristics and loss to follow-up in the first Opioid Substitution Therapy Pilot Program in Kabul, Afghanistan.

BACKGROUND: Kabul has over 12,000 people who inject drugs (PWID), most of them heroin users, and opioid substitution therapy has recently been introduced as an effective method to reduce opioid use. We aimed to evaluate a pilot Opioid Substitution Therapy Pilot Program (OSTPP) in Kabul, Afghanistan, particularly to (1) describe characteristics of the participants enrolled in the program and (2) identify factors associated with client retention in the OSTPP. FINDINGS: Two cross-sectional surveys evaluated participants attending the OSTPP at baseline (n = 83) and 18 months after (n = 57). Questionnaires assessed socio-demographic, drug use behavior, and general and mental health factors. After 18 months, 57 participants remained in the OSTPP. Participants lost to follow-up were younger (p < 0.01) and married (p < 0.01) and had no family contact (p < 0.01). Participants at 18 months reported no criminal activity in the last month and only two (3.5 %) reported heroin use in the last month, constituting significant decreases from baseline. CONCLUSIONS: While preliminary results are promising, further evaluation is needed to determine the feasibility of implementing OSTPP in this setting and effectiveness in reducing injection risk behaviors in Afghanistan.

Estimation of the Population Size of Street- and Venue-Based Female Sex Workers and Sexually Exploited Minors in Rwanda in 2022: 3-Source Capture-Recapture.

BACKGROUND: HIV surveillance among key populations is a priority in all epidemic settings. Female sex workers (FSWs) globally as well as in Rwanda are disproportionately affected by the HIV epidemic; hence, the Rwanda HIV and AIDS National Strategic Plan (2018-2024) has adopted regular surveillance of population size estimation (PSE) of FSWs every 2-3 years. OBJECTIVE: We aimed at estimating, for the fourth time, the population size of street- and venue-based FSWs and sexually exploited minors aged ≥15 years in Rwanda. METHODS: In August 2022, the 3-source capture-recapture method was used to estimate the population size of FSWs and sexually exploited minors in Rwanda. The field work took 3 weeks to complete, with each capture occasion lasting for a week. The sample size for each capture was calculated using shinyrecap with inputs drawn from previously conducted estimation exercises. In each capture round, a stratified multistage sampling process was used, with administrative provinces as strata and FSW hotspots as the primary sampling unit. Different unique objects were distributed to FSWs in each capture round; acceptance of the unique object was marked as successful capture. Sampled FSWs for the subsequent capture occasions were asked if they had received the previously distributed unique object in order to determine recaptures. Statistical analysis was performed in R (version 4.0.5), and Bayesian Model Averaging was performed to produce the final PSE with a 95% credibility set (CS). RESULTS: We sampled 1766, 1848, and 1865 FSWs and sexually exploited minors in each capture round. There were 169 recaptures strictly between captures 1 and 2, 210 recaptures exclusively between captures 2 and 3, and 65 recaptures between captures 1 and 3 only. In all 3 captures, 61 FSWs were captured. The median PSE of street- and venue-based FSWs and sexually exploited minors in Rwanda was 37,647 (95% CS 31,873-43,354), corresponding to 1.1% (95% CI 0.9%-1.3%) of the total adult females in the general population. Relative to the adult females in the general population, the western and northern provinces ranked first and second with a higher concentration of FSWs, respectively. The cities of Kigali and eastern province ranked third and fourth, respectively. The southern province was identified as having a low concentration of FSWs. CONCLUSIONS: We provide, for the first time, both the national and provincial level population size estimate of street- and venue-based FSWs in Rwanda. Compared with the previous 2 rounds of FSW PSEs at the national level, we observed differences in the street- and venue-based FSW population size in Rwanda. Our study might not have considered FSWs who do not want anyone to know they are FSWs due to several reasons, leading to a possible underestimation of the true PSE.

Home and community based care program assessment for people living with HIV/AIDS in Arba Minch, Southern Ethiopia.

BACKGROUND: People Living with HIV/AIDS (PLWHA) require significant care and support; however, most care needs are still unmet. To our knowledge, no studies have described the activities and challenges of care services in Ethiopia. Our objective was to assess the status, shortcomings and prospects of care and support services provided to PLWHA in the town of Arba Minch, Ethiopia, and surrounding areas. METHODS: A cross-sectional quantitative study combined with qualitative methods was conducted in Southern Ethiopia among 226 randomly selected PLWHAs and 10 service providers who were purposively selected. Data was collected using a pre-tested structured interview questionnaire and in-depth interview guideline. Quantitative data was analyzed using SPSS windows based statistical software while qualitative data was analyzed manually using thematic framework analysis. RESULTS: A total of 226 PLWHAs were interviewed. Socio-economic support (material and income generating activities) was being received by 108 (47.8%) of the respondents, counseling services (e.g. psychological support) were being received 128(56.6%), 144 (63.7%) alleviation of stigma and discrimination as human right and legal support for study participants. Inadequate external financial support, lack of proper referral systems between different care providers were among the reasons identified for the low quality and redundancy of care and support activities. Nonetheless, many opportunities and prospects, including easily accessible care receivers (PLWHA), good political and societal will were also implicated. CONCLUSION: Care and support services provided to PLWHAs in the study area are by far lower in terms of coverage and quantity. Strategies for improvement could be facilitated given the observed political will, social support and access to care givers.

Daily Training efficiency during computerized cognitive rehabilitation training (CCRT): an analysis from a randomized trial in Ugandan children with and without severe malaria.

Children in Uganda are at risk for significant cognitive sequelae from severe malaria. Computerized cognitive rehabilitation training (CCRT) represents a potential method to improve working memory, behavior, and executive functioning, cognitive domains most at risk following severe malaria. The primary aim of this study was to complete a secondary analysis of data from a concluded CCRT randomized control trial in order to compare the training efficiency of a commonly used CCRT program under conditions of titrated (adaptive) or non-titrated (non-adaptive) training and with children with increasing malaria severity to determine how various factors may affect potential CCRT improvement. A total of 201 school-aged children (66.2% boys) who were either healthy (n = 102) or previously diagnosed with severe or cerebral malaria (n = 99) were randomized into two active treatment arms (titrated and non-titrated learning). Each child received 24 one-hour sessions of training over 8 weeks using Captain's Log® CCRT by BrainTrain, which includes a comprehensive set of CCRT tasks. Children generally benefited from CCRT over the 24 training sessions, but titrated CCRT showed a clear advantage over non-titrated. Severity of illness or factors such as BMI, did not moderate CCRT performance indicators. These findings support our hypothesis that titrated CCRT would result in steeper improvement in learning, but do not support our hypothesis that history of recent significant illness would affect learning proficiency. Findings were evident across all CCRT performance scores, even given that children were from generally rural, low-resource settings and were generally unfamiliar with computers.ABBREVIATIONS:Computerized Cognitive Rehabilitation Training (CCRT); Mental Processing Index (MPI); Home Observation for the Measurement of the Environment (HOME); Socioeconomic Status (SES); least square means (LSM).

Consistent Condom Use Among Men Who Have Sex With Men in Lomé and Kara, Togo.

High transmission probability of HIV during condomless anal sex puts men who have sex with men (MSM), transgender, and nonbinary individuals at increased risk of infection. This analysis aims to examine the socioeconomic, biological, and behavioral factors that are associated with consistent condom use (CCU) during insertive/receptive anal sex among MSM in the last month in the cities of Lomé and Kara, Togo. A total of 683 MSM ≥18 years of age were surveyed using respondent-driven sampling (RDS) for a cross-sectional survey in Lomé (n = 354; 51.8%) and Kara (n = 329; 48.2%). Participants completed a structured questionnaire and were tested for HIV and syphilis. Statistical analyses included RDS-weighted proportions, bootstrapped confidence intervals (CIs), and logistic regression models. When compared with Lomé, MSM in Kara had lower odds of CCU [adjusted odds ratio (aOR) = 0.29, 95% CI = 0.19-0.44]. Other factors associated with lower CCU were having an income of 2,000 Communaute Financiere Africaine (CFA)-12,000 CFA (aOR = 0.53, 95% CI = 0.36-0.77) or above 12,000 CFA (aOR = 0.34, 95% CI = 0.20-0.57), transgender women (aOR = 0.47, 95% CI = 0.25-0.92), and intersex gender (aOR = 0.42, 95% CI = 0.24-0.73), and ever being forced to have sex (aOR = 0.42, 95% CI = 0.21-0.82). Factors associated with CCU were identified in this study including older age (aOR = 1.49, 95% CI = 1.04-2.14) and having easy access to condoms (aOR = 2.70, 95% CI = 1.23-5.94) and very easy access to condoms (aOR = 2.73, 95% CI = 1.20-6.16). Reported condom use in this study was low, and several factors associated with CCU were identified including older age and access to condoms. This study highlights multiple barriers to preventive services experienced by MSM in Togo and therefore leveraging strategies to address these barriers may improve prevention of HIV and syphilis.

Evaluating Immunopathogenic Biomarkers During Severe Malaria Illness as Modifiers of the Neuropsychologic Benefits of Computer Cognitive Games Rehabilitation in Ugandan Children.

BACKGROUND: We explored 3 immunopathogenic biomarkers collected during acute malaria illness as potential moderators of gains from a computerized cognitive rehabilitation training (CCRT) intervention. METHOD: Von Willebrand Factor (vWF), tumor necrosis factor (TNF) and Regulated on Activation, Normal T Expressed and Secreted (RANTES) were assayed from plasma and cerebral spinal fluid (CSF) of children during acute severe malaria anemia or cerebral malaria. Two years after acute malaria illness, 150 surviving children and 150 nonmalaria community controls (CCs) from their households 6-12 years old entered a 3-arm randomized controlled trial of titrating and nontitrating CCRT against no CCRT. Tests of cognition [Kaufman Assessment Battery for Children (KABC)], Tests of Variables of Attention and Achenbach Child Behavior Checklist (CBCL) were administered before and after 24 CCRT sessions over a 3-month period, and at 1-year follow-up. Differences in outcomes by trial arms and biomarker levels were evaluated using linear mixed effects models. RESULTS: Severe malaria survivors with lower levels of vWF, lower CSF levels of TNF and higher levels of plasma and CSF RANTES had better KABC cognitive performance after both titrating and nontitrating CCRT compared with no CCRT. For the CBCL, high plasma RANTES was associated with no benefit from either the titrating and nontitrating CCRT, whereas high TNF plasma was predictive of the benefit for both interventions. These biomarker moderating effects were not evident for CC children. CONCLUSIONS: Severe malaria immunopathogenic biomarkers may be related to poorer long-term brain/behavior function as evidenced by diminished benefit from a computerized cognitive rehabilitation intervention.

Neuropsychological benefits of computerized cognitive rehabilitation training in Ugandan children surviving severe malaria: A randomized controlled trial.

BACKGROUND: Computerized cognitive rehabilitation training (CCRT) may be beneficial for alleviating persisting neurocognitive deficits in Ugandan severe malaria survivors. We completed a randomized controlled trial of CCRT for both severe malaria and non-malaria cohorts of children. METHODS: 150 school-age severe malaria and 150 non-malaria children were randomized to three treatment arms: 24 sessions of Captain's Log CCRT for attention, working memory and nonverbal reasoning, in which training on each of 9 tasks difficulty increased with proficiency; a limited CCRT arm that did not titrate to proficiency but randomly cycled across the simplest to moderate level of training; and a passive control arm. Before and after 2 months of CCRT intervention and one year following, children were tested with the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), computerized CogState cognitive tests, the Behavior Rating Inventory for Executive Function (BRIEF), and the Achenbach Child Behavior Checklist (CBCL). RESULTS: Malaria children assigned to the limited-CCRT intervention arm were significantly better than passive controls on KABC-II Mental Processing Index (P = 0.04), Sequential Processing (working memory) (P = 0.02) and the Conceptual Thinking subtest (planning/reasoning) (P = 0.02). At one year post-training, the limited CCRT malaria children had more rapid CogState card detection (attention) (P = 0.02), and improved BRIEF Global Executive Index (P = 0.01) as compared to passive controls. Non-malaria children receiving CCRT significantly benefited only on KABC-II Conceptual Thinking (both full- and limited-CCRT; P < 0.01), CogState Groton maze chase and learning (P < 0.01), and CogState card identification (P = 0.05, full CCRT only). Improvements in KABC-II Conceptual Thinking planning subtest for the non-malaria children persisted to one-year follow-up only for the full-CCRT intervention arm. CONCLUSION: For severe malaria survivors, limited CCRT improved attention and memory outcomes more than full CCRT, perhaps because of the greater repetition and practice on relevant training tasks in the absence of the performance titration for full CCRT. There were fewer significant cognitive and behavior benefits for the non-malaria children, with the exception of the planning/reasoning subtest of Conceptual Thinking, with stronger full- compared to limited-CCRT improvements persisting to one-year follow-up.

Building capacity in neurodevelopment assessment of children in sub-Saharan Africa: A quality assurance model to implement standardized neurodevelopment testing.

Compromised neurodevelopment (ND) among infants and children is prevalent in sub-Saharan Africa. Standardized testing of ND is frequently prohibitive in these contexts, as tests require skilled staff for their application. In this paper, we present a quality assurance (QA) model (QualiND) for standardized ND testing, discussing findings and implications from our experience applying the Kaufman Assessment Battery for Children second edition (KABC-II). The QualiND model was implemented within IMPAACT P1104s study, a multisite, prospective study including 615 children affected by HIV. From 2014 to 2016, the QualiND managed 18 testers across 6 sites located in 4 African countries applying the KABC-II in 9 local languages. The QualiND is a multilevel, video-assisted iterative model incorporating remote evaluation, feedback, and supervision roles. Using an ad hoc rubric, videos of test application were evaluated by experienced staff in a centralized QA center. At each study site, testers and supervisors reviewed feedback from videos received via email from the QA center and devised an action plan to address testing errors and deficiencies. There were few instances of invalid tests and few barriers to test completion. Over 97% of KABC-II tests across sites were considered to be valid by the QA center. Overall, the QualiND model was a useful platform for remote supervision to nonspecialist and minimally trained research staff. The QualiND model may be useful to researchers and organizations involved in measuring early child development using standardized tests in low and middle-income countries.

Neurodevelopmental effects of ante-partum and post-partum antiretroviral exposure in HIV-exposed and uninfected children versus HIV-unexposed and uninfected children in Uganda and Malawi: a prospective cohort study.

BACKGROUND: Antiretroviral medication during pregnancy and breastfeeding substantially decreases the risk of HIV transmission from mothers to infants, but its effects on the child's neurodevelopment are unknown. This study compared neurodevelopmental outcomes of ante-partum and post-partum antiretroviral exposure in HIV-exposed and uninfected children with HIV-unexposed and uninfected children at ages 12, 24, 48, and 60 months. METHODS: For this study, a prospective cohort of HIV-exposed and uninfected children was identified from two research sites in the PROMISE-BF trial (at Blantyre, Malawi, and Kampala, Uganda), in which pregnant HIV-infected mothers were randomly assigned to triple antiretroviral prophylaxis (lopinavir-ritonavir plus either lamivudine and zidovudine or emtricitabine and tenofovir), versus zidovudine alone. Post partum, the mother-infant pairs were randomly assigned to maternal triple antiretroviral treatment or infant nevirapine during breastfeeding. HIV-unexposed and uninfected children matched for age, sex, and socioeconomic background were enrolled at vaccination and well-child clinics at the study sites. We included only children without a history of documented brain infection or injury or substantial malnutrition, and whose mothers were randomly assigned and maintained within their assigned ante-partum and post-partum phases throughout their treatment arm periods. Primary outcomes were the Mullen Scales of Early Learning (MSEL) cognitive composite score at age 12 months, 24 months, and 48 months; and the mental processing index for the Kaufman Assessment Battery for Children, second edition (KABC-II) global score at 48 months and 60 months. Repeated measures were analysed using a linear mixed-effects model controlling for data collection site. FINDINGS: Between Aug 23, 2013, and Dec 17, 2014, we co-enrolled 861 children. For MSEL assessments, 738 were eligible for inclusion at age 12 months, 790 at age 24 months, and 692 at age 48 months. For KABC-II assessments, 685 were eligible for inclusion at age 48 months and 445 at age 60 months. There were no differences in MSEL cognitive composite scores according to exposure at age 12 and 24 months (p=0·19 and 0·24, respectively, for comparison of all groups). At 48 months, MSEL cognitive composite scores were worse for children of mothers who did not remain on triple antiretroviral treatment throughout both the ante-partum and post-partum treatment phases (adjusted means 80·64 [95% CI 77·74-83·54] and 81·34 [78·19-84·48], respectively), compared with those who did remain on triple treatment (adjusted mean 85·93, 95% CI 83·05-88·80; p=0·0486 for the comparison of all groups). The KABC-II composite scores (mental processing index) did not differ at 48 or 60 months according to exposure (p=0·81 and 0·89, respectively, for comparison of all groups). Scores for MSEL and KABC-II for children of mothers on triple antiretrovirals in both the ante-partum and post-partum treatment phases were similar to those for children in the HIV-unexposed and uninfected reference group at all timepoints. INTERPRETATION: Maternal triple antiretroviral exposure during both the ante-partum and post-partum phases did not result in greater developmental risks for the mothers' HIV-exposed and uninfected children through age 60 months, compared with children who were HIV-unexposed and uninfected. This might be because ante-partum triple antiretroviral protection of the health of mothers with HIV during pregnancy might be neuroprotective for the child, and when continued post partum, could enhance the quality of caregiving for the child through better clinical care for the mother. FUNDING: National Institutes of Health and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Neruodevelopmental Outcomes in Preschool Children Living With HIV-1 Subtypes A and D in Uganda.

BACKGROUND: HIV is a neuropathogenic virus that may result in detrimental neurodevelopmental (ND) outcomes early in life. This is the first study to evaluate the effect of HIV-1 subtype on neurodevelopment of Ugandan preschool children. METHODS: Neurodevelopment of 87 HIV-1 infected and 221 HIV exposed uninfected Ugandan children 1.8-4.9 years of age was assessed using 4 scales of the Mullen Scales of Early Learning (MSEL), 2 scales of the Color Object Association Test (COAT), and 1 score of the Early Childhood Vigilance Test. HIV-1 subtype was defined by phylogenetic analyses. General linear models were used to relate test scores to HIV-1 subtype (A versus D) while adjusting for relevant covariates. The scores were benchmarked against HIV exposed uninfected group to facilitate the interpretation. RESULTS: Seventy-one percentage of children infected with subtype A versus 60% of children with subtype D were currently on antiretroviral therapy (P = 0.49). Children with HIV-1 subtype A infection were older when compared with subtype D (3.29 vs. 2.76 years, respectively, P = 0.03), but similar regarding sex, socioeconomic status, weight-for-age z-score, CD4+ and CD8+ (% and total), viral load. No statistically significant differences by HIV-1 subtype were observed in the MSEL, COAT and Early Childhood Vigilance Test. Differences ≥ 0.33 of the SD were observed for the MSEL Composite Score, Receptive Language (MSEL) and Total Memory (COAT). CONCLUSIONS: In contrast to previously reported differences in ND outcomes of school-age children by HIV-1 subtype, ND scores among preschool children were similar for subtypes A and D, with few potential differences on language production and memory outcomes that favored subtype A. Further investigation with larger sample sizes and longitudinal follow-up is needed.