High prevalence of low high-density lipoprotein cholesterol and insulin resistance among children and adolescents living with HIV in Uganda: harbinger for metabolic syndrome?

BACKGROUND: Antiretroviral therapy-associated adverse effects and comorbidities are still pervasive in people living with HIV, especially metabolic syndrome (MetS). We investigated the age-dependent prevalence of components of MetS and insulin resistance in children and adolescents living with HIV (CALWH). METHODS: A cross-sectional pilot study of CALWH treated at the Baylor Uganda Clinical Centre of Excellence in Kampala, Uganda, May to August 2021. The primary outcome of MetS was defined by both the International Diabetes Federation (IDF) and the Adult Treatment Panel (ATP III) criteria. We estimated the prevalence of MetS and its components for all participants and by the stratification factors. RESULTS: We enrolled 90 children and adolescents, aged 6 to <10 years (n = 30), 10 to <16 years (n = 30), and ≥ 16 to <19 years (n = 30). Fifty-one percent were females. The estimated prevalence of MetS was 1.11% (1 of 90) using either IDF or ATPIII criteria for all participants, and 3.33% in the oldest age group. Notably, while only one among study participants met the criterion based on having central obesity or blood pressure, over 55% of participants had one or more IDF component, with 47% having low high-density lipoprotein (HDL) cholesterol. Two participants (6.67%) in the group aged 10 to <16 years met one of the definitions for insulin resistance (IR) using the Homeostatic Model Assessment (HOMA-IR) index. For every 1-year increase in age, HOMA-IR index increased by 0.04 (95% confidence interval: 0.01-0.08; p = 0.02). CONCLUSIONS: With increasing survival of CALWH into adulthood, lifetime exposure to ART, the frequency of MetS in this population may rise, increasing the lifetime risk for associated health problems. There is a need to study the natural history of MetS in CALWH to inform preventative and treatment interventions as needed.

High prevalence of impaired glucose metabolism among children and adolescents living with HIV in Ghana.

BACKGROUND: Antiretroviral therapy (ART)-associated metabolic abnormalities, including impairment of glucose metabolism, are prevalent in adults living with HIV. However, the prevalence and pathogenesis of impaired glucose metabolism in children and adolescents living with HIV, particularly in sub-Saharan Africa, are not well characterized. We investigated the prevalence of impaired glucose metabolism among children and adolescents living with perinatally infected HIV in Ghana. METHODS: In this multicentre, cross-sectional study, we recruited participants from 10 paediatric antiretroviral treatment clinics from January to June 2022 in 10 facilities in Greater Accra and Eastern regions of Ghana. We determined impaired glucose metabolism in the study sample by assessing fasting blood sugar (FBS), insulin resistance as defined by the homeostatic model assessment for insulin resistance (HOMA-IR) index and glycated haemoglobin (HbA1c) levels. The prevalence of impaired glucose metabolism using each criterion was stratified by age and sex. The phenotypic correlates of glucose metabolism markers were also assessed among age, sex, body mass index (BMI) and waist-to-hip ratio (WHR). RESULTS: We analysed data from 393 children and adolescents living with HIV aged 6-18 years. A little over half (205/393 or 52.25%) of the children were female. The mean age of the participants was 11.60 years (SD = 3.50), with 122/393 (31.00%) aged 6-9 years, 207/393 (52.67%) aged 10-15 years, and 62/393 (15.78%) aged 16-18 years. The prevalence rates of glucose impairment in the study population were 15.52% [95% confidence interval (CI): 12.26-19.45], 22.39% (95% CI: 18.54-26.78), and 26.21% (95% CI: 22.10-30.78) using HbA1c, HOMA-IR, and FBS criteria, respectively. Impaired glucose metabolism detected by FBS and HOMA-IR was higher in the older age group, whereas the prevalence of abnormal HbA1c levels was highest among the youngest age group. Age and BMI were positively associated with FBS and HOMA-IR (p < 0.001). However, there was negative correlation of WHR with HOMA-IR (p < 0.01) and HbA1c (p = 0.01). CONCLUSION: The high prevalence of impaired glucose metabolism observed among the children and adolescents living with HIV in sub-Saharan Africa is of concern as this could contribute to the development of metabolic syndrome in adulthood.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

A continent-wide effort and solidarity at curbing COVID-19 pandemic: the Africa task force for novel coronavirus (AFTCOR) infection prevention and control technical working group's experience.

A continent-wide Africa Task Force for Coronavirus with its six technical working groups was formed to prepare adequately and respond to the novel Coronavirus disease (COVID-19) outbreak in Africa. This research in practice article aimed to describe how the infection prevention and control (IPC) technical working group (TWG) supported Africa Centre for Disease Control and Prevention (Africa CDC) in preparedness and response to COVID-19 on the continent. To effectively address the multifaceted IPC TWG mandate of organizing training and implementing rigorous IPC measures at healthcare service delivery points, the working group was sub-divided into four sub-groups-Guidelines, Training, Research, and Logistics. The action framework was used to describe the experiences of each subgroup. The guidelines subgroup developed 14 guidance documents and two advisories; all of which were published in English. In addition, five of these documents were translated and published in Arabic, while three others were translated and published in French and Portuguese. Challenges faced in the guidelines subgroup included the primary development of the Africa CDC website in English, and the need to revise previously issued guidelines. The training subgroup engaged the Infection Control Africa Network as technical experts to carry out in-person training of IPC focal persons and port health personnel across the African continent. Challenges faced included the difficulty in conducting face-to-face IPC training and onsite technical support due to the lockdown. The research subgroup developed an interactive COVID-19 Research Tracker on the Africa CDC website and conducted a context-based operation and implementation research. The lack of understanding of Africa CDC's capacity to lead her own research was the major challenge faced by the research subgroup. The logistics subgroup assisted African Union (AU) member states to identify their IPC supply needs through capacity building for IPC quantification. A notable challenge faced by the logistics subgroup was the initial lack of experts on IPC logistics and quantifications, which was later addressed by the recruitment of professionals. In conclusion, IPC cannot be built overnight nor can it be promoted abruptly during outbreaks of diseases. Thus, the Africa CDC should build strong national IPC programmes and support such programmes with trained and competent professionals.

Higher intensive care unit consultations for COVID-19 patients living with HIV compared to those without HIV coinfection in Uganda.

Coronavirus disease-2019 (COVID-19) is the leading cause of death worldwide from a single infectious agent. Whether or not HIV infection affects clinical outcomes in patients with COVID-19 remains inconclusive. This study aimed to compare the clinical outcomes of people living with HIV (PLWH) and non-HIV-infected patients hospitalized during the second wave of the COVID-19 pandemic in Uganda. We retrospectively retrieved data on patients with COVID-19 who were admitted to the Mulago National Referral Hospital in Uganda between April 2021 and mid-July 2021. We performed propensity-score-matching of 1:5 to compare outcomes in COVID-19 patients living with and those without HIV coinfection (controls). We included 31 PLWH and 155 non-HIV controls. The baseline characteristics were similar across groups (all p values > 0.05). PLWH had close to threefold higher odds of having ICU consultation compared to controls (odds ratio [OR]: 2.9, 95% CI: 1.2-6.9, p = 0.015). There was a trend toward having a severe or critical COVID-19 illness among PLWHIH compared to controls (OR: 1.9, 95% CI: 0.8-4.7, p = 0.164). Length of hospitalization was not significantly different between PLWH and non-HIV controls (6 days vs. 7 days, p = 0.184). Seven-day survival was 63% (95% CI: 42%-78%) among PLWH and 72% (95% CI: 61%-82%) among controls while 14-day survival was 50% (95% CI: 28%-69%) among PLWH and 65% (95% CI: 55%-73%) among controls (p = 0.280). There was another trend toward having 1.7-fold higher odds of mortality among PLWH compared to controls (OR: 1.7, 95% CI: 0.8-3.8, p = 0.181). Our data suggest that PLWH may be at an increased risk of severe or critical COVID-19 illness requiring ICU consultation. Further studies with larger sample sizes are recommended.

Development of a community-based COVID-19 intervention in rural Ghana: a document analysis.

BACKGROUND: The COVID-19 pandemic has caused the loss of millions of lives and economic breakdowns in many countries across the globe. Despite the limited availability of vaccines and the challenges of poor health infrastructure, few interventions have been developed and implemented for those who live in rural areas, particularly in sub-Saharan Africa. In response, Cocoa360, a global health nonprofit in rural Ghana designed an intervention called Cocoa360's COVID-19 Preparedness and Outbreak Prevention Plan (CoCoPOPP). This paper aimed to examine the extent to which CoCoPOPP's design aligned with the Promoting Action on Research Implementation in Health Services (PARIHS) framework. METHODS: We reviewed documents influencing CoCoPOPP's design between March and June 2021. A total of 11 documents were identified for analysis. Using the Promoting Action on Research Implementation in Health Services (PARIHS) framework as a guide, thematic analysis was done to analyze the extracted data. RESULTS: Overall, CoCoPOPP's design aligned with the evidence, context, and facilitation domains of the PARIHS framework. It positioned CoCoPOPP as an intervention that considered the unique context of a rural Ghanaian setting. It was guided by robust and high-quality published and non-published evidence and engaged external and internal stakeholders during its implementation. CoCoPOPP's context-dependent nature positions it for potential replication in sub-Saharan Africa's rural communities with similar farming contexts. Specific areas that were less well and/or not addressed were the unintended negative consequences of community engagement, the absence of primary data in the guiding evidence, and the lack of a facilitation continuum coupled with the role of power during the facilitation process. CONCLUSION: CoCoPOPP, Cocoa360's response to the COVID-19 pandemic in rural Ghana, is an evidence-driven, context-dependent public health intervention that has been designed to reduce COVID-19 infections and prevent potential deaths. This study underscores the importance of considering the unique community and cultural contexts, employing evidence, and engaging local and external actors as facilitators when designing interventions to respond to global health pandemics.

Severe Acute Respiratory Syndrome Coronavirus 2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth.

OBJECTIVE: To characterize the demographic and clinical features of pediatric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) syndromes and identify admission variables predictive of disease severity. STUDY DESIGN: We conducted a multicenter, retrospective, and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at 8 sites in New York, New Jersey, and Connecticut. RESULTS: We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into 3 groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% vs 18%, P = .02). Seven patients (2%) died and 114 (41%) were admitted to the intensive care unit. In multivariable analyses, obesity (OR 3.39, 95% CI 1.26-9.10, P = .02) and hypoxia on admission (OR 4.01; 95% CI 1.14-14.15; P = .03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR 8.33 per unit decrease in 109 cells/L, 95% CI 2.32-33.33, P = .001) and greater C-reactive protein (OR 1.06 per unit increase in mg/dL, 95% CI 1.01-1.12, P = .017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity. CONCLUSIONS: We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

The clinical epidemiology of coronavirus disease 2019 in children and adolescents mirrors the widening gap in healthcare disparities.

PURPOSE OF REVIEW: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has exacerbated the longstanding racial/ethnic health disparities in the USA, with a disproportionately negative effect on children of color. This review summarizes recently published studies that describe the clinical epidemiology and racial/ethnic disparities associated with SARS-CoV-2 in children. RECENT FINDINGS: Children with SARS-CoV-2 infections manifest with a wide spectrum of disease. Most are either asymptomatic or mildly symptomatic with fever, gastrointestinal, and/or upper respiratory disease. Some children can progress to develop severe lower respiratory disease or a hyper-inflammatory, Kawasaki-like syndrome leading to cardiovascular shock. Although SARS-CoV-2-related deaths in children are rare, more children died within the first nine months of the pandemic than have died during any influenza season over the last decade.Black and Hispanic children represent less than 41% of the US population but account for three out of every four SARS-CoV-2-related hospitalizations and deaths in the USA. The drivers of these disparities in children are complex and likely a combination of societal, biological, and behavioral influences. SUMMARY: This pandemic brought to light longstanding health disparities in historically marginalized populations, and minority children have suffered tremendously. It provides an opportunity to understand how a virus hijacked deep-rooted inequities, address these inequities, and work to prevent this outcome in future pandemics/epidemics.

Illness Narratives of Children Living with HIV Who Do Not Know Their HIV Status in Ghana: I'm Sick, But I Don't Know the Sickness-A Qualitative Study.

Despite available guidelines for disclosure of HIV status to children, most children living with HIV are unaware of their diagnosis. We sought to characterize the concepts of illness and treatment among children living with HIV who do not know their status. As part of the Sankofa trial we interviewed 435 children aged 6-18 enrolled in clinical care at pediatric HIV clinics at two teaching hospitals in Ghana. Theoretic thematic analysis generated themes among responses. The children believe they come to the clinic to collect medication, to address specific symptoms, to prevent and treat 'sickness', or as part of their routine. Most children learned of their 'illness' from a family member. A majority (73.5%) of children had never talked about their 'illness' with anyone else; many feared consequences. Children living with HIV who do not know their status exhibit signs of anticipated and internalized stigma regarding their unknown 'illness.' An understanding of the way children conceptualize their illness has implications for health promotion and the provision of appropriate information to children living with HIV.ClinicalTrials.gov Identifier NCT01701635.

RESUMEN: A pesar de las pautas disponibles para la divulgación del estado del VIH a los niños, la mayoría de los niños que viven con el VIH desconocen su diagnóstico. Intentamos describir los conceptos de enfermedad y tratamiento entre los niños que viven con el VIH que no conocen su estado de infeccion. Como parte del ensayo Sankofa, entrevistamos a 435 niños de 6 a 18 años inscritos en atención clínica cuidado en clínicas pediátricas de VIH en dos hospitales docentes en Ghana. El análisis temático teórico generó temas entre las respuestas obtenidas. Los niños creen que vienen a la clínica a recoger medicamentos, a tratar síntomas específicos, a prevenir y tratar "condiciones" o como parte de su cuidado rutinario. A traves de entrevistas, aprendimos que la mayoría de los niños aprendieron de su "enfermedad" de un miembro de la familia. Esta mayoría (73.5%) nunca habían hablado sobre su "enfermedad" con nadie más; debido a muchas consecuencias temidas. Los niños que viven con VIH que no conocen su estado, exhiben signos de estigma anticipado e internalizado con respecto a su "enfermedad" desconocida. El entender la forma en que los niños conceptualizan su enfermedad tiene implicaciones para la promoción de la salud y el suministro de información adecuada a los niños que viven con el VIH.

Sankofa pediatric HIV disclosure intervention did not worsen depression scores in children living with HIV and their caregivers in Ghana.

BACKGROUND: The 'Sankofa' pediatric HIV disclosure study (2013-2017) was an intervention that aimed to address the low prevalence of disclosure of HIV status in Ghana. METHODS: We conducted a cross-sectional study at the intervention site in Kumasi, Ghana, in 2019, (2 years after study closure) and administered the 21-item Beck Depression Inventory (BDI) and the 10-item Child Depression Inventory (CDI) to caregiver-child dyads who received the intervention. RESULTS: We enrolled 65% (N = 157) of the original dyads in the present study. Between Sankofa enrollment baseline and the present study, both children and caregivers had significant (p < 0.0001) mean reductions in CDI scores and BDI scores, respectively. CDI scores of the children were significantly correlated with BDI scores of the caregivers (r = 0.019, p = 0.019). No statistically significant associations between disclosure status and either CDI score or BDI score were found. CONCLUSIONS: Our findings did not support caregivers' fears that disclosure leads to depression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01701635 (date of registration Oct 5, 2012).

Prototype Development, Usability, and Preference of a Culturally-relevant Pictorial Aid to Facilitate Comprehension of Likert-type Levels of Agreement in Caregivers of Children Living With HIV in Ghana.

Pictorial illustrations of Likert-type scales are culturally useful and may reduce error associated with usage of Westernized self-report measures in low- and middle-income countries. Pictorial illustrations can be encounter-specific decision aids in populations with low literacy or English proficiency. In an unanticipated finding from the SANKOFA study, caregivers of children living with human immunodeficiency virus experienced challenges comprehending Likert-type scales. A cross-sectional, qualitative study was conducted with a SANKOFA participant subset (n = 30) in Ghana. Using an informatics-based formative design approach, we developed a culturally-relevant pictorial aid to assess usability and preference when compared to a Likert-type self-report measure. Ninety percent (n = 27) of substudy participants preferred the pictorial of a traditional Bolga basket over a shallow basket. Forty-three percent (n = 13) preferred the pictorial aid over the Likert-type measure. Fifty percent reported the pictorial aid was easy to use. Fifty-seven percent preferred the Likert-type measure, potentially because English proficiency is regarded in Ghana as a means of upward social and financial mobility. Such cultural norms may have contributed to the lack of consensus and must be considered for pictorial aids to be meaningful. Pictorial aids have been designed for use in clinical and research settings. They reduce barriers associated with lower textual literacy while facilitating comprehension and decision-making.

A Case for Girl-child Education to Prevent and Curb the Impact of Emerging Infectious Diseases Epidemics.

Not only do epidemics such as HIV/AIDS, Ebola Virus Disease (EVD), and the current Coronavirus Disease (COVID-19) cause the loss of millions of lives, but they also cost the global economy billions of dollars. Consequently, there is an urgent need to formulate interventions that will help control their spread and impact when they emerge. The education of young girls and women is one such historical approach. They are usually the vulnerable targets of disease outbreaks - they are most likely to be vehicles for the spread of epidemics due to their assigned traditional roles in resource-limited countries. Based on our work and the work of others on educational interventions, we propose six critical components of a cost-effective and sustainable response to promote girl-child education in resource-limited settings.

A comparison of machine learning techniques for classification of HIV patients with antiretroviral therapy-induced mitochondrial toxicity from those without mitochondrial toxicity.

BACKGROUND: Antiretroviral therapy (ART) has significantly reduced HIV-related morbidity and mortality. However, therapeutic benefit of ART is often limited by delayed drug-associated toxicity. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of ART regimens. NRTIs compete with endogenous deoxyribonucleotide triphosphates (dNTPs) in incorporation into elongating DNA chain resulting in their cytotoxic or antiviral effect. Thus, the efficacy of NRTIs could be affected by direct competition with endogenous dNTPs and/or feedback inhibition of their metabolic enzymes. In this paper, we assessed whether the levels of ribonucleotides (RN) and dNTP pool sizes can be used as biomarkers in distinguishing between HIV-infected patients with ART-induced mitochondrial toxicity and HIV-infected patients without toxicity. METHODS: We used data collected through a case-control study from 50 subjects. Cases were defined as HIV-infected individuals with clinical and/or laboratory evidence of mitochondrial toxicity. Each case was age, gender, and race matched with an HIV-positive without evidence of toxicity. We used a range of machine learning procedures to distinguish between patients with and without toxicity. Using resampling methods like Monte Carlo k-fold cross validation, we compared the accuracy of several machine learning algorithms applied to our data. We used the algorithm with highest classification accuracy rate in evaluating the diagnostic performance of 12 RN and 14 dNTP pool sizes as biomarkers of mitochondrial toxicity. RESULTS: We used eight classification algorithms to assess the diagnostic performance of RN and dNTP pool sizes distinguishing HIV patients with and without NRTI-associated mitochondrial toxicity. The algorithms resulted in cross-validated classification rates of 0.65-0.76 for dNTP and 0.72-0.83 for RN, following reduction of the dimensionality of the input data. The reduction of input variables improved the classification performance of the algorithms, with the most pronounced improvement for RN. Complex tree-based methods worked the best for both the deoxyribose dataset (Random Forest) and the ribose dataset (Classification Tree and AdaBoost), but it is worth noting that simple methods such as Linear Discriminant Analysis and Logistic Regression were very competitive in terms of classification performance. CONCLUSIONS: Our finding of changes in RN and dNTP pools in participants with mitochondrial toxicity validates the importance of dNTP pools in mitochondrial function. Hence, levels of RN and dNTP pools can be used as biomarkers of ART-induced mitochondrial toxicity.

Transfer is not a transition - voices of Jamaican adolescents with HIV and their health care providers.

Increasing access to antiretroviral therapy in resource-limited settings (RLS) has resulted in the survival of perinatally HIV-infected children into adulthood. We characterized the transition process from pediatric to adult care by conducting semi-structured interviews of HIV-infected adolescents and health care providers in Jamaica. Using an inductive content analytic approach, four themes emerged: (1) Transition should be holistic and a process; (2) Pediatric clinics were like families; (3) Rootedness in the pediatric clinic; and (4) Need for adolescent-centered services to bridge the gap between pediatric and adult-centered services. Adolescent informed- and centered-transition approach may result in better outcomes for HIV-infected adolescents.

High prevalence of non-adherence to antiretroviral therapy among undisclosed HIV-infected children in Ghana.

Adherence to antiretroviral therapy (ART) remains one of the greatest obstacles in pediatric HIV care. We sought to determine the prevalence of adherence to ART among undisclosed HIV-infected children and adolescents in Ghana. We analyzed baseline data from HIV-infected children and adolescents aged 7-18 years old enrolled in the SANKOFA Pediatric HIV disclosure intervention study in Ghana. Antiretroviral medication adherence was measured using caregiver 3-day recall; child 3-day recall; and pharmacy records for antiretroviral time-to-refill. Four hundred and twenty child-caregiver dyads were enrolled from January 2013 to June 2016. The median adherence (interquartile range), as measured by time-to-refill, was 93.2% (68.0%-100.0%). However, only 47.5% of children had ≥95% adherence ("good adherence") using time-to-refill data. Children of caregivers who had received secondary or higher level of education versus no school (aOR, 2.90, 95% Confidence Interval, CI 1.29-6.56), p = 0.010) or elementary education only (aOR, 2.20, CI, 1.24-3.88, p = 0.007) were more likely to have "good adherence" (≥95%). In this cohort of children unaware of their HIV positive status, median ART adherence rate was sub-optimal (by World Health Organization definition) while 38% had poor adherence (<85%).

Prevalence and correlates of depression among caregivers of children living with HIV in Ghana: findings from the Sankofa pediatric disclosure study.

Prior studies show an association between caregiver depression and child health outcomes. There has been little examination of depression among caregivers of HIV-infected children in sub-Saharan countries where pediatric HIV is concentrated. Using baseline data collected in the pediatric HIV disclosure intervention trial, Sankofa, we examined the prevalence and factors associated with depression among caregivers (N = 446) of children infected with HIV in Ghana. Data were analyzed with descriptive and regression analyses. The mean age of the caregivers was 42.2 ± 10.4 years. Eighty percent of the caregivers were female and 59% were HIV-infected. Twenty-eight percent (n = 126) of the caregivers were found to have mild to severe depression. In the adjusted model, factors significantly associated with caregiver depression included: HIV-positive caregiver status (P = 0.04), low income (P = 0.02), lower social support, (P = 0.01), lower HIV knowledge, (P = 0.01), worse HIV illness perceptions (P≤0.001), and greater perceived HIV stigma (P≤0.001). Although we found a high prevalence of depression among our study participants, several of the risks factors identified are modifiable and amenable to interventions that are locally available and affordable.

Recovery of Infectious Hepatitis C Virus From Injection Paraphernalia: Implications for Prevention Programs Serving People Who Inject Drugs.

Background: Controlling hepatitis C virus (HCV) transmission among people who inject drugs (PWID) has focused on preventing sharing syringes and drug preparation paraphernalia, but it is unclear whether HCV incidence linked to sharing paraphernalia reflects contamination of the paraphernalia or syringe-mediated contamination when drugs are shared. Methods: In experiments designed to replicate real-world injection practices when drugs are shared, the residual contents of HCV-contaminated syringes with detachable or fixed needled were passed through the "cookers" and filters used by PWID in preparing drugs for injection and then introduced into a second syringe. All items were tested for the presence of infectious HCV using a chimeric HCV with a luciferase gene. Results: Hepatitis C virus could not be recovered from cookers regardless of input syringe type or cooker design. Recovery was higher when comparing detachable needles to fixed needles for residue in input syringes (73.8% vs 0%), filters (15.4% vs 1.4%), and receptive syringes (93.8% vs 45.7%). Conclusions: Our results, consistent with the hypothesis that sharing paraphernalia does not directly result in HCV transmission but is a surrogate for transmissions resulting from sharing drugs, have important implications for HCV prevention efforts and programs that provide education and safe injection supplies for PWID populations.

Combination of Tenofovir and Emtricitabine with Efavirenz Does Not Moderate Inhibitory Effect of Efavirenz on Mitochondrial Function and Cholesterol Biosynthesis in Human T Lymphoblastoid Cell Line.

Efavirenz (EFV), the most popular nonnucleoside reverse transcriptase inhibitor, has been associated with mitochondrial dysfunction in most in vitro studies. However, in real life the prevalence of EFV-induced mitochondrial toxicity is relatively low. We hypothesized that the agents given in combination with EFV moderate the effect of EFV on mitochondrial function. To test this hypothesis, we cultured a human T lymphoblastoid cell line (CEM cells) with EFV alone and in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) to investigate the effects on mitochondrial respiration and function and cholesterol biosynthesis. There was a statistically significant concentration- and time-dependent apoptosis, reduction in mitochondrial membrane potential, and increase in production of reactive oxygen species in cells treated with either EVF alone or in combination with TDF plus FTC. Compared to dimethyl sulfoxide-treated cells, EFV-treated cells had significant reduction in oxygen consumption rate contributed by basal mitochondrial respiration and decreased protein expression of electron transport chain complexes (CI, CII, and CIV). Treatment with EFV resulted in a decrease in mitochondrial DNA content and perturbation of more coding genes (n = 13); among these were 11 genes associated with lipid or cholesterol biosynthesis. Our findings support the growing body of knowledge on the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis. Interestingly, combining TDF and FTC with EFV did not alter the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis. The gap between the prevalence of EFV-induced mitochondrial toxicity in in vitro and in vivo studies could be due to individual differences in the pharmacokinetics of EFV.

Upregulation of Apoptosis Pathway Genes in Peripheral Blood Mononuclear Cells of HIV-Infected Individuals with Antiretroviral Therapy-Associated Mitochondrial Toxicity.

A case-control study of the effect of antiretroviral therapy (ART) on apoptosis pathway genes comprising 16 cases (HIV infected with mitochondrial toxicity) and 16 controls (HIV uninfected) was conducted. A total of 26 of 84 genes of the apoptosis pathway were differentially expressed. Two of the upregulated genes, DFFA and TNFRSF1A, classified 75% of study participants correctly as either a case or control. Thus, apoptosis may be in the causal pathway of ART-associated mitochondrial toxicity. These two genes could be markers for detecting and monitoring ART-induced mitochondrial toxicity.