Antiretroviral Therapy Responses Among Children Attending a Large Public Clinic in Soweto, South Africa

Antiretroviral therapy access with successful outcomes for children is expanding in resource limited countries. The aim of this study was to determine treatment responses of children in a routine setting where first line therapy with lopinavir/ritonavir is routinely included for young children

Achieving UNAIDS 90-90-90 targets for pregnant and postpartum women in sub-Saharan Africa: progress, gaps and research needs

The implementation of the 2013 World Health Organization Option B+ recommendations for HIV treatment during pregnancy has helped drive significant progress in achieving universal treatment for pregnant and postpartum women in sub-Saharan Africa (SSA). Yet, critical research and implementation gaps exist in achieving the UNAIDS 90-90-90 targets. To help guide researchers, programmers and policymakers in prioritising these areas, we undertook a comprehensive review of the progress, gaps and research needs to achieve the 90-90-90 targets for this population in the Option B+ era, including early infant HIV diagnosis (EID) for HIV-exposed infants. Salient areas where progress has been achieved or where gaps remain include: (1) knowledge of HIV status is higher among people with HIV in southern and eastern Africa compared to western and central Africa (81% versus 48%, UNAIDS); (2) access to antiretroviral therapy (ART) for pregnant women has doubled in 22 of 42 SSA countries, but only six have achieved the second 90, and nearly a quarter of pregnant women initiating ART become lost to follow-up; (3) viral suppression data for this population are sparse (estimates range from 30% to 98% peripartum), with only half of women maintaining suppression through 12 months postpartum; and (4) EID rates range from 15% to 62%, with only three of 21 high-burden SSA countries testing >50% HIV-exposed infants within the first 2 months of life. We have identified and outlined promising innovations and research designed to address these gaps and improve the health of pregnant and postpartum women living with HIV and their infants

Marginal structural models for repeated measures where intercept and slope are correlated: An application exploring the benefit of nutritional supplements on weight gain in HIV-infected children initiating antiretroviral therapy

BackgroundThe impact of nutritional supplements on weight gain in HIV-infected children on antiretroviral treatment (ART) remains uncertain. Starting supplements depends upon current weight-for-age or other acute malnutrition indicators, producing time-dependent confounding. However, weight-for-age at ART initiation may affect subsequent weight gain, independent of supplement use. Implications for marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) are unclear.MethodsIn the ARROW trial, non-randomised supplement use and weight-for-age were recorded monthly from ART initiation. The effect of supplements on weight-for-age over the first year was estimated using generalised estimating equation MSMs with IPTW, both with and without interaction terms between baseline weight-for-age and time. Separately, data were simulated assuming no supplement effect, with use depending on current weight-for-age, and weight-for-age trajectory depending on baseline weight-for-age to investigate potential bias associated with different MSM specifications.ResultsIn simulations, despite correctly specifying IPTW, omitting an interaction in the MSM between baseline weight-for-age and time produced increasingly biased estimates as associations between baseline weight-for-age and subsequent weight trajectory increased. Estimates were unbiased when the interaction between baseline weight-for-age and time was included, even if the data were simulated with no such interaction. In ARROW, without an interaction the estimated effect was +0.09 (95%CI +0.02,+0.16) greater weight-for-age gain per month's supplement use; this reduced to +0.03 (-0.04,+0.10) including the interaction.DiscussionThis study highlights a specific situation in which MSM model misspecification can occur and impact the resulting estimate. Since an interaction in the MSM (outcome) model does not bias the estimate of effect if the interaction does not exist, it may be advisable to include such a term when fitting MSMs for repeated measures

Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort

BACKGROUND: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line. METHODS: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event. RESULTS: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor-based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively. CONCLUSIONS: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years

Prevalence of potentially traumatic events and symptoms of depression, anxiety, hazardous alcohol use, and post-traumatic stress disorder among people with HIV initiating HIV care in Cameroon

BACKGROUND: This study explored the relationship between specific types of potentially traumatic events (PTEs) and symptoms of mental health disorders among people with HIV (PWH) in Cameroon. METHODS: We conducted a cross-sectional study with 426 PWH in Cameroon between 2019-2020. Multivariable log binominal regression was used to estimate the association between exposure (yes/no) to six distinct types of PTE and symptoms of depression (Patient Health Questionnaire-9 score \u3e 9), PTSD (PTSD Checklist for DSM-5 score \u3e 30), anxiety (Generalized Anxiety Disorder-7 scale score \u3e 9), and hazardous alcohol use (Alcohol Use Disorders Identification Test score \u3e 7 for men; \u3e 6 for women). RESULTS: A majority of study participants (96%) reported exposure to at least one PTE, with a median of 4 PTEs (interquartile range: 2-5). The most commonly reported PTEs were seeing someone seriously injured or killed (45%), family members hitting or harming one another as a child (43%), physical assault or abuse from an intimate partner (42%) and witnessing physical assault or abuse (41%). In multivariable analyses, the prevalence of PTSD symptoms was significantly higher among those who reported experiencing PTEs during childhood, violent PTEs during adulthood, and the death of a child. The prevalence of anxiety symptoms was significantly higher among those who reported experiencing both PTEs during childhood and violent PTEs during adulthood. No significant positive associations were observed between specific PTEs explored and symptoms of depression or hazardous alcohol use after adjustment. CONCLUSIONS: PTEs were common among this sample of PWH in Cameroon and associated with PTSD and anxiety symptoms. Research is needed to foster primary prevention of PTEs and to address the mental health sequelae of PTEs among PWH

Psychiatric comorbidity and psychosocial stressors among people initiating HIV care in Cameroon

BACKGROUND: Psychiatric comorbidity, the presence of two or more mental health disorders, has been associated with suboptimal HIV treatment outcomes. Little is known about the prevalence of psychiatric comorbidity among people with HIV (PWH) in sub-Saharan Africa. METHODS: We conducted interviews with PWH initiating HIV care in Cameroon between June 2019 and March 2020. Depression, anxiety, post-traumatic stress disorder (PTSD), and harmful drinking were dichotomized to represent those with and without symptoms of each. Psychiatric comorbidity was defined as having symptoms of two or more disorders assessed. Moderate or severe household hunger, high anticipatory HIV-related stigma, low social support, and high number of potentially traumatic events were hypothesized as correlates of psychiatric comorbidity. Bivariable log binomial regression models were used to estimate unadjusted associations between psychosocial stressors and psychiatric comorbidity. RESULTS: Among 424 participants interviewed, the prevalence of psychiatric comorbidity was 16%. Among those with symptoms of at least one mental health or substance use disorder (n = 161), the prevalence of psychiatric comorbidity was 42%. The prevalence of psychiatric comorbidity was 33%, 67%, 76%, and 81% among those with symptoms of harmful drinking, depression, anxiety, and PTSD, respectively. Among individuals with symptoms of a mental health or substance use disorder, a high number of potentially traumatic events (prevalence ratio (PR) 1.71 [95% CI 1.21, 2.42]) and high anticipatory HIV-related stigma (PR 1.45 [95% CI 1.01, 2.09]) were associated with greater prevalence of psychiatric comorbidity. CONCLUSION: Psychiatric comorbidity was common among this group of PWH in Cameroon. The effectiveness and implementation of transdiagnostic or multi-focus mental health treatment approaches in HIV care settings should be examined

Coping strategies and symptoms of mental health disorders among people with HIV initiating HIV care in Cameroon

Little is known about the coping strategies used among people with HIV (PWH), especially in sub-Saharan Africa, and the extent to which adaptive or maladaptive coping strategies are associated with symptoms of mental health disorders. We interviewed 426 PWH initiating HIV care in Cameroon and reported the prevalence of adaptive and maladaptive coping strategies, overall and by presence of symptoms of depression, anxiety, and PTSD. Log binominal regression was used to estimate the association between each type of coping strategy (adaptive or maladaptive) and symptoms of each mental health disorder, separately. Adaptive and maladaptive coping strategies were commonly reported among PWH enrolling in HIV care in Cameroon. Across all mental health disorders assessed, greater maladaptive coping was associated with higher prevalence of depression, anxiety, and PTSD. Adaptive coping was not associated with symptoms of any of the mental health disorders assessed in bivariate or multivariable models. Our study found that PWH endorsed a range of concurrent adaptive and maladaptive coping strategies. Future efforts should explore the extent to which coping strategies change throughout the HIV care continuum. Interventions to reduce maladaptive coping have the potential to improve the mental health of PWH in Cameroon

Using intervention mapping to develop an implementation strategy to improve timely uptake of streamlined birth-dose vaccines in the Democratic Republic of the Congo

Despite the policy recommendation and effectiveness of administering the hepatitis B birth-dose vaccine (HepB-BD) to newborns to prevent mother-to-child hepatitis B transmission, timely uptake remains an issue. Countries adopting the HepB-BD to their national immunization schedule report programmatic challenges to administering the vaccine within the recommended 24-hour window after delivery. Further, while the World Health Organization recommends streamlining three birth-dose vaccines (HepB-BD, BCG, and OPV0), scarce Sub-Saharan(SSA)-based literature reports on a streamlined and timely approach to birth-dose vaccines. As more SSA countries adopt the new birth-dose vaccine to their immunization schedules, a systematically developed implementation strategy—Vaccination of Newborns–Innovative Strategies to Hasten Birth-Dose vaccines’ delivery (VANISH-BD)—will facilitate the adoption and implementation of timely birth-dose vaccine uptake. In this paper, we describe the development of the implementation strategy using intervention mapping, an evidence-based and theory-driven approach. We report on the development of our intervention, beginning with the needs assessment based in Kinshasa Province, Democratic Republic of the Congo (DRC), informing step 1 of intervention mapping. The intervention is contextually relevant, locally produced, sustainable, and designed to improve timely birth-dose vaccine uptake in the DRC. We intend to inform future implementers about improving timely and streamlined birth-dose vaccine uptake and for VANISH-BD to be adapted for similar contexts

Psychiatric comorbidity and psychosocial stressors among people initiating HIV care in Cameroon

Background Psychiatric comorbidity, the presence of two or more mental health disorders, has been associated with suboptimal HIV treatment outcomes. Little is known about the prevalence of psychiatric comorbidity among people with HIV (PWH) in sub-Saharan Africa. Methods We conducted interviews with PWH initiating HIV care in Cameroon between June 2019 and March 2020. Depression, anxiety, post-traumatic stress disorder (PTSD), and harmful drinking were dichotomized to represent those with and without symptoms of each. Psychiatric comorbidity was defined as having symptoms of two or more disorders assessed. Moderate or severe household hunger, high anticipatory HIV-related stigma, low social support, and high number of potentially traumatic events were hypothesized as correlates of psychiatric comorbidity. Bivariable log binomial regression models were used to estimate unadjusted associations between psychosocial stressors and psychiatric comorbidity. Results Among 424 participants interviewed, the prevalence of psychiatric comorbidity was 16%. Among those with symptoms of at least one mental health or substance use disorder (n = 161), the prevalence of psychiatric comorbidity was 42%. The prevalence of psychiatric comorbidity was 33%, 67%, 76%, and 81% among those with symptoms of harmful drinking, depression, anxiety, and PTSD, respectively. Among individuals with symptoms of a mental health or substance use disorder, a high number of potentially traumatic events (prevalence ratio (PR) 1.71 [95% CI 1.21, 2.42]) and high anticipatory HIV-related stigma (PR 1.45 [95% CI 1.01, 2.09]) were associated with greater prevalence of psychiatric comorbidity. Conclusion Psychiatric comorbidity was common among this group of PWH in Cameroon. The effectiveness and implementation of transdiagnostic or multi-focus mental health treatment approaches in HIV care settings should be examined

Whole-genome sequencing for drug resistance profile prediction in Mycobacterium tuberculosis

Whole-genome sequencing allows rapid detection of drug-resistant; Mycobacterium tuberculosis; isolates. However, the availability of high-quality data linking quantitative phenotypic drug susceptibility testing (DST) and genomic data have thus far been limited. We determined drug resistance profiles of 176 genetically diverse clinical; M. tuberculosis; isolates from the Democratic Republic of the Congo, Ivory Coast, Peru, Thailand, and Switzerland by quantitative phenotypic DST for 11 antituberculous drugs using the BD Bactec MGIT 960 system and 7H10 agar dilution to generate a cross-validated phenotypic DST readout. We compared DST results with predicted drug resistance profiles inferred by whole-genome sequencing. Classification of strains by the two phenotypic DST methods into resistotype/wild-type populations was concordant in 73 to 99% of cases, depending on the drug. Our data suggest that the established critical concentration (5 mg/liter) for ethambutol resistance (MGIT 960 system) is too high and misclassifies strains as susceptible, unlike 7H10 agar dilution. Increased minimal inhibitory concentrations were explained by mutations identified by whole-genome sequencing. Using whole-genome sequences, we were able to predict quantitative drug resistance levels for the majority of drug resistance mutations. Predicting quantitative levels of drug resistance by whole-genome sequencing was partially limited due to incompletely understood drug resistance mechanisms. The overall sensitivity and specificity of whole-genome-based DST were 86.8% and 94.5%, respectively. Despite some limitations, whole-genome sequencing has the potential to infer resistance profiles without the need for time-consuming phenotypic methods