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

Characteristics of HIV-infected Children at Enrollment Into Care and at Antiretroviral Therapy Initiation in Central Africa

BACKGROUND: Despite the World Health Organization (WHO) regularly updating guidelines to recommend earlier initiation of antiretroviral therapy (ART) in children, timely enrollment into care and initiation of ART in sub-Saharan Africa in children lags behind that of adults. The impact of implementing increasingly less restrictive ART guidelines on ART initiation in Central Africa has not been described. MATERIALS AND METHODS: Data are from the Central Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) pediatric cohort of 3,426 children (0-15 years) entering HIV care at 15 sites in Burundi, DRC, and Rwanda. Measures include CD4 count, WHO clinical stage, age, and weight-for-age Z score (WAZ), each at enrollment into HIV care and at ART initiation. Changes in the medians or proportions of each measure by year of enrollment and year of ART initiation were assessed to capture potential impacts of changing ART guidelines. RESULTS: Median age at care enrollment decreased from 77.2 months in 2004-05 to 30.3 months in 2012-13. The median age at ART initiation (n = 2058) decreased from 83.0 months in 2004-05 to 66.9 months in 2012-13. The proportion of childre

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

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

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

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

Natural polymorphisms in mycobacterium tuberculosis conferring resistance to delamanid in drug-naïve patients.

Mutations in the genes of the F420 signaling pathway, including dnn, fgd1, fbiA, fbiB, fbiC, and fbiD, of Mycobacterium tuberculosis (Mtb) complex can lead to delamanid resistance. We searched for such mutations among 129 Mtb strains from Asia, South-America, and Africa using whole-genome sequencing; 70 (54%) strains had at least one mutation in one of the genes. For ten strains with mutations, we determined the minimum inhibitory concentration (MIC) of delamanid. We found one strain from a delamanid-naïve patient carrying the natural polymorphism Tyr29del (ddn) that was associated with a critical MIC to delamanid

Underestimation of Potentially Traumatic Events Resulting From Underreporting of Physical and Sexual Violence Among People Entering Care for HIV in Cameroon

Objective: Measures ascertaining exposure to potentially traumatic events (PTEs) frequently ask respondents about experienced physical and sexual violence. However, little is known about the performance of physical and sexual violence questions on PTE assessments and its effect on PTE classification overall. We estimated underreporting of physical and sexual violence on a PTE assessment among individuals entering HIV care in Cameroon. Method: We compared reports of physical and sexual violence captured via a behaviorally specific measure of intimate partner violence (IPV; Demographic and Health Survey [DHS] domestic violence module = referent) to those captured via two single-item questions that assessed exposure to physical and sexual PTEs during one’s adult life to determine the degree of underreporting on the single-item PTE assessment questions. We explored correlates of underreporting on the PTE assessment using Pearson’s chisquared tests. Results: Overall, 99 (23%) and 113 (27%) of 426 total participants reported instances of sexual and physical violence in their most recent partnership on the behaviorally specific DHS IPV module, respectively. Of those reporting sexual and physical IPV on the DHS module, just 6% (n = 6) and 52% (n = 59) reported sexual and physical violence as an adult on the single-item PTE assessment questions, respectively. Underreporting of physical violence on the PTE assessment was associated with lower educational attainment (p <.05) and reporting being punched (p <.01) or having one’s hair pulled or arm twisted (p <.05) by one’s most recent partner. Conclusions: PTE assessment tools should assess exposure to behaviorally specific acts of violence to ensure appropriate referral to services among survivors of IPV

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 > 9), PTSD (PTSD Checklist for DSM-5 score > 30), anxiety (Generalized Anxiety Disorder-7 scale score > 9), and hazardous alcohol use (Alcohol Use Disorders Identification Test score > 7 for men; > 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