Grace McHugh

Chronic Morbidity Among Older Children and Adolescents at Diagnosis of HIV Infection.

Background:Substantial numbers of children with HIV present to health care services in older childhood and adolescence, previously undiagnosed. These “slow-progressors” may experience considerable chronic ill health, which is not well characterized. We investigated the prevalence of chronic morbidity among children aged 6–15 years at diagnosis of HIV infection. Methods:A cross-sectional study was performed at 7 primary care clinics in Harare, Zimbabwe. Children aged 6–15 years who tested HIV positive following provider-initiated HIV testing and counseling were recruited. A detailed clinical history and standardized clinical examination was undertaken. The association between chronic disease and CD4 count was investigated using multivariate logistic regression. Results:Of the 385 participants recruited [52% female, median age 11 years (interquartile range 8–13)], 95% were perinatally HIV infected. The median CD4 count was 375 (interquartile range 215–599) cells per cubic millimeter. Although 78% had previous contact with health care services, HIV testing had not been performed. There was a high burden of chronic morbidity: 23% were stunted, 21% had pubertal delay, 25% had chronic skin disease, 54% had a chronic cough of more than 1 month-duration, 28% had abnormal lung function, and 12% reported hearing impairment. There was no association between CD4 count of <500 cells per cubic millimeter or <350 cells per cubic millimeter with WHO stage or these chronic conditions. Conclusions:In children with slow-progressing HIV, there is a substantial burden of chronic morbidity even when CD4 count is relatively preserved. Timely HIV testing and prompt antiretroviral therapy initiation are urgently needed to prevent development of chronic complications.

The effect of community-based support for caregivers on the risk of virological failure in children and adolescents with HIV in Harare, Zimbabwe (ZENITH): an open-label, randomised controlled trial

Summary Background Children and adolescents have poorer HIV treatment outcomes than adults. We aimed to assess the effect of community-based support for caregivers of HIV-infected children and adolescents, who are key mediators to children engaging with care, on treatment outcomes. Methods In this open-label, randomised contolled trial, we recruited children aged 6–15 years with newly-diagnosed HIV attending primary health-care clinics in Harare, Zimbabwe. Children were randomly assigned to receive decentralised primary health-care clinic-based HIV care (control group), according to national guidelines for 18 months, or decentralised care plus structured support visits by trained community health workers (intervention group) according to national guidelines for 18 months. Primary outcomes were the proportion of participants who died or had an HIV viral load of 400 copies per mL or higher at 12 months after antiretroviral therapy (ART) initiation (among those who started ART within 6 months of enrolment); and the proportion who missed two or more scheduled clinic visits by 18 months post-enrolment (among all participants). Analyses were complete-case, modified-intention-to-treat. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201212000442288. Findings Between January, 2013, and January, 2015, 470 participants tested HIV-positive at seven study primary health-care clinics and were screened for eligibility. Of the 334 eligible children and adolescents, 166 were randomly assigned to the intervention group and 168 to the control group. The median age of participants was 11 years (IQR 8–13) and 178 (53%) were girls. Among the 238 participants who started ART within 6 months of enrolment, the proportion who died or had a viral load of 400 copies/mL or higher at 12 months post-ART initiation was significantly lower in the intervention group than in the control group (31 [33%] of 94 participants vs 42 [49%] of 86 participants, respectively, adjusted odds ratio [aOR] 0·46, 95% CI 0·23–0·89; p=0·02). The proportion of children missing two or more scheduled visits was similar in the intervention group and control group (27 [17%] of 155 vs 30 [18%] of 165, aOR 0·92, 95% CI 0·49–1·74; p=0·79). One participant withdrew from the trial 240 days after enrolment and 12 died during follow-up (five in the intervention group; seven in the control group). Interpretation Community-based support for caregivers has high potential for scalability and could have a substantial effect on HIV virological suppression in children and adolescents, a group with disproportionately poor treatment outcomes. Funding Wellcome Trust.

Chronic lung disease in Hiv-infected children established on antiretroviral therapy

Objective:Respiratory disease is a major cause of morbidity and mortality in HIV-infected children. Despite antiretroviral therapy (ART), children suffer chronic symptoms. We investigated symptom prevalence, lung function and exercise capacity among older children established on ART and an age-matched HIV-uninfected group. Design:A cross-sectional study in Zimbabwe of HIV-infected children aged 6–16 years receiving ART for over 6 months and HIV-uninfected children attending primary health clinics from the same area. Methods:Standardized questionnaire, spirometry, incremental shuttle walk testing, CD4+ cell count, HIV viral load and sputum culture for tuberculosis were performed. Results:A total of 202 HIV-infected and 150 uninfected participants (median age 11.1 years in each group) were recruited. Median age at HIV diagnosis and ART initiation was 5.5 (interquartile range 2.8–7.5) and 6.1 (interquartile range 3.6–8.4) years, respectively. Median CD4+ cell count was 726 cells/&mgr;l, and 79% had HIV viral load less than 400 copies/ml. Chronic respiratory symptoms were rare in HIV-uninfected children [n = 1 (0.7%)], but common in HIV-infected participants [51 (25%)], especially cough [30 (15%)] and dyspnoea [30 (15%)]. HIV-infected participants were more commonly previously treated for tuberculosis [76 (38%) vs 1 (0.7%), P < 0.001], had lower exercise capacity (mean incremental shuttle walk testing distance 771 vs 889 m, respectively, P < 0.001) and more frequently abnormal spirometry [43 (24.3%) vs 15 (11.5%), P = 0.003] compared with HIV-uninfected participants. HIV diagnosis at an older age was associated with lung function abnormality (P = 0.025). No participant tested positive for Mycobacterium tuberculosis. Conclusion:In children, despite ART, HIV is associated with significant respiratory symptoms and functional impairment. Understanding pathogenesis is key, as new treatment strategies are urgently required.

Validation of a screening tool to identify older children living with HIV in primary care facilities in high HIV prevalence settings.

Objective:We previously proposed a simple tool consisting of five items to screen for risk of HIV infection in adolescents (10–19 years) in Zimbabwe. The objective of this study is to validate the performance of this screening tool in children aged 6–15 years attending primary healthcare facilities in Zimbabwe. Methods:Children who had not been previously tested for HIV underwent testing with caregiver consent. The screening tool was modified to include four of the original five items to be appropriate for the younger age range, and was administered. A receiver operator characteristic analysis was conducted to determine a suitable cut-off score. The sensitivity, specificity and predictive value of the modified tool were assessed against the HIV test result. Results:A total of 9568 children, median age 9 (interquartile, IQR: 7–11) years and 4971 (52%) men, underwent HIV testing. HIV prevalence was 4.7% (95% confidence interval, CI:4.2–5.1%) and increased from 1.4% among those scoring zero on the tool to 63.6% among those scoring four (P < 0.001). Using a score of not less than one as the cut-off for HIV testing, the tool had a sensitivity of 80.4% (95% CI:76.5–84.0%), specificity of 66.3% (95% CI:65.3–67.2%), positive predictive value of 10.4% and a negative predictive value of 98.6%. The number needed to screen to identify one child living with HIV would drop from 22 to 10 if this screening tool was used. Conclusion:The screening tool is a simple and sensitive method to identify children living with HIV in this setting. It can be used by lay healthcare workers and help prioritize limited resources.

Community burden of undiagnosed HIV infection among adolescents in Zimbabwe following primary healthcare-based provider-initiated HIV testing and counselling: A cross-sectional survey

Background Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe. Methods and findings Over the course of 2 years (January 2013–January 2015), 7 primary health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC for all attendees aged 6–15 years. In February 2015–December 2015, we conducted a representative cross-sectional survey of 8–17-year-olds living in the 7 communities served by the study PHCs, who would have had 2 years of exposure to PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire, and anonymised HIV testing was carried out using oral mucosal transudate (OMT) tests. After 1 participant taking antiretroviral therapy was observed to have a false negative OMT result, from July 2015 urine samples were obtained from all participants providing OMTs and tested for antiretroviral drugs to confirm HIV status. Children who tested positive through PITC were identified from among survey participants using gender, birthdate, and location. Of 7,146 children in 4,251 eligible households, 5,486 (76.8%) children in 3,397 households agreed to participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6% (95% CI 2.2%–3.1%), and over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%–46.2%). Similarly, among the subsample of 2,643 (48.2%) participants with a urine test result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%–47.9%). Based on extrapolation from the survey sample to the community, we estimated that PITC over 2 years identified between 18% and 42% of previously undiagnosed children in the community. The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 measures (OMT, self-report, and urine test), none of which were perfect. Conclusions Facility-based approaches are inadequate in achieving universal coverage of HIV testing among older children and adolescents. Alternative, community-based approaches are required to meet the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age group.

The role of community health workers in improving HIV treatment outcomes in children: lessons learned from the ZENITH trial in Zimbabwe

Abstract Reliance on community health workers (CHWs) for HIV care continues to increase, particularly in resource-limited settings. CHWs can improve HIV service use and adherence to treatment, but effectiveness of these programmes relies on providing an enabling work environment for CHWs, including reasonable workload, supportive supervision and adequate training and supplies. Although criteria for effective CHW programmes have been identified, these have rarely been prospectively applied to design and evaluation of new interventions. For the Zimbabwe study for Enhancing Testing and Improving Treatment of HIV in Children (ZENITH) randomized controlled trial, we based our intervention on an existing evidence-based framework for successful CHW programmes. To assess CHWs’ experiences delivering the intervention, we conducted longitudinal, qualitative semi-structured interviews with all 19 CHWs at three times during implementation. The study aimed to explore CHWs’ perceptions of how the intervention’s structure and management affected their performance, and consider implications for the programme’s future scale-up and adoption in other settings. CHWs expressed strong motivation, commitment and job satisfaction. They considered the intervention acceptable and feasible to deliver, and levels of satisfaction rose over interview rounds. Intensive supervision and mentoring emerged as critical to ensuring CHWs’ long-term satisfaction. Provision of job aids, standardized manuals and refresher training were also important, as were formalized links between clinics and CHWs. Concerns raised by CHWs included poor remuneration, their reluctance to stop providing support to individual families following the requisite number of home visits, and disappointment at the lack of programme sustainability following completion of the trial. Furthermore, intensive supervision and integration with clinical services may be difficult to replicate outside a trial setting. This study shows that existing criteria for designing successful CHW programmes are useful for maximizing effectiveness, but challenges remain for ensuring long-term sustainability of ‘task shifting’ strategies.

Human Immunodeficiency Virus-Associated Chronic Lung Disease in Children and Adolescents in Zimbabwe: Chest Radiographic and High-Resolution Computed Tomographic Findings

There is a substantial burden of chronic lung disease among treated children with human immunodeficiency virus infection in this study from Zimbabwe. The radiological findings, coupled with functional test results, indicate that the key pathological lesion is constrictive obliterative bronchiolitis.

False‐negative HIV tests using oral fluid tests in children taking antiretroviral therapy from Harare, Zimbabwe

Introduction: Rapid diagnostic tests (RDT) for HIV infection have high sensitivity and specificity, but in the setting of longstanding antiretroviral therapy (ART), can give false results that can lead to misinterpretation, confusion and inadequate management. The objective of this study was to evaluate the proportion of falsely negative results of a RDT performed on oral fluid in HIV‐infected children on longstanding ART.

It is not possible to go inside and have a discussion: how fear of stigma affects delivery of community-based support for children's HIV care.

ABSTRACT Caregivers mediate children’s access to HIV care and their adherence to treatment. Support for caregivers may improve health outcomes in children, but fear of HIV stigma and discrimination can affect both uptake and delivery of support services. Within a trial evaluating community-based support for caregivers of newly HIV diagnosed children in Harare, Zimbabwe, we conducted a longitudinal qualitative study to explore how stigma affected delivery and acceptance of the intervention. We conducted semi-structured interviews with 36 caregivers, 15 children, and 20 community health workers (CHWs). Children and caregivers described experiencing or witnessing stigma and discrimination, causing some to resist home visits by CHWs. Anxiety around stigma made it difficult for CHWs to promote key messages. In response, CHWs adapted the intervention by meeting caregivers outside the home, pretending to be friends or relatives, and proactively counteracting stigmatising beliefs. As members of local communities, some CHWs shared concerns about discrimination. HIV stigma can hinder “getting a foot over the threshold” in community-based programmes, particularly for households most affected by discrimination and thus least likely to engage with services. For community support programmes to be effective, stigma-related resistance should be addressed from the outset, including CHWs’ own concerns regarding HIV stigma.

Economic incentives for HIV testing by adolescents in Zimbabwe: a randomised controlled trial

Summary Background HIV testing is the important entry point for HIV care and prevention service, but uptake of HIV testing and thus coverage of antiretroviral therapy are much lower in older children and adolescents than in adults. We investigated the effect of economic incentives provided to caregivers of children aged 8–17 years on uptake of HIV testing and counselling in Harare, Zimbabwe. Methods This randomised controlled trial was nested within a household HIV prevalence survey of children aged 8–17 years in Harare. Households with one or more survey participants whose HIV status was unknown were eligible to participate in the trial. Eligible households were randomly assigned (1:1:1) to either receive no incentive, receive a fixed US