Effect of antiretroviral therapy care interruptions on mortality in children living with HIV.

OBJECTIVE: To evaluate the characteristics and outcomes of HIV-infected children that have care interruptions, during which the child's health status and use of medication is unknown. DESIGN: We included data on children initiating ART between 2004 and 2016 at less than 16 years old at 16 International Epidemiologic Databases to Evaluate AIDS Southern Africa cohorts. Children were classified as loss to follow up (LTFU) if they had not attended clinic for more than 180 days. Children had a care interruption if they were classified as LTFU, and subsequently returned to care. Children who died within 180 days of ART start were excluded. METHODS: The main outcome was all cause mortality. Two exposed groups were considered: those with a first care interruption within the first 6 months on ART, and those with a first care interruption after 6 months on ART. Adjusted hazard ratios were determined using a Cox regression model. RESULTS: Among 53 674 children included, 23 437 (44%) had a care interruption, of which 10 629 (20%) had a first care interruption within 6 months on ART and 12 808 (24%) had a first care interruption after 6 months on ART. Increased mortality was associated with a care interruption within 6 months on ART [adjusted hazard ratio (AHR) = 1.52, 95% CI 1.12-2.04] but not with a care interruption after 6 months on ART (AHR = 1.05, 95% CI 0.77-1.44). CONCLUSION: The findings suggest that strengthening retention of children in care in the early period after ART initiation is critical to improving paediatric ART outcomes.

Service Use and Resilience among Adolescents Living with HIV in Blantyre, Malawi.

INTRODUCTION: Adolescents living with HIV (ALHIV) experience social and health challenges that warrant the provision of services and relational support to build resilience. Little is known about how social, community and health services help. We examine formal and alternative service use by and resilience of ALHIV participating in an enhanced teen-club clinic (TCC) programme. DESCRIPTION: TCC is an adolescent-centred differentiated care model offering a 'one-stop-shop' for HIV/Sexual and Reproductive Health (SRH) services to ALHIV. A survey was conducted with 406 ALHIV to determine frequency of use and satisfaction with services. In addition, we conducted 26 in-depth interviews with ALHIV, 12 group discussions with 144 caregivers, and observations of workshops held for 35 health workers to capture multiple perspectives on service use and relational support systems for adolescent's wellbeing. DISCUSSION: About 70% of ALHIV were concurrently clients of three or more services. The multi-method analysis showed variations on risks, range of services, frequency of use and satisfaction. Interview data reflected complex factors influencing access to formal services, and caregivers and adolescents also sought alternative care from spiritual and traditional healers. CONCLUSION: Adolescent centred-approaches have the potential to enhance resilience promoting resources and outcomes. A multi-sectoral approach to service use and provision is critical to inform adolescent intervention programs and wellbeing.

Validating a Child Youth Resilience Measurement (CYRM-28) for Adolescents Living With HIV (ALHIV) in Urban Malawi.

Resilience as a strength-based notion, measured across cultures, age groups, and sub-populations, contributes to understanding health and well-being. Yet, there is limited evidence of how the construct performs in resource-limited countries. We explored the psychometric properties of the CYRM-28 and validated the scale with adolescents living with HIV (ALHIV), a key sub-population. The participants included members of an advisory panel and 406 ALHIV, aged 15-19 years, attending an antiretroviral therapy and teen-club clinic in Blantyre, Malawi. This study employed a mixed-method study using an exploratory sequential design. The advisory panel discussed the CYRM-28, and select ALHIV then translated it into Chichewa, pilot-tested it using cognitive interviews, and back-translated it for clarity and appropriateness. The resultant CYRM-28 was tested using a survey with purposefully selected ALHIV. The overall median score was 123, with an interquartile range of 110-130. Minimum and maximum scores were 53 and 140. Cronbach's alpha of 0.863 and Kaiser-Meyer-Olkin measure (0.866) confirmed internal consistency and the sample size adequacy, respectively. Bartlett's tests of sphericity (p < 0.001) informed factor analysis. Exploratory factor analysis determined possible dimensions of resilience and the sub-scales. The confirmatory factor analysis (CFA) confirmed the construct validity and supported a three-factor model consistent with the conceptualization of resilience as a multi-dimensional construct. Structural equation modeling was applied to perform CFA to measure model of resilience. Multiple fit indices showed a good fit for the model. The CYRM-28 has good internal consistency, test and re-test reliability, and moderate convergent validity which render it useful as a self-report resilience measure to inform and evaluate interventions for the health and well-being of adolescents in Malawi.

Adolescents living with HIV, complex needs and resilience in Blantyre, Malawi.

BACKGROUND: Adolescents living with HIV (ALHIV) in Malawi experience multiple challenges associated with their illness and various social, environmental, economic and cultural factors. In exploring their various medical concerns and social vulnerabilities, we consider the role of multiple services in creating a pathway for resilience. METHODS: Multiple methods and case studies allowed for triangulation of evidence and provided a holistic understanding of resilience among adolescents with complex needs. The research methods included: (1) a survey to identify examples of young people with complex needs, (2) qualitative interviews and field notes to further explore these needs, (3) patient files and health passports to identify clinical challenges, and (4) ecomapping exercises to personalize cases and identify resilience-enabling resources and supports. We present four case studies to highlight the complex experiences and access to services of ALHIV, and to illustrate their growing power and decision-making capacity over time. RESULTS: Adversity experienced by ALHIV varied by gender, family situation, years of schooling, and use of teen-clubs for support. The two female adolescents emphasised their need to be accepted and how this impacted sexuality and reproduction. The two males illustrated how ideas of masculinity influenced their sexual practice and involvement with health services and the correctional justice system. Multiple risks (alcohol use, sexual activities) and complex needs (belonging, having a purpose in life/productive activities, autonomy, desire for offspring) influence pathways to resilience. ALHIV were able to strengthen their own wellbeing by resisting negative behaviours and peer pressure and caregiver interactions through 'strategic silence'. CONCLUSION: ALHIV experienced self-transformation as a result of taking ART, with fewer severe episodes of illness and distressing skin conditions. Continuous engagement at the teen-club clinic transformed both productive activities and social relationships among ALHIV as they set life goals, gained a sense of empowerment, requested SRH services, and formed intimate relationships. These transformative opportunities allowed them to learn ways of minimizing risk of reinfection and violence, and of navigating health worker-caregiver-adolescent interactions.

High Cancer Burden Among Antiretroviral Therapy Users in Malawi: A Record Linkage Study of Observational Human Immunodeficiency Virus Cohorts and Cancer Registry Data.

BACKGROUND: With antiretroviral therapy (ART), AIDS-defining cancer incidence has declined and non-AIDS-defining cancers (NADCs) are now more frequent among human immunodeficiency virus (HIV)-infected populations in high-income countries. In sub-Saharan Africa, limited epidemiological data describe cancer burden among ART users. METHODS: We used probabilistic algorithms to link cases from the population-based cancer registry with electronic medical records supporting ART delivery in Malawi's 2 largest HIV cohorts from 2000-2010. Age-adjusted cancer incidence rates (IRs) and 95% confidence intervals were estimated by cancer site, early vs late incidence periods (4-24 and >24 months after ART start), and World Health Organization (WHO) stage among naive ART initiators enrolled for at least 90 days. RESULTS: We identified 4346 cancers among 28 576 persons. Most people initiated ART at advanced WHO stages 3 or 4 (60%); 12% of patients had prevalent malignancies at ART initiation, which were predominantly AIDS-defining eligibility criteria for initiating ART. Kaposi sarcoma (KS) had the highest IR (634.7 per 100 000 person-years) followed by cervical cancer (36.6). KS incidence was highest during the early period 4-24 months after ART initiation. NADCs accounted for 6% of new cancers. CONCLUSIONS: Under historical ART guidelines, NADCs were observed at low rates and were eclipsed by high KS and cervical cancer burden. Cancer burden among Malawian ART users does not yet mirror that in high-income countries. Integrated cancer screening and management in HIV clinics, especially for KS and cervical cancer, remain important priorities in the current Malawi context.

Unstructured treatment interruption: an important risk factor for arterial stiffness in adult Malawian patients with antiretroviral treatment.

OBJECTIVES: The aim of the study was to evaluate the impact of unstructured antiretroviral treatment (ART) interruption on arterial stiffness in adult Malawians who are on ART for at least 35 years. DESIGN: The number of treatment interruption events for at least 60 days during ART treatment was quantified in patients for at least 35 years using retrospective routinely collected clinic data. Treatment interruption data were linked to patient carotid-femoral pulse wave velocity (PWV); PWV more than 10 m/s was set as the threshold for clinically significant cardiovascular disease risk. METHODS: PWV was measured in patients (on ART ≥ 18 months), during routine ART clinic visits in Blantyre, Malawi, between November 2014 and July 2015. Multivariable linear regression was used to estimate the change in PWV m/s associated with treatment interruption. Multivariable logistic regression was used to estimate risk of PWV more than 10 m/s. All models were controlled for demographic and cardiometabolic risk factors. RESULTS: In 220 patients (median age 45 years, range 37-80 years), 86 (37.4%) patients had at least one treatment interruption event. Median length of treatment interruption events was 75 days (range 31 days to 8 years). Overall, 31 (14%) patients had a PWV more than 10 m/s. In multivariable analysis, we found a 0.2 increase in PWV m/s per treatment interruption event (0.2, 95% confidence interval 0.1-0.4) and a two-fold increased risk of PWV more than 10 m/s per treatment interruption event (adjusted odds ratio 2.2, 95% confidence interval 1.2-4.0). CONCLUSION: Treatment interruption in patients with ART for at least 35 years is a common and important risk factor for arterial stiffness. Therefore, the link between treatment interruption and cardiovascular disease in this setting in which traditional risks factors are less prevalent needs to be explored further.