71 research outputs found
Burden of HIV infection and HIV-associated morbidity in Zimbabwean adolescents
No full textThis thesis concerns the clinical epidemiology of HIV infection in Zimbabwean adolescents. Without treatment, there is a very high risk of death in the early years of life in HIV-infected infants. However, in recent years increasing numbers of adolescents have been presenting to health care services with symptomatic HIV infection and with features suggesting longstanding disease. Population-based surveys in Southern Africa have shown HIV prevalence rates among older children and adolescents to be much higher than would be anticipated if HIV-infants were not surviving early childhood. The burden and spectrum of HIV-associated morbidity among adolescents was investigated with two studies at secondary and primary care level, respectively. The main finding was of an extremely high prevalence of HIV infection at both levels of the health system, with HIV infection being the single most common cause of hospital admission and death among adolescents. Mother-to-child transmission was the most likely source of HIV infection in the majority, suggesting a substantial epidemic of older survivors of vertical HIV infection. Other countries with severe HIV epidemics may be experiencing a similar trend as their HIV epidemics mature. The lack of awareness of the possibility of survival to older childhood and adolescence with maternally-acquired, untreated HIV infection results in many missed opportunities for diagnosis, with HIV infection frequently not diagnosed until presentation with a severe HIV-related illness. The median CD4 count in 3 HIV-infected adolescents in primary care was 350cells/µl compared to a median CD4 count of 151cells/µl among hospitalised adolescents, suggesting that HIV testing in primary care identifies HIV-infected adolescents at an earlier stage of infection. Provider-initiated HIV testing and counselling in primary care was highly acceptable to adolescents and guardians. Provision of care has been adversely affected by under-appreciation of the numbers of surviving adolescents living with HIV, and the special needs of this age-group have not been distinguished from those of younger children. Young people who have acquired HIV perinatally are stigmatised by society who assume they must have acquired it through "bad" behaviour themselves, since it is not widely appreciated that long-term survival following vertical infection is possible. Immediate priorities are earlier diagnosis of HIV infection and improved management of HIV-infected adolescents. Possible areas of intervention are discussed in the final chapter. Similar studies are needed in neighbouring countries to investigate the generalisability of these findings
The impact of HIV infection on skeletal maturity in peripubertal children in Zimbabwe: a cross-sectional study
No full textIntroduction: HIV infection and its treatment compromises skeletal development (growth and maturation). Skeletal maturity is assessed as bone age (BA) on hand and wrist radiographs. BA younger than chronological age (CA) indicates delayed development. We conducted a cross-sectional study to determine differences between BA and CA (i.e., skeletal maturity deviation [SMD]), and risk factors associated with SMD in peripubertal children with and without HIV established on antiretroviral therapy (ART) including use of tenofovir disoproxil fumarate (TDF). Methods: children with HIV taking ART for at least two years and a comparison group of HIV-negative children, aged 8–16 years and frequency-matched by age and sex, were recruited from HIV clinics and local schools in the same catchment area, in Harare, Zimbabwe. BA was assessed from non-dominant hand-wrist radiographs using the Tanner Whitehouse 3 method. Negative SMD values correspond to delayed development, i.e., BA younger than CA. Multivariable linear regression models determined factors associated with SMD overall, and in children with HIV. Results: in total, 534 participants (54% males) were included; by design CA was similar in males and females, whether living with or without HIV. Mean (SD) SMD was more negative in CWH than in HIV-negative children in both males [-1.4(1.4) vs. -0.4(1.1) years] and females [-1.1(1.3) vs. -0.0(1.2) years]. HIV infection and weight-for-age Z-score<-2 were associated with more negative SMD in both males and females after adjusting for socio-economic status, orphanhood, pubertal stage, and calcium intake. Age at ART initiation was associated with SMD in both males and females with those starting ART later more delayed: starting ART aged 4–8 years 1.14 (-1.84, -0.43), or over 8 years 1.47 (-2.30, -0.65) (p-value for trend < 0.001). Similar non-significant trends were seen in males. TDF exposure TDF exposure whether < 4years or ≥ 4 years was not associated with delayed development. Conclusion: perinatally-acquired HIV infection and being underweight were independently associated with delayed skeletal maturation in both males and females. Starting ART later was independently associated with skeletal maturation delay in CWH. Given the known effects of delayed development on later health, it is important to find interventions to ensure healthy weight gain through early years and in CWH to initiate ART as early as possible.</p
Prevalence, factors and quality of life associated with frailty and pre-frailty in middle-aged and older adults living with HIV in Zimbabwe: a cross-sectional study
No full textObjectives: we investigated associations between HIV, frailty and health-related quality of life (HRQoL).Methods: this cross-sectional study recruited men and women aged ≥40 years in Zimbabwe. A researcher collected clinical and HRQoL data, and performed physical assessments and HIV testing. Frailty was defined using five criteria: unintentional weight loss, exhaustion, low physical activity, low gait speed, low handgrip strength. The presence of three or more criteria defined frailty, one to two pre-frailty, and zero non-frail. Data analysis used adjusted regression modelling.Results: of 1034 adults (mean ± SD, 62.0 ± 14.0 years), 21.6% (n = 223) were living with HIV: 93.3% knew their status, of whom 96.2% were on antiretroviral therapy (ART) and 89.7% of these had a viral load <50 copies/mL. Mean age at HIV diagnosis was 44.6 ± 10.4 years (only 8.1% were ≥70 years), people had been living with HIV for 9.8 ± 5.0 years and had been on ART for 9.4 ± 5.2 years. Overall, HIV was not associated with frailty: adjusted odds ratio (aOR) was 0.99 [95% confidence interval (CI): 0.42–2.33] for frailty versus non-frailty. However, each 5 years lived with HIV was associated with twice the odds of frailty/pre-frailty (aOR = 2.03, 95% CI: 1.03–4.13), independent of age and ART duration. Furthermore, each 5 years of ART use was associated with 60% lower odds of frailty/pre-frailty (aOR = 0.39, 95% CI: 0.19–0.78), independent of age and years lived with HIV. Older age, minimal education and poverty were associated with frailty. Frailty was associated with lower HRQoL in people both with and without HIV.Conclusion: reduced survival and good viral suppression may explain the lack of association between HIV and frailty. Early ART initiation could reduce future risk of frailty
Update: Vitamin D 3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial
No full textBackground: Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV. This paper is an update to an already existing protocol that was previously published in Trials in 2022 and details changes in the trial outcomes. Methods/design: We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500 mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥ 6 months will be enrolled and followed up for 96 weeks. The primary outcome is DXA-measured total body less-head bone mineral density Z-score (TBLH-BMD) at 48 weeks and is an update to the previous primary outcome total body less-head bone mineral content adjusted for lean mass (TBLH-BMCLBM) Z-score. The primary outcome was updated to address the substantial differences in distributions of TBLH-BMCLBM Z-score between the two sites as a result of software differences of the DXA machines. Secondary outcomes are DXA-measured TBLH-BMD Z-score adjusted for height at 48 weeks a new secondary outcome, lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip-strength at 48 and 96 weeks, and TBLH-BMD Z-score at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function. Discussion: This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual through childhood is critical for optimising adolescent and early adult bone health, and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings. Trial registration: Pan African Clinical Trials Registry PACTR20200989766029. Registered on September 3, 2020. URL of trial registry record: https://pactr.samrc.ac.za Trial status: Participant follow-up completed; data analysis ongoing
Are concepts of adolescence from the Global North appropriate for Africa? A debate
No full textAdolescence is widely defined as a distinct phase in the life-course during which an individual completes their biological development and transitions from childhood to adulthood. This article presents a debate, conducted in 2018 at a scientific symposium in Mwanza, Tanzania, of the appropriateness of this for Africa, and by extension whether health interventions and global health policy that are shaped by such concepts can be universally applicable and relevant. The proponents for the motion argued that adolescence is indeed a distinct developmental phase when puberty is achieved and the neurocognitive development that occurs shapes behaviours that impact health outcomes. This occurs universally, is marked by cultural rites, and recognised in legal frameworks and therefore geographical distinctions in understanding are unnecessary. The opponents argued that adolescence is more than a biological or legally recognised transition to adulthood: instead, concepts, including that of adolescence, are shaped by beliefs, values and expectations founded within a cultural milieu. The concept is dissonant to Africa as it prioritises individualism over communalism, and attributes gender and social roles as accepted in the Global North. Thus, many interventions targeted at adolescents in Africa have remained ineffective. The notion that the concept of adolescence, which originated in the Global North but is universally applied, is a consequence of colonialism giving less value to the lived realities and understandings of peoples from the Global South. For achieving both epistemic justice and effective health policy and programmes in global health, acknowledgement and centralisation of context are critical. However, in a more interlinked and open world, there is a massive potential for cross-learning and collaboration across geographies to develop a concerted approach to improve the health of adolescents and for a more equitable global health practice. However, adolescence is also a social entity shaped by beliefs and values within different cultural contexts. A move away from universal, often western-defined concepts of adolescence, to centring the distinct sociocultural factors that shape adolescence in different societies will enable more effective policies and programming
"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.
No full textCaregivers 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
Implementation and Operational Research: The Effectiveness of Routine Opt-Out HIV Testing for Children in Harare, Zimbabwe.
No full textOBJECTIVE: HIV testing is the entry point to access HIV care. For HIV-infected children who survive infancy undiagnosed, diagnosis usually occurs on presentation to health care services. We investigated the effectiveness of routine opt-out HIV testing (ROOT) compared with conventional opt-in provider-initiated testing and counseling (PITC) for children attending primary care clinics. METHODS: After an evaluation of PITC services for children aged 6-15 years in 6 primary health care facilities in Harare, Zimbabwe, ROOT was introduced through a combination of interventions. The change in the proportion of eligible children offered and receiving HIV tests, reasons for not testing, and yield of HIV-positive diagnoses were compared between the 2 HIV testing strategies. Adjusted risk ratios for having an HIV test in the ROOT compared with the PITC period were calculated. RESULTS: There were 2831 and 7842 children eligible for HIV testing before and after the introduction of ROOT. The proportion of eligible children offered testing increased from 76% to 93% and test uptake improved from 71% to 95% in the ROOT compared with the PITC period. The yield of HIV diagnoses increased from 2.9% to 4.5%, and a child attending the clinics post intervention had a 1.99 increased adjusted risk (95% CI: 1.85 to 2.14) of receiving an HIV test in the ROOT period compared with the preintervention period. CONCLUSION: ROOT increased the proportion of children undergoing HIV testing, resulting in an overall increased yield of positive diagnoses, compared with PITC. ROOT provides an effective approach to reduce missed HIV diagnosis in this age group
Engagement of private healthcare providers for case finding of tuberculosis and diabetes mellitus in Pakistan.
No full textBACKGROUND: The rising co-epidemic of tuberculosis (TB) and diabetes mellitus (DM) is a challenge for constrained health systems in low and middle-income countries. Diabetes is a known risk factor for tuberculosis and associated with poor tuberculosis treatment outcomes, while tuberculosis is associated with worsening glycemic control. We investigated the performance of bi-directional TB and DM case finding approaches through a private-sector engagement model in Karachi, Pakistan. METHODS: Between July 2016 and July 2018, private health care providers were engaged to generate referrals for bi-directional TB and DM screening at private diagnostic and treatment centers in Karachi, Pakistan. Individuals diagnosed with TB underwent glycated hemoglobin (HbA1c) testing at the time of anti-tuberculous treatment initiation and at three -month follow up stage. All individuals with a history of diabetes or random blood sugar of greater than 200 mg/dl were screened for TB using a chest X-ray and Xpert MTB/RIF. RESULTS: A total of 6312 persons with tuberculosis were tested on HbA1c at treatment initiation, of whom 1516 (24%) were newly diagnosed with DM. About one third of those with HbA1c in the diabetic range (≥ 6.5%) at baseline were found to have a normal HbA1c ( 200 mg/dl, underwent chest x-ray and Xpert MTB/RIF testing, with 321 (13.4%) known and 54 (3.8%) new diabetics respectively identified with tuberculosis. CONCLUSION: This study demonstrates a high yield of TB and DM through bidirectional screening and the feasibility of engagement of private sector in finding missing cases of tuberculosis and diabetes. Given the high prevalence of undiagnosed DM in individuals with TB tuberculosis patients, there is a need to scale-up DM screening within TB programmes. Increased awareness of the high risk of TB among individuals with DM is needed among private health providers and screening for TB among diabetics should be strongly considered
Mycobacterium tuberculosis transmission from patients with drug-resistant compared to drug-susceptible tuberculosis: a systematic review and meta-analysis
No full textThe extent to which drug-resistant (DR) Mycobacterium tuberculosis strains cause infection and progression to tuberculosis (TB) disease in comparison to drug-susceptible (DS) strains is unknown. Studies in guinea pigs and in vitro experiments have suggested a reduced fitness of organisms that harbour mutations that confer drug resistance [1, 2]; it was therefore believed that transmitted drug resistance was a rare event. However, more recent work using molecular typing has shown transmission events occurring in the context of DR-TB [3]. Understanding the risk of transmission, infection and progression to disease in the context of DR-TB is important to guide control measures and help predict the evolution and magnitude of the multidrug-resistant (MDR)-TB epidemic. Hence, we performed a systematic review and meta-analysis to assess whether M. tuberculosis transmission and progression to TB disease (risk/rate of M. tuberculosis infection in all contacts, risk/rate of TB disease in all contacts and risk/rate of TB disease in infected contacts) differ between DR- and DS-TB
Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial.
No full textBACKGROUND: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. METHODS: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0-24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014-002632-14), and the ISRCTN registry (ISRCTN91737921). FINDINGS: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4-17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08-2·11) for Ctrough, 1·23 (0·99-1·53) for AUC0-24 h, and 0·94 (0·76-1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30-40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. INTERPRETATION: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB. FUNDING: Penta Foundation, ViiV Healthcare, UK Medical Research Council
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