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STUDY FOR ENHANCING TESTING AND IMPROVING TREATMENT OF HIV IN CHILDREN (ZENITH PROJECT)

Funder: The Wellcome Trust, UK
Award Period: May 2012 – April 2016
Goal: To strengthen HIV testing and care services for older children in Harare, Zimbabwe
Principal Investigator: Dr Rashida Ferrand
Project Coordinator: Ms Ethel Dauya
Data Manager: Ms Tsitsi Bandason
Collaborators: BRTI, Harare City Health, Ministry of Health and Child Welfare AIDS and TB Unit, Population Services
International and the  London School of Hygiene and Tropical Medicine

Aim

To investigate whether a package of services at primary care level will adequately meet the needs of vertically HIV-infected children and adolescents, or alternatively whether further decentralisation to provide community-level HIV testing and/or treatment support is required.

Objectives

  1. To conduct a cluster-randomised trial comparing a) optimised primary HIV care services alone with b) optimised primary HIV care services plus treatment support provided by lay volunteers to households with one or more HIV-infected older children.
  2. To investigate whether routine facility-based HIV testing and counselling of children aged 6-15 years attending acute care services provides high coverage of timely diagnosis of HIV in the clinic catchment areas, as assessed through a prevalence survey for undiagnosed infection after two years of intervention. Participating clinics will also provide decentralised HIV care, including antiretroviral therapy (ART) initiation.
  3. To add serial lung function and anthropometry to the routine follow-up schedule of newly diagnosed children retained in care, in order to investigate the safety of current deferred-start ART guidelines in this age-group (WHO stage 3/4 disease or CD4 count < 350cells/μl).

Background

About a third of all HIV-infected infants have slow progressing disease with a 50% probability of surviving to adolescence even in the absence of prior HIV care. The combination of the high regional adult HIV prevalence rates during the 1990s and the lack of interventions to prevent mother-to-child HIV transmission at the time has given rise to an emerging epidemic of “slow-progressors”, with substantial numbers of older children and adolescents now presenting to healthcare services with previously undiagnosed vertically-acquired HIV.

Given the high risk of disease progression in HIV-infected infants and the high mortality rates observed among infants in the pre-ART era, the possibility that a significant proportion of infants would survive to older childhood without treatment was not anticipated. Consequences of the under-estimation of this phase of the HIV epidemic include delayed HIV diagnosis and a lack of appropriate HIV care services for older children.

Late diagnosis in children is associated not only with a risk of the well-recognised HIV-associated infections, but also with risk of chronic conditions that are not manifest in infants or adults, such as growth failure and life-threatening chronic lung and heart disease, the natural history and pathogenesis of which is not well understood. Current recommendations for ART initiation in children over two years assume that treatment can be safely deferred until CD4 count/WHO Stage criteria (CD4 < 350cells/μl and/or WHO Stage 3/4 disease) are met. However, this may result in an unacceptably high risk of developing these chronic complications.

Once ART is started, older children have a disproportionately high risk of poor adherence, with much worse treatment outcomes reported for adolescents than adults. With the tremendous pressures on health systems as a consequence of the HIV epidemic, there has been a move towards involvement of community health workers in supporting healthcare provision and as ART programmes scale up, lay workers as a community-based extension of health services may provide an effective and sustainable means of supporting care of HIV-infected children.

Methodology

I) Primary care-based provider-initiated HIV testing and counseling (PITC)

All children aged 6-15 years attending for acute care at primary health care clinics (PHC) will be routinely offered HIV testing during a two year period. An HIV prevalence survey of children in the catchment areas of these clinics will be conducted after two years of the PITC intervention. This will not only provide data on community prevalence of HIV prevalence by age (thus far unavailable), but also an indication of the effectiveness of primary care-based PITC through an estimate of undiagnosed HIV.

II) Cluster-randomised trial of a household-level Adherence support intervention

Decentralised nurse-led HIV care clinics will be initiated in six primary health care facilities (PHC) serving 6 high-density suburbs in southwest Harare. Current National guidelines will be used to decide ART eligibility with drugs provided through the National ART programme. The six suburbs will be divided into 15 intervention and 15 control clusters (approx cluster size 1000 children), with each cluster 500m apart to avoid contamination. Children aged 6-15 years who test positive at a PHC and reside within a cluster will be randomized to either standard of care (nurse-led HIV care in PHC) or a household-level intervention delivered by a volunteer lay worker (VLW). The primary outcome will be retention in care at two years of follow-up. The VLW will carry out regular visits to the household of the HIV-infected child over the intervention period, providing health (including HIV) education, and reporting any concerns to the respective primary care clinic health workers.

III) Complications of HIV infection in older children: prospective cohort study

Follow-up of the same cohort that is enrolled into the trial will include lung function testing, growth, and clinical assessment, to investigate the safety of current ART guidelines with respect to prevention of chronic lung disease and growth impairment. Children who register for HIV care at the PHC but are not enrolled into the trial will also be recruited
into the cohort.

Outcomes

· Proportion of undiagnosed HIV-infected children aged 8 to 15 years and overall HIV prevalence by age in the considered age-group.

· Trial primary outcome: proportion of children who miss ≥2 routine appointments by the end of 2years of follow-up. Trial secondary outcome: proportion of children on ART with treatment failure defined as an HIV-1 viral load >400copies/ml at 12 months after starting ART or death in the first year of ART.

· Rates of lung disease, growth, mortality and morbidity, by ART status.

 

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