Sustainable East Africa Research in Community Health (SEARCH)

• Cumulative HIV incidence [ Time Frame: 5 year ] [ Designated as safety issue: No ]
  To determine the effect of a strategy to start ART in HIV diagnosed persons (men and women >=15 years) at any CD4 count with streamlined delivery of HIV care compared to a country based ART guidelines on 5-year cumulative HIV incidence in rural communities with annual HIV testing.
  
  

• Time from diagnosis to AIDS [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare time from diagnosis to AIDS between the 2 study arms.
  
  
• HIV care implementation [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]

  Analysis of HIV care cascade:

  1. HIV testing, linkage, retention, re-engagement
  2. Clinic efficiencies
  3. Provider attitude and behavior
  4. Patient social networks
  5. Patient satisfaction
  
  
• Total TB and incident TB cases [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare proportion of total TB and incident TB cases associated with HIV between the 2 study arms.
  
  
• Overall mortality [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: Yes ]
  To compare mortality between the 2 study arms.
  
  
• Maternal and child mortality [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare number of maternal and child deaths between the 2 study arms.
  
  
• Mother to child transmission [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare mother to child HIV transmission between the 2 study arms.
  
  
• Population HIV RNA metrics [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare population HIV RNA metrics between the 2 study arms. HIV metrics include: % with HIV viral suppression; median population HIV RNA level; % HIV RNA by strata i.e. greater than 100,000 vs. <100,000 copies/ml
  
  
• Association between population HIV RNA metrics and HIV incidence [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To determine the association between population HIV RNA metrics and HIV incidence. HIV metrics include: % with HIV viral suppression; median population HIV RNA level; % HIV RNA by strata i.e. greater than 100,000 vs. <100,000 copies/ml
  
  
• Transmitted HIV drug-resistance mutations [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the prevalence of transmitted HIV drug-resistance mutations between the 2 study arms.
  
  
• Rates of linkage and retention for hypertension and diabetes [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To evaluate predictors of linkage and retention for hypertension and diabetes care
  
  
• Virologic suppression in high CD4 count individuals [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: Yes ]
  rate of virologic suppression in high CD4 count individuals (CD4>350)
  
  
• Five year cumulative incidence of internally derived HIV infections [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the five year cumulative incidence of internally derived HIV infections (infections genetically linked to a prior infection among members of the same community) between the 2 study arms.
  
  
• Average levels of adults' on- and off-farm employment [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the trends in average levels of adults' on- and off-farm employment between the 2 study arms.
  
  
• Average levels of children's on- and off-farm employment [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the trends in average levels of children's on- and off-farm employment (child labor) between the 2 study arms.
  
  
• Average levels of children's time allocation to schooling and household activities [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the trends in average levels of children's time allocation to schooling and household activities between the 2 study arms.
  
  
• Average asset holdings [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the trends in average asset holdings (durable good and livestock) between the 2 study arms.
  
  
• Agricultural output and other economic production [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the trends in agricultural output and other economic production, such as fishing, between the 2 study arms.
  
  
• Average levels of cash and in-kind transfers [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the trends in average levels of cash and in-kind transfers between the 2 study arms.
  
  
• Costs of programming [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare costs of programming (campaigns, ART) between the 2 study arms: overall; per person identified, linked to care, and started on ART; and per ART-month, CD4 level recovered, and viral load suppressed.
  
  
• Disease burden [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare disease burden (expressed in disability adjusted life years, DALYs) between the 2 study arms, during and modelled beyond the study period.
  
  
• Savings from averted disease associated treatment costs [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the savings from averted disease associated treatment costs between the 2 study arms.
  
  
• Occurrence and consequences of false positive HIV diagnosis [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To compare the occurrence and consequences of false positive HIV diagnosis (new).
  
  
• Cost-effectiveness of the intervention [ Time Frame: After 1, 3 and 5 years follow up ] [ Designated as safety issue: No ]
  To calculate the incremental cost-effectiveness of the intervention, as net cost per DALY averted.
  
  
• Cumulative HIV incidence [ Time Frame: 3 year ] [ Designated as safety issue: No ]
  To determine the effect of a strategy to start ART in HIV diagnosed persons at any CD4 count with streamlined delivery of HIV care compared to a country based ART guidelines on 3-year cumulative HIV incidence in rural communities with annual HIV testing.
  
  
• Streamlined care of HIV patients [ Time Frame: 3 year ] [ Designated as safety issue: No ]
  To evaluate streamlined vs. non- streamlined care including time in motion studies for staff and clients
  
  

The SEARCH study is a cluster randomized community trial of 32 communities each with approximately 10,000 residents. Community health campaigns will be conducted in all study communities and will offer HIV testing and multi-disease prevention and treatment services. The intervention is antiretroviral therapy (ART), independent of CD4 cell count, delivered in a streamlined approach for all HIV infected adults and children. Components of streamlined care include ongoing HIV combination prevention strategies including male circumcision. Control communities ART treatment will follow country guidelines.

HIV incidence will be measured using an efficient community cohort design (ECCO) comprised of three key elements: A) baseline household community level census, B) community health campaigns (CHC) incorporating HIV testing that use unique identifiers to link individuals between successive waves of the intervention, and C) tracking and evaluation of individuals who do not participate in CHCs.