- Category: HIV Treatment
- Published on Tuesday, 08 March 2016 00:00
- Written by Roger Pebody
Making point-of-care CD4 T-cell count diagnostics available, revising adherence counseling requirements, and giving extra training to healthcare workers can almost quadruple the number of patients who begin antiretroviral therapy (ART) on the day that they are eligible, Gideon Amanyire of Makerere University reported at the at the Conference on Retroviruses and Opportunistic Infections (CROI 2016)last month in Boston. The package of health system reforms was provided to a typical "real world" group of clinics in Uganda and was embedded in everyday practice, suggesting that the same intervention could have a similar impact elsewhere.
Recent findings from the START and Temprano trials have shown that starting HIV treatment early, while the CD4 cell count remains above 500 cells/mm3, reduces the occurrence of AIDS-related events, serious non-AIDS-related illness, and death. Although the World Health Organization now recommends that everyone diagnosed with HIV should start treatment, most people with HIV in sub-Saharan Africa start treatment too late. Last year, a meta-analysis found that Ugandans typically first present for care with a CD4 cell count of 370 cells/mm3 and begin treatment at 119 cells/mm3.
Package of Interventions to Speed Treatment Initiation
The package of interventions was developed using a health planning framework used in implementation science known as "PRECEDE." This model states that a combination of predisposing factors, enabling factors, and reinforcing factors are needed to facilitate change. The researchers used the model to identify barriers to rapid initiation of ART and interventions which could address those barriers.
Predisposing factors are attitudes, beliefs, or knowledge that influence people toward particular behaviors. The researchers believe that knowledge from recent randomized trials demonstrating the benefit of rapid ART initiation had not reached all frontline healthcare providers in Uganda -- the lack of diffusion of knowledge was therefore a barrier to quick uptake of treatment. The intervention was face-to-face teaching and coaching by medical opinion leaders, focusing on the benefits of prompt treatment and the dangers of delays.
Enabling factors are materials or skills that facilitate the desired behavior. In terms of barriers, the researchers identified problems with diagnostics for CD4 cell counts -- the criteria for determining eligibility for ART in Uganda. Testing generally required overnight processing, and therefore patients needed a second clinic visit to receive results, introducing the opportunity for a missed or delayed visit. The intervention was introduction of the Pima point-of-care test for CD4 counts, which provides results immediately.
In terms of enabling factors, a second identified barrier was the requirement for 3 pre-ART adherence counseling sessions or for patients to identify a "treatment supporter." The intervention was to revise the counseling protocol so that adherence counseling could be provided concurrently with ART initiation.
Reinforcing factors are rewards following actions and behaviors. The barrier identified was a lack of motivation among providers to start treatment rapidly; the intervention was giving quarterly feedback to clinics on their performance.
Study Setting and Design
The study was conducted at 20 HIV clinics operated by the Ugandan Ministry of Health, in a mix of rural and urban settings. Clinics, rather than individual patients, were randomized to receive the package of interventions. Nonetheless, the study outcomes (beginning ART within 2 weeks of being assessed as eligible, undetectable viral load 1 year later, and retention in care) were evaluated among patients who had never taken ART but were eligible to start.
The trial adopted a stepped wedge randomized design, which means that the intervention was gradually introduced to all 20 clinics over a 3-year period, with the sequence of allocation determined by the randomization process. In the first year, 5 clinics received the intervention, in the second year another 10 clinics began to receive it, and in the third year the last 5 clinics received it, so that all clinics were receiving it. This pragmatic trial design is often used for the evaluation of service delivery changes. Comparisons are made between periods in which clinics had not yet received the intervention and periods in which they had.
There were 12,024 patients who became eligible for ART, with a median CD4 count of 310 cells/mm3 (interquartile range 179-424). Two thirds were under the age of 35 and a little over a third were men.
During the control periods, 18.3% of patients began ART on the same day and 37.7% did so within 2 weeks. During the intervention periods, 70.8% began on the same day and 79.6% did so within 2 weeks.
The intervention increased the number of people starting on the same day by almost 4-fold (risk ratio 3.9) and doubled the number starting within 2 weeks (risk ratio 2.1).
The proportion with an undetectable viral load was evaluated in a random sample of 437 patients 1 year later. The 102 patients who could not be located were assumed to have a detectable viral load. In control and intervention periods respectively, 57.7% and 65.6% of patients were undetectable, but the difference was not statistically significant. There was no difference in retention between the 2 groups.
"If we take this intervention to scale we could enhance the efficiency and effectiveness of the care cascade in Africa," concluded Amanyire.
G Amanyire, F Collins Semitala, J Namusobya, et al. Streamlining Antiretroviral Therapy Uptake: A Stepped-Wedge Cluster Randomized Trial. 2016 Conference on Retroviruses and Opportunistic Infections (CROI 2016). Boston, February 22-25, 2016. Abstract 112.