Article and Study Summary

HIV testing and treatment with the use of a community health approach in rural Africa.

Published in:
N Engl J Med 2019; 381:219-229.
https://www.nejm.org/doi/full/10.1056/NEJMoa1809866

Authors:
Havlir DV, Balzer LB, Charlebois ED, et al.

Summary:
The Sustainable East Africa Research in Community Health (SEARCH) trial was a cluster-randomized trial that evaluated whether universal HIV treatment and annual testing, delivered through a community-based, multi-disease, patient-centered approach, would lower HIV incidence in rural communities in Kenya and Uganda. Thirty-two communities were randomized to receive community-based HIV and multi-disease testing and either antiretroviral therapy (ART) based on national guidelines (control group) or universal ART combined with annual community-based HIV testing and a patient-centered approach to providing clinical services (intervention group). The primary outcome of interest was cumulative HIV incidence among adult residents of the communities at three years. While the intervention shortened the time to ART initiation and increased viral suppression among people living with HIV in those communities, there was no significant difference in cumulative HIV incidence compared to the control communities. The intervention communities also had a reduced risk of tuberculosis or death among people living with HIV. The results of the SEARCH study and other recent population-level universal test and treat studies were impacted by changes in ART eligibility in the control group, with their interventions showing modest or no impact on HIV incidence when compared to the standard of care. Taken together, these findings highlight that HIV testing and ART coverage need to be truly universal, and treatment as prevention needs to be supplemented with other HIV prevention approaches, in order to achieve epidemic control.

Discussion Questions:

1. Could the intervention described in this article be applied to the programs that you work with?
2. What else do you think needs to be done to reduce HIV incidence in the communities you work in? Do you have any experiences to share?

Please share your thoughts and experiences with us in the comments section below.

Full Synopsis:

PDF version available in English, French, and Portuguese. 

Study Summary 

The Sustainable East Africa Research in Community Health (SEARCH) trial was a cluster-randomized trial conducted between 2013 and 2017 that evaluated whether universal HIV treatment and annual testing, delivered through a community-based, multi-disease, patient-centered approach, would result in a lower number of new HIV infections and better community health than the current standard of care.

Study Setting

• Thirty-two communities of 9,000 to 11,000 people in three regions of rural Uganda and Kenya.

Methods

• Communities were pair-matched on the basis of geography, population density, number of trading centers, variety of occupations, and mobility patterns, and then randomly assigned to either an intervention group or a control group.
• In both groups, a baseline household census was conducted to enumerate and enroll residents >15 years of age. The survey collected sociodemographic information and biometric data for tracking participation in testing and care activities during the study.
• Following the census, baseline HIV and multi-disease testing was conducted on all communities through mobile, two-week health campaigns, conducted under large tents during weekdays, evenings, and weekends. For residents who did not attend the campaign, testing was performed at their home or other location of their choice.
• Individuals found to have HIV infection, diabetes, or hypertension received counseling and clinic appointments. People with HIV infection also had their CD4 count and viral load (VL) measured and received a one-time round-trip transportation voucher for their first clinic visit.
• In intervention communities, repeat testing campaigns were conducted annually, antiretroviral therapy (ART) was offered to all HIV-positive individuals, and hypertension and diabetes were managed using standard algorithms.
• Additionally, residents in intervention communities received patient-centered care, including:
  • People with HIV infection who were not on ART received appointments to initiate or restart ART within seven days following HIV testing.
  • Clinic staff introduced themselves in person or by phone, provided patients with a hotline to contact by phone or text message if they had questions or needed support, and called or sent text message reminders about clinic visits.
  • Clinical care included three-month visit intervals, flexible hours, reduced wait time, and welcoming staff.
• At clinics in control communities, ART, hypertension, and diabetes were managed according to national guidelines.
  • The threshold for ART eligibility in these countries expanded during the trial period from a specific CD4 count (ranging from ≤350 cells/cubic millimeter to <500 cells/cubic millimeter) to universal treatment regardless of CD4 count.
• After three years, campaigns were conducted in all communities for assessment of the trial end points.
• The primary end point was cumulative incidence of HIV infection after three years among HIV-negative residents enumerated in the baseline census.
• Secondary end points included time to initiation of ART and if viral suppression was achieved (defined as VL <500 copies/milliliter) for those found to be HIV-positive, and death and control of hypertension among HIV-positive individuals and the overall population.

Study Population and Follow-up

• During the baseline census, 150,395 residents >15 years of age were enumerated.
• Of these residents, 45% were male, 64% had an education below primary school level, 24% were employed in the formal sector, and 96% were stable residents, defined as having spent at least six months of the previous year in the trial community.
• Among 135,484 residents whose HIV status was known, the baseline prevalence of HIV infection was 19% in Kenya, 7% in western Uganda, and 4% in eastern Uganda.
• Among 13,529 residents known to be living with HIV at baseline, 52% had a CD4 count >500 cells/cubic millimeter.
• During baseline testing campaigns, 90% of all census-enumerated residents were tested for HIV in the intervention group and 91% in the control group.
• By the three-year assessment, cumulative HIV testing coverage was 98% of residents in the intervention group and 96% of residents in the control group, including residents who migrated into the communities.

Primary Outcome

• Among the 117,114 individuals who were >15 years of age, HIV-negative at baseline, and considered stable residents of the community, the primary end point was evaluated in 80% (n = 49,590/61,676) of persons in the intervention group and 82% (n = 45,493/55,438) of persons in the control group.
• A total of 704 new HIV infections occurred, for a three-year cumulative HIV incidence of 0.77% (0.25 cases per 100 person-years) in the intervention group and 0.81% (0.27 cases per 100 person-years) in the control group, which were not significantly different (relative risk [RR], 0.95, 95% confidence interval [CI], 0.77–1.17).

Secondary Outcomes

• After three years, in the intervention group, an estimated 92% of HIV-positive individuals knew their status, 95% of these individuals had received ART, and 90% of those who received ART had achieved viral suppression. In the control group, 91% of HIV-positive individuals knew their status, 86% of these individuals had received ART, and 87% of those who received ART had achieved viral suppression.
• Among 5,952 HIV-infected individuals not on ART, a higher percentage initiated ART in the intervention group than in the control group after six months (60% vs. 17%, RR 3.49, 95% CI 2.86–4.26), and a significant difference was still observed after 36 months (83% vs. 50%, RR 1.66, 95% CI 1.51–1.81).
• At three years, the prevalence of population-level viral suppression was higher in the intervention group than in the control group (79% vs. 68%, relative prevalence 1.15, 95% CI 1.11–1.20).
• The cumulative probability of death due to illness by year three among adults who were HIV-positive at baseline was lower in the intervention group than in the control group (0.99 deaths per 100 person-years vs. 1.29 deaths per 100 person-years; RR 0.77, 95% CI 0.64–0.93).
• In a post-hoc analysis, the TB incidence rate after three years among persons who were HIV-positive at baseline was lower in the intervention group than in the control group (relative rate 0.41, 95% CI 0.19–0.86), but the TB incidence rate did not differ significantly by study arm among those who were HIV-negative at baseline.
• Among adults with hypertension, the percentage who achieved control of their hypertension was higher in the intervention group than in the control group at three years (47% vs. 37%, relative prevalence 1.26, 95% CI 1.15–1.39).

Critical Analysis  

This cluster-randomized trial found that universal HIV treatment with annual HIV testing, using a community-based, multi-disease, patient-centered approach, did not result in lower HIV incidence in rural communities in Uganda and Kenya compared to the standard of care. However, with this approach intervention communities did achieve the UNAIDS 90-90-90 goals, with a shorter time to ART initiation and greater prevalence of population-level viral suppression. There was also a lower risk of death and TB among HIV-positive individuals in intervention communities than in control communities.

The following points should be considered when interpreting the study findings:

• In both countries, national guidelines changed to universal ART within one year of the start of the trial, likely diminishing the effect of the intervention as originally hypothesized; as a result, the trial follow-up period was shortened from five years to three years.
• The comprehensive baseline HIV testing received by the control group communities meant that the intervention was not being compared to the standard of care in these regions, which may have further diminished the relative impact of the intervention.
• The communities studied were small and rural, and the population had low levels of formal sector employment, education, and migration, which may limit generalizability of these results to other communities with different demographic characteristics.
• These results did not account for coverage of other prevention interventions that may impact population-level HIV incidence, such as voluntary male medical circumcision or pre-exposure prophylaxis.
• There were notable regional variations in baseline HIV prevalence and change in HIV incidence from the first to third year, suggesting there may be other contextual drivers of HIV infection in these communities.
• In both the intervention and control communities, additional study staff provided HIV services at government clinics, which may limit generalizability of this intervention in real-world, resource-limited settings.

Implications

This large cluster-randomized trial in rural communities in Kenya and Uganda found no significant difference in three-year cumulative incidence of HIV infection with annual HIV testing and a universal ART approach, compared to standard of care, despite a greater increase in population-level viral suppression. However, the patient-centered study intervention resulted in a shorter time to ART initiation, lower TB incidence, and lower overall mortality among people living with HIV in the intervention communities, compared to control communities. These findings, along with other recently published population-level universal test and treat trials (1,2), suggest that interventions can be effective in increasing community-level viral suppression but do not necessarily have a clear impact on HIV incidence. This is likely due in part to changes in national guidelines over the trial periods towards universal ART, making the standard of care more effective. However, this finding also suggests that in order to achieve epidemic control, HIV testing and ART coverage need to be truly universal, and treatment as prevention needs to be supplemented with other HIV prevention approaches.

References

1. Makhema J, Wirth KE, Pretorius Holme M, et al. Universal testing, expanded treatment, and incidence of HIV infection in Botswana. N Engl J Med 2019;381:230-242
2. Hayes RJ, Donnell D, Floyd S, et al. Effect of universal testing and treatment on HIV incidence — HPTN 071 (PopART). N Engl J Med 2019;381:207-218.

This article synopsis was written by Cassia Wells. Share your thoughts on this article or suggest an article for Journal Club by emailing her at caw2208@columbia.edu

Articles of Note

• Effect of Universal Testing and Treatment on HIV Incidence — HPTN 071 (PopART)
• Universal Testing, Expanded Treatment, and Incidence of HIV Infection in Botswana
• Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1