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New HIV intervention highly effective in Botswana

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In Botswana, an intervention in 15 communities to test for and treat HIV infection in all adult residents was effective in increasing population viral suppression to very high levels (meaning that the virus becomes undetectable and can’t be transmitted while patients are taking effective treatment), according to a study led by researchers from Harvard TH Chan School of Public Health and the Botswana-Harvard AIDS Institute Partnership, and collaborators at several other institutions. The intervention likely also contributed to a nearly one-third reduction in the incidence of HIV infection in participating communities.

“Using approaches that are feasible in most settings, we achieved levels of HIV diagnosis, treatment, and viral suppression that are among the highest levels reported globally,” said senior author Shahin Lockman, associate professor in the department of immunology and infectious diseases. “These high rates of treatment coverage are a testimony to the long-standing commitment that Botswana has shown to tackling HIV. We also believe that our approaches and findings are highly relevant for other countries.”

HIV prevalence in Botswana is high, despite efforts by the government to increase access to testing, treatment, and preventive services. In 2017, an estimated 23% of adults had HIV. Combination antiretroviral therapy (ART) can essentially eliminate the risk of HIV transmission from a person who adheres to treatment and who has an undetectable viral load.

For the current study, researchers analysed data from 23,401 people in the Ya Tsie Botswana Prevention Project, a randomised trial in 30 rural and semi-urban communities (with a total population of approximately 180,000). From 2013 to 2018, 15 communities received an intervention that included universal HIV testing and counselling, support for accessing care, expanded and more rapid ART initiation, and increased access to male circumcision services (which lowers the risk of acquiring HIV). A control group of 15 communities received standard HIV testing and treatment.

By the end of the study period, in the intervention group, the proportion of persons living with HIV who had a suppressed viral load increased from 70% to 88%, while the proportion in the standard care group increased from 75% to 83%. The population level of viral suppression in the intervention group is among the highest to be reported globally. Incidence of HIV infection in the intervention group was 31% lower than incidence in the standard care group, which is borderline statistically significant.

Among the methods tried during the intervention, male circumcision uptake was relatively low and was hence likely the least significant, according to the researchers. The successful HIV testing campaigns in homes and mobile venues, along with support for linkage to care, both contributed to the very high ART initiation and viral suppression achieved. According to the researchers, these efforts in turn likely led to the nearly one-third reduction in the rate of new HIV infections in the intervention communities.

“Universal HIV testing and treatment can contribute substantially toward improving health and reducing the rate of new HIV infections in the community,” said Lockman. “This reduction, if sustained over time, will help us achieve the UNAIDS target of 90% reduction in the rate of new HIV infections by 2030.”

Other Harvard Chan School authors include Kathleen Wirth, Molly Pretorius Holme, Sikhulile Moyo, Kathleen Powis, Scott Dryden-Peterson, Vlad Novitsky, Simani Gaseitsiwe, Roger Shapiro, Haben Michael, Victor DeGruttola, Quanhong Lei, Rui Wang, and Eric Tchetgen Tchetgen.

Other collaborating institutions included the US Centres for Disease Control and Prevention (CDC), the Botswana-Harvard AIDS Institute Partnership and the Botswana Health Ministry.

Abstract
Background: The feasibility of reducing the population-level incidence of human immunodeficiency virus (HIV) infection by increasing community coverage of antiretroviral therapy (ART) and male circumcision is unknown.
Methods: We conducted a pair-matched, community-randomized trial in 30 rural or periurban communities in Botswana from 2013 to 2018. Participants in 15 villages in the intervention group received HIV testing and counseling, linkage to care, ART (started at a higher CD4 count than in standard care), and increased access to male circumcision services. The standard-care group also consisted of 15 villages. Universal ART became available in both groups in mid-2016. We enrolled a random sample of participants from approximately 20% of households in each community and measured the incidence of HIV infection through testing performed approximately once per year. The prespecified primary analysis was a permutation test of HIV incidence ratios. Pair-stratified Cox models were used to calculate 95% confidence intervals.
Results: Of 12,610 enrollees (81% of eligible household members), 29% were HIV-positive. Of the 8974 HIV-negative persons (4487 per group), 95% were retested for HIV infection over a median of 29 months. A total of 57 participants in the intervention group and 90 participants in the standard-care group acquired HIV infection (annualized HIV incidence, 0.59% and 0.92%, respectively). The unadjusted HIV incidence ratio in the intervention group as compared with the standard-care group was 0.69 (P=0.09) by permutation test (95% confidence interval [CI], 0.46 to 0.90 by pair-stratified Cox model). An end-of-trial survey in six communities (three per group) showed a significantly greater increase in the percentage of HIV-positive participants with an HIV-1 RNA level of 400 copies per milliliter or less in the intervention group (18 percentage points, from 70% to 88%) than in the standard-care group (8 percentage points, from 75% to 83%) (relative risk, 1.12; 95% CI, 1.09 to 1.16). The percentage of men who underwent circumcision increased by 10 percentage points in the intervention group and 2 percentage points in the standard-care group (relative risk, 1.26; 95% CI, 1.17 to 1.35).
Conclusions: Expanded HIV testing, linkage to care, and ART coverage were associated with increased population viral suppression.

Authors
Joseph Makhema, Kathleen E Wirth, Molly Pretorius Holme, Tendani Gaolathe, Mompati Mmalane, Etienne Kadima, Unoda Chakalisa, Kara Bennett, Jean Leid

Harvard TH Chan School of Public Health material
New England Journal of Medicine abstract


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