番茄社区

Universal test-and-treat programs, where patients are tested and then immediately offered treatment for HIV, have produced variable results in Africa, and ultimately may not go far enough, a researcher argued.

Most of these programs have failed to significantly reduce the incidence of HIV, which will be key to ending the epidemic, reported Salim S. Abdool Karim, MB, ChB, PhD, of the Centre for the AIDS Programme of Research in South Africa in Durban, South Africa.

Writing in a editorial, Abdool Karim examined the results of three previously presented trials on universal HIV testing and treatment:

• PopART in Zambia and South Africa

• SEARCH in Uganda and Kenya

• in Botswana

"The three trials collectively signal a way forward. They indicate that increasing viral suppression is achievable, even by routinely available care, but also that reaching universal coverage is very difficult, even with substantial effort," Abdool Karim wrote.

He cited several common limitations to the studies, though he did acknowledge that intervention in these trials increased viral suppression, which ranged from 68% to 88% in the intervention groups.

"However, the modest differences in viral suppression at trial completion between the intervention and control groups, ranging from five to 12 percentage points, indicated that experimental interventions did marginally better than routinely available care in improving [antiretroviral therapy] coverage," Abdool Karim wrote. "Additional analyses are needed to better understand the potential role of differing baseline and actual levels of viral suppression in determining HIV incidence in these trials."

Abdool Karim also argued that the source of incident infections could be outside the trial population and, "unlike trials with individual randomization, which can exclude phylogenetically determined external infections, these three trials of universal testing and treatment were not able to eliminate this confounding effect."

He also cited the gap between HIV acquisition to a positive test and the logistics of reaching everyone with HIV infection as limitations to these studies.

PopART

Results from PopART, or (HPTN 071), were presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in March 2019. Richard Hayes, DSc, of the London School of Hygiene & Tropical Medicine, and colleagues that there was a significant reduction in HIV incidence with an intervention that included community health workers going door-to-door with testing, linkage to care, and treatment according to in-country guidelines versus standard of care (adjusted IRR 0.70, 95% CI 0.55-0.88, P=0.006).

However, there was no difference in HIV incidence when comparing the most intensive arm in the study -- where patients were provided immediate access to antiretroviral therapy (ART) versus standard of care (adjusted IRR 0.93, 95% CI 0.74-1.18, P=0.51).

Back in March, the National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci, MD, whose organization helped to fund the research, told 番茄社区 that the fundamental principle of studies like this is to show "in the field that [test-and-treat] actually works when you do it," and that this proactive strategy can potentially have an impact on HIV incidence in a community.

"The universal 'test' component of a 'test and treat' strategy is vital, as is continued attention to primary HIV prevention interventions," Hayes and colleagues wrote, adding that studies such as PopART highlighted the challenges of achieving ART coverage among populations such as young people, men, and communities with high mobility.

SEARCH

Results of the second study, SEARCH, or , were presented at the International AIDS Conference (IAC) in July 2018. Diane Havlir, MD, of the University of California San Francisco and colleagues that in a study population of over 150,000 people, there was no significant difference in 3-year cumulative incidence of HIV infections between an intervention and a control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77-1.17).

Havlir and colleagues noted that though there was no significant difference in the 3-year cumulative incidence of HIV infection, the annual incidence of HIV infection declined by 32% from the first to the third year in the intervention group.

"These data support accumulating evidence from other large universal test-and-treat and cohort studies in sub-Saharan Africa that population-level increases in viral suppression are associated with a reduction in the incidence of HIV infection," the authors wrote.

Back in July 2018, Havlir said at a press conference that the intervention "didn't eliminate all HIV infections, so we still need programs along this multi-disease, multi-financed approach."

Ya Tsie

A third study , also presented at IAC by Moeketsi Joseph Makhema, MBBS, of the Botswana Harvard AIDS Institute Partnership, and colleagues examining a universal testing and expanded treatment strategy, found a non-significant unadjusted HIV incidence ratio in the intervention group versus controls of 0.69 (95% CI 0.46-0.90 by pair-stratified Cox model).

The authors argued that, given similar findings from sensitivity analyses and models used to construct 95% confidence intervals, "in the context of significantly higher (and earlier) levels of viral suppression in communities in the intervention group, these results suggest that the observed approximately 30% lower incidence of HIV infection may be related to the intervention."

Abdool Karim was a bit less optimistic in his editorial, writing that, "the percentage of HIV-positive participants who had viral suppression was five percentage points higher in intervention communities than in control communities, with a concomitant 31% lower HIV incidence, which was not significant, over a period of 2.5 years."

Ultimately, Abdool Karim concluded that these programs are a good start, but do not go far enough in combating the HIV epidemic.

"In these settings, programs need to consider going beyond universal testing and treatment to universal testing, treatment, and prophylaxis to achieve HIV epidemic control," he wrote.