Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy.

Graeme Meintjes,Jennifer Nash,Catherine Orrell,Moeketsi Mathe,Yunus Moosa,Thandekile C Manzini,Sipho Dlamini,John Black,Gary Maartens,Francois Venter,Douglas Wilson,Francesca Conradie,Michelle Moorhouse

doi:10.4102/sajhivmed.v16i1.428

Abstract

The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART) guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults). The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

Highlights

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The rationale was that insufficient evidence existed to advise a ‘test-and-treat’ approach to HIV at that time, and it was stated that we awaited the results of the TEMPRANO and Strategic timing of antiretroviral therapy (START) trials.[1]
The relative reduction in the rate of primary endpoint events was greater in START (57% reduction compared with 44%)

Summary

The strategic timing of antiretroviral therapy and TEMPRANO trials

Both the START and TEMPRANO trials enrolled patients with high CD4 counts The absolute benefit of immediate ART was greater in the TEMPRANO trial (conducted in Cote d’Ivoire) than in the START trial (which was conducted in countries across the world), because the event rate in the control arms (mainly from TB and invasive bacterial infections) was higher in the TEMPRANO trial, reflecting the high co-infection risks that exist for individuals living with HIV infection in Africa, even with higher CD4 counts. The HPTN052 trial[4] previously demonstrated that ART prevented onward transmission of HIV within serodiscordant couples, which suggested that ART at HIV diagnosis for all may be an important strategy to help prevent the growth of the HIV epidemic at a public health level Such an approach would be difficult to justify if there were no individual benefit and potential individual harm. What these two trials have demonstrated is that there is individual clinical benefit with no signal of harm during ~3 years of follow-up, providing significant additional support for the ‘test-and-treat’ strategy

Main contributors to finding Deaths

Viral load suppression Adverse events

Isoniazid preventive therapy in patients on antiretroviral therapy

Findings

Specific patient groups