A case for immediate ART initiation in all HIV diagnosed, regardless of CD4+ count?

The year 2013 saw the WHO recommended threshold for treatment of HIV+ patients with ART rise from a count of 350 CD4+ per mm3 to one of 500 CD4+ per mm3.. The threshold had been fixed as early as three years before (2010) at 350 CD4+ per mm3 (WHO ART recommendations). These recommendations have doubtless been made with a view both to improving individual outcomes and preventing transmission. However, their implementation poses, and will continue to pose, a serious challenge, especially in resource-poor settings. Writing in 2010, Hamilton and Crowley (STIs) estimated that setting the threshold for ART initiation at 250 CD4+ would by 2012 increase the need for treatment by a median of 15%, whereas setting at 350 CD4+ would increase it by 42% and 500 CD4+ by 84%. Contributors like Hallett & Garnett (STIs) (Zimbabwe) and Zwahlen (STIs) have sought to develop projections for individual countries.

It may not be so long before the modellers have, once again, to revise their calculations. Results of the Strategic Timing of Antiretroviral Therapy (START) trial, a recent multi-continental RCT, make a case for not deferring ART initiation, regardless of the patient’s CD4+ count. A total of 4,865 patients in 35 countries were randomized to an immediate and a deferred initiation group, and followed over a three-year period. The trial compared primary end-points, including death and serious AIDS-related, and non-AIDS-related, health events, over a three-year period. Among the commonest AIDS-related events were tuberculosis, Kaposi’s sarcoma and malignant lymphoma. Non-AIDS related events included cardio-vascular disease and non-AIDS related cancers. Hazard ratios for serious AIDS-related and non-AIDS related, events were 0.28 and 0.61, respectively. There have been concerns about the negative health impact of ART especially on cardio-vascular disease. But no safety concerns in the immediate-initiation group were identified. However, as the authors recognize, the study was underpowered for investigating the potential negative effects of early ART initiation on individual non-AIDS related events, because of the relatively limited number of events and early termination of the deferred therapy strategy.

In principle, the benefits of raising the threshold for linkage to care are clear. In due course, we may expect to see yet another upward adjustment in the WHO threshold. However, recent studies point to inadequate availability of care, late diagnosis (even by current standards), and poor retention in care as significant factors in suboptimal health outcomes (Mubezi & Shuha (STIs); Hussey (STIs). So what such a change in guidelines would deliver in real terms is hard to evaluate, and no doubt depends on the context of implementation. Yet, even in the relatively more resource rich settings (US), some recent research has argued for the reallocation of resources from linkage to retention in HIV care, in order to optimize utilization of scarce resources (Retention in Care (STI/blogs); Sherer (STIs). This recommendation would seem hard to square with the prioritization of ever lower thresholds for linkage to care.

At all events, this study demonstrates the benefits to the individual of prompt linkage to care whatever the stage in the progression of his/her infection.