I missed the START session as I was presenting and noticed there's no ASHM blog on what is a tremendously important study, hence thought I'd quickly rectify this. You will all recall the landmark SMART study published in NEJM in 2006 where they enrolled 5472 HIV-infected patients, with a CD4 of >350 into an RCT with a a drug conservation arm (start when CD4 <250, stop when >350) and a viral suppression arm where they started ART immediately and didn't stop. The drug conservation arm was associated with increased risk of opportunistic infections, increased death from any cause and increased major cardiovascular, renal and hepatic diseases. We learnt then that drug holidays were unwise, and we needed to start ART earlier.
Since then, we have had some strong observational data and implied data through basic science research suggesting starting at an even more robust CD4 was wise. Earlier ART not only reduces OI and complications but also improves CD4 recovery and reduces the HIV viral reservoir etc. The US for instance has been recommending for early ART in all patients for a number of years. We have been somewhat slow in adopting this.
The START study now gives unequivocal data that all patients should start ART regardless of their CD4 count. In brief, they enrolled 4685 HIV-infected patients with CD4s >500 in 35 high-income and resource-limited settings. This study was stopped by the data and safety monitoring board in May 2015 as interim analysis showed their primary outcome had been met. The median VL was 12749, and median CD4 was 651. The composite primary end point (any serious AIDS-related event, serious non-AIDS-related event, or death from any cause) occurred in 42 patients in the immediate-initiation group (1.8%) as compared with 96 patients in the deferred-initiation group (4.1%); hazard ratio of 0.43. Frequency of TB, Kaposi, lymphoma, and cancer were lower in the immediate arm. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. You will find the full paper in this week's NEJM.
The TEMPRANO study, also published in the same NEJM issue, enrolled HIV-infected patients with a CD4<800 in Cote d'Ivoire. They examined the role of immediate vs deferred ART and isoniazid prophylaxis in comparison to WHO guidelines. They found that immediate ART and 6 months of IPT led to reduced rates of severe illness overall and also among those with CD4 >500.
WHO will be publishing new guidelines recommending ART for ALL. We will need to reflect on how we can do this better (and quicker) in Australia. What is the lag time from acquisition to testing; from testing to diagnosis; from diagnosis to treatment?? San Francisco General Hospital is able to start ART within 24hours in patients with newly diagnosed HIV. The Thai group led by Dr Aranowich are able to start ART at acute HIV infection. The TEMPRANO group was able to do this is Cote d'Ivoire. How will we respond in Australia?????