At the 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, two presentations provided results that describe the benefits to starting HIV treatment "early" in terms of time (within three months of infection) and in terms of CD4 count (>350 cells).
Temprano ANRS 12136 Study
A large, 7-year randomized study of 2,056 people from the Ivory Coast assessed the health outcomes of providing HIV treatment immediately or delayed (according to WHO guidelines) and with or without IPT. (IPT, or isoniazid, is often used to treat TB but in this study was used as prevention.) Ivory Coast is a low-income country with high rates of serious bacterial infections such as TB, particularly among people with HIV.
All participants were new to both HIV treatment and IPT and most were women (78%) with a median age of 35. About 40% had CD4s over 500 and all were below 800 cells (median 465). The great majority was followed for more than two years. No one had active TB. All took regimens of emtricitabine/tenofovir (Truvada) with either efavirenz (Sustiva), lopinavir/r (Kaletra) or zidovudine (AZT, Retrovir).
The results showed that immediate HIV treatment and IPT both independently lowered the risk for severe conditions (AIDS diagnosis, severe bacterial infections, non-AIDS cancers, and any-cause death), even when started at CD4 counts above 500. HIV treatment on its own lowered the risk by 44% and IPT on its own lowered it by 35%.
However, throughout the study, WHO guidelines changed a couple of times by increasing the CD4 count at which HIV treatment was recommended. When looking only at those who started at >500 CD4s, IPT's effect was no longer significant. However, early HIV treatment continued to lower the risk of severe conditions by 44% in this CD4 range.
Royal Free Hospital Study
A small retrospective study from London looked at the optimal immune reconstitution of 142 people who had started HIV treatment either within three months of infection (37 people) or during chronic infection but above 350 CD4s (115). Optimal immune reconstitution was defined for this study as a CD4 count >800, CD4 percent at or >40%, and a CD4:CD8 ratio at or >1.
All participants had stayed on continuous treatment for at least 5 years. Median age was about 33 and the great majority were male and men who have sex with men. Median viral loads at study entry were 511,000 for the early starters vs. 278,000 for the late starters.
Results showed that the immune system responses to treatment were excellent in both groups. However, those who started meds earlier showed persistently better outcomes in CD4 counts, CD4 percentage and CD4:CD8 ratios at all 1-, 5- and 10-year time points.
At one year, average CD4 counts were 743 (early) vs. 600 (late), while they were 850 vs. 779 at 5 years, and 966 vs. 874 at 10 years. Average CD4 percentages were 35 vs. 28 at 1 year, 39 vs. 33 at 5 years, and 38 vs. 33 at 10 years. Average CD4:CD8 ratios were 0.95 vs. 0.52 at 1 year, 1.05 vs. 0.78 at 5 years, and 1.09 vs. 0.85 at 10 years.
Of particular note, average time to reaching a CD4:CD8 ratio of more than 1 (a sign of a healthier immune system) was 36 weeks for the early starters vs. 187 weeks for the late starters. Whether this observation results in different health outcomes remains to be determined.
C Danel, et al. "Early ART and IPT in HIV-Infected African Adults With High CD4 Count (Temprano Trial)". 2015 CROI, Seattle, WA.
S Kinloch, et al. "Enhanced Immune Reconstitution With Initiation of ART at HIV-1 Seroconversion". 2015 CROI, Seattle, WA.