Strategic Timing of AntiRetroviral Treatment (START)
Research type
Research Study
Full title
Strategic Timing of AntiRetroviral Treatment (START)
IRAS ID
7979
Sponsor organisation
Regents of the University of Minnesota, USA
Eudract number
2008-006439-12
Clinicaltrials.gov Identifier
Research summary
Research Summary:
HIV medicines prevent AIDS-related illnesses. These illnesses are rare when the immune system is relatively strong (as measured by a CD4 count above 350 cells). Therefore, most guidelines recommend that HIV-infected People'should only start medicine when their CD4 count falls below 350 cells. Recent research suggests that people with HIV may be at increased risk of developing serious illnesses other than AIDS. These other illnesses (non-AIDS illnesses) include heart, liver, and kidney disease and cancers that occur at higher CD4 cell counts.The START study will evaluate if starting HIV medicines earlier - before CD4 cells drop to below 500 cells/mmü - will reduce the risk of developing serious non-AIDS illnesses as well as reduce the risk of the traditional AIDS illnesses.Eligible participants will have never had HIV medicines (antiretroviral therapy, ART) before, and will have a CD4 count greater 500 cells/mm3. Participants will be assigned to either the EARLY or DEFERRED treatment group:* EARLY Group will start treatment immediately (i.e. with a CD4 cell count above 500)* DEFERRED Group (provided they remain well) will wait until their CD4 cells drop to below 350 before starting treatment (this group is treated following current guidelines). Treatment will be with standard licensed ART drugs. Patients will be seen every 4 months during the study for routine blood tests and clinical evaluation. The rate of development of AIDS and serious non-AIDS events will be compared between the two groups.
Summary of results:
In 2015, the START study was able to address the primary objective of START: to determine whether starting AntiRetroviral treatment (ART) early (at CD4 > 500) is superior to deferring ART until indicated by (then-current) guidelines at delaying the occurrence of a composite outcome consisting of AIDS, non-AIDS, or death from any cause.
A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. The study results demonstrated a 57% reduced risk of AIDS and serious non-AIDS health outcomes among participants who began ART when their CD4+ T-cell counts—a key indicator of immune system health—were greater than 500 cells per cubic millimeter (mm³) compared with those who did not begin ART until either their CD4+ counts fell below 350 cells/mm³ or they developed AIDS.
The study showed that:
• Treatment was safe for people starting at CD4 counts above 500.
• People on the early treatment group had fewer serious HIV-related illnesses.
• The results were similar in all geographic regions.These results were important enough to change the study and everyone in the study was offered treatment, at any CD4 count, no matter how high, and participants were followed until the planned study end in 2016.
In 2017, the START study was extended through 2021 to answer additional questions. Although START had proved the benefit of early ART initiation, longer-term follow-up of 4,446 participants was undertaken to determine whether the health benefits of early ART compared with deferred ART increased, remained constant, or declined after the participants in the deferred arm were advised to begin ART. The primary study endpoints included the number of participants who developed AIDS; those who developed serious non-AIDS health conditions, such as major cardiovascular disease, kidney failure, liver disease and cancer; and those who died.
In 2023 the full results of this follow up became available .
The follow up period showed that for participants who began ART before the end of 2015, the median CD4+ cell count at the time of ART initiation was 648 cells/mm³ for the immediate arm and 460 cells/mm³ for the deferred arm. The analysis compared the primary study endpoints before the end of 2015, with those in the extended follow-up period, from Jan. 1, 2016, to Dec. 31, 2021. In the latter period, most deferred-arm participants were taking ART. During the follow up period, people initiating ART in the deferred group had rapid and sustained declines in HIV viral load (less than or equal to 200 copies/mL); however, CD4+ cell counts remained, on average, 155 cells lower compared with that of individuals in the immediate ART group. While the risk of serious health outcomes was substantially diminished soon after ART was initiated in the deferred treatment group, some excess risk remained compared with the immediate treatment group. The deferred ART group continued to have a somewhat greater risk (21%) of serious health consequences or death in comparison to the immediate treatment group. Twenty-seven cases of AIDS occurred in the five-year follow-up period in the deferred treatment group compared with 15 cases in the early treatment group. Similarly, 88 cases of serious non-AIDS health issues occurred in the deferred treatment arm compared with 76 cases in the immediate treatment arm. Lastly, there were 57 deaths in the deferred treatment group compared to 47 in the immediate treatment arm. The study concluded that among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained.
The START study findings confirm that ART significantly improves the health of an individual with HIV and reduce the person’s risk of developing AIDS and serious health issues, and that early diagnosis and treatment are key to maximizing these benefits and reducing risk.
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https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3t%2Fwww.ncbi.nlm.nih.gov%252Fpubmed%252F37213438%2FNBTI%2FaF64AQ%2FAQ%2F2f7289c7-f19b-4a1a-b095-5ba59386b02c%2F3%2FUUq1nmCtnp&data=05%7C02%7Cleedseast.rec%40hra.nhs.uk%7C26b069c7efc44e6086f508dce169f784%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638633092441512728%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=15D6mKLp%2FRRBy8NHai5QKWXyrJcA19U3L65NK0kh38g%3D&reserved=0REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
09/H1306/64
Date of REC Opinion
29 Jul 2009
REC opinion
Further Information Favourable Opinion