Start Antiretroviral Therapy Sooner Than Later

By: Ranier Simons, ADAP Blog Guest Contributor

As medical science strives towards eradicating HIV, research and discourse regarding treatment and prevention continue to evolve. Antiretroviral therapy (ART) is the primary method of treatment. ART is drug therapy consisting of various combinations of medications whose purpose is reducing the HIV viral load in the body. The ultimate goal is to reduce the viral levels in the body to the point of being undetectable. Undetectable means that the viral load is so low that a viral load test cannot detect it.[1] Reaching undetectable status means that a person has no risk of sexually transmitting HIV to others, commonly referred to as "U=U" (undetectable equals untransmittable). Research has also shown that maintaining undetectable status enables people living with HIV/AIDS (PLWHA) to live long, healthy lives. 

Photo Source: Very Well Health

The timeline of starting patients on treatment is an ongoing inquiry at the forefront of ART discourse. In addition to viral load, historically, many other factors have been considered when starting PLWHA on drug therapy. Those who are asymptomatic and seemingly very healthy with good CD4 counts sometimes don’t see the benefits of starting early treatment out of concerns about possible long-term side effects and emotionally handling the prospect of lifetime medication adherence.[2] Notwithstanding various psychosocial, financial, and logistical issues, the main clinical criteria inquiry is the CD4 count. 

CD4 cells are white blood cells in the body that help the immune system to fight infection. HIV attacks and destroys CD4 cells.[3] An insufficient number of CD4 cells leaves the body susceptible to many forms of illness that healthy HIV-negative people are protected against. PLWHA are diagnosed with AIDS when the CD4 count reaches 200 cells/mm3.AIDS diagnosis means a high risk of developing life-threatening illnesses or even cancers.

Over time consensus has evolved regarding the appropriate CD4 count threshold for beginning ART. For a long time, the established guidelines recommended ART to begin when CD4 counts dropped below 350 cells/mm3 or if a patient had symptoms of AIDS. In December 2009, U.S. guidelines were issued, including a recommendation that ART commences if the CD4 count is between 350 and 500 cells/mm3.[4] However, that recommendation was based on observational studies, not randomized trials, in the manner that previous guidelines were developed. A randomized trial results in more definitive information since randomization means groups tested are very similar except for received treatment.[4]

To obtain randomized trial results concerning early ART intervention, the Strategic Timing of Antiretroviral Therapy (START) trial was first initiated in 2009, enrolling 4,684 HIV-positive patients (median age 36, 27% women), who had a CD4 count of ≥500 cells/mm3 (median 651 cells/mm3 ) at least two weeks apart within the 60 days before enrollment. Of these patients, 2,325 were randomized to start ART immediately, and 2,359 were randomized to defer treatment until their CD4 count was ≤350 cells/mm3.[5] Subjects were followed for a minimum of three years. START is a multinational endeavor.

Photo Source: everydayhealth.com

In 2015, results were published in the New England Journal of Medicine. Data showed that early initiation of ART lowered the risk of severe AIDS-related outcomes, serious non-AIDS-related outcomes, and death by 57%.[4] When the results were published, the subjects who had previously been in the deferred ART group started drug therapy. Another analysis was done in October 2022, which included 4,436 patients who were followed from January 2016 through December 2021. This analysis supported the benefits of starting ART early, even for patients with CD4 counts over 500 cells/mm3 at diagnosis. An additional finding was that adverse outcomes of delayed treatment were more pronounced in patients aged 35 and younger.[4] Research is continuing to examine the outcome difference by age.

Given that the START study shows the importance of early initiation of ART, it is imperative to increase efforts to identify HIV-positive patients. Many people don’t find out until clinically, a lot of damage has occurred. By increasing testing efforts, especially for those in higher-risk groups, HIV infection can be caught at earlier stages, and patients can initiate therapy. Early therapy means a much lower risk of AIDS progression, fewer instances of non-AIDS-related serious issues, and shorter time spans to reaching undetectable status. Diagnosing people earlier means a better quality of life for those infected and an expedited reduction in the number of people with viral loads high enough to be a transmission risk.

[1] National Institute of Health. (2021, August 16). HIV Treatment. Retrieved from https://hivinfo.nih.gov/understanding-hiv/fact-sheets/when-start-hiv-medicines#:~:text=When%20is%20it%20time%20to,possible%20after%20HIV%20is%20diagnosed
[2] Ross, J. et al. (2021) How early is too early? Challenges in ART initiation and engaging in HIV care under Treat All in Rwanda-A qualitative study. PloS one, 16(5), e0251645. https://doi.org/10.1371/journal.pone.0251645
[3] National Institute of Health. (2022, August 22). CD4 Lymphocyte Count. Retrieved from https://medlineplus.gov/lab-tests/cd4-lymphocyte-count/
[4] Hein, I. (2022, October 25). Start HIV Antiretroviral Therapy ASAP, Experts Urge. Retrieved from https://www.medpagetoday.com/meetingcoverage/idweek/101419
[5] National Institute of Health. (October 4, 2022). Strategic Timing of Antiretroviral Treatment (START). Retrieved from https://clinicaltrials.gov/ct2/show/study/NCT00867048

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.