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The coming of age of rapid ART initiation in HIV
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When to begin ART once HIV diagnosis is confirmed has been an area of research and debate for many years. The standard of care in the United States is to start ART when patients are agreeable to begin therapy, regardless of CD4 count. Often, though, there are barriers that may delay the start of HIV treatment. Lack of insurance coverage, active injection drug use, patient and provider attitudes toward treatment and opportunistic infection testing are all obstacles to beginning treatment, as well as numerous other factors. In many cases, HIV testing is done in settings other than where treatment is offered. This can delay ART by weeks or even months, depending on when the patient can be linked to HIV care. There are now clinics offering rapid ART initiation on the same day of HIV diagnosis to circumvent a delay in starting therapy due to a failure of patients to engage in care after their initial HIV diagnosis. Unfortunately, current HIV treatment guidelines are inconsistent when it comes to rapid initiation of ART. Both WHO and the International Antiviral Society (IAS)-USA treatment recommendations support immediate ART once HIV is diagnosed, including same-day ART initiation. However, HHS states that despite the potential benefits, ART initiation on the day of diagnosis remains investigational regarding its efficacy.
Evidence supporting rapid initiation of ART
Randomized trials in resource-limited countries have demonstrated that offering ART at the time of diagnosis results in earlier initiation of ART and higher rates of retention in care and viral suppression without compromising safety. A systemic review of published randomized trials shows that starting ART on the same day of diagnosis increases viral suppression at 12 months (RR = 1.17; 95% CI, 0.99-1.26), retention of care (RR = 0.11; 95% CI, 0.99-1.27) and the likelihood of starting ART at 90 days (RR = 1.35, 95% CI, 1.13-1.62). The studies also showed a trend toward a reduced likelihood of being lost to follow-up and reduced mortality at 12 months. However, some observational trials have shown that same-day ART may increase the risk of loss to follow-up among select groups of patients, such as pregnant women. This might indicate that specialized education or resources are needed for these patients. Additional information and study are required to identify barriers in certain groups of patients, including those who are pregnant.
Researchers in San Francisco’s Ward 86 HIV clinic have reported results from their Rapid ART Program for Individuals with an HIV diagnosis program. This clinic serves a challenging population with high rates of publicly insured individuals along with other challenges, such as poverty, substance use, mental health disorders, food insecurity and housing instability. In 2013, they adopted immediate ART at the first visit after HIV diagnosis. Between 2013 to 2017, 225 patients were referred to their program, and immediate ART was started in 96% of these patients. The majority (88%) were referred to the clinic within 30 days of HIV diagnosis. Viral suppression was achieved in 95.8% of patients within 1 year, and more than 90% had a viral load less than 200 copies/µL with their last viral load measurement.
One of the questions is whether rapid ART can reduce HIV transmission rates. We know that reducing a patient’s viral load reduces risk for transmission, so the sooner we start ART and hold viremia in check, the risk for transmission should theoretically be lower. The Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) trial also tried to answer this question. This was a large study (n = 48,301) in Zambia and South Africa in patients aged 18 to 44 years. The trial measured HIV incidence through in-home HIV testing, and patients who were HIV positive were referred to treatment, whereas those who tested negative were offered prevention measures. Patients were randomly assigned to one of three study arms. Study Arm A patients were offered the full PopART prevention package, which included offering immediate ART; arm B patients received the PopART intervention with ART per local guidelines; and arm C patients were treated according to the current standard of care. The HIV baseline prevalence was similar in all three treatment groups (21% to 22%). There was a 30% decline in new HIV infections in arm B compared with those in the standard-of-care group. However, the surprise finding in this trial was that in arm A, which included those who were offered immediate ART, the researchers observed only a 7% decline in new HIV cases compared with standard of care, which was not statistically significant. It is unclear why there was not a larger decline in new HIV cases among those who were offered immediate ART, but there may have been unrecognized differences among the communities enrolled in the study. The researchers are analyzing the data further to explain this finding.
Treatment options
All ambulatory patients with HIV are eligible for ART, including rapid initiation, unless there are symptoms of an opportunistic infection or if the HIV diagnosis is unclear. Once the decision is made to start ART before genotypic or phenotypic resistance testing is available, the ART regimen should not include a non-nucleoside reverse transcriptase inhibitor because of concerns with transmitted drug resistance (K103N mutation), which could put the patient at risk for virologic failure. In addition, abacavir should not be part of the regimen until results of HLA-B*5701 testing are available. Although most published trials of rapid ART do not state which antiretrovirals were used, IAS-USA has recommended agents to initiate treatment for these patients (see Box). When the decision is reached to begin immediate ART in a new HIV diagnosis, it is important to choose a regimen that has empiric coverage of hepatitis B to prevent a flare in disease.
The data indicate that rapid initiation of ART is a viable option and may lead to better clinical outcomes by increasing the number of patients starting ART in a timely manner and increasing retention in care in certain populations. More data are needed to determine if early ART initiation will have an impact on decreasing the incidence of new HIV cases.
There are major limitations of implementing a rapid ART program, which must be taken into consideration. These programs are resource intense, needing enough staff to help patients navigate the clinical environment, help complete paperwork and provide patient education. Additionally, because clinic providers are typically already stretched thin, these programs will need dedicated providers who have the ability to see new rapid-entry patients in order to make it work on a programmatic level. Additional funding to develop and sustain these programs will be needed, especially in areas where the demand for HIV care is exceeding the capacity of the current workforce.
- References:
- AIDSinfo. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. https://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed October 8, 2019.
- Coffey S, et al. AIDS. 2019;doi:10.1097/QAD.0000000000002124.
- Colasanti J, et al. Open Forum Infect Dis. 2018;doi:10.1093/ofid/ofy104.
- Ford N, et al. AIDS. 2018;doi:10.1097/QAD.0000000000001671.
- Halperin J, et al. Open Forum Infect Dis. 2019;doi:10.1093/ofid/ofz161.
- Hayes, RJ, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1814556.
- Pilcher CD, et al. J Acquir Immune Defic Syndr. 2017;doi:10.1097/QAI.0000000000001134.
- Saag MS, et al. JAMA. 2018;doi:10.1001/jama.2018.8431.
- WHO. Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy. https://apps.who.int/iris/bitstream/handle/10665/255884/9789241550062-eng.pdf;jsessionid=BC12AD37A3B5CFA5319FEC9AB2989D47?sequence=1. Accessed October 14, 2019.
- For more information:
- Jeff Brock, PharmD, MBA, BCPS-AQ ID, is an infectious disease pharmacy specialist at Mercy Medical Center in Des Moines, Iowa. He can be reached at: jbrock@mercydesmoines.org.
Disclosure: Brock reports no relevant financial disclosures.