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The indisputable benefits of ART and pre-exposure prophylaxis (PrEP) for both individual and public health, including extending the lifespan of persons living with HIV and curtailing HIV transmission, have set the stage for the ambitious goal of ending the HIV epidemic within this decade. Launched in February 2019, this initiative has provided funding to the 48 counties and 7 states in the southern United Stated with the greatest overall burden of HIV to deploy 4 key strategies toward eliminating HIV as a public health threat: (1) early diagnosis, (2) rapid treatment, (3) prevention of new transmissions, and (4) rapid response to potential outbreaks.
One pillar of this plan is to start ART as soon as possible upon diagnosis to rapidly achieve virologic suppression, which will reduce the risk of ongoing transmission. Offering ART to newly diagnosed patients during their first clinic visit also empowers them to take immediate agency of their health and diagnosis.
The pioneering Rapid ART Program Initiative for HIV Diagnoses (RAPID) was launched at Ward 86 of the San Francisco General Hospital in 2013 and was expanded citywide in 2015. At the time, randomized trials in South Africa and Haiti had demonstrated efficacy in achieving greater retention in care and higher rates of virologic suppression among patients who received same-day ART vs standard-of-care ART initiation, the latter of which required several subsequent clinic visits and could take several weeks to dispense ART.[2-4] Indeed, in Haiti, investigators reported a 50% reduction in mortality with same-day ART, which was one of the factors that prompted the Data and Safety Monitoring Board to terminate the study early in favor of immediate ART for everyone.
In this pilot study at Ward 86, patients with HIV infection who were referred to the clinic with CD4+ cell counts < 200 cells/mm3 or with acute infection (diagnosed in the previous 6 months) were assigned to the RAPID protocol. This protocol included a comprehensive same-day appointment providing an evaluation by a medical provider, laboratory testing, and an assessment of social, insurance, housing, substance abuse, and mental health needs. The patients received their first dose of ART in a 5-day starter pack during this first visit.
The investigators compared the time to virologic suppression (HIV-1 RNA < 200 copies/mL) in patients assigned to the RAPID ART protocol vs 2 historical cohorts: (1) patients treated at Ward 86 according to universal ART guidelines from 2010-2013 (pre-RAPID) and (2) patients who received CD4-guided ART treatment from 2006-2009 if their CD4+ cell count was < 500 cells/mm3. The RAPID protocol led to faster HIV-1 RNA suppression vs the historical cohorts, with a median time to virologic suppression of 1.8 months vs 4.3 months in the pre-RAPID group and 7.2 months in the CD4-guided ART group (P = .0001).
Most patients on the RAPID protocol received INSTI-based regimens (89.7%). Once available, the genotype results revealed that 25% of patients had transmitted mutations, and 22% of those were major NNRTI mutations; there were no resistance-driven ART changes in patients on the RAPID protocol based on genotype results.
In a retrospective analysis of longer-term outcomes in patients who participated in the Ward 86 RAPID program, the investigators reported high uptake, with 96% of referred patients initiating immediate ART. Of the 225 patients who were referred between 2013 and 2017, 4 patients declined, 3 were excluded by providers, and 2 were excluded from the analysis due to limited virologic follow-up data. As demonstrated by the baseline characteristics of the patients assessed, Ward 86 provides care for a challenging population with a significant burden of substance use disorder, major mental health disorders, and homelessness or unstable housing.
The virologic suppression rate 1 year after initiating ART was 95.8%. Encouragingly, the sustained virologic suppression after 3 years was 91.0%. These data offer forceful commentary regarding the attributes of RAPID ART initiation. It is not only effective in suppressing HIV-1 RNA, but we believe that introducing ART early on engenders a connectiveness to care and provides a sense of hope about controlling this disease for newly diagnosed patients.
In 2015, the RAPID program was expanded from Ward 86 to all of San Francisco as part of the citywide Getting to Zero Consortium. The mission of this consortium is to reduce HIV transmission and HIV-related deaths in San Francisco by 90% through achieving zero new infections, zero new deaths, and zero stigma. The RAPID protocol was formally made available for all new confirmed cases of HIV infection, and patients were linked to care within 5 working days, where they were offered immediate ART. During the first intensive visit, patients received all of the typical baseline laboratory tests, counseling, and medical and psychosocial assessments. Patients who were considered to have no risk for a potential fatal immune reconstitution inflammatory syndrome (IRIS) event, particularly from comorbid tuberculosis or cryptococcal meningitis, received their first dose of ART that day.
The graph shows that as the program grew from 2013 to 2016, the in-care rates remained high, going from 93% to 97%. The percentage of patients who started ART increased from 78% to 81%, and the proportion of patients receiving INSTI-based regimens grew from 47% to 74%. Of importance, the percentage of patients who fulfilled the criteria for enrollment in the RAPID program grew substantially from 6% to 30%. With this shift from 2013 to 2016 as the program expanded, the time to first virologic suppression decreased remarkably from 134 days to 61 days, and the median time from linkage to care to starting ART decreased from 27 days to 1 day.
A systematic analysis of 4 randomized controlled trials that were primarily from resource-limited settings in Haiti and Africa demonstrated the positive attributes of same-day ART initiation, including improved likelihood of starting ART within 90 days, retention in care at 12 months, and virologic suppression. Moreover, same-day ART was associated with fewer negative outcomes, such as loss to follow-up at 12 months and death within 12 months.
Additional studies have shown that earlier ART initiation, particularly among persons with acute HIV, can reduce the viral reservoir.[9-12] This has implications in cure research and may limit the degree of persistent inflammation and immune dysfunction, which can block responses to preventive vaccines and increase the risk for comorbidities and end-organ damage. Hence, there are benefits for the individual and for broader public health.
The first advisory panel to recommend the same-day ART strategy was the WHO in 2017. The WHO guidance recommends ART for all persons with HIV, including on the same day of diagnosis, if that person is ready. The WHO defines rapid initiation as within 7 days of diagnosis and states that priority should be given to patients with advanced disease, the latter of which is particularly relevant in resource-limited settings.
In 2018, IAS-USA released guidelines in support of starting ART as soon as possible, including immediately after diagnosis if the patient is ready.
Prior to December 2019, the DHHS regarded rapid ART initiation as an investigational approach, as much of the data was initially generated outside of the United States and there was limited clinical trial data from the United States. However, the DHHS updated their guidance in December 2019 to recommend rapid ART initiation upon initial diagnosis, while pointing out the caveat that this strategy is resource intensive—it may require additional staff and multidisciplinary coordination, and the consolidation of a spectrum of patient services into a single clinic visit may take 2-3 hours. Of note, this is rated as an AII recommendation, and the goals are to increase rates of ART uptake, decrease the time for linkage to care, and achieve more frequent and more rapid virologic suppression among individuals with newly diagnosed HIV infection.
What information is needed to offer ART on the first clinic visit? First, providers must have a conversation with the patient and express that the practices for rapid ART initiation have been assessed in many settings both in the United States and abroad and that the benefits are clear in terms of more rapid virologic response and improved retention in care. We should also explain the attributes of the Undetectable = Untransmittable (U=U) campaign. Then, if the patient is interested, we can quickly move toward the physical examination to rule out the very few circumstances where we would not initiate same-day ART, which include any concerns for active cryptococcal meningitis, tuberculosis infection or any other AIDS-defining conditions that could increase morbidity or mortality in the setting of rapid ART initiation.[13,15] Patient readiness should also be assessed from a mental health standpoint and adherence counseling should be provided.
Following the physical assessment and counseling, we can collect specimens for laboratory testing. Of importance, those laboratory results are not needed prior to initiating ART. Providers do not need to know CD4+ cell count, HIV-1 RNA, HIV genotype, baseline resistance, hepatitis status, HLA-B*5701 status, sexually transmitted infection screening results, or pregnancy testing results before prescribing ART. Although these samples should all be collected, the results do not need to be in-hand before starting the patient on ART.