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Rapid Initiation of HIV Care: Assessing Safety and Efficacy
How should treating clinicians approach risk-benefit discussions concerning the rapid initiation of antiretroviral therapy (ART) in treatment-naive patients with newly diagnosed HIV?
We have found that persons requesting HIV testing in our clinic and are positive by point-of-care testing may have already anticipated that they have HIV and are prepared to take the next steps in controlling this infection. They have some knowledge that there are effective medications for HIV, and their expectation is to start therapy right away. So we describe to them the effectiveness and safety of contemporary ART and the advantages of starting ART early. Additionally, we have our patients meet with our clinical pharmacists who show patients the actual pills, review side effects, emphasize the importance of adherence, and offer adherence tools such as pill boxes or key chains that hold 1 to 2 pills if patients are not home. You’d be surprised at how many like the idea of these pill boxes, even with single-tablet regimens.
We assure our patients that medications will be available to them through our in-house pharmacy while insurance coverage or approval for the AIDS Drug Assistance Program may be pending. In our clinic, case managers and patient-peer navigators usually follow up with a phone call within a week to see how our patients are tolerating their ART.
If patients are not prepared to start ART upon their first clinical encounter, we make sure to follow up with them within 1 month to ensure ongoing linkage to care and to further the discussion on ART initiation. Our case managers and patient navigators keep in contact with these patients using a strength-based case management that stresses patients’ abilities and assets, allowing our patients to control the direction of engagement in care.
Which patients do you believe will benefit the most from a rapid initiation model of HIV care?
Let’s start with understanding the HIV care continuum in the United States, a framework that visualizes the discrete stages along an HIV-positive person’s care from diagnosis to virologic control. The HIV cascade of care reflects the steps needed to improve an individual’s HIV health and identifies areas of opportunity within a population for interventions to optimize disease management and reduce ongoing HIV transmission. Because immense personal and societal benefit could potentially be generated by improving the proportion of patients in the latter stages of the cascade, it has been used as a performance metric for national and local HIV care programs.
For patients diagnosed with HIV, rapid linkage to care and retention in care are critical for achieving successful virologic control. Delays in diagnosis, poor engagement, and inconsistent retention in care have all been shown to negatively affect both individual and public health outcomes.
Data from the Centers for Disease Control and Prevention show receipt of care among persons living with HIV is well below the target set by the National HIV/AIDS Strategy, which aims to increase the percentage of newly diagnosed persons linked to HIV care within 1 month of their HIV diagnosis to at least 85%.1
Examples of successful models for rapid initiation of ART have been shown in resource-limited settings in randomized trials, with significant improvements in viral load suppression and retention in care with rapid initiation of therapy.2,3
In the United States, a citywide rapid ART program was implemented in San Francisco in which newly diagnosed persons were linked to care within 5 days from diagnosis and offered treatment on the day of their clinic visit. Of 265 newly diagnosed persons, 97% were linked to care (30% within 5 days), and 81% started ART. Time from diagnosis to HIV RNA <200 copies/mL decreased by more than 50%, with time from first care visit to ART initiation reduced from 27 days to 1 day.4,5 A large HIV clinic in Atlanta implemented rapid access to ART on the day of the initial visit. In this study, time to viral suppression decreased from 77 days to 57 days, and time to ART initiation decreased from 21 days to 7 days.6 The program, however, was not sustainable because of increased patient load and inadequate funding for staffing.
These data have led to new recommendations for ART initiation from the International Antiviral Society (IAS) published recently7, including rapid start initiatives, for all infected ambulatory patients committed to starting ART unless the patient has symptoms that suggest an opportunistic infection for which immediate ART is contraindicated.
These recommendations dovetail on the 2017 World Health Organization guidelines that recommend rapid ART initiation be offered to all people living with HIV following a confirmed HIV diagnosis and clinical assessment.8 Rapid ART initiation here was defined as ART initiated within 7 days from the day of HIV diagnosis. Furthermore, people with advanced HIV disease should be given priority for assessment and ART initiation.
Rapid ART initiation is especially important for people with a very low CD4 cell count, for whom the risk of death is high. This good practice statement emphasizes that people should not be coerced to start immediately and should be supported in making an informed choice regarding when to start ART.
The US Department of Health and Human Services guidelines recognize as well that rapid ART initiation may potentially increase engagement in care and the proportion of individuals achieving/maintaining viral suppression, though still regards this approach as investigational.
So based upon these expert guidelines, as well as the data outlined here, it appears most people newly diagnosed with HIV would benefit from a rapid initiation model of care.
What effects can widespread rapid initiation of ART have on HIV transmission at the population level in the United States?
I believe the San Francisco experience offers an aspirational story with data-driven results that can speak to the impact of rapid ART initiation as a vital component in Getting to Zero initiatives. This strategic plan comprises a comprehensive approach based upon 3 signature initiatives: Rapid ART Program Initiative for HIV Diagnoses (RAPID), retention in care, and pre-exposure prophylaxis (PrEP) expansion. The goal by 2020 is zero new HIV infections, zero HIV deaths, and zero HIV stigma.10 The city has made remarkable progress since implementing RAPID in 2013. From 2013 to 2016, the median time from first care to initiating therapy decreased from 27 days to 1 day.4
Other figures are likewise impressive: ART to first suppression saw a decrease of 46% from 70 days to 38 days.4 Among African Americans, by 2016, time from diagnosis to care ranged from 3 days (youth aged 13 to 29 years) to 6 days.4 Time from first care to ART was lowest among youth, Latinos, and Asians/Pacific Islanders (0 days) and highest among African Americans and the homeless (6 days), despite improvements in these latter 2 traditionally vulnerable populations, with 82% and 76% decreases in 2013-2016, respectively.4
These results affirm the basis for the U=U (Undetectable=Untransmittable) campaign, for which an undetectable viral load may be achieved more expediently through rapid ART initiation models of care.
What are the current barriers to uniformly instituting rapid ART initiation programs in the United States? How can these barriers be addressed?
ART initiation on the same day of HIV diagnosis is resource-intensive, requiring “on-call” clinicians, nurses, social workers, and laboratory staff to coordinate patient transportation, conduct registrations, perform clinical evaluation, ensure disclosure and counseling, obtain accelerated insurance coverage, perform intake laboratory testing, assess housing, evaluate for substance abuse, and address mental health needs, as well as to ensure systems are in place to maintain linkage to ongoing care. These resources may not be available in all settings.
Onsite medication dispensing is preferable, although not always available in some clinical settings. As mentioned earlier, the program in Atlanta was not sustainable because of increased patient load and inadequate funding for staffing.
As with most programmatic shifts, it appears funding for staffing, resources, and medication availability will be important for the viability of rapid initiation models.
How can data from the DIAMOND study further reassure medical providers who may be reluctant to prescribe ART with minimal patient laboratory data available?
Healthcare providers have less clinical information available in a rapid initiation model of care, so it is important to consider a regimen’s effectiveness in the setting of possible transmitted drug resistance, its safety profile, and the patient’s ability to adhere to the regimen. An optimal ART regimen for use in this setting should have a high barrier to resistance, be a single-tablet regimen, be abacavir-sparing, and be active in the setting of potential HIV/hepatitis B virus coinfection.
We presented preliminary week-24 data from the DIAMOND study using darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF), which is the first known phase 3 clinical trial to examine a single-tablet regimen in a rapid initiation model of care, at the 22nd International AIDS Conference in Amsterdam.11 No patients met stopping criteria based upon their baseline genotype results as there were no darunavir primary mutations, nor was there resistance to tenofovir.
An M184V or I mutation at baseline was allowed; 2 participants had this M184 mutation and both achieved virologic suppression by week 24. Even among the 5 participants who met baseline laboratory stopping criteria by having aspartate aminotransferase or alanine aminotransferase levels ≥2.5 times the upper limit of normal, 2 participants continued on the study because the principal investigator felt the benefits of D/C/F/TAF initiation outweighed the risks of stopping. All liver function test abnormalities showed improvement when D/C/F/TAF was either stopped or continued.
Retention was high among the 109 participants enrolled, with 91% continuing in the study by week 24. Virologic suppression by intention-to-treat analysis was achieved by 81%, and 90% were virologically suppressed by observed analysis on therapy by week 24. No participants stopped therapy due to resistance.
Participant satisfaction with D/C/F/TAF and the study as measured by both clinical and lifestyle survey metrics was very high overall.
So these results are encouraging as we await the primary end point, 48 week data to be available and support the use of D/C/F/TAF as a recommended regimen within the new International Antiviral Society guidelines for rapid initiation models of care.
Dr Huhn has received research funding from Janssen, Viiv, Gilead, Proteus, BMS, and NIH and has served on advisory boards for Janssen, Viiv, Gilead, Theratechnologies, and Seqirus.
1. Centers for Disease Control and Prevention. Selected National HIV Prevention and Care Outcomes in the United States. Atlanta, GA: Centers for Disease Control: National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of HIV/AIDS Prevention; 2018: 1-3.
2. Labhardt ND, Ringera I, Lejone TI, et al. Effect of offering same-day ART vs usual health facility referral during home-based HIV testing on linkage to care and viral suppression among adults with HIV in Lesotho: the CASCADE randomized clinical trial. JAMA. 2018;319(11):1103-1112.
3. Amanyire G, Semitala FC, Namusobya J, et al. Effects of a multicomponent intervention to streamline initiation of antiretroviral therapy in Africa: a stepped-wedge cluster-randomised trial. Lancet HIV. 2016;3(11):e539-e548.
4. Bacon O, Chin JC, Hsu L, et al. The RAPID ART program initiative for HIV diagnoses (RAPID) in San Francisco. Presented at: 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018; Boston, MA. Abstract 93.
5. Pilcher CD, Ospina-Norvell C, Dasgupta A, et al. The effect of same-day observed initiation of antiretroviral therapy on HIV viral load and treatment outcomes in a US public health setting. J Acquir Immune Defic Syndr. 2017;74(1):44-51.
6. Colasanti J, Sumitani J, Mehta CC, et al. Implementation of a rapid entry program decreases time to viral suppression among vulnerable persons living with HIV in the Southern United States. Open Forum Infect Dis. 2018;5(6):1-8
7. Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and prevention of HIV infection in adults: 2018 recommendations of the International Antiviral Society-USA Panel. JAMA. 2018;320(4):379-396.
8. World Health Organization. Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy, July 2017. Geneva, Switzerland: World Health Organization; 2017:1-56.
9. US Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living With HIV. Washington, DC: US Dept of Health and Human Services; 2018.
10. Buchbinder SP, Cohen SE, Hecht J, et al. Getting to zero new HIV diagnoses in San Francisco: What will it take? Presented at: 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018; Boston, MA. Abstract 87.
11. Huhn GD, Crofoot G, Ramgopal M, et al. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in a test-and-treat model of care for HIV-1 infection: interim analysis of the DIAMOND study. Presented at: 22nd International AIDS Conference. July 23-27, 2018; Amsterdam, The Netherlands. Poster WEPEC200
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