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Management Recommendations > Immediate ART Initiation

Ward 86 Management Recommendations

Immediate Initiation of Antiretroviral Therapy in the Outpatient Clinic

Contributors: Susa Coffey, MD
Oliver Bacon, MD

In 2013, the Ward 86 HIV Clinic at the University of California, San Francisco (UCSF) at San Francisco General Hospital (SFGH) became the first clinic in the United States to provide immediate antiretroviral therapy (ART) upon HIV diagnosis. Our program, called RAPID (Rapid ART Program for Individuals with an HIV Diagnosis), aims to initiate ART as close to the time of HIV diagnosis as possible, ideally on the same day, with the goal of mitigating impediments to linkage to care, helping patients maintain treatment after initiation, and enhancing the health of highly vulnerable individuals and communities with HIV. This treatment strategy also is known as "rapid start," "same-day ART," or "treatment upon diagnosis." Other potential benefits of initiating ART immediately upon HIV diagnosis include reducing the risk of onward transmission of HIV and, among persons with acute HIV infection, reducing the size of the latent HIV reservoir.

Analysis of the pilot phase of RAPID during 2013-14 showed participants had earlier linkage to care, earlier start of ART, and a shorter time to HIV RNA suppression compared with historical controls.(1) An analysis of San Francisco citywide data conducted after rapid initiation of ART was promoted as standard practice in the city showed the median time from HIV diagnosis to first virologic suppression was shortened by more than 50% in 2016 compared with 2013 (from 134 to 61 days).(2,3) Subsequent demonstration projects from clinics in New Orleans, Los Angeles, and Atlanta similarly found that implementation of immediate ART programs also led to earlier linkage to care and shorter time to virologic suppression than seen in historical controls.(4,5) A more recent analysis of 225 patients referred to our Ward 86 RAPID program from 2013-17 revealed 97% of them were started on immediate ART, indicating high acceptability.(6) Of note, 51.4% of these participants had an active substance use disorder, 48.1% had a mental health diagnosis, and 30.6% were unstably housed, which is reflective of the public health population we serve. Yet, by 1 year after intake, 95.8% had achieved viral suppression (HIV viral load <200 copies/mL), and 92.1% were suppressed at the time of their last recorded viral load (at a median 1.09 [range 0-3.92] years).

Current guidelines from the International Antiviral Society--USA endorse ART initiation "as soon as possible after diagnosis, including immediately after diagnosis, unless [the] patient is not ready to commit to starting therapy (evidence rating A1a)."(7) However, the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV from the U.S. Department of Health and Human Services state that, despite its potential benefits, ART initiation on the day of diagnosis "remains investigational."(8)

Implementing Immediate ART in the Outpatient Clinic

In our experience, success of rapid ART programs is greatly enhanced by coordinated activity among HIV testing sites, immediate-ART clinical care site(s), and, ideally, involvement of HIV care navigators and public health tracking systems. Within the HIV clinic itself, optimal implementation of a rapid ART program includes the following elements:

  • Efficient and reliable identification of all persons with new HIV diagnosis (for example, referral from testing sites via a single point of contact such as a dedicated pager or specific staff person).
  • Activation of a "rapid" multidisciplinary team (social work, eligibility/insurance specialist, clinician) that can mobilize quickly to see the patient on a same-day basis.
  • Capacity to provide follow-up care within 1 week.

Appropriate patients to offer immediate ART include:

  • Individuals with confirmed new diagnoses of HIV infection.
  • Persons with suspected acute HIV infection whose HIV diagnosis may not yet be confirmed (eg, the HIV antigen or antibody test results may be negative at the time of evaluation).
  • Persons with positive results of rapid HIV antibody tests, before confirmatory test results are available, if the pretest probability of HIV infection is high (after counseling, immediate ART is offered with the understanding that, if confirmatory test results are negative, the patient would stop ART and start pre-exposure antiretroviral prophylaxis, if appropriate).
  • Chronically infected patients returning to care after being out of care, if they have a known wild-type virus or their viral resistance pattern is predictable.

Immediate ART should not be offered to:

  • Patients with an untreated opportunistic infection (OI) in which a short period of treatment for the OI is recommended before initiation of ART in order to reduce risk of a dangerous immune reconstitution inflammatory syndrome (eg, those with cryptococcal meningitis, tuberculosis meningitis, another central nervous system OI with inflammation, or cytomegalovirus retinitis).
  • Patients who are unwilling or unready to start ART. Such individuals should be followed closely and offered ART at subsequent visits. In our experience, patients who are not ready at the first visit may be ready as soon as several days later.

The Immediate ART Clinic Intake Visit

The immediate-ART intake appointment should focus on the goals of providing HIV education, emotional support, and counseling, insurance enrollment or optimization, obtaining specimens for baseline laboratory tests, and initiation of ART. In our setting, a specialized multidisciplinary team comprised of a social worker, a nurse, and a clinician meet with the patient and conduct the intake, either together or sequentially, usually for a duration of 2-3 hours.

All clinicians provide the patient with emotional support and reassurance around the diagnosis of HIV and education about HIV infection. The social worker assists with insurance enrollment or optimization for both care and prescription medications and addresses any immediate needs for stabilization. The clinician takes the patient's history and performs an assessment with the following goals:

  • Obtaining sufficient information from the history to determine whether immediate ART is indicated, whether the patient is willing to start ART, and what medications to use
  • Beginning education about HIV, ART (eg, possible benefits of early ART, adherence), and preventing transmission to others
  • Engaging the patient in committing to return to clinic for follow-up appointments

Our recommended laboratory tests for the intake visit are listed in Table 1, and specific ART regimens we recommend are listed in Table 2. We have purchased starter medication packs, which contain a 3- to 5-day supply of the selected ART regimen, to give patients at the intake visit when necessary. Starter packs may not be necessary if immediate access to antiretroviral medication can be assured (eg, via an in-clinic pharmacy or good coordination with an off-site specialty pharmacy that is skilled in serving patients with the AIDS Drug Assistance Program [ADAP] or other public assistance insurance programs).

Follow-Up Visits

Patients who are started on ART at the first clinic visit often need additional education and support in the days and weeks that follow. Because they recently have been diagnosed with HIV and started on ART with little or no advance preparation upon diagnosis, they will need additional HIV-related education, reinforcement regarding adherence, counseling about preventing HIV transmission, and information and encouragement about living healthy lives with HIV.

We recommend scheduling a phone check-in with a social worker, nurse, or clinician 2-3 days after the intake appointment, and scheduling a clinic follow-up appointment at 1-2 weeks. The timing of the follow-up visit will depend on the needs of the patient, but in general, it should take place no later than 1 month after the patient is started on ART. The frequency of subsequent visits should be determined by the primary care provider in consultation with the patient.

At the follow-up appointment, clinicians should review baseline laboratory results with the patient, evaluate ART adherence, screen for side effects, and provide further counseling and education. Once the genotype result is available (from the baseline lab draw), the clinician can decide whether a change in the ART regimen is indicated, though unnecessary changes generally should be avoided.

Table 1. Recommended Laboratory Tests at Immediate ART Intake Visit

  • Confirmatory HIV testing (if needed)
  • HIV viral load
  • CD4 cell count
  • HIV genotype, including integrase genotype
  • HLA-B*5701
  • Metabolic panel (creatinine, electrolytes, glucose, liver function tests)
  • Hepatitis A IgG
  • Hepatitis B sAb, cAb, Ag
  • HCV IgG
  • STD testing: serum RPR or VDRL, chlamydia and gonorrhea NAAT tests (urine, pharynx, rectum, depending on sites of sexual exposure)
  • Pregnancy test (if indicated)
  • Consider: lipids, G6PD, toxoplasma IgG

Table 2. Recommended Immediate ART Regimens

Since ART is initiated during the initial clinic visit, before results of baseline testing (including HIV RNA, CD4 count, genotype, HLA-B*5701, and creatinine) are available, we recommend prescribing regimens that will be potent and effective in the setting of high viral load and/or transmitted viral resistance. Once results of the HIV genotype are available, the regimen can be modified, if indicated. The ART regimens should also be simple to adhere to and confer minimal risk of adverse effects.

Preferred regimens (based on clinical trial data and clinical experience):
  • Dolutegravir (Tivicay®) + tenofovir alafenamide/emtricitabine (Descovy®) or tenofovir disoproxil fumarate/ emtricitabine (Truvada®) or tenofovir disoproxil fumarate/lamivudine (eg, Temixys®, Cimduo®)
  • Darunavir (Prezista®)/cobicistat/tenofovir alafenamide/emtricitabine (the coformulation Symtuza®), or darunavir + a booster (ritonavir or cobicistat [darunavir/cobicistat is coformulated in a single pill marketed as Prezcobix®]) + tenofovir alafenamide/emtricitabine (Descovy®) or tenofovir disoproxil fumarate/ emtricitabine (Truvada®) or tenofovir disoproxil fumarate/lamivudine (eg, Temixys®, Cimduo®)
Alternative regimen (based on clinical trial data in first-line ART, though no data or clinical experience in immediate ART):
  • Bictegravir/tenofovir alafenamide/emtricitabine (Biktarvy®); as clinical experience with this medication is gained and the frequency of transmitted resistance to bictegravir is better defined, this formulation may become a preferred regimen
If the above regimens are not available, next best choices are:
  • Raltegravir (Isentress®) + tenofovir alafenamide/emtricitabine (Descovy®) or tenofovir disoproxil fumarate/emtricitabine (Truvada®) or tenofovir disoproxil fumarate/lamivudine (eg, Temixys®, Cimduo®)
  • Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine (Genvoya®) or elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine (Stribild®)

For women who are pregnant, wish to become pregnant, or are at risk of becoming pregnant:

Dolutegravir is not currently recommended for use at the time of conception or in the early weeks of pregnancy. Elvitegravir/cobicistat and darunavir/cobicistat are not recommended for pregnant women. Bictegravir and tenofovir alafenamide have not been studied in pregnancy. Thus, rapid-ART regimens for a woman who is pregnant or who may become pregnant must be selected individually, after careful discussion with the woman.(9)

For patients who had been taking antiretroviral prophylaxis as pre- or postexposure prophylaxis (PrEP or PEP) at the time of HIV infection or since becoming infected with HIV:

  • Take a careful history to determine the last time the patient took PrEP or PEP medications.
  • If we have concern that resistance to the antiretrovirals may have developed, we generally start a reinforced ART regimen consisting of an integrase inhibitor (dolutegravir or bictegravir) + boosted darunavir + a tenofovir/emtricitabine or tenofovir/lamivudine formulation while awaiting the results of the genotype assay.

Antiretroviral drugs to AVOID for immediate ART:

  • Avoid nonnucleoside reverse transcriptase inhibitors (NNRTIs): high risk of transmitted NNRTI resistance.
  • Avoid abacavir (including coformulations that include abacavir): risk of hypersensitivity reaction if positive for HLA-B*5701.
  • Avoid 2-drug antiretroviral regimens (eg, dolutegravir + lamivudine or dolutegravir + rilpivirine [Juluca®]): may increase the risk of virologic failure in patients with a high viral load. Two-drug regimens have not been studied for use in immediate ART.

References

  1. 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 U.S. public health setting. J Acquir Immune Defic Syndr. 2017 Jan 1;74(1):44-51.
  2. Getting to Zero San Francisco. RAPID ART Program Initiative: How immediate ART improves health outcomes.
  3. Scheer S, Hsu L, Schwarcz S, et al. Trends in the San Francisco human immunodeficiency virus epidemic in the "Getting to Zero" era. Clin Infect Dis. 2018 Mar 19;66(7):1027-1034.
  4. Halperin J, Butler I, Conner K, et al. Linkage and antiretroviral therapy within 72 hours at a federally qualified health center in New Orleans. AIDS Patient Care STDS. 2018 Feb 1;32(2):39-41.
  5. 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 Jun 28;5(6).
  6. Coffey S, Bacchetti P, Sachdev D, et al. RAPID ART: High virologic suppression rates with immediate ART initiation in a vulnerable urban clinic population. AIDS. 2019 Apr 1;33(5):825-832.
  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 Jul 24;320(4):379-396.
  8. HHS Panel on Antiretroviral Guidelines for Adults and Adolescents Panel Members and Consultants. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. October 25, 2018, update.
  9. HHS Panel on Treatment of Pregnant Women with HIV Infection. Update to the Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States. December 7, 2018, update.