When to Initiate ART, With Protocol for Rapid Initiation

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

A NEW HIV DIAGNOSIS IS A CALL TO ACTION

In support of the October 30, 2019, NYSDOH and NYC Health confirmation of rapid ART initiation as the standard of care for HIV treatment in New York, this committee supports rapid, and ideally, same-day initiation of ART in patients newly diagnosed with HIV. In support of the NYSDOH AIDS Institute’s January 2018 call to action for patients newly diagnosed with HIV, this committee stresses the following: Immediate linkage to care is essential for any person diagnosed with HIV. For the person with HIV, antiretroviral therapy (ART) dramatically reduces HIV-related morbidity and mortality. Viral suppression helps to prevent HIV transmission to sex partners of people with HIV and prevents perinatal transmission of HIV. The urgency of ART initiation is even greater if the newly diagnosed patient is pregnant, has acute HIV infection, is ≥50 years of age, or has advanced disease. For these patients, every effort should be made to initiate ART immediately, and ideally, on the same day as diagnosis. All clinical care settings should be prepared, either on-site or with a confirmed referral, to support patients in initiating ART as rapidly as possible after diagnosis. For HIV therapy to be successful over time, the initiation of ART should involve both the selection of the most appropriate regimen and the acceptance of the regimen by the patient, bolstered by education and adherence counseling. All are critical in achieving the goal of durable and complete viral suppression. See the NYSDOH AI guideline Selecting an Initial ART Regimen.

This guideline was developed by the New York State Department of Health (NYSDOH) AIDS Institute (AI) for primary care providers and other practitioners to encourage initiation of antiretroviral therapy (ART) at the time of HIV diagnosis in ART-naive adults, and ideally, on the same day, or within 72 hours, an approach referred to as “rapid initiation of ART.” The NYSDOH AI January 2018 call to action emphasized the importance of starting ART at the time of HIV diagnosis and promotes scale-up of this approach to treating people newly diagnosed with HIV. The NYSDOH and NYC Health Dear Colleague Letter of October 30, 2019, confirms that initiation of ART on the same day that an individual has a reactive result on an HIV screening test, or is diagnosed with HIV, or on the first clinic visit is the recommended standard of care for HIV treatment in New York. To support the standard of ART initiation upon diagnosis, toward that end, this guideline:

• Provides guidance for choosing safe and efficacious ART regimens based on known patient characteristics, before results of recommended resistance testing or baseline laboratory testing are available.
• Identifies antiretroviral regimens to avoid for rapid ART initiation.
• Provides guidance for recognizing when rapid initiation is not appropriate.
• Encourages clinicians to seek the assistance of an experienced HIV care provider when managing patients with extensive comorbidities.
• Integrates current evidence-based clinical recommendations into the healthcare-related implementation strategies of the NYS Ending the Epidemic initiative, which seeks to end the AIDS epidemic in NYS by the end of 2020.
• Provides guidance on funding sources for sustainable access to ART.

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

RECOMMENDATIONS
Benefits and Risks of ART Clinicians should recommend antiretroviral therapy to all patients with HIV infection. (A1)

Antiretroviral therapy (ART) refers to the use of pharmacologic agents that have specific inhibitory effects on HIV replication. The use of fewer than three agents is not recommended for initiating rapid treatment. These agents belong to six distinct classes of drugs: the nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs, NtRTIs), the non-nucleoside reverse transcriptase inhibitors (NNRTIs), the protease inhibitors (PIs), the fusion inhibitors (FIs), the CCR5 co-receptor antagonists, and the integrase strand transfer inhibitors (INSTIs). See all commercially available antiretroviral drugs that are approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV/AIDS.

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

RECOMMENDATIONS

Rationale for Rapid ART Initiation Clinicians should recommend antiretroviral therapy (ART) for all patients with a diagnosis of HIV infection. (A1) Clinicians should offer rapid initiation of ART—preferably on the same day (A1) or within 72 hours—to all individuals who are candidates for rapid ART initiation (see text) and who have: A confirmed HIV diagnosis (A1), or A reactive HIV screening result pending results of a confirmatory HIV test (A2), or Suspected acute HIV infection, i.e., HIV antibody negative and HIV RNA positive (A2). Clinicians should counsel patients with seronegative partners about the reduction of HIV transmission risk after effective ART is initiated and viral suppression is achieved, and should strongly recommend ART for patients with seronegative partners. (A1) Clinicians should evaluate and prepare patients for ART initiation as soon as possible; completion of the following should not delay initiation: Discuss benefits and risks of ART with the patient. (A3) Assess patient readiness. (A3) Identify and ameliorate factors that might interfere with successful adherence to treatment, including inadequate access to medication, inadequate supportive services, psychosocial factors, active substance use, or mental health disorders. (A2) Clinicians should refer patients for supportive services as necessary to address modifiable barriers to adherence. An ongoing plan for coordination of care should be established. (A3) Clinicians should involve patients in the decision-making process regarding initiation of ART and which regimen is most likely to result in adherence. The patient should make the final decision of whether and when to initiate ART. (A3) If the patient understands the benefits of rapid initiation but declines ART, then initiation should be revisited as soon as possible. In patients with advanced HIV (or AIDS), ART should be initiated even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support. (A2) After ART has been initiated, response to therapy should be monitored by, or in consultation with, a clinician with experience in managing ART. (A2)

The New York State Department of Health (NYSDOH) HIV Clinical Guidelines Program and the U.S. Department of Health and Human Services (DHHS) recommend initiation of ART for all patients with a confirmed HIV diagnosis regardless of their CD4 cell count or viral load, for the benefit of the individual with HIV (reduced morbidity and mortality) Zolopa, et al. 2009; Lundgren, et al. 2015 and to reduce the risk of transmission to others Cohen, et al. 2016. Initiating ART during early HIV infection may improve immunologic recovery (CD4 T cell counts) and reduce the size of the HIV reservoir Jain, et al. 2013; there is also evidence that initiating ART at the time of diagnosis reduces treatment delays and improves retention in care and viral suppression at 12 months Ford, et al. 2018.

KEY POINTS

Rapid ART initiation, the standard of care in New York State, is efficacious, safe, and highly acceptable, with few patients declining the offer of immediate ART. Patients with active substance use, untreated mental health conditions, immigration issues, or unstable housing deserve the highest standard of HIV care, including the option of rapid initiation of ART. Potential barriers to medication adherence and care continuity can be addressed with appropriate counseling and linkage to support services.

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee; updated August 11, 2022

RECOMMENDATIONS

Counseling and Patient Education Counseling and education should include the following: Basic education about HIV, CD4 cells, viral load, and resistance. (A3) Available treatment options and potential risks and benefits of therapy (see text). (A3) The need for strict adherence to avoid the development of viral drug resistance. (A2) Use of safer-sex practices and avoidance of needle-sharing activity, regardless of viral load, to prevent HIV transmission or superinfection. (A3) Clinicians should involve the patient in the decision-making process regarding initiation of ART. (A3)

Discussion of ART should occur when a positive HIV test result is obtained, regardless of CD4 count. The clinician and patient should discuss the benefits of early ART (see below) and individual factors that may affect the decision to initiate, such as patient readiness or reluctance and adherence barriers. Clinicians should involve the patient in the decision-making process regarding initiation of ART Salzberg Global Seminar 2011. When clinicians and patients engage in shared decision-making, patients are more likely to choose to initiate ART and to achieve an undetectable viral load Beach, et al. 2007. Misconceptions about treatment initiation should be addressed, including the implication that starting ART represents advanced HIV illness or that taking ART may adversely affect therapeutic levels of gender-affirming hormones Braun, et al. 2017. Initiating ART before symptoms occur allows patients to stay healthier and live longer.

The risks and benefits of early ART to discuss with patients when making the decision of whether and when to initiate ART are outlined below. It should be emphasized that the START trial provided definitive evidence that the benefits of early initiation of ART outweigh the potential disadvantages.

Benefits of early ART in asymptomatic patients:
(early therapy = initiation at CD4 counts >500 cells/mm³)

• Reduction in HIV-related and non–HIV-related morbidity and mortality Phillips, et al. 2007; Kitahata, et al. 2009; Marin, et al. 2009; Sterne, et al. 2009; Ray, et al. 2010; Silverberg, et al. 2011; Ho, et al. 2012; Lewden, et al. 2012; Lundgren, et al. 2015.
• Delay or prevention of immune system compromise Lewden, et al. 2007.
• Possible lower risk of antiretroviral resistance Uy, et al. 2009.
• Decreased risk of sexual transmission of HIV Quinn, et al. 2000; Castilla, et al. 2005; Donnell, et al. 2010; Cohen, et al. 2011. HIV cannot be transmitted sexually when the plasma viral load is undetectable; ART is not a substitute for primary HIV prevention measures, such as avoidance of needle sharing Politch, et al. 2012.
• Decreased risk of several severe bacterial infections O'Connor, et al. 2017.
• Potential decrease in size of viral reservoir and preservation of gut-associated lymphoid tissue with initiation during acute HIV, i.e., within the first 6 weeks Jain, et al. 2013; Novelli, et al. 2018.

Disadvantages of early ART in asymptomatic patients:

• Possibility of greater cumulative side effects from ART Volberding and Deeks 2010.
• Possibility for earlier development of drug resistance and limitation in future Barth, et al. 2012 antiretroviral options if adherence and viral suppression are suboptimal.
• Possibility for earlier onset of treatment fatigue.

Resources

Patients who do not have health insurance may qualify for Medicaid or the NYSDOH HIV Uninsured Care Program, which provides access to free health care (HIV drugs, primary care, home care, and the ADAP Plus Insurance Continuation Program, or APIC) for residents who have HIV and are uninsured or underinsured. The program is open Monday-Friday, 8:00AM-5:00PM and can be reached: in state 1-800-542-2437; out-of-state 1-518-459-1641; TDD 1-518-459-0121.If eligible, patients may also consider treatment options through enrollment in clinical trials. A resource that may help with this process is the AIDS Clinical Trials Information Service (1-800-TRIALS-A).

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

RECOMMENDATIONS

Protocol for Rapid ART Initiation To determine whether a patient is a candidate for rapid antiretroviral therapy (ART) initiation, the clinician should confirm that the individual has any of the following (A1): A reactive point-of-care HIV test result, or confirmed HIV diagnosis, or suspected acute HIV infection, or known HIV infection, and No prior ART (i.e., treatment naive) or limited prior use of antiretroviral medications, and No medical conditions or opportunistic infections that require deferral of rapid ART initiation, including suspected cryptococcal or tuberculous meningitis. Clinicians should perform baseline laboratory testing listed in Box 2: Baseline Laboratory Testing Checklist for all patients who are initiating ART immediately; ART can be started while awaiting laboratory test results. (A3)

SELECTED GOOD PRACTICE REMINDERS

Protocol for Rapid ART Initiation For patients with a reactive HIV antibody screening test that is pending confirmation, make sure the patient understands the benefits of rapid ART initiation and the following: 1. Reactive screening test results are not formally diagnostic, because false-positive results are still possible; 2. A confirmatory (diagnostic) HIV test will be performed; 3. ART will be discontinued if the confirmatory test result is negative and continued if it is positive; 4. The benefit of starting ART early, after a presumptive positive screening test, outweighs the negligible risk of taking ART for a few days and then stopping it if confirmed HIV negative. Provide the result of the confirmatory HIV test as soon as it is available; discontinue ART if the result is negative and reinforce adherence and next steps if it is positive. If a patient declines rapid ART initiation, discuss options for deferred initiation of ART, link the patient with HIV primary care, and outline next steps.

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee; updated August 11, 2022

RECOMMENDATIONS

General Principles in Choosing a Regimen for Rapid ART Initiation Clinicians should involve their patients when deciding which antiretroviral therapy (ART) regimen is most likely to result in adherence. (A3) Before initiating ART, clinicians should: Assess the patient’s prior use of antiretroviral medications, including pre-exposure prophylaxis (PrEP), which may increase the risk for baseline resistance. (A2) Assess for any comorbidities and chronic coadministered medications that may affect the choice of regimen for initial ART. (A2) At the time of HIV diagnosis, obtain genotypic resistance testing for the protease (A2), reverse transcriptase (A2), and integrase (B2) genes. Ask individuals of childbearing potential about the possibility of pregnancy, their reproductive plans, and their use of contraception. (A3) For ART-naive patients, clinicians should select an initial ART regimen that is preferred; see Table 1: Preferred and Alternative Regimens for Rapid ART Initiation in Nonpregnant Adults. (A1) Clinicians should reinforce medication adherence regularly. (A3) Clinicians should obtain a viral load test 4 weeks after ART initiation to assess the response to therapy. (A3) See the NYSDOH AI guideline Virologic and Immunologic Monitoring in HIV Care for more information.

SELECTED GOOD PRACTICE REMINDERS

General Principles in Choosing a Regimen for Rapid ART Initiation Follow up within 24 to 48 hours, by telephone or another preferred method, with a patient who has initiated ART to assess medication tolerance and adherence. If feasible, schedule an in-person visit for 7 days after ART initiation.

Choosing a Regimen for Rapid ART Initiation

The preferred medications for rapid ART initiation are based on the established regimens for individuals who are ART-naive and are restricted to those that can be safely initiated in the absence of readily available baseline laboratory testing results, such as viral load, CD4 count, and HLA-B*5701. The preferred regimens have a high barrier to resistance, are well tolerated, and limit the potential for drug-drug interactions. Initial regimens should be selected on the basis of patient preferences and clinical characteristics, and a preferred regimen should be used whenever possible (see Table 1, below).

The 2-drug ART regimen of dolutegravir/lamivudine (DTG/3TC) cannot be used for rapid ART because a baseline HIV genotypic resistance profile and hepatitis B virus status are required prior to prescription of this regimen (see the NYSDOH AI guideline Selecting an Initial Antiretroviral Therapy Regimen for more information.)

One alternative regimen (tenofovir alafenamide/emtricitabine/darunavir/cobicistat [TAF/FTC/DRV/COBI]) has been studied formally in the setting of rapid ART initiation, in a phase 3, open-label, single-arm, prospective, multicenter study without the benefit of resistance testing, and produced high rates (96%) of viral suppression (HIV RNA level <50 copies/mL) at 48 weeks Huhn, et al. 2020.

When following a rapid ART initiation protocol, care providers should avoid regimens containing abacavir because results of HLA-B*5701 testing are not likely to be available. Similarly, rilpivirine should be avoided in any patient who has a viral load >100,000 copies/mL and in any patient whose viral load is unknown.

Efavirenz is associated with a higher risk of central nervous system side effects and of transmitted drug resistance mutations Kagan, et al. 2019; therefore, it is not recommended for rapid ART initiation.

Clinics that have implemented rapid ART initiation frequently design pre-approved regimens that consider local patterns of transmitted drug resistance and drug toxicity Pilcher, et al. 2017.

There is a greater possibility that HIV drug resistance mutations may emerge and reduce the efficacy of an initial ART regimen in patients with a new reactive HIV screening test or a new HIV diagnosis who have taken tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or tenofovir alafenamide fumarate/emtricitabine (TAF/FTC) as PrEP since their last negative HIV test. Results of a recent study in New York City demonstrated that individuals who had taken PrEP in the 3 months prior to a new HIV diagnosis were significantly more likely than those who never used PrEP (26% vs. 2%; P<.0001) to have resistance mutations (M184I/V/IV/MV) to lamivudine/emtricitabine (3TC/FTC) Misra, et al. 2019. For such patients, the initial regimen should consist of an integrase strand transfer inhibitor plus a boosted protease inhibitor and 2 nucleoside reverse transcriptase inhibitors. An option for treatment in this scenario is provided in Table 1, below. The initial regimen may be simplified once results of baseline genotypic testing have been reviewed.

• See the NYSDOH AI guideline Selecting an Initial ART Regimen for more information.

Preferred and Alternative Regimens for Rapid ART Initiation

Table 1: Preferred and Alternative Regimens for Rapid ART Initiation in Nonpregnant Adults, below, includes initial preferred and alternative regimens for rapid ART initiation in nonpregnant adults. The regimens are listed alphabetically. For specific details on choosing a regimen, see the discussions in other sections of this guideline and the package inserts for the drugs listed below.

Providing ART: Some clinics provide patients with the first dose of ART and a 30-day prescription when a rapid ART initiation protocol is being followed Pilcher, et al. 2017. Others may provide a 7-day ART starter pack or a 30-day prescription.

Reducing the risk of perinatal transmission of HIV requires timely identification of HIV infection in a pregnant individual and 3-drug ART initiated as soon as possible after diagnosis. Pregnancy is not a contraindication to rapid ART initiation. Adherence to an ART regimen during pregnancy should be encouraged, as should coordination among HIV and obstetric care providers (see the NYSDOH AI guidance NYS Good Practices to Prevent Perinatal HIV Transmission).

Table 2, below, includes initial preferred regimens for rapid ART initiation in pregnant adults.

Rapid ART Initiation Follow-Up

Standard good practice is to follow up by telephone or in-person within 48 hours after a person initiates ART, to assess for adverse effects, answer questions, and encourage adherence. If feasible, based on clinic protocol and individual patient needs, an in-person follow-up visit with a medical care provider is encouraged within 7 days of ART initiation. If an in-person visit is not feasible, then follow-up by telephone is encouraged.

Once laboratory test results are available, ART should be discontinued if an HIV diagnosis is not confirmed. In this case, the patient may be assessed or referred for PrEP if there is ongoing risk of HIV exposure (see the NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health > PrEP for Individuals at Risk of Acquiring HIV). If the HIV diagnosis is confirmed, the ART regimen may be adjusted if necessary (e.g., if there is significant renal disease). Further adjustments may be required if major resistance mutations are found that will compromise the effectiveness of the initial regimen. Arrangements should be made for a viral load test 4 weeks after ART initiation to assess adherence and troubleshoot any problems with maintaining treatment. See the NYSDOH AI guideline Virologic and Immunologic Monitoring in HIV Care for more information.

Paying for Rapid ART Initiation

Lack of insurance coverage for antiretroviral therapy (ART), a high co-pay, or large out-of-pocket costs may pose a significant barrier to rapid ART initiation for some patients. Addressing financial requirements for ART initiation and helping patients identify sources of payment assistance is an essential component of the rapid ART initiation protocol. Options for residents of New York State (NYS), regardless of immigration status, are described below.

For patients who are underinsured or uninsured: The NYS Department of Health Uninsured Care Programs (UCP) provide access to free medications, outpatient primary care, home care, and insurance premium payments for NYS residents who are uninsured or underinsured. Acknowledging the critical need for rapid access to ART, UCP has revised the enrollment process to facilitate same-day enrollment.

NYS residents who do have health insurance but need help with out-of-pocket costs (co-pays, deductibles, etc.) and meet eligibility criteria may be eligible for help from the UCP.

Information for contacting the new enrollment unit is listed below.

RESOURCE: NYSDOH UNINSURED CARE PROGRAMS

Hours of Operation: Monday – Friday, 8:00 AM – 5:00 PM Telephone: In state, toll free: 1-800-542-2437 or 1-844-682-4058 Out of state: 1-518-459-1641 TDD: 1-518-459-0121 Address: Empire Station, P.O. Box 2052, Albany, NY 12220-0052

A care provider must be enrolled as an AIDS Drug Assistance Program Plus provider on the day that services are provided to receive reimbursement. New York State Medicaid Program providers are eligible to enroll in the UCP. To become an enrolled provider, contact the UCP Provider Relations Department at 1-518-459-1641 or email damarys.feliciano@health.ny.gov. Eligible providers will be activated on the date the application is received.

For patients with existing health insurance: People who have insurance coverage may be eligible for medication and co-pay assistance to cover the cost of out-of-pocket expenses.

• For dolutegravir: https://www.myviivcard.com/.
• For emtricitabine, tenofovir disoproxil fumarate, and bictegravir: https://www.gileadadvancingaccess.com/get-started-advancing-access.
• For darunavir/cobicistat/emtricitabine/tenofovir alafenamide: https://www.janssencarepath.com/patient/symtuza/cost-support.

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee; updated August 11, 2022

RECOMMENDATIONS
Long-Term Nonprogressors and Elite Controllers Decisions to initiate ART in long-term nonprogressors (A2) and elite controllers (A3) should be individualized. Clinicians should consult with a provider experienced in the management of ART when considering whether to initiate ART in long-term nonprogressors and elite controllers. (A3) Patients With Acute Opportunistic Infections Clinicians should recommend that patients beginning treatment for acute opportunistic infections (OIs) initiate ART within 2 weeks of OI diagnosis (see next recommendation for exceptions). (A1) Clinicians should not immediately initiate ART in patients with tuberculous meningitis (TB) or cryptococcal meningitis. (A1) Consultation with a clinician with experience in management of ART in the setting of acute OIs is recommended. (A3) For all other manifestations of TB, clinicians should initiate ART in patients with HIV as follows: For patients with CD4 counts ≥50 cells/mm3: as soon as they are tolerating anti-TB therapy and no later than 8 to 12 weeks after initiating anti-TB therapy. (A1) For patients with CD4 counts <50 cells/mm3: within 2 weeks of initiating anti-TB therapy. (A1) Notes: For recommendations on initiating ART in pregnant women with HIV, refer to the DHHS Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Initial ART regimens for patients with chronic hepatitis B must include NRTIs that are active against hepatitis B. See the NYSDOH AI guideline Prevention and Management of Hepatitis B Virus Infection in Adults With HIV. In co-infected patients with HCV, attention should be paid to interactions between the planned ART and HCV therapy.
Notes: For recommendations on initiating ART in pregnant women with HIV, refer to the DHHS Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Initial ART regimens for patients with chronic hepatitis B must include NRTIs that are active against hepatitis B. See the NYSDOH AI guideline Prevention and Management of Hepatitis B Virus Infection in Adults With HIV. In co-infected patients with HCV, attention should be paid to interactions between the planned ART and HCV therapy.

Long-Term Nonprogressors and Elite Controllers

• Long-term nonprogressors demonstrate a lack of disease progression, marked by no symptoms and low viral loads in the absence of therapy during long-term follow-up. Most published studies of long-term nonprogressors include 7-10 years of follow-up Casado, et al. 2010.
• Elite controllers suppress HIV to low but detectable levels (<50-75 copies/mL) for many years Okulicz, et al. 2010.

The role of early ART initiation in long-term nonprogressors or elite controllers is unclear. At this time, there are not enough data to recommend for or against initiation of ART in long-term nonprogressors and elite controllers. Close monitoring of CD4 count and viral load level may be an acceptable approach. Declines in CD4 count should prompt consideration of initiation of ART. Elite controllers have demonstrated CD4 cell increases after initiation of ART Okulicz, et al. 2010. Another study found higher rates of hospitalizations in elite controllers compared to treatment suppressed patients, particularly for cardiovascular and psychiatric conditions Crowell, et al. 2015; however, there were important limitations in this analysis and it does not provide definitive evidence in favor of treating this rare population based on current information Karris and Haubrich 2015. The clinician and patient should discuss the current data on the risks and benefits of early ART as well as individual factors that may affect the decision to initiate, such as patient readiness and reluctance, adherence barriers, CD4 cell count and viral load, comorbidities, age, and partner serodiscordance. If treatment is delayed, clinicians should counsel patients about the risk of HIV transmission to partners.

Barriers to Adherence

Although the current first-line regimens used for ART are much easier to tolerate with fewer side effects than earlier combinations, they are not free of side effects (see the NYSDOH AI guideline Selecting an Initial ART Regimen > Available ART Regimens). Their use requires a lifelong commitment from the patient. Patients who prefer not to take medication, or who do not understand the significance of skipping doses, are at high risk for poor adherence and subsequent viral resistance. In patients with barriers to adherence, the risk of viral resistance and eventual treatment failure may outweigh any clinical benefit from earlier treatment Politch, et al. 2012. These patients should remain under particularly close observation for clinical and laboratory signs of disease progression Wallis, et al. 2012. ART should be initiated as soon as the patient seems prepared to adhere to a treatment regimen. When initiation of treatment is clinically urgent, such as for patients who are pregnant, have HIV-related malignancies, HIV-associated nephropathy, symptomatic HIV, older age, severe thrombocytopenia from HIV, chronic hepatitis, or advanced AIDS, it is appropriate to initiate ART even if some barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support.

Barriers such as alcohol or drug use; lack of insurance, transportation, or housing; depression; mistrust of medical providers; or a poor social support system should not necessarily preclude rapid initiation of ART. The option of rapid initiation of ART should be offered to all individuals with HIV, except when medically contraindicated. Barriers to care can be addressed with appropriate counseling and support services. In some cases, patients will require ongoing attention and use of supportive services.

Patients With Acute Opportunistic Infections

In a randomized study, patients who initiated ART at a median of 12 days from the start of OI therapy had better outcomes, as measured by disease progression and death, without an increase in adverse events, compared to those who initiated ART at a median of 45 days from presentation Zolopa, et al. 2009. Although this study excluded patients with active TB, three randomized controlled trials in patients newly diagnosed with HIV and pulmonary TB have demonstrated a significant mortality benefit when ART was initiated during the first 2 months of starting anti-TB therapy and a further benefit when those who were severely immunocompromised initiated therapy in the first 2 weeks Abdool Karim, et al. 2011; Blanc, et al. 2011; Havlir, et al. 2011. Although antiretroviral agents and anti-TB medications can have overlapping toxicities, ART should be initiated within the first 8 to 12 weeks of starting anti-TB therapy. Patients with CD4 counts <50 cells/mm³ should receive ART within the first 2 weeks of initiating anti-TB therapy.

Tuberculous meningitis and cryptococcal meningitis are exceptions; there are data showing that early initiation of ART increases adverse events and mortality in this setting Lawn, et al. 2011; Torok, et al. 2011; NIAID 2012; Bisson, et al. 2013; Boulware, et al. 2014. Close attention should be paid to possible drug-drug interactions between OI therapy and ART. In some cases, determining the optimal timing for initiating ART in patients with OIs can be complex and may require consultation with a clinician with experience in management of ART in this context.

After initiating ART, clinicians need to be alert to the possibility of immune reconstitution syndromes as CD4 cell counts are restored (see the NYSDOH AI guideline Management of IRIS).

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee; updated August 11, 2022

ALL RECOMMENDATIONS: WHEN TO INITIATE ANTIRETROVIRAL THERAPY, WITH PROTOCOL FOR RAPID INITIATION
Benefits and Risks of ART Clinicians should recommend antiretroviral therapy to all patients with HIV infection. (A1) Rationale for Rapid ART Initiation Clinicians should recommend antiretroviral therapy (ART) for all patients with a diagnosis of HIV infection. (A1) Clinicians should offer rapid initiation of ART—preferably on the same day (A1) or within 72 hours—to all individuals who are candidates for rapid ART initiation (see text) and who have: A confirmed HIV diagnosis (A1), or A reactive HIV screening result pending results of a confirmatory HIV test (A2), or Suspected acute HIV infection, i.e., HIV antibody negative and HIV RNA positive (A2). Clinicians should counsel patients with seronegative partners about the reduction of HIV transmission risk after effective ART is initiated and viral suppression is achieved, and should strongly recommend ART for patients with seronegative partners. (A1) Clinicians should evaluate and prepare patients for ART initiation as soon as possible; completion of the following should not delay initiation: Discuss benefits and risks of ART with the patient. (A3) Assess patient readiness. (A3) Identify and ameliorate factors that might interfere with successful adherence to treatment, including inadequate access to medication, inadequate supportive services, psychosocial factors, active substance use, or mental health disorders. (A2) Clinicians should refer patients for supportive services as necessary to address modifiable barriers to adherence. An ongoing plan for coordination of care should be established. (A3) Clinicians should involve patients in the decision-making process regarding initiation of ART and which regimen is most likely to result in adherence. The patient should make the final decision of whether and when to initiate ART. (A3) If the patient understands the benefits of rapid initiation but declines ART, then initiation should be revisited as soon as possible. In patients with advanced HIV (or AIDS), ART should be initiated even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support. (A2) After ART has been initiated, response to therapy should be monitored by, or in consultation with, a clinician with experience in managing ART. (A2) Counseling and Patient Education Counseling and education should include the following: Basic education about HIV, CD4 cells, viral load, and resistance. (A3) Available treatment options and potential risks and benefits of therapy (see text). (A3) The need for strict adherence to avoid the development of viral drug resistance. (A2) Use of safer-sex practices and avoidance of needle-sharing activity, regardless of viral load, to prevent HIV transmission or superinfection. (A3) Clinicians should involve the patient in the decision-making process regarding initiation of ART. (A3) Protocol for Rapid ART Initiation To determine whether a patient is a candidate for rapid antiretroviral therapy (ART) initiation, the clinician should confirm that the individual has any of the following (A1): A reactive point-of-care HIV test result, or confirmed HIV diagnosis, or suspected acute HIV infection, or known HIV infection, and No prior ART (i.e., treatment naive) or limited prior use of antiretroviral medications, and No medical conditions or opportunistic infections that require deferral of rapid ART initiation, including suspected cryptococcal or tuberculous meningitis. Clinicians should perform baseline laboratory testing listed in Box 2: Baseline Laboratory Testing Checklist for all patients who are initiating ART immediately; ART can be started while awaiting laboratory test results. (A3) General Principles in Choosing a Regimen for Rapid ART Initiation Clinicians should involve their patients when deciding which antiretroviral therapy (ART) regimen is most likely to result in adherence. (A3) Before initiating ART, clinicians should: Assess the patient’s prior use of antiretroviral medications, including pre-exposure prophylaxis (PrEP), which may increase the risk for baseline resistance. (A2) Assess for any comorbidities and chronic coadministered medications that may affect the choice of regimen for initial ART. (A2) At the time of HIV diagnosis, obtain genotypic resistance testing for the protease (A2), reverse transcriptase (A2), and integrase (B2) genes. Ask individuals of childbearing potential about the possibility of pregnancy, their reproductive plans, and their use of contraception. (A3) For ART-naive patients, clinicians should select an initial ART regimen that is preferred; see Table 1: Preferred and Alternative Regimens for Rapid ART Initiation in Nonpregnant Adults. (A1) Clinicians should reinforce medication adherence regularly. (A3) Clinicians should obtain a viral load test 4 weeks after ART initiation to assess the response to therapy. (A3) See the NYSDOH AI guideline Virologic and Immunologic Monitoring in HIV Care for more information. Long-Term Nonprogressors and Elite Controllers Decisions to initiate ART in long-term nonprogressors (A2) and elite controllers (A3) should be individualized. Clinicians should consult with a provider experienced in the management of ART when considering whether to initiate ART in long-term nonprogressors and elite controllers. (A3) Patients With Acute Opportunistic Infections Clinicians should recommend that patients beginning treatment for acute opportunistic infections (OIs) initiate ART within 2 weeks of OI diagnosis (see next recommendation for exceptions). (A1) Clinicians should not immediately initiate ART in patients with tuberculous meningitis (TB) or cryptococcal meningitis. (A1) Consultation with a clinician with experience in management of ART in the setting of acute OIs is recommended. (A3) For all other manifestations of TB, clinicians should initiate ART in patients with HIV as follows: For patients with CD4 counts ≥50 cells/mm3: as soon as they are tolerating anti-TB therapy and no later than 8 to 12 weeks after initiating anti-TB therapy. (A1) For patients with CD4 counts <50 cells/mm3: within 2 weeks of initiating anti-TB therapy. (A1) Notes: For recommendations on initiating ART in pregnant women with HIV, refer to the DHHS Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Initial ART regimens for patients with chronic hepatitis B must include NRTIs that are active against hepatitis B. See the NYSDOH AI guideline Prevention and Management of Hepatitis B Virus Infection in Adults With HIV. In co-infected patients with HCV, attention should be paid to interactions between the planned ART and HCV therapy.
Notes: For recommendations on initiating ART in pregnant women with HIV, refer to the DHHS Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Initial ART regimens for patients with chronic hepatitis B must include NRTIs that are active against hepatitis B. See the NYSDOH AI guideline Prevention and Management of Hepatitis B Virus Infection in Adults With HIV. In co-infected patients with HCV, attention should be paid to interactions between the planned ART and HCV therapy.

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee; updated August 11, 2022

ALL GOOD PRACTICES: WHEN TO INITIATE ANTIRETROVIRAL THERAPY, WITH PROTOCOL FOR RAPID INITIATION

Protocol for Rapid ART Initiation For patients with a reactive HIV antibody screening test that is pending confirmation, make sure the patient understands the benefits of rapid ART initiation and the following: 1. Reactive screening test results are not formally diagnostic, because false-positive results are still possible; 2. A confirmatory (diagnostic) HIV test will be performed; 3. ART will be discontinued if the confirmatory test result is negative and continued if it is positive; 4. The benefit of starting ART early, after a presumptive positive screening test, outweighs the negligible risk of taking ART for a few days and then stopping it if confirmed HIV negative. Provide the result of the confirmatory HIV test as soon as it is available; discontinue ART if the result is negative and reinforce adherence and next steps if it is positive. If a patient declines rapid ART initiation, discuss options for deferred initiation of ART, link the patient with HIV primary care, and outline next steps. General Principles in Choosing a Regimen for Rapid ART Initiation Follow up within 24 to 48 hours, by telephone or another preferred method, with a patient who has initiated ART to assess medication tolerance and adherence. If feasible, schedule an in-person visit for 7 days after ART initiation.

Download Printable PDF   |  Download Pocket Guide   |  Download Slide Set

Guideline Information
Intended users	NYS clinicians who are initiating ART at the time of HIV diagnosis in ART-naive adults
Last reviewed and updated	August 11, 2022
Lead author(s)	Asa Radix, MD, MPH; Noga Shalev, MD
Original publication	January 2020
Writing group
Committee	Medical Care Criteria Committee
Developer and funding	New York State Department of Health AIDS Institute (NYSDOH AI)
Development	See Guideline Development and Recommendation Ratings Scheme, below.
Updates
August 11, 2022	MCCC: The recommendation regarding discussion of the small risk of teratogenicity with DTG in the first trimester and the need for birth control while using DTG was removed. DTG has been shown to be safe throughout pregnancy. See the MCCC’s statement on Use of Dolutegravir in Individuals of Childbearing Capacity for further discussion.
October 08, 2021	New in the section General Principles in Choosing a Regimen for Rapid ART Initiation: The 2-drug ART regimen of dolutegravir/lamivudine (DTG/3TC) cannot be used for rapid ART because a baseline HIV genotypic resistance profile and hepatitis B virus status are required prior to prescription of this regimen (see the NYSDOH AI guideline Selecting an Initial ART Regimen for more information.) One alternative regimen (tenofovir alafenamide/emtricitabine/cobicistat/darunavir [TAF/FTC/COBI/DRV]) has been studied formally in the setting of rapid ART initiation, in a phase 3, open-label, single-arm, prospective, multicenter study without the benefit of resistance testing, and produced high rates (96%) of viral suppression (HIV RNA <50 copies/mL) at 48 weeks. Removed from the table of preferred and alternative regimens for rapid ART: Tenofovir alafenamide/emtricitabine and raltegravir HD (TAF 25 mg/FTC and RAL HD; Descovy and Isentress HD)

Abdool Karim S. S., Naidoo K., Grobler A., et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 2010;362(8):697-706. [PMID: 20181971]

Abdool Karim S. S., Naidoo K., Grobler A., et al. Integration of antiretroviral therapy with tuberculosis treatment. N Engl J Med 2011;365(16):1492-501. [PMID: 22010915]

Althoff K. N., Gange S. J., Klein M. B., et al. Late presentation for human immunodeficiency virus care in the United States and Canada. Clin Infect Dis 2010;50(11):1512-20. [PMID: 20415573]

Amanyire G., Semitala F. C., 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. [PMID: 27658873]

Barth R. E., Aitken S. C., Tempelman H., et al. Accumulation of drug resistance and loss of therapeutic options precede commonly used criteria for treatment failure in HIV-1 subtype-C-infected patients. Antivir Ther 2012;17(2):377-86. [PMID: 22297391]

Beach M. C., Duggan P. S., Moore R. D. Is patients' preferred involvement in health decisions related to outcomes for patients with HIV?. J Gen Intern Med 2007;22(8):1119-24. [PMID: 17514382]

Bisson G. P., Molefi M., Bellamy S., et al. Early versus delayed antiretroviral therapy and cerebrospinal fluid fungal clearance in adults with HIV and cryptococcal meningitis. Clin Infect Dis 2013;56(8):1165-73. [PMID: 23362285]

Blanc F. X., Sok T., Laureillard D., et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med 2011;365(16):1471-81. [PMID: 22010913]

Boulware D. R., Meya D. B., Muzoora C., et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 2014;370(26):2487-98. [PMID: 24963568]

Braun H. M., Candelario J., Hanlon C. L., et al. Transgender women living with HIV frequently take antiretroviral therapy and/or feminizing hormone therapy differently than prescribed due to drug-drug interaction concerns. LGBT Health 2017;4(5):371-375. [PMID: 28876170]

Bruyand M., Thiebaut R., Lawson-Ayayi S., et al. Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort. Clin Infect Dis 2009;49(7):1109-16. [PMID: 19705973]

Cain L. E., Logan R., Robins J. M., et al. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study. Ann Intern Med 2011;154(8):509-15. [PMID: 21502648]

Casado C., Colombo S., Rauch A., et al. Host and viral genetic correlates of clinical definitions of HIV-1 disease progression. PLoS One 2010;5(6):e11079. [PMID: 20552027]

CASCADE Collaboration. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med 2011;171(17):1560-9. [PMID: 21949165]

Castilla J., Del Romero J., Hernando V., et al. Effectiveness of highly active antiretroviral therapy in reducing heterosexual transmission of HIV. J Acquir Immune Defic Syndr 2005;40(1):96-101. [PMID: 16123689]

CDC. Diagnoses of HIV infection and AIDS in the United States and dependent areas, 2008. Vol. 20. 2010. http://www.cdc.gov/hiv/pdf/statistics_2008_hiv_surveillance_report_vol_20.pdf [accessed 2018 Apr 3]

CDC. Reported CD4+ T-lymphocyte results for adults and adolescents with HIV infection—37 States, 2005–2007. HIV Surveillance Supplemental Report 2010. 2011. https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-supplemental-report-vol-16-1.pdf [accessed 2018 Apr 3]

CDC. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention. Division of AIDS Prevention. Mortality slide series. 2017. https://www.cdc.gov/hiv/pdf/statistics_surveillance_hiv_mortality.pdf [accessed 2017 Jun 27]

CDC. Understanding the HIV care continuum. 2018. https://www.cdc.gov/hiv/pdf/library/factsheets/cdc-hiv-care-continuum.pdf [accessed 2019 Jun 19]

CDC. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 dependent areas, 2017. 2019. https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-supplemental-report-vol-24-3.pdf [accessed 2020 Jan 28]

Coffey S., Bacchetti P., Sachdev D., et al. RAPID antiretroviral therapy: high virologic suppression rates with immediate antiretroviral therapy initiation in a vulnerable urban clinic population. Aids 2019;33(5):825-832. [PMID: 30882490]

Cohen M. S., Chen Y. Q., McCauley M., et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med 2016;375(9):830-9. [PMID: 27424812]

Cohen M. S., Chen Y. Q., McCauley M., et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365(6):493-505. [PMID: 21767103]

Colasanti J., Sumitani J., Mehta C. C., 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):ofy104. [PMID: 29992172]

Connor E. M., Sperling R. S., Gelber R., et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med 1994;331(18):1173-80. [PMID: 7935654]

Crowell T. A., Gebo K. A., Blankson J. N., et al. Hospitalization rates and reasons among HIV elite controllers and persons with medically controlled HIV infection. J Infect Dis 2015;211(11):1692-702. [PMID: 25512624]

Donnell D., Baeten J. M., Kiarie J., et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet 2010;375(9731):2092-8. [PMID: 20537376]

Ellis R. J., Badiee J., Vaida F., et al. CD4 nadir is a predictor of HIV neurocognitive impairment in the era of combination antiretroviral therapy. Aids 2011;25(14):1747-51. [PMID: 21750419]

El-Sadr W. M., Lundgren J., Neaton J. D., et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006;355(22):2283-96. [PMID: 17135583]

Ford N., Migone C., Calmy A., et al. Benefits and risks of rapid initiation of antiretroviral therapy. Aids 2018;32(1):17-23. [PMID: 29112073]

Friis-Moller N., Thiebaut R., Reiss P., et al. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil 2010;17(5):491-501. [PMID: 20543702]

Garvey L., Surendrakumar V., Winston A. Low rates of neurocognitive impairment are observed in neuro-asymptomatic HIV-infected subjects on effective antiretroviral therapy. HIV Clin Trials 2011;12(6):333-8. [PMID: 22189152]

Granich R. M., Gilks C. F., Dye C., et al. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model. Lancet 2009;373(9657):48-57. [PMID: 19038438]

Guay L. A., Musoke P., Fleming T., et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet 1999;354(9181):795-802. [PMID: 10485720]

Guiguet M., Boue F., Cadranel J., et al. Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study. Lancet Oncol 2009;10(12):1152-9. [PMID: 19818686]

Havlir D. V., Kendall M. A., Ive P., et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med 2011;365(16):1482-91. [PMID: 22010914]

Hileman C. O., Funderburg N. T. Inflammation, immune activation, and antiretroviral therapy in HIV. Curr HIV/AIDS Rep 2017;14(3):93-100. [PMID: 28434169]

Ho J. E., Deeks S. G., Hecht F. M., et al. Initiation of antiretroviral therapy at higher nadir CD4+ T-cell counts is associated with reduced arterial stiffness in HIV-infected individuals. Aids 2010;24(12):1897-905. [PMID: 20543654]

Ho J. E., Scherzer R., Hecht F. M., et al. The association of CD4+ T-cell counts and cardiovascular risk in treated HIV disease. Aids 2012;26(9):1115-20. [PMID: 22382147]

Hoy J. F., Grund B., Roediger M., et al. Immediate initiation of antiretroviral therapy for HIV infection accelerates bone loss relative to deferring therapy: Findings from the START Bone Mineral Density Substudy, a randomized trial. J Bone Miner Res 2017;32(9):1945-1955. [PMID: 28650589]

Huhn G. D., Crofoot G., Ramgopal M., et al. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in a rapid-initiation model of care for human immunodeficiency virus type 1 infection: Primary analysis of the DIAMOND study. Clin Infect Dis 2020;71(12):3110-3117. [PMID: 31879782]

Jain V., Hartogensis W., Bacchetti P., et al. Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J Infect Dis 2013;208(8):1202-11. [PMID: 23852127]

Kagan R. M., Dunn K. J., Snell G. P., et al. Trends in HIV-1 drug resistance mutations from a U.S. reference laboratory from 2006 to 2017. AIDS Res Hum Retroviruses 2019;35(8):698-709. [PMID: 31169022]

Karris M. Y., Haubrich R. H. Antiretroviral therapy in the elite controller: justified or premature?. J Infect Dis 2015;211(11):1689-91. [PMID: 25512628]

Kitahata M. M., Gange S. J., Abraham A. G., et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009;360(18):1815-26. [PMID: 19339714]

Koenig S. P., Dorvil N., Dévieux J. G., et al. Same-day HIV testing with initiation of antiretroviral therapy versus standard care for persons living with HIV: A randomized unblinded trial. PLoS Med 2017;14(7):e1002357. [PMID: 28742880]

Lawn S. D., Torok M. E., Wood R. Optimum time to start antiretroviral therapy during HIV-associated opportunistic infections. Curr Opin Infect Dis 2011;24(1):34-42. [PMID: 21150593]

Lewden C., Bouteloup V., De Wit S., et al. All-cause mortality in treated HIV-infected adults with CD4 >/=500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. Int J Epidemiol 2012;41(2):433-45. [PMID: 22493325]

Lewden C., Chene G., Morlat P., et al. HIV-infected adults with a CD4 cell count greater than 500 cells/mm3 on long-term combination antiretroviral therapy reach same mortality rates as the general population. J Acquir Immune Defic Syndr 2007;46(1):72-7. [PMID: 17621240]

Li X., Margolick J. B., Jamieson B. D., et al. CD4+ T-cell counts and plasma HIV-1 RNA levels beyond 5 years of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2011;57(5):421-8. [PMID: 21602699]

Li Z., Purcell D. W., Sansom S. L., et al. Vital signs: HIV transmission along the continuum of care - United States, 2016. MMWR Morb Mortal Wkly Rep 2019;68(11):267-272. [PMID: 30897075]

Lichtenstein K. A., Armon C., Buchacz K., et al. Low CD4+ T cell count is a risk factor for cardiovascular disease events in the HIV outpatient study. Clin Infect Dis 2010;51(4):435-47. [PMID: 20597691]

Long L. C., Maskew M., Brennan A. T., et al. Initiating antiretroviral therapy for HIV at a patient's first clinic visit: a cost-effectiveness analysis of the rapid initiation of treatment randomized controlled trial. Aids 2017;31(11):1611-1619. [PMID: 28463879]

Lundgren J. D., Babiker A. G., Gordin F., et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015;373(9):795-807. [PMID: 26192873]

Marin B., Thiebaut R., Bucher H. C., et al. Non-AIDS-defining deaths and immunodeficiency in the era of combination antiretroviral therapy. Aids 2009;23(13):1743-53. [PMID: 19571723]

Misra K., Huang J. S., Udeagu C. N. Ongoing disparities in prediagnosis preexposure prophylaxis use among persons recently diagnosed with HIV in New York City, 2015-2017. Am J Public Health 2019;109(9):1212-1215. [PMID: 31318600]

Monteiro N., Branco M., Peres S., et al. The impact of tenofovir disoproxil fumarate on kidney function: four-year data from the HIV-infected outpatient cohort. J Int AIDS Soc 2014;17(4 Suppl 3):19565. [PMID: 25394072]

NIAID. Bulletin: HIV treatment study in patients with cryptococcal meningitis ends enrollment early, higher mortality rate found with early antiretroviral therapy. 2012. https://www.thebodypro.com/article/hiv-treatment-study-in-patients-with-cryptococcal- [accessed 2020 Jan 28]

Novelli S., Lecuroux C., Avettand-Fenoel V., et al. Long-term therapeutic impact of the timing of antiretroviral therapy in patients diagnosed with primary human immunodeficiency virus type 1 infection. Clin Infect Dis 2018;66(10):1519-1527. [PMID: 29211834]

NYCDHMH. HIV surveillance annual report, 2017. 2018. https://www1.nyc.gov/assets/doh/downloads/pdf/dires/hiv-surveillance-annualreport-2017.pdf [accessed 2019 Jul 22]

O'Connor J., Vjecha M. J., Phillips A. N., et al. Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per muL: secondary outcome results from a randomised controlled trial. Lancet HIV 2017;4(3):e105-e112. [PMID: 28063815]

Okulicz J. F., Grandits G. A., Weintrob A. C., et al. CD4 T cell count reconstitution in HIV controllers after highly active antiretroviral therapy. Clin Infect Dis 2010;50(8):1187-91. [PMID: 20218878]

Pathela P., Jamison K., Braunstein S. L., et al. Initiating antiretroviral treatment for newly diagnosed HIV patients in sexual health clinics greatly improves timeliness of viral suppression. Aids 2021;35(11):1805-1812. [PMID: 33973874]

Phillips A. N., Gazzard B., Gilson R., et al. Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count. Aids 2007;21(13):1717-21. [PMID: 17690569]

Pilcher C. D., 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. [PMID: 27434707]

Politch J. A., Mayer K. H., Welles S. L., et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. Aids 2012;26(12):1535-43. [PMID: 22441253]

Quinn T. C., Wawer M. J., Sewankambo N., et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000;342(13):921-9. [PMID: 10738050]

Ray M., Logan R., Sterne J. A., et al. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. Aids 2010;24(1):123-37. [PMID: 19770621]

Rodger A. J., Cambiano V., Bruun T., et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner Is using suppressive antiretroviral therapy. Jama 2016;316(2):171-81. [PMID: 27404185]

Rosen S., Maskew M., Fox M. P., et al. Correction: Initiating antiretroviral therapy for HIV at a patient's first clinic visit: the RapIT Randomized Controlled Trial. PLoS Med 2016;13(6):e1002050. [PMID: 27258028]

Rosen S., Maskew M., Fox M. P., et al. Initiating antiretroviral therapy for HIV at a patient's first clinic visit: the RapIT Randomized Controlled Trial. PLoS Med 2016;13(5):e1002015. [PMID: 27163694]

Sabin C. A., Smith C. J., d'Arminio Monforte A., et al. Response to combination antiretroviral therapy: variation by age. Aids 2008;22(12):1463-73. [PMID: 18614870]

Salzberg Global Seminar. Salzberg statement on shared decision making. BMJ 2011;342():d1745. [PMID: 21427038]

Scherrer A. U., von Wyl V., Yang W. L., et al. Emergence of acquired HIV-1 drug resistance almost stopped in Switzerland: A 15-year prospective cohort analysis. Clin Infect Dis 2016;62(10):1310-1317. [PMID: 26962075]

Severe P., Juste M. A., Ambroise A., et al. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med 2010;363(3):257-65. [PMID: 20647201]

Siddiqi A. E., Hall H. I., Hu X., et al. Population-based estimates of life expectancy after HIV diagnosis: United States 2008-2011. J Acquir Immune Defic Syndr 2016;72(2):230-6. [PMID: 26890283]

Sigel K., Wisnivesky J., Gordon K., et al. HIV as an independent risk factor for incident lung cancer. Aids 2012;26(8):1017-25. [PMID: 22382152]

Silverberg M. J., Chao C., Leyden W. A., et al. HIV infection, immunodeficiency, viral replication, and the risk of cancer. Cancer Epidemiol Biomarkers Prev 2011;20(12):2551-9. [PMID: 22109347]

Skarbinski J., Rosenberg E., Paz-Bailey G., et al. Human immunodeficiency virus transmission at each step of the care continuum in the United States. JAMA Intern Med 2015;175(4):588-96. [PMID: 25706928]

Sterne J. A., May M., Costagliola D., et al. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 2009;373(9672):1352-63. [PMID: 19361855]

Torok M. E., Yen N. T., Chau T. T., et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)--associated tuberculous meningitis. Clin Infect Dis 2011;52(11):1374-83. [PMID: 21596680]

Tozzi V., Balestra P., Bellagamba R., et al. Persistence of neuropsychologic deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 2007;45(2):174-82. [PMID: 17356465]

Uy J., Armon C., Buchacz K., et al. Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr 2009;51(4):450-3. [PMID: 19474757]

van Lelyveld S. F., Gras L., Kesselring A., et al. Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort. Aids 2012;26(4):465-74. [PMID: 22112603]

Volberding P. A., Deeks S. G. Antiretroviral therapy and management of HIV infection. Lancet 2010;376(9734):49-62. [PMID: 20609987]

Wallis C. L., Papathanasopolous M. A., Fox M., et al. Low rates of nucleoside reverse transcriptase inhibitor resistance in a well-monitored cohort in South Africa on antiretroviral therapy. Antivir Ther 2012;17(2):313-20. [PMID: 22293461]

WHO. Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy. 2017. https://apps.who.int/iris/bitstream/handle/10665/255884/9789241550062-eng.pdf;jsessionid=7B7901DF1D162BB7D16B83C444A2D417?sequence=1 [accessed 2019 Jun 18]

Winston A., Puls R., Kerr S. J., et al. Dynamics of cognitive change in HIV-infected individuals commencing three different initial antiretroviral regimens: a randomized, controlled study. HIV Med 2012;13(4):245-51. [PMID: 22151608]

Wright S. T., Carr A., Woolley I., et al. CD4 cell responses to combination antiretroviral therapy in patients starting therapy at high CD4 cell counts. J Acquir Immune Defic Syndr 2011;58(1):72-9. [PMID: 21654498]

Wu Z., Zhao Y., Ge X., et al. Simplified HIV testing and treatment in China: Analysis of mortality rates before and after a structural intervention. PLoS Med 2015;12(9):e1001874. [PMID: 26348214]

Young J., Psichogiou M., Meyer L., et al. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE. PLoS Med 2012;9(3):e1001194. [PMID: 22448150]

Zash, et al. 2022. Update on neural tube defects with antiretroviral exposure in the Tsepamo Study, Botswana.. AIDS; 2022 Jul 29-Aug 2; . https://www.natap.org/2022/IAC/IAC_31.htm

Zolopa A., Andersen J., Powderly W., et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One 2009;4(5):e5575. [PMID: 19440326]

Zulliger R., Black S., Holtgrave D. R., et al. Cost-effectiveness of a package of interventions for expedited antiretroviral therapy initiation during pregnancy in Cape Town, South Africa. AIDS Behav 2014;18(4):697-705. [PMID: 24122044]