Purpose of This Guideline
Reviewed and updated: Antonio E. Urbina, MD; August 11, 2022
Writing group: Joseph P. McGowan, MD, FACP, FIDSA; Steven M. Fine, MD, PhD; Rona Vail, MD; Samuel T. Merrick, MD; Asa Radix, MD, MPH, PhD; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Medical Care Criteria Committee
Date of original publication: January 2017
This guideline was developed by the New York State Department of Health AIDS Institute (NYSDOH AI) for primary care providers and other practitioners who are initiating therapy in nonpregnant, antiretroviral therapy (ART)-naive adults with HIV. The guideline aims to achieve the following goals:
- Provide a clear and concise roadmap for clinicians to follow in choosing from among several equally efficacious ART regimens based on individual patient characteristics and preferences.
- Provide a list of ART regimens to avoid.
- Provide dosing considerations for individuals with renal or hepatic impairment and important drug-drug and food interactions.
- Encourage clinicians to seek the assistance of an experienced HIV care provider when treating patients with extensive comorbidities.
- Integrate current evidence-based clinical recommendations into the healthcare-related implementation strategies of the New York State Ending the Epidemic initiative.
The NYSDOH AI is publishing this guideline at a critical time: 1) prompt initiation of ART is now recommended for all individuals diagnosed with HIV; 2) identifying and linking individuals with HIV to care and treatment that achieves optimal virologic suppression are crucial to the success of the New York State Ending the Epidemic initiative; and 3) the ability of primary care providers and other clinicians in New York State to properly select initial ART is key to the successful treatment of individuals with HIV.
Introduction: The NYSDOH AI Medical Care Criteria Committee recommendations for prescribing ART regimens for treatment-naive, nonpregnant adults (age ≥18 years) with HIV-1 and without acquired resistance are based on a comprehensive review of available clinical trial data. (For guidelines specific to treatment of adolescents with HIV, please consult the U.S. Department of Health and Human Services [DHHS] Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV). In formulating its recommendations for New York State, this Committee balanced the strength of published evidence regarding efficacy of treatment regimens with factors that influence adherence, including pill burden, tolerability, and dosing schedule. Preferred regimens are supported by evidence and have favorable adherence profiles, with lower pill burdens, fewer adverse effects, and dosing schedules that may be easier for individuals to manage. Ranking of regimens in this manner is designed to inform discussion and decision-making with patients.
How to use this guideline: Tables presenting preferred and alternative regimens appear first (see the Available ART Regimens section of this guideline: Tables 2 and 3). To help guide the choice among regimens of similar efficacy, each table includes comments that address selected pertinent issues regarding each regimen, such as limitations based on a patient’s kidney function and drug-drug interactions.
Other sections of the guideline include a review of relevant issues, patient considerations, essential laboratory assessments, and the rationale for the recommendations. Reference to the expanded information is crucial for addressing factors that may be of particular importance when individualizing a patient’s treatment, such as loss of bone mineral density with a regimen that includes tenofovir disoproxil fumarate and the conflicting data on cardiac risk with abacavir; see the guideline section Specific Factors to Consider and Discuss With Patients. In addition, a review of psychosocial factors and individual patient preferences may help in the selection of an initial ART regimen. Importantly, a patient-centered approach that incorporates both clinical and nonclinical issues should be prioritized.
Scope: This guideline addresses initial treatment of HIV-1 infection with ART in nonpregnant adults. For information regarding ART in individuals who are or who may become pregnant, please refer to the DHHS guideline Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States [DHHS 2021b]. Please refer to the NYSDOH AI guideline Diagnosis and Management of HIV-2 in Adults for recommendations regarding treatment of HIV-2 infection. For recommendations regarding second-line regimens, please refer to the DHHS guideline on management of the treatment-experienced patient [DHHS 2021a].
For the NYSDOH definition of “experienced HIV care provider,” see HIV Care Provider Definitions.
References
DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. 2021a Aug 16. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines [accessed 2018 May 1]
DHHS. Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States. 2021b Feb 10. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new-guidelines [accessed 2018 May 1]
Available ART Regimens
Reviewed and updated: Antonio E. Urbina, MD, with the Medical Care Criteria Committee; August 11, 2022
| Abbreviations used in this section: | |||
| Drug names: | Other: | ||
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Note: The recommendations in this guideline pertain to initial ART regimens for adults with HIV who are not pregnant.
| RECOMMENDATIONS |
Regimen Selection
Expert Consultation
Follow-up
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Available Antiretroviral Agents and Regimens
An initial ART regimen should be selected on the basis of patient preferences and clinical characteristics, and a preferred regimen should be used whenever possible (see Table 2, below). Each of the preferred, alternative, and other initial ART regimens for nonpregnant adults is expected to produce full viral suppression; however, the regimens differ in tolerability, possible toxicities, convenience, and the potential for drug-drug interactions, all of which can affect overall adherence and, therefore, suppression rates.
Preferred backbone: This Committee recommends that either formulation of tenofovir (TAF or TDF) can be used as part of the backbone in preferred regimens. A recent meta-analysis of 14 clinical trials [Pilkington, et al. 2020], comparing the efficacy and safety of TAF versus TDF in boosted and unboosted subgroups, found comparable efficacy and safety profiles with the use of unboosted TDF compared with TAF (see Table 1, below). Studies have shown that TDF-related renal toxicity is more common when using TDF in a regimen containing COBI or RTV [Pilkington, et al. 2020; Hill, et al. 2018; Cuzin, et al. 2017; Ryom, et al. 2013; Goicoechea, et al. 2008]. Therefore, this Committee does not recommend TDF use with boosted regimens when initiating therapy.
In a study of ART-naive individuals, RAL HD 1200 mg once daily was noninferior to 400 mg tablets dosed twice daily and is thus preferred [Cahn, et al. 2017].
Greater weight gain has also been observed after initiation of TAF or with a switch from TDF to TAF, especially in conjunction with INSTIs [Łomiak, et al. 2021; Surial, et al. 2021; Bourgi, et al. 2020a; Bourgi, et al. 2020b; Calmy, et al. 2020; Lake, et al. 2020; Sax, et al. 2020; Venter, et al. 2020; Venter, et al. 2019]. However, the predictors, mechanisms of actions, and clinical significance of these findings is unknown.
Third drug: An INSTI as the third drug is preferred over PIs and NNRTIs based on tolerability and a lower incidence of drug-drug interactions. RPV is not appropriate for patients with a viral load >100,000 copies/mL or CD4 count ≤200 cells/mm3 and is contraindicated with PPIs. TAF/FTC/RPV is included as an alternative regimen.
EFV-containing regimens, although efficacious, have been shown to be less well tolerated than the preferred or alternative regimens in Tables 2 and 3, below.
LPV/RTV-containing regimens are no longer included among the options for initial treatment because of pill burden and reduced tolerability in comparison with other boosted PIs.
When initiating ART at the time of HIV diagnosis (i.e., “rapid start” or “test and treat”), avoid regimens containing ABC unless the result of HLA-B*5701 testing is known to be negative.
Single-Tablet Regimens Versus Multi-Tablet Regimens
The advantages of STRs compared with MTRs include simplicity, convenience, and lower risk of selective nonadherence [Gardner, et al. 2008]. A recent meta-analysis demonstrated that STRs had better adherence rates when compared with MTRs of any frequency (once daily or twice daily) and had higher 48-week viral suppression rates with comparable adverse effects [Clay, et al. 2015].
In another retrospective study, INSTI-based regimens generally had greater rates of suppression and a lower probability of viral rebound after suppression in comparison to NNRTI-based regimens, regardless of whether an STR or MTR was used, but STR INSTI-based therapy was more durable [Mills, et al. 2016b]. In the same study, STR NNRTI-based therapy led to greater rates of suppression than MTR NNRTI-based therapy [Mills, et al. 2016b].
| Table 1: Important Clinical Considerations With Either TDF/FTC or TAF/FTC as Initial ART [a] Download PDF |
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If the patient is at risk of chronic kidney disease (e.g., age >40 years, with hypertension, diabetes, or preexisting mild kidney disease): The greater possibility of kidney disease among individuals who have risk factors is an essential component of the risk-benefit discussion and shared decision-making regarding initiation of tenofovir-containing regimens.
If the patient has osteopenia, osteomalacia, or osteoporosis:
If the patient has concerns about weight gain, hyperlipidemia, or metabolic disorders:
If the patient is an adolescent or youth:
If the patient is pregnant or attempting to conceive:
If the patient has active chronic HBV:
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Abbreviations: 3TC, lamivudine; ART, antiretroviral therapy; COBI, cobicistat; CrCl, creatinine clearance; DHHS, U.S. Department of Health and Human Services; FDA, U.S. Food and Drug Administration; FTC, emtricitabine; HBV, hepatitis B virus; INSTI, integrase strand transfer inhibitor; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; RTV, ritonavir; TAF, tenofovir alafenamide fumarate; TDF, tenofovir disoproxil fumarate. Notes:
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Other studies have demonstrated better efficacy and adherence, lower cost to patients, and fewer hospital admissions associated with STRs than with MTRs [Griffith, et al. 2019; Mills, et al. 2016b; Armstrong, et al. 2015; Maggiolo, et al. 2015; Hanna, et al. 2014; Nachega, et al. 2014; Sweet, et al. 2014; Cohen, et al. 2013; Colombo, et al. 2013; Raboud, et al. 2011; Bangalore, et al. 2007].
There are 3 STRs listed below as preferred regimens. It is possible that these regimens may contain 1 or more components that are not appropriate for an individual patient, do not allow for adjustment of individual components for renal function, have significant drug-drug interactions, are poorly tolerated, or may be more expensive than the individual components prescribed separately, particularly if available as generic formulations. With full adherence, any of the preferred or alternative regimens should lead to full suppression. This includes MTRs, which can be used when an STR is not possible or not tolerated. Cost and access may also be determinative factors.
For patients with impaired baseline renal function, separating the drugs into individual components and adjusting each may be appropriate (see Table 9: Recommended Dose Adjustments for Use of Selected Fixed-Dose Combination Antiretroviral Medications in Patients With Hepatic or Renal Impairment).
Table 2 includes initial ART regimens preferred by this Committee; Table 3 lists alternative initial regimens. Table 4 lists other available ART regimens that this Committee considers neither preferred nor alternative. Within each table, regimens are listed alphabetically. For specific details on choosing a regimen, see the discussions in other sections of this guideline and/or the package inserts for the drugs listed below.
| Table 2: Preferred Initial Antiretroviral Therapy Regimens for Nonpregnant Adults [a] (listed alphabetically; for specific details, see Specific Factors to Consider and Discuss With Patients and drug package inserts) Download PDF |
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| Regimen | Comments | Rating |
| Available as a Single-Tablet Formulation | ||
| Abacavir/lamivudine/dolutegravir [b,c] (ABC/3TC/DTG; Triumeq) |
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A1 |
| Lamivudine/dolutegravir [b,c] (3TC/DTG; Dovato) |
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A1 |
| Tenofovir alafenamide/ emtricitabine/bictegravir [c] (TAF 25 mg/FTC/BIC; Biktarvy) |
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A1 |
| Available as a Multi-Tablet Regimen With Once-Daily Dosing | ||
| Tenofovir alafenamide/ emtricitabine or tenofovir disoproxil fumarate/emtricitabine and dolutegravir [b,c] (TAF 25 mg/FTC or TDF 300 mg/FTC and DTG; Descovy or Truvada and Tivicay) |
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A1 |
| Tenofovir alafenamide/ emtricitabine or tenofovir disoproxil fumarate/emtricitabine and raltegravir HD [c] (TAF 25 mg/FTC or TDF 300 mg/FTC and RAL HD; Descovy or Truvada and Isentress HD) |
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A2 |
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Abbreviations: ART, antiretroviral therapy; CrCl, creatinine clearance; DHHS, U.S. Department of Health and Human Services; NRTI, nucleoside/nucleotide reverse transcriptase inhibitors; PEP, post-exposure prophylaxis. Notes:
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| Table 3: Alternative Initial ART Regimens for Nonpregnant Adults [a] (listed alphabetically; for specific details, see Specific Factors to Consider and Discuss With Patients and drug package inserts) Download PDF |
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| Regimen | Comments | Rating |
| Available as a Single-Tablet Formulation | ||
| Tenofovir alafenamide/ emtricitabine/darunavir/cobicistat [b] (TAF 10 mg/FTC/DRV/COBI; Symtuza) |
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B2 |
| Tenofovir alafenamide/ emtricitabine/elvitegravir/cobicistat [b] (TAF 10 mg/FTC/EVG/COBI; Genvoya) |
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B1 |
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Tenofovir alafenamide/ |
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B3 |
| Tenofovir disoproxil fumarate/ lamivudine/doravirine [b] (TDF/3TC/DOR; Delstrigo) |
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B1 |
| Available as a Multi-Tablet Regimen With Once-Daily Dosing | ||
| Abacavir/lamivudine and doravirine [b] (ABC/3TC and DOR; Epzicom and Pifeltro) [Molina, et al. 2018] |
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B2 |
| Tenofovir alafenamide/emtricitabine and doravirine [b] (TAF 25 mg/FTC and DOR; Descovy and Pifeltro) |
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B2 |
| Available as a Multi-Tablet Regimen With Twice-Daily Dosing | ||
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Tenofovir alafenamide/emtricitabine or tenofovir disoproxil fumarate/emtricitabine and raltegravir [b] |
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B3 |
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Abbreviations: ART, antiretroviral therapy; CrCl, creatinine clearance; CYP, cytochrome P450; DHHS, U.S. Department of Health and Human Services. Notes:
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| Table 4: Other ART Regimens Not Included as Preferred or Alternative for Nonpregnant Adults [a] (listed alphabetically; for specific details, see Specific Factors to Consider and Discuss With Patients and drug package inserts) Download PDF |
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| Regimen | Comments | Rating |
| Available as a Single-Tablet Regimen | ||
| Tenofovir disoproxil fumarate/ emtricitabine/efavirenz [b] (TDF/FTC/EFV; Atripla) |
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B1 |
| Tenofovir disoproxil fumarate/ emtricitabine/rilpivirine [b] (TDF/FTC/RPV; Complera) |
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B1 |
| Available as a Multi-Tablet Regimen With Once-Daily Dosing | ||
| Abacavir/lamivudine and atazanavir and ritonavir [b,e] (ABC/3TC and ATV and RTV; Epzicom and Reyataz and Norvir) |
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C1 |
| Abacavir/lamivudine and darunavir/cobicistat [b,e] (ABC/3TC and DRV/COBI; Epzicom and Prezcobix) |
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B3 |
| Abacavir/lamivudine and darunavir and ritonavir [b,e] (ABC/3TC and DRV and RTV; Epzicom and Prezista and Norvir) |
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B2 |
| Abacavir/lamivudine and efavirenz [b,e] (ABC/3TC and EFV; Epzicom and Sustiva) |
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C1 |
| Tenofovir alafenamide/emtricitabine and efavirenz [b] (TAF 25 mg/FTC and EFV; Descovy and Sustiva) |
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B3 |
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Abacavir/lamivudine and raltegravir HD [b,e] |
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B3 |
| Available as a Multi-Tablet Regimen With Twice-Daily Dosing | ||
| Tenofovir disoproxil fumarate/emtricitabine and raltegravir [b] (TDF/FTC and RAL; Truvada and Isentress) |
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B1 |
| Abacavir/lamivudine and raltegravir [b,e] (ABC/3TC and RAL; Epzicom and Isentress) |
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B1 |
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Abbreviations: ART, antiretroviral therapy; CrCl, creatinine clearance; DHHS, U.S. Department of Health and Human Services; PPI, proton pump inhibitor. Notes:
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| Use of Dolutegravir in Individuals of Childbearing Capacity Lead author: Geoffrey A. Weinberg, MD, with the MCCC, updated May 2021 |
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Evidence from multiple studies indicates no difference in rates of total birth defects among infants exposed to antiretroviral (ARV) medications during the first trimester compared with infants exposed later in pregnancy. ARVs are generally considered safe and may be taken by pregnant patients with HIV without increasing the risk of infant birth defects. The MCCC is providing the following updated information for medical care providers concerning preliminary reports that previously had linked dolutegravir (DTG) to neural tube defects (NTDs) in infants exposed to dolutegravir during the periconception period [Zash, et al. 2018; Zash, et al. 2019; Reefhuis, et al. 2020]. Read the full statement. |
References
Armstrong B, Chan DJ, Stewart MJ, et al. Single tablet regimen usage and efficacy in the treatment of HIV infection in Australia. AIDS Res Treat 2015;2015:570316. [PMID: 26550490]
Bangalore S, Kamalakkannan G, Parkar S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007;120(8):713-719. [PMID: 17679131]
Bourgi K, Jenkins CA, Rebeiro PF, et al. Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada. J Int AIDS Soc 2020a;23(4):e25484. [PMID: 32294337]
Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis 2020b;70(7):1267-1274. [PMID: 31100116]
Cahn P, Kaplan R, Sax PE, et al. Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial. Lancet HIV 2017;4(11):e486-e494. [PMID: 28918877]
Calmy A, Tovar Sanchez T, Kouanfack C, et al. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV 2020;7(10):e677-e687. [PMID: 33010241]
Clay PG, Nag S, Graham CM, et al. Meta-analysis of studies comparing single and multi-tablet fixed dose combination HIV treatment regimens. Medicine (Baltimore) 2015;94(42):e1677. [PMID: 26496277]
Cohen CJ, Meyers JL, Davis KL. Association between daily antiretroviral pill burden and treatment adherence, hospitalisation risk, and other healthcare utilisation and costs in a US Medicaid population with HIV. BMJ Open 2013;3(8):e003028. [PMID: 23906955]
Colombo GL, Di Matteo S, Maggiolo F. Antiretroviral therapy in HIV-infected patients: a proposal to assess the economic value of the single-tablet regimen. Clinicoecon Outcomes Res 2013;5:59-68. [PMID: 23430273]
Cuzin L, Pugliese P, Allavena C, et al. Antiretroviral therapy as a risk factor for chronic kidney disease: Results from traditional regression modeling and causal approach in a large observational study. PLoS One 2017;12(12):e0187517. [PMID: 29216208]
Eron JJ, Orkin C, Gallant J, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. Aids 2018;32(11):1431-1442. [PMID: 29683855]
Gardner EM, Sharma S, Peng G, et al. Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance. Aids 2008;22(1):75-82. [PMID: 18090394]
Goicoechea M, Liu S, Best B, et al. Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis 2008;197(1):102-108. [PMID: 18171292]
Griffith DC, Farmer C, Gebo KA, et al. Uptake and virological outcomes of single- versus multi-tablet antiretroviral regimens among treatment-naïve youth in the HIV Research Network. HIV Med 2019;20(2):169-174. [PMID: 30561888]
Hanna DB, Hessol NA, Golub ET, et al. Increase in single-tablet regimen use and associated improvements in adherence-related outcomes in HIV-infected women. J Acquir Immune Defic Syndr 2014;65(5):587-596. [PMID: 24326606]
Hill A, Hughes SL, Gotham D, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate: is there a true difference in efficacy and safety? J Virus Erad 2018;4(2):72-79. [PMID: 29682298]
Lake JE, Wu K, Bares SH, et al. Risk factors for weight gain following switch to integrase inhibitor-based antiretroviral therapy. Clin Infect Dis 2020;71(9):e471-e477. [PMID: 32099991]
Łomiak M, Stępnicki J, Mikuła T, et al. Weight and body mass index increase after switch from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate-containing treatment in an antiretroviral therapy-experienced group. Int J STD AIDS 2021;32(6):570-577. [PMID: 33612018]
Maggiolo F, Colombo GL, Di Matteo S, et al. Cost-effectiveness analysis of antiretroviral therapy in a cohort of HIV-infected patients starting first-line highly active antiretroviral therapy during 6 years of observation. Patient Relat Outcome Meas 2015;6:53-60. [PMID: 25733942]
McComsey GA, Kitch D, Daar ES, et al. Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: AIDS Clinical Trials Group A5224s, a substudy of ACTG A5202. J Infect Dis 2011;203(12):1791-1801. [PMID: 21606537]
Mills A, Arribas JR, Andrade-Villanueva J, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. Lancet Infect Dis 2016a;16(1):43-52. [PMID: 26538525]
Mills A, Fusco J, Schulman K, et al. The impact of antiretroviral tablet burden and polypharmacy on viral suppression in treatment naïve patients. Open Forum Infect Dis 2016b;3(suppl_1):1512. https://doi.org/10.1093/ofid/ofw172.1214
Molina JM, Squires K, Sax PE, et al. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV 2018;5(5):e211-220. [PMID: 29592840]
Nachega JB, Parienti JJ, Uthman OA, et al. Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials. Clin Infect Dis 2014;58(9):1297-1307. [PMID: 24457345]
Perrot S, Aslangul E, Szwebel T, et al. Bone pain due to fractures revealing osteomalacia related to tenofovir-induced proximal renal tubular dysfunction in a human immunodeficiency virus-infected patient. J Clin Rheumatol 2009;15(2):72-74. [PMID: 19265350]
Pilkington V, Hughes SL, Pepperrell T, et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated meta-analysis of 14 894 patients across 14 trials. AIDS 2020;34(15):2259-2268. [PMID: 33048869]
Pozniak A, Arribas JR, Gathe J, et al. Switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-infected patients with renal impairment: 48-week results from a single-arm, multicenter, open-label phase 3 study. J Acquir Immune Defic Syndr 2016;71(5):530-537. [PMID: 26627107]
Raboud J, Li M, Walmsley S, et al. Once daily dosing improves adherence to antiretroviral therapy. AIDS Behav 2011;15(7):1397-1409. [PMID: 20878227]
Ryom L, Mocroft A, Kirk O, et al. Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study. J Infect Dis 2013;207(9):1359-1369. [PMID: 23382571]
Sax PE, Erlandson KM, Lake JE, et al. Weight gain following initiation of antiretroviral therapy: Risk factors in randomized comparative clinical trials. Clin Infect Dis 2020;71(6):1379-1389. [PMID: 31606734]
Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: Two randomised, double-blind, phase 3, non-inferiority trials. Lancet 2015;385(9987):2606-2615. [PMID: 25890673]
Souza SJ, Luzia LA, Santos SS, et al. Lipid profile of HIV-infected patients in relation to antiretroviral therapy: A review. Rev Assoc Med Bras (1992) 2013;59(2):186-198. [PMID: 23582562]
Stellbrink HJ, Orkin C, Arribas JR, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis 2010;51(8):963-972. [PMID: 20828304]
Surial B, Mugglin C, Calmy A, et al. Weight and metabolic changes after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people living with HIV: A cohort study. Ann Intern Med 2021;174(6):758-767. [PMID: 33721521]
Sweet D, Song J, Zhong Y, et al. Real-world medication persistence with single versus multiple tablet regimens for HIV-1 treatment. J Int AIDS Soc 2014;17(4 Suppl 3):19537. [PMID: 25394046]
Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med 2019;381(9):803-815. [PMID: 31339677]
Venter WDF, Sokhela S, Simmons B, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): Week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV 2020;7(10):e666-676. [PMID: 33010240]
Zash R, Holmes LB, Diseko M, et al. Update on neural tube defects with antiretroviral exposure in the Tsepamo Study, Botswana. AIDS; 2022 Jul 29-Aug 2; Montreal, Canada. https://www.natap.org/2022/IAC/IAC_31.htm
General Principles in Choosing an Initial ART Regimen
Reviewed and updated: Antonio E. Urbina, MD, with the Medical Care Criteria Committee; August 11, 2022
| Abbreviations used in this section: | |||
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Goals of ART: The issue of when to start ART was settled with the publication of the START and TEMPRANO studies early in 2015 [Danel, et al. 2015; Lundgren, et al. 2015]. Treatment is now recommended for all individuals with confirmed HIV regardless of CD4 cell count or viral load (see the NYSDOH guideline Rapid ART Initiation).
The goal of ART is complete and durable suppression of plasma viremia while minimizing toxicity and maximizing quality of life. Properly selected ART may never require a change or adjustment once started. Treatment interruptions should be avoided [El-Sadr, et al. 2006].
Since the approval of ZDV on March 19, 1987, there have been 30 individual agents approved for the treatment of HIV and 1 pharmacokinetic enhancer or “booster,” COBI, which is currently used to enhance the pharmacokinetics of EVG, ATV, or DRV. RTV at treatment doses is poorly tolerated and is used only at lower doses for pharmacokinetic boosting of PIs. An additional 18 FDA-approved FDCs are also available. These FDCs include STRs, of which there are 9 currently available that provide a complete and effective treatment regimen for HIV that is combined into 1 pill for use in properly selected individuals. The goal of initial therapy is to start a regimen that suits an individual’s lifestyle and is appropriate given existing baseline medical comorbidities (see Table 5, below).
Active drugs from 2 different classes: Although regimen options for treatment-naive, nonpregnant adults are constantly evolving, the same general principles that were established with the first effective and durable therapies are still true today [Gulick, et al. 2000]. The backbone of therapy has traditionally been 2 NRTIs paired with 1 of the following: an NNRTI, a boosted PI, or a boosted or unboosted INSTI. In a large meta-analysis, INSTIs were superior to other drug classes as a third drug [Lee, et al. 2014], and DTG may have specific advantages because of the lack, to date, of documented resistance developing in ART-naive patients who initiate DTG-containing regimens [Wainberg and Mesplede 2015]. The entry inhibitors and fusion inhibitors are not recommended for initial therapy (see Table 6, below), but they may have a role in ART for treatment-experienced patients with extensive drug resistance (see All FDA-Approved HIV Medications, including generic and trade names).
The only 2-drug regimen that this committee recommends for ART initiation is DTG/3TC, although other dual- and even monotherapy regimens have been and continue to be studied [Cahn, et al. 2020; Cahn, et al. 2019; Baril, et al. 2016; Cahn, et al. 2017; Maggiolo, et al. 2016; Bedimo, et al. 2014; Cahn, et al. 2014; Raffi, et al. 2014; Taiwo, et al. 2011]. Importantly, use of DTG/3TC is recommended only after the result of HIV resistance and HBV testing are known. Further, this committee recommends against the use of DTG/3TC in patients with major NRTI resistance, including the M184V/I mutation.
If DTG/3TC is started in a patient with HBV infection, a third antiviral agent with activity against HBV should be added. Because the Gemini 1 and 2 studies restricted entry to patients with HIV-1 RNA ≤500,000 copies/mL, this committee recommends against use of DTG/3TC in patients with HIV-1 RNA >500,000 copies/mL.
TAF, a prodrug formulation for tenofovir, was developed as an alternative to TDF and has been approved as part of the following STRs:
- TAF 10 mg/FTC/COBI/EVG
- TAF 25 mg/FTC/RPV
- TAF 25 mg/FTC/BIC [FDA 2018a, 2016b, 2016c]
- TAF 10 mg/FTC/COBI/DRV [FDA 2018b] and the FDC TAF 25 mg/FTC [FDA 2016a]
Oral administration of TAF results in lower circulating levels of tenofovir in plasma and affects markers of renal toxicity and bone mineral density less adversely than does TDF [Mills, et al. 2016; Pozniak, et al. 2016; Sax, et al. 2015]. Bioequivalence studies in healthy volunteers show that the TAF 10 mg dose administered with COBI 150 mg is equivalent to the TAF 25 mg dose without COBI [Zack, et al. 2016a; Zack, et al. 2016b].
A switch study showed good maintenance of viral suppression when changing from TDF/FTC to TAF 10 mg/FTC if the third drug was a boosted PI, or to TAF 25 mg/FTC if the third drug was an unboosted NNRTI or INSTI [Gallant, et al. 2016]. Note that TAF 10 mg alone and TAF 10 mg/FTC are not currently FDA-approved.
Until further safety data are available, this Committee has not included TAF 25 mg/FTC in combination with COBI or RTV as recommended regimens and recommends caution when using TAF 25 mg/FTC with regimens that contain either COBI or RTV in the setting of CrCl <50 mL/min.
COBI-boosted DRV was approved based on bioavailability studies [FDA 2016d; Kakuda, et al. 2014]. DRV/COBI has demonstrated comparable efficacy to RTV-boosted DRV in a single-arm study [Tashima, et al. 2014]. However, because randomized clinical trials that compare COBI- versus RTV-boosted DRV are not yet available, it has a lower strength of evidence rating. COBI-boosted ATV showed noninferiority when compared with RTV-boosted ATV with a TDF/FTC backbone in a randomized, double-blind study [Gallant, et al. 2013].
| KEY POINT |
|
All of the currently recommended preferred regimens have similar virologic efficacy when measured by an “on-treatment” metric, but adherence, the potential for drug interactions, and tolerability under real-life conditions may inform the choice of preferred versus alternative versus other regimens.
The following general conclusions can be drawn based on currently available evidence from a number of pivotal studies:
- When ABC/3TC is used as a backbone with EFV or boosted ATV, time to failure was shorter in the ≥100,000 copies/mL viral load stratum when compared with a backbone of TDF/FTC [Sax, et al. 2011; Post, et al. 2010; Sax, et al. 2009].
- DTG is as efficacious as (i.e., noninferior to) RAL [Raffi, et al. 2013] and superior to both DRV/RTV [Molina, et al. 2014] and coformulated TDF/FTC/EFV [Walmsley S, et al. 2015]. DTG was superior at 48 weeks when combined with ABC/3TC as compared to TDF/FTC/EFV [Walmsley SL, et al. 2013].
- RAL, although dosed twice daily, has a favorable tolerability profile, provides durable virologic control [Lennox, et al. 2014; DeJesus, et al. 2012; Young, et al. 2010], and was superior to both DRV/RTV and ATV/RTV based on the cumulative incidence of virologic failure and tolerability [Lennox, et al. 2014].
- In a study of ART-naive individuals, RAL HD 1200 mg once daily was noninferior to RAL 400 mg tablets dosed twice daily [Cahn, et al. 2017].
- TAF/FTC/COBI/EVG as an STR was noninferior to the STR TDF/FTC/COBI/EVG, with fewer adverse effects on kidney function and bone mineral density [Sax, et al. 2015].
- In 2 separate trials of treatment-naive individuals, TAF/FTC/BIC was noninferior to both TAF/FTC and DTG [Sax, et al. 2017] and ABC/3TC/DTG [Gallant, et al. 2017].
- RPV has equivalent efficacy relative to EFV when baseline viral load is <100,000 copies/mL and is better tolerated [van Lunzen, et al. 2016; Behrens, et al. 2014; Cohen C, et al. 2014; Cohen CJ, et al. 2013; Cohen CJ, et al. 2012]. But RPV should not be initiated in individuals with baseline viral load >100,000 copies/mL or CD4 counts <200 cells/mm3.
- In 2 separate trials of treatment-naive individuals, TDF/3TC/DOR was noninferior to TDF/FTC/EFV, or DRV/RTV with either TDF/FTC or ABC/3TC [Orkin, et al. 2019; Molina, et al. 2018].
- DRV/RTV once daily is better tolerated and noninferior to either ATV/RTV or LPV/RTV [Lennox, et al. 2014; Orkin, et al. 2013], although LPV/RTV shows excellent efficacy when combined with either commonly used NRTI backbone [Smith, et al. 2009] and when compared with ATV/RTV [Molina, et al. 2008]. One open-label study using ABC/3TC as the backbone combined with DRV/RTV showed good safety and efficacy [Trottier, et al. 2012].
| Table 5: Individual Antiretroviral Medications or Combinations to Avoid in Initial Therapy for Nonpregnant Adults | |
| Antiretroviral Medication | Comments |
| Nevirapine (NVP; Viramune) | Life-threatening rash: Stevens-Johnson syndrome and toxic epidermal necrolysis are possible. |
|
Serious toxicities: Potentially fatal lactic acidosis, peripheral neuropathy, pancreatitis, lipoatrophy, and hepatic steatosis are possible. |
| Delavirdine (DLV; Rescriptor) | Thrice-daily dosing and inferior efficacy. |
| Etravirine (ETR; Intelence) | ETR does not have an FDA indication in ART-naive patients. |
|
Inferior efficacy and durability. |
| Zidovudine (ZDV; Retrovir) | Not well tolerated because of bone marrow suppression (notably anemia), headache, and myopathies. |
| Unboosted PIs | Inferior efficacy relative to boosted PIs. |
|
Either not well-studied or limited by dosing and side effects relative to recommended PIs. |
| Abbreviations: FDA, U.S. Food and Drug Administration; NRTI, nucleoside/nucleotide reverse transcriptase inhibitor; PI, protease inhibitor. | |
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Zack J, Chuck S, Chu H, et al. Bioequivalence of the rilpivirine/emtricitabine/tenofovir alafenamide single-tablet regimen. J Bioequiv Availab 2016b;8:49-54. https://www.longdom.org/open-access/bioequivalence-of-the-rilpivirineemtricitabinetenofovir-alafenamidesingletablet-regimen-jbb-1000266.pdf
General Considerations With Initial ART Regimens
Reviewed and updated: Antonio E. Urbina, MD, with the Medical Care Criteria Committee; August 11, 2022
| Abbreviations used in this section: | |||
| Drug names: | Other: | ||
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The recommended ART regimens should work well for the majority of patients, but some circumstances may make 1 regimen more favorable than another for a given individual. In general, an INSTI-based regimen will be the best option for most patients [Mills, et al. 2016; Lee, et al. 2014]. To date, no resistance has been reported in ART-naive patients treated with DTG as part of a registrational trial of combination therapy, suggesting that this medication may be an excellent choice, particularly given its tolerability and lack of drug-drug interactions [Cevik, et al. 2020; Wainberg and Mesplede 2015]. Regimens containing a boosted PI or DTG may be more appropriate when adherence is a concern, given the higher barrier to resistance. For patients with acute symptomatic infection or advanced HIV with an opportunistic infection, some experts would use both DTG and boosted DRV together with the NRTI backbone given the possibility of transmitted NRTI resistance until genotypic information is available, at which time the regimen can be adjusted. Consultation with an experienced HIV care provider is recommended when choosing a regimen for patients with extensive comorbidities, impaired renal function, HBV or HCV coinfection, or very high viral loads.
Early clinical trials in HIV used surrogate markers, such as viral load and CD4 cell count, or clinical endpoints, such as morbidity and mortality, to demonstrate superiority of new therapies over the “gold standard” treatment of the era. One of the trials that led to the 1996 approval of IDV compared IDV alone versus ZDV/3TC versus ZDV/3TC/IDV in ZDV- treatment-experienced patients, given that, at the time, dual NRTI treatment was considered acceptable [Gulick, et al. 1997].
As treatment has evolved and become more effective, the use of clinical end points has become challenging; most trials in the current era of HIV therapy are powered to detect noninferiority when compared with standard of care. For a variety of reasons, including cost and complexity, it would be impractical to conduct head-to-head comparisons of all available regimens. Some STRs and FDCs have been approved primarily based on bioequivalence studies when compared with the individual components, such as TDF/FTC/EFV, ABC/3TC/DTG, TAF/FTC/RPV, TAF/FTC, and DRV/COBI.
Some of the cutoff values used for comparisons, such as viral load <100,000 copies/mL or CD4 count ≥200 cells/mm3, are somewhat arbitrary. For example, most studies including RPV show that its efficacy is diminished when initiated at viral loads ≥100,000 copies/mL, and 1 study showed that RPV worked less well than EFV-based therapy at a viral load of ≥500,000 copies/mL [Domingo and Ribera 2013].
Some agents have been approved based on noninferiority to the relatively less well-tolerated TDF/FTC/EFV regimen, which is, nevertheless, a potent and effective regimen for those who tolerate it well. The higher prevalence of NNRTI resistance mutations when transmitted drug resistance occurs has prompted most experts to avoid NNRTI-based regimens if treatment is indicated before genotypic resistance testing results are available [Panichsillapakit, et al. 2016; Rhee, et al. 2015; Stekler, et al. 2015]. Although coformulated TAF/FTC/COBI/EVG is approved for use at any starting viral load, reports of failure using TDF/FTC/COBI/EVG, with resistance, have been documented in individuals with very high baseline viral loads >1,000,000 copies/mL [Adams, et al. 2016; Rhee, et al. 2015].
A paucity of data is available demonstrating how different antiretroviral medications perform based on race and gender, although studies have suggested, for instance, that DRV/RTV is less well tolerated in women than in men and that discontinuation of DRV/RTV occurs at a higher rate among Black patients than among others [Smith, et al. 2012; Currier, et al. 2010].
Long-acting injectable therapy: An injectable long-acting formulation of the INSTI CAB and the NNRTI RPV (CAB/RPV LA) has been approved by the FDA as replacement ART for adults and adolescents ≥12 years old who [FDA 2021]:
- Weigh ≥35 kg
- Do not have chronic hepatitis B virus infection
- Are virally suppressed (HIV-1 RNA level <50 copies/mL) on a stable ART regimen
- Have no history of treatment failure
- Have no known or suspected resistance to either CAB or RPV
Although not FDA-approved as initial ART or for individuals with detectable viremia, the use of CAB/RPV LA as replacement ART in virally suppressed patients engaged in care may be a suitable option for those who would prefer an alternative to daily oral therapy. For more information on use of CAB/RPV LA, refer to the NYSDOH AI guideline Use of Injectable CAB/RPV LA as Replacement ART in Virally Suppressed Adults.
References
Adams JL, Byrne D, Pepe R, et al. Virological failure in two patients with HIV-1 RNA viral loads >1,000,000 copies/ml initiated on elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate. Antivir Ther 2016;21(2):175-180. [PMID: 26308882]
Cevik M, Orkin C, Sax PE. Emergent resistance to dolutegravir among INSTI-naive patients on first-line or second-line antiretroviral therapy: a review of published cases. Open Forum Infect Dis 2020;7(6):ofaa202. [PMID: 32587877]
Currier J, Averitt Bridge D, Hagins D, et al. Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial. Ann Intern Med 2010;153(6):349-357. [PMID: 20855799]
Domingo P, Ribera E. [Data on rilpivirine in treatment-naive patients. Lessons from ECHO, THRIVE and STaR]. Enferm Infecc Microbiol Clin 2013;31(Suppl 2):20-29. [PMID: 24252530]
FDA. Cabenuva (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension), co-packaged for intramuscular use. Package insert. 2021 Jan. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212888s000lbl.pdf [accessed 2022 June 6]
Gulick RM, Mellors JW, Havlir D, et al. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N Engl J Med 1997;337(11):734-739. [PMID: 9287228]
Lee FJ, Amin J, Carr A. Efficacy of initial antiretroviral therapy for HIV-1 infection in adults: a systematic review and meta-analysis of 114 studies with up to 144 weeks’ follow-up. PLoS One 2014;9(5):e97482. [PMID: 24830290]
Mills A, Fusco J, Schulman K, et al. The impact of antiretroviral tablet burden and polypharmacy on viral suppression in treatment naïve patients. Open Forum Infect Dis 2016;3(suppl_1):1512. https://academic.oup.com/ofid/article/3/suppl_1/1512/2635860
Panichsillapakit T, Smith DM, Wertheim JO, et al. Prevalence of transmitted HIV drug resistance among recently infected persons in San Diego, CA 1996-2013. J Acquir Immune Defic Syndr 2016;71(2):228-236. [PMID: 26413846]
Rhee SY, Blanco JL, Jordan MR, et al. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: An individual-patient- and sequence-level meta-analysis. PLoS Med 2015;12(4):e1001810. [PMID: 25849352]
Smith KY, Garcia F, Kumar P, et al. Assessing darunavir/ritonavir-based therapy in a racially diverse population: 48-week outcomes from GRACE. J Natl Med Assoc 2012;104(7-8):366-376. [PMID: 23092052]
Stekler JD, McKernan J, Milne R, et al. Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. Antivir Ther 2015;20(1):77-80. [PMID: 24831260]
Wainberg MA, Mesplede T. Implications for the future of the HIV epidemic if drug resistance against dolutegravir cannot occur in first-line therapy. J Int AIDS Soc 2015;18(1):20824. [PMID: 26642452]
Specific Factors to Consider and Discuss With Patients
Reviewed and updated: Antonio E. Urbina, MD, with the Medical Care Criteria Committee; August 11, 2022
| Abbreviations used in this section: | |||
| Drug names: | Other: | ||
|
|
|
|
Before initiating ART, the following factors are important to consider and discuss with patients.
Age: As individuals with HIV age, they have a higher prevalence of comorbidities than younger patients with HIV and are likely to be on more non–HIV-specific medications, particularly cardiovascular or gastrointestinal agents, posing a higher risk for adverse interactions [Marzolini, et al. 2011]. For individuals older than 50 years, careful regimen selection, with the use of INSTIs when possible rather than cytochrome P450 inhibitors, such as COBI or RTV, can help minimize interactions. And use of TAF rather than TDF can lower the risk of renal and bone toxicity.
Comorbidities: Assessment for existing cardiovascular risk, renal disease or risk factors for the development of renal disease, hepatic disease, bone health, mental health, and substance use should be performed. Additionally, the risk for greater weight gain and potential exacerbation of metabolic complications with TAF- versus TDF-containing regimens, especially when combined with certain INSTI-based regimens, should be discussed prior to initiation of ART.
Cost: STRs may be favorable because of the lower copays that could be associated with fewer prescriptions. Conversely, the individual components of these regimens may be available generically as separate pills.
Dosing requirements (daily vs. twice daily): Most patients express a preference for once-daily dosing, especially if they are not taking other medications or are taking other medications that are dosed once daily. If individuals are already taking other medications that are dosed twice daily and report no adherence issues, twice-daily dosing is an acceptable option.
Drug-drug interactions: Because of some key drug-drug interactions, coadministration of some medications is to be avoided (Table 6, below). For instance, PPIs should not be coadministered with oral RPV; however, injectable RPV can be used with PPIs. Given the availability of over-the-counter PPIs and the possibility that these drugs may be prescribed by a different care provider, this interaction is especially important to discuss with patients. In this case, to avoid unnecessary regimen changes once started, even patients who are not currently taking a PPIs should be asked whether they have needed PPIs in the past or may need them in the future. Dose limitations for metformin may also be required when combined with DTG and possibly BIC.
RTV and COBI have many significant and important interactions, including with cardiac medications. Methadone maintenance requirements may also change with some antiretroviral agents. A detailed review of all of a patient’s medications, including over-the-counter medications or supplements, is essential.
Before prescribing an ART regimen, using an automated interaction checker embedded in the electronic medical record or tools such as the following to check for potential drug-drug interactions with currently prescribed medications can help avoid serious problems:
| Table 6: Selected Drug-Drug Interactions to Discuss Before Initiating ART in Treatment-Naive Patients | |
| Drugs | ARV(s): Comments |
| H2-blockers |
|
|
|
| Polyvalent cations [a] |
|
| PPIs |
|
| Metformin |
|
| Ethinyl estradiol and norethindrone [b] |
|
| Factor Xa inhibitors |
|
| Platelet inhibitors |
|
|
Abbreviations: ART, antiretroviral therapy; ARV, antiretroviral medication; ATV, atazanavir; BIC, bictegravir; COBI, cobicistat; CrCl, creatinine clearance; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; PPI, proton pump inhibitor; RAL, raltegravir; RPV, rilpivirine; RTV, ritonavir. Notes:
|
|
Food requirements: Because an individual may have a strong preference for taking medication with or without food, it is important to discuss which medications must be taken on an empty stomach, which must be taken with food, and which can be taken with or without food, as listed in Box 1, below.
| Box 1: Antiretroviral Medications That Can be Taken With or Without Food, Must Be Taken With Food, or Must Be Taken on an Empty Stomach | ||||
| Take With or Without Food |
Take With Food | Take on Empty Stomach | ||
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|
|
||
| Abbreviations: 3TC, lamivudine; ABC, abacavir; ATV, atazanavir; BIC, bictegravir; COBI, cobicistat; DOR, doravirine; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; RAL, raltegravir; RPV, rilpivirine; RTV, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. | ||||
Known adverse effects and toxicities: Review known and potential adverse effects in advance.
Number of pills: Some patients feel strongly that the fewer the number of pills, the better. For others, the greatest concern may be the ability to take all pills (regardless of the number) together once daily. Sometimes using individual agents rather than a multi-agent FDC or STR may be attractive depending on pill size. In rare cases, individuals who either cannot or will not swallow pills may need liquid formulations or pill crushing. Table 7, below, presents an abbreviated summary of commonly used ARVs and their availability in liquid formulation and/or the acceptability of crushing or dissolving them prior to ingestion.
|
Table 7: Acceptable Alternative Formulations and Methods of Administration of Antiretroviral Medications |
||
| Drug | Available as Liquid, Powder, or Chewable Tablet? | Can Tablet Be Split/Crushed/Dissolved? |
| Single-Tablet Formulations | ||
| Abacavir/lamivudine/dolutegravir (ABC/3TC/DTG; Triumeq) |
No | Probably acceptable to split/crush |
| Tenofovir alafenamide/ emtricitabine/bictegravir (TAF/FTC/BIC; Biktarvy) |
No | No data; not recommended |
| Tenofovir alafenamide/ emtricitabine/cobicistat/darunavir (TAF/FTC/COBI/DRV; Symtuza) |
No | No data; not recommended |
| Tenofovir alafenamide/ emtricitabine/elvitegravir/cobicistat (TAF/FTC/COBI/EVG; Genvoya) |
No | No data; not recommended |
| Tenofovir alafenamide/ emtricitabine/rilpivirine (TAF/FTC/RPV; Odefsey) |
No | No data; not recommended |
|
Tenofovir disoproxil fumarate/ |
No | No data; not recommended |
| Tenofovir disoproxil fumarate/ emtricitabine/efavirenz (TDF/FTC/EFV; Atripla) |
No | No data; not recommended |
| Dolutegravir/lamivudine (DTG/3TC; Dovato) |
No | No data; not recommended |
| Tenofovir disoproxil fumarate/ emtricitabine/rilpivirine (TDF/FTC/RPV; Complera) |
No | No data; not recommended |
| Fixed-Dose Combinations | ||
| Abacavir/lamivudine (ABC/3TC; Epzicom) |
See individual components below | Probably acceptable to split/crush |
| Darunavir/cobicistat (DRV/COBI; Prezcobix) |
No | No |
| Tenofovir alafenamide/emtricitabine (TAF/FTC; Descovy) |
No | No |
| Tenofovir disoproxil fumarate/ emtricitabine (TDF/FTC; Truvada) |
See individual components below | Acceptable to crush/dissolve |
| Zidovudine/lamivudine (ZDV/3TC; Combivir) |
See individual components below | Probably acceptable to split/crush |
| Individual Drugs | ||
| Abacavir (ABC; Ziagen) |
Oral solution (20 mg/mL) | No data |
| Atazanavir (ATV; Reyataz) |
Oral dispersible powder (50 mg/packet) | Can open capsule and sprinkle contents |
| Darunavir (DRV; Prezista) |
Oral suspension (100 mg/mL) | Probably acceptable to crush |
| Doravirine (DOR; Pifeltro) |
No | No data |
| Dolutegravir (DTG; Tivicay) |
No | Acceptable to crush |
| Efavirenz (EFV; Sustiva) |
No | No |
| Elvitegravir (EVG; Vitekta) |
No | No data |
| Emtricitabine (FTC; Emtriva) |
Oral solution (10 mg/mL) | Acceptable to open and dissolve in water |
| Lamivudine (3TC; Epivir) |
Oral solution (10 mg/mL) | Acceptable to crush or split |
| Raltegravir (RAL; Isentress) |
Chewable tablet (25 mg, 100 mg); oral powder for suspension (100 mg/packet); neither is bioequivalent to the 400 mg adult dose | Not recommended |
| Raltegravir HD (RAL HD; Isentress HD) |
No | No data, not recommended |
| Rilpivirine (RPV; Edurant) |
No | No data, not recommended |
| Ritonavir (RTV; Norvir) |
Oral solution (80 mg/mL) | No |
| Tenofovir alafenamide (TAF; Vemlidy) | No | Acceptable to crush |
| Tenofovir disoproxil fumarate (TDF; Viread) |
Oral powder mixed with soft food only (40 mg/1 g) | Acceptable to dissolve in water |
Pill size: Use images or real examples to give patients an idea of pill size before they fill the prescription. TAF/FTC/BIC and TAF/FTC/RPV are the smallest STR pills.
Pregnancy or conception planning: Individuals of childbearing potential should receive a pregnancy test and be assessed for use of contraception. When selecting an initial regimen for those who are not using effective contraception or who are contemplating pregnancy, clinicians should consult the DHHS guideline Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States.
All patients should be assessed for conception plans, which also provides an opportunity to discuss PrEP for partners without HIV (see the NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health). Additionally, all individuals with HIV should be informed that maintaining a plasma HIV RNA level <200 copies/mL with ART prevents sexual transmission of HIV to their partners (see the NYSDOH AI guidance U=U Guidance for Implementation in Clinical Settings).
Reference
Marzolini C, Back D, Weber R, et al. Ageing with HIV: medication use and risk for potential drug-drug interactions. J Antimicrob Chemother 2011;66(9):2107-2111. [PMID: 21680580]
Special Considerations for Comorbid Conditions
Reviewed and updated: Antonio E. Urbina, MD, with the Medical Care Criteria Committee; August 11, 2022
| Abbreviations used in this section: | |||
| Drug names: | Other: | ||
|
|
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Bone disease: TDF causes a decrease in bone mineral density in all patients after initiation of ART and should be used with caution in patients with preexisting severe osteoporosis [McComsey, et al. 2011; Stellbrink, et al. 2010; Perrot, et al. 2009]. Some experts recommend baseline bone densitometry screening for osteoporosis in postmenopausal women and in men and transgender women older than 50 years who have HIV [Aberg, et al. 2014]. The TAF formulation available currently in TAF/FTC, TAF/FTC/EVG/COBI, TAF/FTC/BIC, and TAF/FTC/RPV is an alternative, with lower markers of bone turnover in clinical trials [Bonora, et al. 2016; Pozniak, et al. 2016].
Cardiovascular risks: COBI- or RTV-containing regimens typically elevate lipids; TAF and certain INSTIs can cause greater weight gain than other ART regimens, with the potential for increased risk of metabolic complications [Łomiak, et al. 2021; Surial, et al. 2021; Bourgi, et al. 2020a; Bourgi, et al. 2020b; Calmy, et al. 2020; Lake, et al. 2020; Sax, et al. 2020; Venter, et al. 2020; Venter, et al. 2019]. TDF-containing regimens can have a beneficial effect on lipids [Souza, et al. 2013]. ABC has been associated with a higher risk of myocardial infarction in some studies [Marcus, et al. 2016; Choi, et al. 2011; Obel, et al. 2010; Sabin, et al. 2008; SMART/INSIGHT and D:A:D Study Groups 2008], whereas other studies have not confirmed this association [Ding, et al. 2012; Bedimo, et al. 2011; Ribaudo, et al. 2011; Brothers, et al. 2009]. Based on the available data, ABC should be used with caution in patients with multiple cardiac risk factors or known coronary heart disease; however, the absolute risk of myocardial infarction remains low, and no clear causality has been established. In the appropriate clinical circumstance, such as for a patient with impaired renal function, the use of ABC would be acceptable [Llibre and Hill 2016]. Clinicians should be made aware of the conflicting study data and share this information with patients.
Liver disease: In patients with existing liver disease of any etiology, dose adjustment of ARVs may be required depending on the severity of hepatic impairment (see Table 9: Recommended Dose Adjustments for Use of Selected Fixed-Dose Combination Antiretroviral Medications in Patients With Hepatic or Renal Impairment).
Mental health and substance use: Factors that may influence adherence should be addressed. There are also potential interactions between illicit (e.g., methamphetamine) and licit substances (e.g., methadone) and ARVs [Kumar, et al. 2015].
| KEY POINT |
|
Renal function: TDF can cause renal tubular dysfunction, such as acquired Fanconi syndrome [Zimmermann, et al. 2006; Karras, et al. 2003]. The risk of renal impairment has been shown to be elevated in patients with preexisting renal disease, longer treatment duration, low body weight, and when used in conjunction with RTV- or COBI-boosted regimens [Mocroft, et al. 2016; Gervasoni, et al. 2013]. In general, full-dose TDF should be used with caution in patients with baseline CrCl <70 mL/min and should be adjusted or changed to an alternative agent if CrCl decreases to <50 mL/min; TAF is a better choice in these patients. As noted above, TAF 25 mg/FTC should be used with caution in boosted regimens when CrCl is <50 mL/min.
Both ATV/RTV and LPV/RTV have also been independently associated with a greater decrease in renal function over time than NNRTI-based regimens [Quesada, et al. 2015; Goicoechea, et al. 2008]. COBI, and to a lesser extent DTG, can inhibit the excretion of creatinine, with expected elevations of creatinine at initiation of therapy. However, such increases are not clinically relevant and do not significantly affect glomerular filtration rate [Lepist, et al. 2014; Koteff, et al. 2013; German, et al. 2012].
Although DTG is highly bound to plasma proteins and is unlikely to be removed by dialysis, it has not been studied in this population [FDA 2013]; therefore, RAL or a boosted PI with renally adjusted 3TC and either ABC or once-weekly TDF are usually the regimens of choice in this population.
Additional information on prescribing agents for patients with reduced renal function is available in Table 9: Recommended Dose Adjustments for Use of Selected Fixed-Dose Combination Antiretroviral Medications in Patients With Hepatic or Renal Impairment.
Very high viral load (HIV RNA level >750,000 copies/mL): In some cases, experts will recommend use of both boosted DRV and DTG in addition to 2 NRTIs when a patient’s viral load is very high, with possible simplification once viral suppression is achieved. Numerous switch studies have demonstrated the safety of simplifying ARV regimens in virally suppressed individuals with no preexisting drug resistance [Cazanave, et al. 2015; Arribas, et al. 2014; Mills, et al. 2013; Fisher, et al. 2009]. Consultation with an experienced HIV care provider in these situations is helpful.
| KEY POINTS |
|
References
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Arribas JR, Pialoux G, Gathe J, et al. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial. Lancet Infect Dis 2014;14(7):581-589. [PMID: 24908551]
Bedimo RJ, Westfall AO, Drechsler H, et al. Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis 2011;53(1):84-91. [PMID: 21653308]
Bonora S, Calcagno A, Trentalange A, et al. Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults. Expert Opin Pharmacother 2016;17(3):409-419. [PMID: 26642079]
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Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment-naive persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis 2020b;70(7):1267-1274. [PMID: 31100116]
Brothers CH, Hernandez JE, Cutrell AG, et al. Risk of myocardial infarction and abacavir therapy: no increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. J Acquir Immune Defic Syndr 2009;51(1):20-28. [PMID: 19282778]
Calmy A, Tovar Sanchez T, Kouanfack C, et al. Dolutegravir-based and low-dose efavirenz-based regimen for the initial treatment of HIV-1 infection (NAMSAL): week 96 results from a two-group, multicentre, randomised, open label, phase 3 non-inferiority trial in Cameroon. Lancet HIV 2020;7(10):e677-e687. [PMID: 33010241]
Cazanave C, Reigadas S, Mazubert C, et al. Switch to rilpivirine/emtricitabine/tenofovir single-tablet regimen of human immunodeficiency virus-1 RNA-suppressed patients, Agence Nationale de Recherches sur le SIDA et les Hepatites Virales CO3 Aquitaine Cohort, 2012-2014. Open Forum Infect Dis 2015;2(1):ofv018. [PMID: 26034768]
Choi AI, Vittinghoff E, Deeks SG, et al. Cardiovascular risks associated with abacavir and tenofovir exposure in HIV-infected persons. Aids 2011;25(10):1289-1298. [PMID: 21516027]
Ding X, Andraca-Carrera E, Cooper C, et al. No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis. J Acquir Immune Defic Syndr 2012;61(4):441-447. [PMID: 22932321]
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Fisher M, Moyle GJ, Shahmanesh M, et al. A randomized comparative trial of continued zidovudine/lamivudine or replacement with tenofovir disoproxil fumarate/emtricitabine in efavirenz-treated HIV-1-infected individuals. J Acquir Immune Defic Syndr 2009;51(5):562-568. [PMID: 19561519]
German P, Liu HC, Szwarcberg J, et al. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J Acquir Immune Defic Syndr 2012;61(1):32-40. [PMID: 22732469]
Gervasoni C, Meraviglia P, Landonio S, et al. Low body weight in females is a risk factor for increased tenofovir exposure and drug-related adverse events. PLoS One 2013;8(12):e80242. [PMID: 24312465]
Goicoechea M, Liu S, Best B, et al. Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis 2008;197(1):102-108. [PMID: 18171292]
Karras A, Lafaurie M, Furco A, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis 2003;36(8):1070-1073. [PMID: 12684922]
Koteff J, Borland J, Chen S, et al. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. Br J Clin Pharmacol 2013;75(4):990-996. [PMID: 22905856]
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Sabin CA, Worm SW, Weber R, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: A multi-cohort collaboration. Lancet 2008;371(9622):1417-1426. [PMID: 18387667]
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Stellbrink HJ, Orkin C, Arribas JR, et al. Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis 2010;51(8):963-972. [PMID: 20828304]
Surial B, Mugglin C, Calmy A, et al. Weight and metabolic changes after switching from tenofovir disoproxil fumarate to tenofovir alafenamide in people living with HIV: A cohort study. Ann Intern Med 2021;174(6):758-767. [PMID: 33721521]
Venter WDF, Moorhouse M, Sokhela S, et al. Dolutegravir plus two different prodrugs of tenofovir to treat HIV. N Engl J Med 2019;381(9):803-815. [PMID: 31339677]
Venter WDF, Sokhela S, Simmons B, et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): Week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV 2020;7(10):e666-676. [PMID: 33010240]
Zimmermann AE, Pizzoferrato T, Bedford J, et al. Tenofovir-associated acute and chronic kidney disease: A case of multiple drug interactions. Clin Infect Dis 2006;42(2):283-290. [PMID: 16355343]
ART-Initiation Laboratory Testing
Reviewed and updated: Antonio E. Urbina, MD, with the Medical Care Criteria Committee; August 11, 2022
| Abbreviations used in this section: | |||
| Drug names: | Other: | ||
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|
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Baseline CD4 cell count: Some regimens should not be used when the CD4 count is <200 cells/mm3 because of an increased risk of treatment failure (see Table 8, below). When Pneumocystis jiroveci pneumonia prophylaxis is indicated, it may be prudent to defer ART for 7 to 10 days if 2 medications that may cause rash will be started, such as TMP-SMX and EFV.
Baseline HIV genotypic resistance profile: Genotypic resistance testing that includes the protease, reverse transcriptase, and integrase genes should be obtained at diagnosis (or initial visit if not done previously), but ART initiation should not be delayed pending the results [Kuritzkes, et al. 2008; Borroto-Esoda, et al. 2007].
Transmitted integrase resistance was identified in 0.7% of genotypic resistance tests obtained within 3 months of HIV diagnosis from 2013 to2017 in New York State [Wang, et al. 2019]. Similarly, 0.8% of baseline genotypic resistance tests across 23 U.S. jurisdictions of the CDC reported INSTI resistance, which had a higher prevalence (1.6%) in metropolitan areas (population 50,000 to 500,000) [McClung, et al. 2019]. Although INSTI resistance overall remains rare, most experts believe that transmission of INSTI resistance will increase over time, given that this class of ARV has become the preferred therapy for ART initiation (including rapid ART initiation) in all major guidelines.
Consultation with a care provider experienced in ART management is warranted when patients have baseline resistance that requires treatment with a regimen other than the listed preferred or alternative regimens. If treatment is indicated before genotypic resistance testing results are available, NNRTI-based regimens should be avoided because of the higher prevalence of transmitted resistance in NNRTIs than in PIs or INSTIs [Panichsillapakit, et al. 2016; Rhee, et al. 2015; Stekler, et al. 2015]. In the case of, for example, a patient with symptomatic acute HIV or advanced HIV with an opportunistic infection, some experts would include a second-generation INSTI (DTG or BIC or boosted DRV, or both together) with the NRTI backbone, given the possibility of transmitted NRTI resistance, with possible simplification once genotypic information is available.
Baseline viral load: Some regimens should not be used when the HIV RNA level is ≥100,000 copies/mL (see Table 8, below, and comments in the tables of preferred and alternative ART regimens).
Coinfections: Patients should be assessed for chronic HBV, HCV coinfection, and TB. The ART regimen for individuals with chronic HBV should treat both HIV and HBV when possible (see the NYSDOH AI guideline Prevention and Management of Hepatitis B Virus Infection in Adults With HIV). For those planning concurrent HCV treatment or treatment for active TB, drug-drug interactions will play an important role in the selection of a regimen. The University of Liverpool HEP Drug Interactions Checker is a useful resource for identifying drug-drug interactions.
Creatinine clearance level: Some ARVs are contraindicated below a given CrCl level, and some may need adjustments that require the use of individual elements of an FDC or STR rather than the single-tablet version of the drug (see Table 9: Recommended Dose Adjustments for Use of Selected Fixed-Dose Combination Antiretroviral Medications in Patients With Hepatic or Renal Impairment for more information).
Hepatic profile: Some ARVs require dose adjustment in the presence of impaired liver function; patients with abnormal liver enzyme levels or evidence of decreased synthetic function should be assessed for underlying liver disease (see the guideline section Special Considerations for Comorbid Conditions and Table 9: Recommended Dose Adjustments for Use of Selected Fixed-Dose Combination Antiretroviral Medications in Patients With Hepatic or Renal Impairment).
| KEY POINTS |
|
HLA-B*5701 testing: To avoid potentially serious or life-threatening hypersensitivity reactions, HLA-B*5701 testing is mandatory before initiating ART that includes ABC [Mallal, et al. 2008; Saag, et al. 2008].
Initiation of the regimens listed in Table 8, below, is contraindicated based on the listed baseline laboratory parameters.
| Table 8: ART Regimens That Are Not Recommended Based on Routine Baseline Laboratory Parameters [a] | |
| Laboratory Parameter | ART Regimens That Are Not Recommended |
| HIV RNA level ≥100,000 copies/mL |
|
| CD4 count <200 cells/mm3 |
|
| CrCl <50 mL/min |
|
| CrCl <30 mL/min |
|
|
Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ATV, atazanavir; BIC, bictegravir; COBI, cobicistat; CrCl, creatinine clearance; DOR, doravirine; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; FTC, emtricitabine; RAL, raltegravir; RPV, rilpivirine; RTV, ritonavir; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate. Notes:
|
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References
Borroto-Esoda K, Waters JM, Bae AS, et al. Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz. AIDS Res Hum Retroviruses 2007;23(8):988-995. [PMID: 17725415]
Kuritzkes DR, Lalama CM, Ribaudo HJ, et al. Preexisting resistance to nonnucleoside reverse-transcriptase inhibitors predicts virologic failure of an efavirenz-based regimen in treatment-naive HIV-1-infected subjects. J Infect Dis 2008;197(6):867-870. [PMID: 18269317]
Mallal S, Phillips E, Carosi G, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008;358(6):568-579. [PMID: 18256392]
McClung RP, Ocfemia CB, Saduvala N, et al. Integrase and other transmitted HIV drug resistance: 23 US jurisdictions, 2013-2016. CROI; 2019 Mar 4-7; Seattle, WA. http://www.croiconference.org/sessions/integrase-and-other-transmitted-hiv-drug-resistance-23-us-jurisdictions-2013-2016
Panichsillapakit T, Smith DM, Wertheim JO, et al. Prevalence of transmitted HIV drug resistance among recently infected persons in San Diego, CA 1996-2013. J Acquir Immune Defic Syndr 2016;71(2):228-236. [PMID: 26413846]
Rhee SY, Blanco JL, Jordan MR, et al. Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: An individual-patient- and sequence-level meta-analysis. PLoS Med 2015;12(4):e1001810. [PMID: 25849352]
Saag M, Balu R, Phillips E, et al. High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clin Infect Dis 2008;46(7):1111-1118. [PMID: 18444831]
Stekler JD, McKernan J, Milne R, et al. Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. Antivir Ther 2015;20(1):77-80. [PMID: 24831260]
Wang Z, Collura RV, Rosenthal M, et al. Integrase genotypic testing and drug resistance among new HIV diagnoses in New York. CROI; 2019 Mar 4-7; Seattle, WA. http://www.croiconference.org/sessions/integrase-genotypic-testing-and-drug-resistance-among-new-hiv-diagnoses-new-york
ARV Dose Adjustments for Hepatic or Renal Impairment
Recommended Dose Adjustments for Use of Selected Fixed-Dose Combination Antiretroviral Medications in Patients With Hepatic or Renal Impairment
Lead authors: Nicole Bradley PharmD, BCPS, BCIDP; Yuman Lee, PharmD, BCIDP, AAHIVP; John M. Conry, PharmD, AAHIVP, FNAP; with the Medical Care Criteria Committee; May 2020
DRUG MANUFACTURER PACKAGE INSERTS
Atripla: FDA. Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate) tablets for oral use. 2006. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021937s037lbl.pdf [accessed 2020 Mar 5].
Biktarvy: FDA. Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide) tablets, for oral use. 2018 Feb. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210251s000lbl.pdf [accessed 2020 Mar 5].
Complera: FDA. Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate) tablets, for oral use. 2013 Jan. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202123s003lbl.pdf [accessed 2020 May 14].
Descovy: FDA. Descovy (emtricitabine and tenofovir alafenamide) tablets, for oral use. 2016 Apr. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208215s000lbl.pdf [accessed 2020 Mar 5].
Delstrigo: FDA. Delstrigo (doravirine, lamivudine, and tenofovir disoproxil fumarate) tablets, for oral use. 2018 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210807s000lbl.pdf [accessed 2020 Mar 5].
Dovato: FDA. Dovato (dolutegravir and lamivudine) tablets, for oral use. 2019 Apr. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211994s000lbl.pdf [accessed 2020 Mar 5].
Epzicom: FDA. Epzicom (abacavir sulfate and lamivudine) tablets for oral use. 2012 Mar. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021652s015lbl.pdf [accessed 2020 Mar 5].
Evotaz: FDA. Evotaz (atazanavir and cobicistat) tablets, for oral use. 2015 Jan. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206353s000lbl.pdf [accessed 2020 May 14].
Genvoya: FDA. Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) tablets, for oral use. 2015 Nov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207561s000lbl.pdf [accessed 2020 Mar 5].
Isentress: FDA. Isentress (raltegravir) tablets for oral use. 2013 June. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022145s029lbl.pdf [accessed 2020 May 14].
Juluca: FDA. Juluca (dolutegravir and rilpivirine) tablets, for oral use. 2017 Nov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210192s000lbl.pdf [accessed 2020 Mar 5].
Odefsey: FDA. Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) tablets, for oral use. 2016 Mar. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208351s000lbl.pdf [accessed 2020 Mar 5].
Reyataz: FDA. Reyataz (atazanavir) capsules, for oral use. 2016 Sept. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021567s039,206352s004lbl.pdf [accessed 2020 May 14].
Stribild: FDA. Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate) tablets, for oral use. 2016 Sep. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/203100s024lbl.pdf [accessed 2020 Mar 5].
Symfi Lo: FDA. Symfi lo (efavirenz, lamivudine, and tenofovir disoproxil fumarate) tablets, for oral use. 2018 Feb. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208255s000lbl.pdf [accessed 2020 Mar 5].
Symtuza: FDA. Symtuza (darunavir, cobicistat, emtricitabine, and tenofovir alafenamide) tablets, for oral use. 2018 Jul. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210455s000lbl.pdf [accessed 2020 Mar 5].
Triumeq: FDA. Triumeq (abacavir, dolutegravir, and lamivudine) tablets, for oral use. 2017 Nov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205551s011lbl.pdf [accessed 2020 Mar 5].
Truvada: FDA. Truvada (emtricitabine/tenofovir disoproxil fumarate) tablets, for oral use. 2004. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021752s047lbl.pdf [accessed 2020 Mar 5].
Tivicay: FDA. Tivicay (dolutegravir) tablets, for oral use. 2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf [accessed 2020 Apr 13].
References
DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. 2021 Aug 16. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines [accessed 2018 May 1]
Eron JJ, Lelievre JD, Kalayjian R, et al. Safety of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in HIV-1-infected adults with end-stage renal disease on chronic haemodialysis: an open-label, single-arm, multicentre, phase 3b trial. Lancet HIV 2018;6(1):e15-24. [PMID: 30555051]
Fischetti B, Shah K, Taft DR, et al. Real-world experience with higher-than-recommended doses of lamivudine in patients with varying degrees of renal impairment. Open Forum Infect Dis 2018;5(10):ofy225. [PMID: 30302352]
German P, Wei X, Mizuno V, et al. Pharmacokinetics of elvitegravir and cobicistat in subjects with severe renal impairment. 13th International Workshop on Clinical Pharmacology of HIV Therapy; 2012 Apr 16-18; Barcelona, Spain. http://www.natap.org/2012/pharm/Pharm_29.htm
Michienzi SM, Schriever CA, Badowski ME. Abacavir/lamivudine/dolutegravir single tablet regimen in patients with human immunodeficiency virus and end-stage renal disease on hemodialysis. Int J STD AIDS 2019;30(2):181-187. [PMID: 30381029]
Zhang H, Shao Y, Garner W, et al. The effect of hepatic or renal impairment on bictegravir pharmacokinetics. 18th International Workshop on Clinical Pharmacology of Antiviral Therapy; 2017 Jun 14-17; Chicago, IL. http://www.natap.org/2017/Pharm/Pharm_31.htm
All Recommendations
Reviewed and updated: Antonio E. Urbina, MD, with the Medical Care Criteria Committee; August 11, 2022
| ALL RECOMMENDATIONS: SELECTING AN INITIAL ART REGIMEN |
Regimen Selection
Expert Consultation
Follow-up
——— Note:
|
Guideline Information and Updates
| Guideline Information | |
| Intended users |
Clinicians in New York State who are initiating therapy in nonpregnant, antiretroviral therapy-naive adults with HIV |
| Last reviewed and updated |
August 11, 2022 |
| Lead author |
Antonio E. Urbina, MD |
| Original publication |
January 2017 |
| Writing group |
Joseph P. McGowan, MD, FACP, FIDSA; Steven M. Fine, MD, PhD; Rona Vail, MD; Samuel T. Merrick, MD; Asa Radix, MD, MPH, PhD; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD |
| 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. |
|
June 16, 2022 |
MCCC: Added statement regarding the use of CAB/RPV LA as initial ART. |
|
October 8, 2021 |
Antonio E. Urbina, MD, with the MCCC:
|
|
January 2019 |
MCCC: Boosted TDF-containing regimens no longer recommended: The MCCC no longer recommends initial ART regimens that include TDF boosted with either COBI or RTV. Studies have shown that TDF-related renal toxicity is more common when using TDF in a regimen containing COBI or RTV; therefore, the MCCC does not recommend TDF use with boosted regimens when initiating ART. Boosted TDF regimens have been deleted from tables throughout the guideline.
General Principles in Choosing an Initial ART Regimen: Added new citation: In 2 separate trials of treatment-naive individuals, TDF/3TC/DOR was non-inferior to TDF/FTC/EFV, or RTV-boosted DRV with either TDF/FTC or ABC/3TC [Molina, et al. 2018; Orkin, et al. 2018]. Specific Factors to Consider and Discuss with Patients: Added to Table 6: Selected Drug-Drug Interactions to Discuss before Initiating ART in Treatment-Naive Patients: If [Metformin is] used concomitantly, total daily dose of metformin should not exceed 1,000 mg without clinical evaluation of efficacy and adverse events. ART-Initiation Laboratory Testing:
|
|
June 2018 |
MCCC:
General Principles in Choosing an Initial ART Regimen: Added new citations of evidence to general conclusions that can be drawn based on currently available evidence:
|
|
May 2018 |
MCCC: Available ART Regimens:
|
|
November 2017 |
MCCC: Available ART Regimens:
|
| Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program | |
| Developer | New York State Department of Health AIDS Institute (NYSDOH AI) Clinical Guidelines Program |
| Funding Source | NYSDOH AI |
| Program Manager |
Clinical Guidelines Program, Johns Hopkins University School of Medicine, Division of Infectious Diseases. See Program Leadership and Staff. |
| Mission | To produce and disseminate evidence-based, state-of-the-art clinical practice guidelines that establish uniform standards of care for practitioners who provide prevention or treatment of HIV, viral hepatitis, other sexually transmitted infections, and substance use disorders for adults throughout New York State in the wide array of settings in which those services are delivered. |
| Expert Committees |
The NYSDOH AI Medical Director invites and appoints committees of clinical and public health experts from throughout NYS to ensure that the guidelines are practical, immediately applicable, and meet the needs of care providers and stakeholders in all major regions of NYS, all relevant clinical practice settings, key NYS agencies, and community service organizations. |
| Committee Structure |
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| Conflicts of Interest Disclosure and Management |
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| Evidence Collection and Review |
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| Recommendation Development |
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| Review and Approval Process |
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| External Reviewers |
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| Update Process |
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| Recommendation Ratings Scheme | |||
| Strength | Quality of Evidence | ||
| Rating | Definition | Rating | Definition |
| A | Strong | 1 | Based on published results of at least 1 randomized clinical trial with clinical outcomes or validated laboratory endpoints. |
| B | Moderate | * | Based on either a self-evident conclusion; conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial. |
| C | Optional | 2 | Based on published results of at least 1 well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes. |
| 2† | Extrapolated from published results of well-designed studies (including nonrandomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline. | ||
| 3 | Based on committee expert opinion, with rationale provided in the guideline text. | ||