Laboratory Monitoring for Adverse Effects of ART

Laboratory Monitoring for Adverse Effects of ART

Purpose of This Guideline

Reviewed and updated: Noga Shalev, MD, lead author; June 2021
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
CommitteeMedical Care Criteria Committee
Date of original publication: September 2019

This guideline was developed by the New York State Department of Health (NYSDOH) AIDS Institute (AI) to establish an evidence-based approach to routine laboratory monitoring of antiretroviral toxicity. Data are lacking regarding the need for and frequency of routine laboratory monitoring in patients receiving antiretroviral therapy (ART). To date, no randomized controlled studies have assessed the optimal type and frequency of monitoring. The data available are based on short-term randomized clinical trials of ART strategies, observational cohort data, and long-term epidemiologic data.

Refer to the NYSDOH AI guideline Comprehensive Primary Care for Adults With HIV for information on other routine laboratory monitoring for patients with HIV.

Frequency of Laboratory Monitoring During ART

Reviewed and updated: Noga Shalev, MD, lead author, with the Medical Care Criteria Committee; June 2021

RECOMMENDATIONS
Frequency of Laboratory Monitoring During ART

This guideline summarizes the recommended minimum frequency of routine laboratory monitoring in healthy patients receiving antiretroviral therapy (ART). Patients with comorbidities, or who take or start additional medications, or who have baseline laboratory abnormalities may require more frequent or additional evaluation. Patients with HIV should also be monitored for relevant age- and sex-specific health problems as per recommendations for the general population [Aberg, et al. 2014] (see the NYSDOH AI guideline Comprehensive Primary Care for Adults With HIV). NYSDOH AI recommendations apply to resource-rich settings; World Health Organization guidelines do not require access to laboratory monitoring as a condition for initiation or continuation of ART [WHO 2016].

This Committee’s recommendations diverge from those of other published guidelines in that they suggest less frequent monitoring for ART-related adverse effects [Sax 2018; Clinical Info HIV.gov 2019]. The reduced frequency of testing reflects the notably reduced toxicities associated with contemporary antiretroviral regimens, earlier initiation of ART, and the absence of data to support more frequent testing. This guideline also suggests less frequent monitoring after the first year of ART or at regimen change, based on the observation that most laboratory-detected toxicities occur in the first year of therapy [Gudina, et al. 2017].

The third section of this guideline, which addresses Screening for Organ-Specific Adverse Effects, discusses the range of adverse effects and toxicities associated with ART. Patients rarely present with symptoms suggestive of antiretroviral toxicity; frequent laboratory monitoring may be needed in such cases.

Table 1: Minimum Laboratory Monitoring Frequency With Initiation of or Change in Antiretroviral Therapy for Patients <50 Years Old and Without Chronic Comorbidities [a] (Rating: A3)
Download PDF
Laboratory Test Year 1 of ART (initiation or change) After 1 Year on ART Regimen
Baseline 3 Months 12 Months Every 6 Months Annual
Hepatic panel (AST, ALT, alkaline phosphates, total bilirubin) All All All All
Random blood glucose All All All
Complete blood count [b] All With ZDV With ZDV With ZDV With TAF
or TDF
eGFR [c] All All With TAF
or TDF
With TAF
or TDF
Test for proteinuria (urinalysis or protein-to-creatinine ratio), glucosuria, serum phosphorus

With TAF
or TDF

With TAF
or TDF
With TAF
or TDF

Abbreviations: ALT, alanine aminotransferase; ART, antiretroviral therapy; AST, aspartate aminotransferase; eGFR, estimated glomerular filtration rate; TAF, tenofovir alafenamide fumarate; TDF, tenofovir disoproxil fumarate; ZDV, zidovudine.

Notes:

  1. More frequent monitoring may be required for patients >50 years old and patients with chronic comorbidities.
  2. See the NYSDOH AI guideline Comprehensive Primary Care for Adults With HIV.
  3. Patients with decreased eGFR at baseline or those taking concomitant nephrotoxic drugs may need more frequent monitoring of renal function. See the section on Screening for Organ-Specific Adverse Events > Nephrotoxicity for more information.
References

Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis 2014;58(1):e1-34. [PMID: 24235263

Clinical Info HIV.gov. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV: Laboratory testing for initial assessment and monitoring of patients with HIV receiving antiretroviral therapy. 2019 Dec 18. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/tests-initial-assessment-and-follow [accessed 2018 Sep 18]

Gudina EK, Teklu AM, Berhan A, et al. Magnitude of antiretroviral drug toxicity in adult HIV patients in Ethiopia: A cohort study at seven teaching hospitals. Ethiop J Health Sci 2017;27(Suppl 1):39-52. [PMID: 28465652

Sax PE. Patient monitoring during HIV antiretroviral therapy. 2018 May 7. https://www.uptodate.com/contents/patient-monitoring-during-hiv-antiretroviral-therapy [accessed 2018 Sep 18]

WHO. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach. 2nd edition. 2016 Jun. http://www.who.int/hiv/pub/arv/arv-2016/en/ [accessed 2018 Sep 18]

Screening for Organ-Specific Adverse Effects

Reviewed and updated: Noga Shalev, MD, lead author, with the Medical Care Criteria Committee; June 2021

Nephrotoxicity

Antiretroviral therapy (ART) has been associated with a range of renal complications that may lead to renal insufficiency or failure [Hall, et al. 2011]. Furthermore, renal impairment requires dose adjustment or discontinuation of several antiretroviral agents (ARVs). Various guidelines recommend screening for ART-induced nephrotoxicity [Gorriz, et al. 2014; Holt, et al. 2014; Lucas, et al. 2014; Clinical Info HIV.gov 2021]. Data to support screening strategies and frequency are most robust for the detection of ART-associated kidney dysfunction than other organ-specific toxicities. Nevertheless, many recommendations continue to rely on expert opinion and consensus. Patients with reduced baseline renal function and those taking concomitant nephrotoxic medications may require more frequent renal monitoring, as clinically indicated.

A number of ARVs have been implicated in kidney dysfunction. However, only medications that contain tenofovir prodrugs are considered directly nephrotoxic to the renal tubules and glomeruli. Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) are both prodrugs of tenofovir and are widely used components of antiretroviral regimens in the United States. Because various forms of renal impairment have been reported in patients receiving tenofovir prodrugs [Laprise, et al. 2013; Zaidan, et al. 2013], specific recommendations regarding frequency of laboratory monitoring for regimens that include these agents have been made in Table 1: Minimum Laboratory Monitoring Frequency With Initiation of or Change in Antiretroviral Therapy for Patients <50 Years Old and Without Chronic Comorbidities.

Plasma concentrations of tenofovir are approximately 4-fold lower with use of TAF than with TDF, and while nephrotoxicity due to TAF is rare, cases of acute renal failure, proximal renal tubulopathy, and Fanconi Syndrome have been reported in clinical use. Therefore, Table 1 provides recommendations for frequency of monitoring of renal function in patients taking tenofovir prodrugs (TDF and TAF) that does not distinguish formulation used.

Either of the MDRD or CKD-EPI equations can be used to measure estimated glomerular filtration rates (GFRs, see the National Institute of Diabetes and Digestive and Kidney Diseases Health Information Center Glomerular Filtration Rate Calculators). Using the same method of estimation over time is recommended. Certain ARVs have been associated with decreased glomerular secretion of creatinine, leading to a small rise in serum creatinine levels without concomitant decline in GFR. These agents include rilpivirine, dolutegravir, bictegravir, and the pharmaco-enhancer cobicistat. A recent consensus statement from Australia recommends that serum creatinine levels be checked 1 month after initiation of these agents to establish a new “baseline” measurement [Holt, et al. 2014]. However, no data suggest this approach alters clinical management. Estimation of GFR with a serum cystatin C measurement may provide a more accurate assessment in patients taking agents that affect creatinine secretion and is increasingly utilized in clinical practice [Galizzi, et al. 2018; Yukawa, et al. 2018].

Finally, a number of protease inhibitors (PIs), including indinavir and atazanavir, have been shown to cause crystal-induced nephropathy.

KEY POINT
  • Testing of serum creatinine levels 1 month after initiation of cobicistat, bictegravir, dolutegravir, and rilpivirine establishes a new “baseline.” These drugs are associated with decreased secretion of creatinine, leading to higher serum creatinine levels without a concomitant decline in GFR.

Hepatotoxicity

Most ARVs have the potential to cause idiopathic abnormalities in liver function, especially in patients with preexisting liver disease. As a class, non-nucleoside reverse transcriptase inhibitors (NNRTIs) show the highest rates of hepatotoxicity, most notably with the first-generation NNRTI nevirapine and, to a lesser extent, efavirenz. Because drug-induced hepatotoxicity of any kind generally occurs within the first 6 to 12 weeks of treatment, there is no recommended distinction in terms of frequency of monitoring based on the ART regimen.

Dyslipidemia, Insulin Resistance, and Diabetes Mellitus

ART has been associated with weight gain, dyslipidemia, metabolic syndrome, insulin resistance, and new-onset diabetes mellitus. A range of untoward lipid effects has been observed with a variety of ARVs, including PIs, NNRTIs, and certain nucleoside reverse transcriptase inhibitors (NRTIs). In general, such changes are small and do not result in pharmacologic changes to lipid management. The traditional risk factors for metabolic disorders—such as age, weight, and diet—are stronger risk factors for metabolic disease than ART toxicity. Nevertheless, in several studies, patients with HIV had a higher rate of cardiovascular disease than controls without HIV [Currier, et al. 2003; Freiberg, et al. 2013] (see 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease). The use of certain ritonavir-boosted PIs has been associated with an increased risk of myocardial infarction in long-term observational studies [Friis-Moller, et al. 2007; Ryom, et al. 2018].

Table 1: Minimum Laboratory Monitoring Frequency With Initiation of or Change in Antiretroviral Therapy for Patients <50 Years Old and Without Chronic Comorbidities does not provide specific recommendations for lipid profile testing in patients on ART. In most patients, screening should follow recommendations for the general population [Goff, et al. 2014; Siu 2015]. However, clinicians may opt to perform more frequent lipid testing in patients with underlying cardiovascular comorbidities and those taking a PI-based therapy.

Cytopenias

Bone marrow suppression as a consequence of ART is rare and most often associated with the use of zidovudine. The most common cytopenia caused by zidovudine is a macrocytic anemia. In resource-rich settings, early treatment and newer regimens have made cytopenias an extremely rare complication of ART. Only patients receiving zidovudine as part of their antiretroviral regimen require monitoring of blood counts.

Pancreatitis and Lactic Acidosis

In the early era of ART, the NRTIs stavudine and didanosine were associated with a significantly increased risk of both pancreatitis and lactic acidosis. However, pancreatitis and lactic acidosis are exceedingly rare complications with current ART regimens. Therefore, routine laboratory monitoring of serum lipase and lactic acid to detect these abnormalities is not recommended with contemporary ART regimens.

References

Clinical Info HIV.gov. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. 2021 Jun 3. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines [accessed 2018 Sep 18]

Currier JS, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr 2003;33(4):506-512. [PMID: 12869840

Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med 2013;173(8):614-622. [PMID: 23459863

Friis-Moller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007;356(17):1723-1735. [PMID: 17460226

Galizzi N, Galli L, Poli A, et al. Glomerular filtration rate estimated by cystatin C formulas in HIV-1 patients treated with dolutegravir, rilpivirine or cobicistat. New Microbiol 2018;41(4):256-261. [PMID: 30252923

Goff DC, Jr., Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;129(25 Suppl 2):S49-73. [PMID: 24222018]

Gorriz JL, Gutierrez F, Trullas JC, et al. Consensus document on the management of renal disease in HIV-infected patients. Nefrologia 2014;34 Suppl 2:1-81. [PMID: 25467377

Hall AM, Hendry BM, Nitsch D, et al. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis 2011;57(5):773-780. [PMID: 21435764

Holt SG, Gracey DM, Levy MT, et al. A consensus statement on the renal monitoring of Australian patients receiving tenofovir based antiviral therapy for HIV/HBV infection. AIDS Res Ther 2014;11:35. [PMID: 25745499

Laprise C, Baril JG, Dufresne S, et al. Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positive patients: results from 10 years of follow-up. Clin Infect Dis 2013;56(4):567-575. [PMID: 23143096

Lucas GM, Ross MJ, Stock PG, et al. Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2014;59(9):e96-138. [PMID: 25234519

Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV 2018;5(6):e291-e300. [PMID: 29731407

Siu AL. Screening for abnormal blood glucose and type 2 diabetes mellitus: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2015;163(11):861-868. [PMID: 26501513

Yukawa S, Watanabe D, Uehira T, et al. Clinical benefits of using inulin clearance and cystatin C for determining glomerular filtration rate in HIV-1-infected individuals treated with dolutegravir. J Infect Chemother 2018;24(3):199-205. [PMID: 29150412

Zaidan M, Lescure FX, Brocheriou I, et al. Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: a clinico-pathological study. Clin J Am Soc Nephrol 2013;8(6):930-938. [PMID: 23430209

All Recommendations

Reviewed and updated: Noga Shalev, MD, lead author, with the Medical Care Criteria Committee; June 2021

ALL RECOMMENDATIONS: LABORATORY MONITORING FOR ADVERSE EFFECTS OF ART
Frequency of Laboratory Monitoring During ART

How This Guideline Was Developed

June 2021

This guideline was developed by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI) Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.

Established in 1986, the goal of the Clinical Guidelines Program is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people with HIV, hepatitis C virus, or sexually transmitted infections; people with substance use issues; and members of the LGBTQ community. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.

Medical Care Criteria Committee (MCCC) for adult HIV care guidelines: The NYSDOH AI charged the MCCC (adult HIV and related guidelines) with developing evidence-based recommendations for clinicians in NYS who provide care to individuals with HIV. The purpose of the Laboratory Monitoring for Adverse Effects of ART clinical practice guideline is to establish an evidence-based approach to routine laboratory monitoring for adverse effects of antiretroviral toxicity.

Committee makeup: Members of the MCCC (see Box A1: MCCC Leaders and Members, below) were appointed by the NYSDOH AI to ensure representation of clinical practice in all major regions of the state, relevant medical disciplines and subspecialties, key NYS agencies, community stakeholders, and patient advocates. Individuals confirmed as MCCC members are required to disclose any potential conflicts of interest; disclosures are reviewed and approved by the NYSDOH AI Office of the Medical Director (see Funding and Disclosure of Potential Conflicts of Interest, below).

Committee role: Committee members actively participate in guideline development, including evidence review, drafting of recommendations and text, manuscript review, consensus approval of all recommendations, and rating of recommendations.

Committee leadership: Working with the lead author, the MCCC Writing Group reviewed and refined the manuscript, facilitated consensus approval of all recommendations, and addressed feedback from the Committee at large.

Johns Hopkins University (JHU) Editorial Role: The JHU editorial team coordinated, guided, and documented all Committee activities and edited the guideline material for clarity, flow, and style.

MCCC Writing Group (all Committee members and reviewers are listed in Box A1, below)

  • Joseph P. McGowan, MD, FACP, FIDSA, Chair
  • Steven Fine, MD, PhD, Co-Vice-Chair (effective January 2021)
  • Rona Vail, MD, Co-Vice-Chair (effective January 2021)
  • Samuel T. Merrick, MD, Chair Emeritus
  • Charles J. Gonzalez, MD, AI Medical Director
  • Asa Radix, MD, MPH, FACP, AAHIVS
  • Christopher J. Hoffmann, MD, MPH, Director, JHU-NYSDOH Guidelines Program

AIDS Institute and JHU Editorial and Program Management Team

  • Laura Duggan Russell, MPH, AI Guidelines Program Manager
  • Mary Beth Hansen, MA, JHU Guidelines Project Director
  • Johanna Gribble, MA, JHU Medical Editor
  • Jen Ham, MPH, JHU Medical Editor
  • Rachel Lastra, JHU Medical Editor
  • Jesse Ciekot, JHU Program Coordinator
Box A1: MCCC Leaders and Members (when this guideline was developed)
Unless noted otherwise, Committee members had no disclosures of financial relationships with commercial entities
Leadership
  • Chair (effective March 2018)Joseph P. McGowan, MD, FACP, FIDSA, North Shore University Hospital, Manhasset, NY
  • Co-Vice-Chair (Vice-Chair effective March 2018; Co-Vice-Chair effective January 2021)Steven M. Fine, MD, PhD, University of Rochester Medical Center, Rochester, NY
  • Co-Vice-Chair (effective January 2021): Rona M. Vail, MD, Callen-Lorde Community Health Center, New York, NY
  • Chair Emeritus (effective March 2018)Samuel T. Merrick, MD, New York-Presbyterian-Weill Cornell, New York, NY
  • Medical Director: Charles J. Gonzalez, MD, New York State Department of Health AIDS Institute, New York, NY (May 2018)
  • Clinical Advisor to the AIDS Institute (effective June 2021)Lyn Stevens, MS, NP, ACRN, New York State Department of Health AIDS Institute, Albany, NY
  • Director, JHU-NYSDOH AI Guidelines Program: Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, MD
Contributing Members
  • Jessica M. Atrio, MD, MSc, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
  • Oni J. Blackstock, MD, MHS, Health Justice, New York, NY
  • James C. M. Brust, MD, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
  • Ethan A. Cowan, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY
  • Elliot DeHaan, MD, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
  • Mary E. Dyer, MD, Hudson River Healthcare, Monticello, NY
  • John J. Faragon, PHARMD, BCPS, AAHIVP, Albany Medical Center, Albany, New York
  • Shauna H. Gunaratne, MD, MPH, Columbia University Medical Center, New York, NY
  • Bruce E. Hirsch, MD, FACP, FIDSA, AAHIVS, North Shore University Hospital, Manhasset, NY
  • Christine A. Kerr, MD, Galileo Health
  • Jeremy D. Kidd, MD, MPH, New York-Presbyterian Hospital, Columbia University, New York, NY
  • Hector I. Ojeda-Martinez, MD, Nuvance Health/Health Quest Medical Practice, Poughkeepsie, NY
  • Asa E. Radix, MD, MPH, FACP, AAHIVS, Callen-Lorde Community Health Center, New York, NY
  • Sanjiv S. Shah, MD, MPH, AAHIVM, AAHIVS, NYC Health + Hospitals/Gotham Health, Gouverneur, New York, NY
  • Noga Shalev, MD, Columbia University Medical Center, New York, NY
  • Eugenia L. Siegler, MD, Weill Cornell Medical College, New York, NY
  • Maria Teresa (Tess) Timoney, MS, RN, CNM, Bronx Prevention Center, ICAP at Columbia, Bronx, NY
  • Benjamin W. Tsoi, MD, MPH, Bureau of HIV/AIDS Prevention and Control, New York City Department of Health and Mental Hygiene, New York, NY
  • Marguerite A. Urban, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY
  • Antonio E. Urbina, MD, The Mount Sinai Hospital, Comprehensive Health Program–Downtown, New York, NY
    • Scientific Advisor: Gilead, ViiV, Merck
  • Geoffrey A. Weinberg, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY

Funding and disclosure of potential conflicts of interest (COIs): NYS funds supported the development of this guideline through a grant awarded to the JHU School of Medicine, Division of Infectious Diseases, from the NYSDOH AI.

All active MCCC members, invited consultants and coauthors, peer reviewers, and program staff are required to disclose financial relationships with commercial entities, including gifts that may be actual conflicts of interest or may be perceived as conflicts. These individuals must disclose financial relationships annually, for themselves, their partners/spouses, and their organization/institution. On their annual disclosures, MCCC members are asked to report for the previous 12 months and the upcoming 12 months. 

All reported financial relationships with commercial entities are reviewed by the NYSDOH AI guidelines program to assess the potential for undue influence on guideline recommendations made by the Committee.

All guideline recommendations received consensus approval of the full MCCC, and the final review and approval of the recommendations were performed by the Committee Chair and the NYSDOH AI Medical Director and Deputy Medical Director, none of whom reported conflicts of interest.

Evidence collection and review: The NYSDOH AI guideline development process is based on a strategic search and analysis of the published evidence. Box A2 illustrates the evidence review and selection process.

Box A2: Evidence Collection and Review Processes
  • NYSDOH AI and MCCC defined the goal of the guideline: To inform NYS clinicians about evidence-based clinical recommendations to guide practitioners in laboratory monitoring for adverse effects of antiretroviral therapy (ART).
  • MCCC appointed a lead author who conducted a systematic literature search in PubMed using MeSH terms; all searches were limited to studies that 1) were published within the previous 5 years; 2) involved only human subjects; and 3) were published in English.
  • Lead authors reviewed studies identified through searches and excluded based on the following criteria: Publication type, study design, participants, and clinical relevance to the guideline.
  • Author and editorial staff conducted additional searches using PubMed and online databases to identify:
    • Studies published prior to the 5-year search limit.
    • Studies published during the guideline development process.
    • Recent conference abstracts.
    • Older studies known to provide strong evidence in support of specific recommendations or to undergird expert opinion.
  • Lead authors developed and the Writing Group and then all MCCC members reviewed and approved evidence-based guideline recommendations:
    • Writing Group reviewed, deliberated, refined, and approved draft recommendations.
    • MCCC members reviewed, provided written comment on, deliberated, and reached consensus on recommendations.
    • Members of the Writing Group reviewed the cited evidence and assigned a 2-part rating to each recommendation to indicate the strength of the recommendation and the quality of the supporting evidence; consensus reached on ratings.
    • Additional evidence identified and cited during the rating process (see below).
  • Ongoing update process:
    • JHU editorial staff will surveil published literature on an ongoing basis to identify new evidence that may prompt changes to existing recommendations or development of new recommendations.
    • JHU editorial staff will ensure that the MCCC reviews new studies at least 4 times per year, and more often if newly published studies, new drug approval, or drug-related warning indicate the need for an immediate change to the published guideline.
    • JHU editorial staff will track, summarize, and publish ongoing changes to the guideline.
    • MCCC will review and approve substantive changes to, additions to, or deletions of recommendations.
    • MCCC will initiate a full review of the guideline 4 years after the original publication date.
    • NYSDOH AI will publish a comprehensive update 5 years after the original publication date.

Recommendation development and rating process: When this guideline was originally developed, the standard development process was followed. Clinical recommendations were developed by consensus based on a synthesis of the current evidence collected through the systematic search described above. If no data were available, the recommendations are based on expert opinion, and this status is indicated in the rating and the text. Once consensus among the Writing Group members was reached, the guideline was reviewed by the full MCCC, and consensus was reached on all recommendations. Writing Group review discussions were recorded, and recordings were reviewed carefully to ensure that all decisions and changes were captured and integrated into the manuscript. Members of the Writing Group then individually reviewed the evidence for each recommendation and assigned a 2-part rating (see below). The individual ratings were compiled into a report distributed to all raters, and conference call discussions were held to deliberate ratings for which consensus was needed. Once all raters agreed on the interpretation of evidence and ratings for all recommendations, the guideline was sent to the NYSDOH AI for review and approval.

The current guideline reflects a review and update that was completed to reflect newly available evidence regarding monitoring for renal toxicity in patients taking TAF. New literature was reviewed by a member of the MCCC writing group, proposed changes were evaluated and agreed upon by the group, signed off on by the committee chair and reviewed and approved by the NYSDOH AI.

AIDS Institute Clinical Guidelines Program: Recommendations Ratings
(updated June 2019 [a])
Strength of Recommendation Ratings
A Strong recommendation
B Moderate recommendation
C Optional
Quality of Supporting Evidence Ratings
1 Evidence is derived from published results of at least one randomized trial with clinical outcomes or validated laboratory endpoints.
* Evidence is strong because it is based on a self-evident conclusion(s); conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial.
2 Evidence is derived from published results of at least one well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes.
2† Evidence has been extrapolated from published results of well-designed studies (including non-randomized 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 Recommendation is based on the expert opinion of the committee members, with rationale provided in the guideline text.
  1. With the June 2019 update, the ratings for quality of supporting evidence were expanded to add the * rating and the 2† rating.

Guideline updates: Members of the MCCC or an invited lead author who is not an MCCC member will monitor developments in an ongoing structured manner to maintain guideline currency. Once the guidelines are published on the program website, www.hivguidelines.org, and indexed in the National Library of Medicine, any updates will be made to the HTML document and all collateral materials as needed as new, peer-reviewed literature is published if evidence is made available that changes best practices.

Notification of newly published studies will be automated, and the Writing Group will review new data as available. Newly published data that provide support for existing recommendations will be cited in the text, and the studies will be added to the reference list(s).

If newly published data prompt a revision to recommendations or rationale, the lead author and the Writing Group will propose appropriate edits and determine whether the changes warrant review and approval by the entire MCCC. If MCCC review is required, JHU will distribute updates via email, and a conference call will be convened if required. Deletion of existing recommendations, addition of any new recommendations, or substantive changes to existing recommendations will prompt MCCC review and consensus.

The full guideline will be reviewed and updated on the third and the fifth anniversary of original publication and more often if an evidence-based change in recommendations is required.

Updates to This Guideline

June 2021