Laboratory Monitoring for Adverse Effects of ART

Laboratory Monitoring for Adverse Effects of ART

Purpose of This Guideline

Lead Author: Noga Shalev, MD, with the Medical Care Criteria Committee, 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 Primary Care Approach for information on other routine laboratory monitoring for patients with HIV.

Frequency of Laboratory Monitoring During ART

Lead Author: Noga Shalev, MD, with the Medical Care Criteria Committee, September 2019

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 Primary Care Approach). 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 [AIDSinfo 2017; Sax 2018]. 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 second 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 Frequency of Laboratory Monitoring During Year 1 of Antiretroviral Therapy or at Regimen Change (Rating: A3) [download PDF]
Laboratory Test Entry to Care or ART Initiation At 4 Weeks At 3 Months At 6 Months At 12 Months
Hepatic panel [a] X   X   X
Random blood glucose X   X   X
eGFR [b] With TDF X X X X X
Without
TDF [c]
X     X X
Proteinuria [d] With TDF X   X   X
Without
TDF
X       X
Complete blood count With ZDV X X X X X
Without
ZDV
X        

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

Notes:

  1. AST, ALT, alkaline phosphates, and total bilirubin.
  2. Patients with decreased eGFR at baseline or those taking concomitant nephrotoxic drugs may need more frequent monitoring of renal function.
  3. Including TAF-containing regimens. See the section on Screening for Organ-Specific Adverse Events > Nephrotoxicity for more information.
  4. Urinalysis or urine protein-to-creatinine ratio.

 

Table 2: Minimum Frequency of Laboratory Monitoring After Year 1 of Antiretroviral Therapy (Rating: A3) [download PDF]
Laboratory Test Every 6 Months Every 1 Year
Hepatic panel [a]   X
Random blood glucose X  
eGFR With TDF X  
Without TDF [b]   X
Proteinuria [c] With TDF   X
Complete blood count With ZDV X  
Without ZDV See the NYSDOH AI guideline
Primary Care Approach

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

Notes:

  1. AST, ALT, alkaline phosphates, and total bilirubin.
  2. See the section on Screening for Organ-Specific Adverse Events > Nephrotoxicity for more information.
  3. Urinalysis or urine protein-to-creatinine ratio.
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]

AIDSinfo. 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. 2017 Oct 17. https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/3/tests-for-initial-assessment-and-follow-up [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

Lead Author: Noga Shalev, MD, with the Medical Care Criteria Committee, September 2019

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. Various guidelines recommend screening for ART-induced nephrotoxicity [Gorriz, et al. 2014; Holt, et al. 2014; Lucas, et al. 2014; AIDSinfo 2018]. 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 antiretroviral agents (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 (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 Frequency of Laboratory Monitoring During Year 1 of Antiretroviral Therapy or at Regimen Change and Table 2: Minimum Frequency of Laboratory Monitoring After Year 1 of Antiretroviral Therapy.

Plasma concentrations of tenofovir are approximately 4-fold lower with use of TAF than with TDF, and nephrotoxicity due to TAF is rarely reported in individuals with a creatinine clearance rate of >30 mL/min. The tables provide recommendations for more frequent monitoring of renal function in patients taking TDF but not TAF. However, in a variety of clinical scenarios, such as when TAF is used in patients with low estimated glomerular filtration rates (eGFRs), or in patients with concomitant use of other nephrotoxic agents, or when a pharmaco-enhancer is added to ARV combination regimens containing the higher-dose (25 mg) TAF formulations, frequency of monitoring for TAF-induced nephrotoxicity may be increased to mirror the suggestions for TDF-containing regimens.

Either of the MDRD or CKD-EPI equations can be used to measure eGFRs (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 antiretroviral agents 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 antiretroviral agents have the potential to cause idiopathic abnormalities in liver function, especially in patients with preexisting liver disease. As a class, nonnucleoside 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, Tables 1 and 2 make no 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 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].

The tables do 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

AIDSinfo. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. 2018 May 30. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf [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

Lead Author: Noga Shalev, MD, with the Medical Care Criteria Committee, September 2019

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

How This Guideline Was Developed

September 2019

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 who have 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 Medical Care Criteria Committee (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 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 sub-specialties, key NYS agencies, community stakeholders, and patient advocates. Individuals confirmed as Committee 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 Planning Group of Committee leaders 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 Planning Group (all Committee members and reviewers are listed in Box A1, below)

  • Joseph P. McGowan, MD, FACP, FIDSA, Chair
  • Steve Fine MD, PhD, Vice-Chair
  • Samuel T. Merrick, MD, Chair Emeritus
  • Charles J. Gonzalez, MD, AI Medical Director
  • Lyn C. Stevens, MS, NP, ACRN, AI Deputy Medical Director
  • Asa Radix, MD, MPH, FACP, AAHIVS
  • Christopher J. Hoffmann, MD, MPH, JHU Principal Investigator

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)

Leadership

  • Chair: Joseph P. McGowan, MD, FACP, FIDSA, North Shore University Hospital, Manhasset, NY; (Chair, effective March 2018)
    No disclosures
  • Vice-Chair (effective March 2018)Steven M. Fine, MD, PhD, University of Rochester Medical Center, Rochester, NY
    No disclosures
  • Chair Emeritus: Samuel T. Merrick, MD, New York Presbyterian-Weill Cornell, New York, NY; (Chair Emeritus, effective March 2018)
    No disclosures
  • Medical Director: Charles J. Gonzalez, MD, New York State Department of Health (NYSDOH) AIDS Institute (AI), New York, NY (May 2018)
    No disclosures
  • Deputy Medical Director: Lyn Stevens, MS, NP, ACRN, New York State Department of Health (NYSDOH) AIDS Institute (AI), Albany, NY
    No disclosures
  • JHU Principal Investigator: Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, MD
    No disclosures

Contributing Members

  • James C. M. Brust, MD, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
    No disclosures
  • John M. Conry, PharmD, AAHIVP, FNAP, St. John’s University, Queens, NY
    No disclosures
  • Elliot DeHaan, MD, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY
    No disclosures
  • Mary Dyer, MD, Hudson River Healthcare, Monticello, NY
    No disclosures
  • Daniel Egan, MD, Columbia University Vagelos College of Physicians and Surgeons, New York, NY
    No disclosures
  • Jack Fuhrer, MD, Stony Brook University School of Medicine, Stony Brook, NY
    No disclosures
  • Christine A. Kerr, MD, Hudson River HealthCare, Beacon, NY
    No disclosures
  • Jeremy D. Kidd, MD, MPH, New York Presbyterian Hospital, Columbia University, New York, NY
    No disclosures
  • Luz Amarilis Lugo, MD, Mount Sinai Comprehensive Health Program-Downtown, New York, NY
    No disclosures
  • Cynthia H. Miller, MD, Albany Medical Center, Albany, NY
    No disclosures
  • Gene Morse, PharmD, FCCP, BCPS, University at Buffalo School of Pharmacy & Pharmaceutical Sciences, Buffalo, NY
    No disclosures
  • Julie E. Myers, MD, MPH, New York City Department of Health and Mental Hygiene, Queens, NY
    No disclosures
  • Hector Ojeda-Martinez, MD, SUNY Downstate Medical Center, Brooklyn, NY
    No disclosures
  • David C. Perlman, MD, Icahn School of Medicine at Mount Sinai, New York, NY
    No disclosures
  • Asa E. Radix, MD, MPH, FACP, AAHIVS, Callen-Lorde Community Health Center, New York, NY
    No disclosures
  • Sanjiv S. Shah, MD, MPH, AAHIVM, AAHIVS, Icahn School of Medicine at Mount Sinai, New York, NY
    No disclosures
  • Noga Shalev, MD, Columbia University Medical Center, New York, NY
    No disclosures
  • Eugenia L. Siegler, MD, Weill Cornell Medical College, New York, NY
    No disclosures
  • Maria Teresa Timoney, MS, RN, CNM, Bronx Lebanon Hospital Center, Bronx, NY
    No disclosures
  • Marguerite A. Urban, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY
    No disclosures
  • Antonio E. Urbina, MD, Mount Sinai Hospital, New York, NY
    Scientific Advisor: Gilead, ViiV, Merck
  • Rona M. Vail, MD, Callen-Lorde Community Health Center, New York, NY
    No disclosures
  • Geoffrey A. Weinberg, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY
    No disclosures

Funding and Disclosure of Potential Conflicts of Interest (COIs)

Funding: NYS funds supported development of the Laboratory Monitoring for Adverse Effects of ART guideline through a grant awarded to the JHU School of Medicine, Division of Infectious Diseases, from the NYSDOH AI.

Conflicts of interest: 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. Box A1, above, lists reported conflicts.

Management of COIs: 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 was 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 provide 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 author 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 author developed, and all MCCC members reviewed and approved, evidence-based guideline recommendations:
    • Planning group reviewed, deliberated, refined, and approved draft recommendations.
    • MCCC members reviewed, provided written comment on, deliberated, and reached consensus on recommendations.
    • Planning 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 four times per year, and more often if newly published studies, new drug approvals, or drug-related warnings 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

The clinical recommendations presented in this guideline 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 in the text.

The Planning Group met via teleconferences over approximately 2 months to finalize the guideline and reach consensus on recommendations and rationale. After consensus among the Planning Group members was reached, the guideline was reviewed by the full MCCC, and consensus was reached on all recommendations. These deliberations were conducted by teleconference and through MCCC comments submitted in writing. Committee 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 Planning 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. After 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.

AIDS Institute HIV Clinical Guidelines Program Recommendations Rating Scheme
Strength of Recommendation Quality of Supporting Evidence
A = Strong 1 = At least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints
B = Moderate 2 = One or more well-designed, nonrandomized trial or observational cohort study with long-term clinical outcomes
C = Optional 3 = Expert opinion

Guideline Updates

Members of the MCCC will monitor developments in laboratory monitoring for adverse effects of ART in an ongoing structured manner to maintain guideline currency. After the guidelines are published on the program website: www.hivguidelines.org, any updates will be made to the HTML document as needed when new peer-reviewed literature is published.

Notification of newly published studies will be automated, and the Planning Group will review new data at least every 4 months. 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 Planning Group will propose appropriate edits and determine whether the changes warrant review and approval by the entire MCCC. If MCCC review is required, a conference call will be convened for that purpose. Deletion of existing recommendations, addition of any new recommendations, and/or substantive changes to existing recommendations will prompt MCCC review and consensus.

If a new medication or formulation is approved, the Planning Group will be convened via conference call to examine the data, consider inclusion in the guideline, and determine the need for MCCC review and approval.

The full guideline will be reviewed and updated on the 4th anniversary of original publication to prepare for publication of an updated guideline on or before the 5th anniversary of original publication.