Virologic and Immunologic Monitoring in HIV Care - AIDS Institute Clinical Guidelines

Purpose of This Guideline

Lead author: Samuel T. Merrick, MD
Reviewed and updated: June 16, 2022
Writing group: Steven M. Fine, MD, PhD; Rona Vail, MD; Joseph P. McGowan, MD, FACP, FIDSA; Asa Radix, MD, MPH, PhD; Jessica Rodrigues; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Medical Care Criteria Committee (MCCC)
Date of last update: November 2019

Periodic laboratory tests are necessary to evaluate a patient’s response to antiretroviral therapy (ART). Monitoring HIV-1 RNA levels (viral load) to confirm appropriate response to treatment and durable viral suppression is the most accurate and meaningful measure of the effectiveness of ART [Gale, et al. 2013]. HIV suppression is essential to the health of the individual with HIV and to preventing HIV transmission through sex; see the NYSDOH AI U=U Guidance for Implementation in Clinical Settings.

Regular immunologic monitoring in patients with consistently undetectable HIV viral loads and CD4 counts >200 cells/mm³ offers little utility in clinical practice today. Clinicians rarely use this information to guide decision-making for clinically stable, virologically suppressed patients.

The New York State Department of Health AIDS Institute has developed these evidence-based recommendations for ambulatory care of patients with HIV to accomplish the following:

Guide clinicians in the use of HIV viral load testing at appropriate times and intervals to assess initial and ongoing ART responses.
Clarify the appropriate use of immunologic (CD4 count) monitoring in the care of patients with HIV.

Reference

Gale HB, Gitterman SR, Hoffman HJ, et al. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >=300 cells/muL and HIV-1 suppression? Clin Infect Dis 2013;56(9):1340-1343. [PMID: 23315315]

Viral Load and CD4 Count Monitoring Intervals

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Lead author: Samuel T. Merrick, MD, with the Medical Care Criteria Committee (MCCC); updated June 16, 2022

Very few studies address the appropriate frequency of viral load monitoring. A retrospective study noted that the strongest predictor of virologic failure at 12 months was a missed or canceled appointment rather than the interval of follow-up [Buscher, et al. 2013]. However, this and other similar studies [Romih, et al. 2010; Reekie, et al. 2008] have significant limitations, including their retrospective nature and short follow-up periods. Data indicate that the linked sexual transmission of HIV in serodiscordant couples in which the partner with HIV maintains sustained viral suppression is negligible [Rodger, et al. 2016]; see the NYSDOH AI U=U Guidance for Implementation in Clinical Settings.

Based on this information, those with HIV may rely on ART as a strategy to prevent viral transmission to an uninfected partner. Studies do not indicate the appropriate interval for viral suppression monitoring for ongoing transmission prevention. Until more definitive data are available, the decision to lengthen monitoring intervals for HIV RNA levels should be individualized. Patients who are monitored at longer intervals should be carefully selected based on length of viral suppression, CD4 count, use of ART for transmission prevention, and adherence to medical care, including visit attendance and retention in care.

KEY POINT

Quarterly HIV RNA monitoring remains appropriate for patients with a recent history of nonadherence, mental health disorders, substance use, homelessness, poor social support system, or other major medical conditions. Semiannual monitoring may be appropriate for patients with persistently undetectable HIV RNA and none of the above characteristics.

Table 1 provides a guide for monitoring HIV RNA levels and CD4 counts.

Table 1: Recommended Viral Load and CD4 Count Monitoring in Nonpregnant Patients With HIV [a] Download PDF
Event	HIV RNA Viral Load	CD4 Count	Comments
Entry into care	Baseline viral load (A1)	Baseline CD4 count (A1)	If a patient is not taking ART, recommend initiation [b] (A1) Monitor as below
Patients Taking ART
ART initiation or change to address virologic failure	Within 4 weeks after ART start or change (A3) At least every 8 weeks until complete virologic suppression is documented (A3)	12 weeks after ART initiation Every 4 months until CD4 count >200 cells/mm³ is obtained on 2 measurements at least 4 months apart (A2), then monitor as below once virologic suppression is achieved	Virologic failure occurs when a viral load <200 copies/mL is either not achieved or not maintained Virologic suppression is defined as a viral load <20 to <50 copies/mL obtained with a highly sensitive assay
ART change for simplification or due to adverse effects	Within 4 weeks after ART change, then as below (A3)	Monitor as below for documented virologic suppression	—
Documented viral suppression	At least every 4 months (A3) May extend interval to 6 months in patients stable on ART with CD4 count >200 cells/mm³ and complete viral suppression for 1 year (B2)	At least every 6 months if CD4 count is ≤350 cells/mm³ (B2) Optional if CD4 count is >350 cells/mm³ (B2)	—
New HIV RNA ≥500 copies/mL after previous viral suppression	Repeat viral load test 2 weeks after first result (A2)	Obtain CD4 count if previous result is >6 months old (B3)	Assess for adherence and drug-drug interactions (A3) Obtain resistance testing (A1)
New HIV RNA level over the limit of detection of sensitive assays, 20 to 50 copies/mL, but <500 copies/mL after previous viral suppression	Repeat viral load test within 4 weeks to differentiate low-level transient viremia (“blip”) from virologic failure [c] (A2)	If repeat viral load is detectable, obtain CD4 count if previous result is >6 months old (B3)	Assess for adherence and drug-drug interactions (A3) If repeat viral load is detectable, consider resistance testing [d] (B3) Patients with low-level viremia ≤200 copies/mL over a period of 12 months without demonstrated failure may continue routine testing intervals of at least every 4 months [e]
Patients Not Taking ART
CD4 count ≤500 cells/mm³(A2)	At least every 4 months	At least every 4 months	At every visit, recommend ART initiation [b]
CD4 count >500 cells/mm³ (A2)	At least every 6 months	At least every 6 months	At every visit, recommend ART initiation [b]
Abbreviation: ART, antiretroviral therapy. Notes: For recommendations on virologic monitoring in pregnancy, see DHHS: Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. See the NYSDOH AI guideline When to Initiate ART, With Protocol for Rapid Initiation. An ART regimen should not be changed based on a single viral load elevation. The risk of virologic rebound (breakthrough) increases when values are ≥500 copies/mL [Grennan, et al. 2012]. Standard genotypic tests may not provide resistance results when viral load is low. For repeated low-level viremia, an assay that detects resistance mutations in archived proviral DNA is available; however, clinical data are insufficient to recommend for or against its use in the patient care setting. In patients with low-level viremia, clinicians should consult with an experienced HIV care provider; low-level viremia can be due to multiple causes, and its clinical effect is not clear.

References

Buscher A, Mugavero M, Westfall AO, et al. The association of clinical follow-up intervals in HIV-infected persons with viral suppression on subsequent viral suppression. AIDS Patient Care STDS 2013;27(8):459-466. [PMID: 23886048]

Grennan JT, Loutfy MR, Su D, et al. Magnitude of virologic blips is associated with a higher risk for virologic rebound in HIV-infected individuals: a recurrent events analysis. J Infect Dis 2012;205(8):1230-1238. [PMID: 22438396]

Reekie J, Mocroft A, Sambatakou H, et al. Does less frequent routine monitoring of patients on a stable, fully suppressed cART regimen lead to an increased risk of treatment failure? AIDS 2008;22(17):2381-2390. [PMID: 18981778]

Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA 2016;316(2):171-181. [PMID: 27404185]

Romih V, Zidovec Lepej S, Gedike K, et al. Frequency of HIV-1 viral load monitoring of patients initially successfully treated with combination antiretroviral therapy. PLoS One 2010;5(11):e15051. [PMID: 21124844]

Virologic Monitoring (HIV Viral Load)

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Lead author: Samuel T. Merrick, MD, with the Medical Care Criteria Committee (MCCC); updated June 16, 2022

Plasma HIV-1 RNA level (viral load): Plasma levels of viral RNA have been shown to correlate with clinical outcomes, including overall mortality, and measurement of HIV RNA levels provides the most precise means of establishing whether a response to antiretroviral therapy (ART) has occurred [HIV Surrogate Marker Collaborative Group 2000; Thiebaut, et al. 2000; Murray, et al. 1999; Marschner, et al. 1998; Mellors, et al. 1997].

HIV RNA levels should be obtained from all patients at baseline [Porter, et al. 2015; Behrens, et al. 2014; Molina, et al. 2013; Tarwater, et al. 2004; Gulick, et al. 2003; Wu, et al. 2003].

For patients beginning ART, or those changing therapy as a result of virologic failure, HIV RNA should be measured at 4 weeks after initiation of ART and should decrease by at least 1 log (10-fold) in the presence of effective therapy [Haubrich, et al. 2011] (see Table 2: Interpretation of Viral Load, below). For patients who do not have background antiretroviral resistance, an undetectable viral load (<50 copies/mL) is usually achieved within 3 months. Patients with a baseline HIV viral load >100,000 copies/mL can be expected to achieve an undetectable viral load within 6 months of effective treatment.

Table 2: Interpretation of Viral Load
HIV-1 RNA Copy Number
Copies/mm³		Log ₁₀
1,000,000 100,000 10,000 1,000 100		6.0 5.0 4.0 3.0 2.0
Reduction With ART If Patient Has 100,000 copies/mm³
Log Change	Percent Decrease	Fold Reduction	Resultant Copy Number
0.5	68.3	3	33,000
1.0	90.00	10	10,000
2.0	99.00	100	1,000
3.0	99.90	1,000	100

An absent or incomplete response of viral load to ART should raise concerns about poor adherence to therapy and/or viral resistance [Townsend, et al. 2009; Baxter, et al. 2000].

Blips: Patients on previously suppressive ART with newly detectable HIV RNA levels of 50 to 500 copies/mL may be experiencing low-level transient viremia (“blip”) and not virologic failure. A blip by definition means that the viral load is again below the level of quantification on repeat testing performed promptly after a detectable result in someone previously suppressed. Persistent elevation, even at low levels, warrants further investigation. Acute concurrent illness and/or recent vaccination may cause this transient rise; however, studies have suggested that low-level transient viremia represents random biologic and statistical variation or false elevations of viral load resulting from laboratory processing [Lee, et al. 2006; Nettles, et al. 2005]. Blips are not known to be associated with the development of resistance mutations or virologic failure and do not require a change in ART [Lee, et al. 2006]. Retesting should be performed within 4 weeks to differentiate low-level transient viremia (a blip) from sustained viremia and possible virologic failure. The risk of virologic rebound (breakthrough) increases when values are >500 copies/mL [Grennan, et al. 2012]. However, ART should not be changed based on a single viral load elevation.

Advances in molecular detection technology have led to the development of HIV nucleic acid tests that are highly sensitive and more reliable than earlier versions. Real-time polymerase chain reaction (PCR) technology has been widely adopted for HIV-1 RNA quantification, but new technologies are continually emerging and being adapted to viral detection and quantification. The currently available HIV-1 viral load tests that use real-time PCR technology offer a larger dynamic range of quantification than early-version viral load tests. The lower and upper limits of quantification of the currently available U.S. Food and Drug Administration (FDA)-approved HIV-1 viral load tests are shown in Table 3. Several different HIV viral load tests have been developed, and 4 are currently approved for use in the United States.

Table 3: FDA-Approved Quantitative HIV-1 RNA Assays for Viral Load Monitoring
Test Name	Method	Lower and Upper LOQ
Abbott RealTime HIV-1 (Abbott Laboratories)	Real-time PCR	40 copies/mL [a] 10,000,000 copies/mL
Cobas AmpliPrep/Cobas TaqMan HIV-1 Test, version 2.0 (Roche Diagnostics)	Real-time PCR	20 copies/mL 10,000,000 copies/mL
Cobas HIV-1 quantitative NAT for use on Cobas 6800/8800 systems (Roche Diagnostics)	Real-time PCR	20 copies/mL 10,000,000 copies/mL
Cobas TaqMan HIV-1 Test, v2.0 for use with the high pure system (Roche Diagnostics)	Real-time PCR	34 copies/mL 10,000,000 copies/mL
Abbreviations: FDA, U.S. Food and Drug Administration; LOQ, limit of quantification; NAT, nucleic acid test, PCR, polymerase chain reaction. Note: This lower LOQ applies when 1.0 mL of plasma is used. When 0.5 and 0.2 mL of plasma are used, the lower LOQ is 75 copies/mL and 150 copies/mL, respectively.

All of the current FDA-approved viral load assays quantify the level of cell-free virus in an individual’s plasma and are approved for monitoring response to ART, tracking viral suppression, and detecting treatment failure. Successful ART should decrease the viral load by 1.5 to 2 logs (30- to 100-fold) within 6 weeks, with the viral load decreasing below the limit of detection within 6 months [DHHS 2022]. Cohort studies strongly suggest that patients with viral loads <50 copies/mL have more sustained viral suppression than patients with viral loads between 50 and 400 copies/mL. Assays that can detect <50 copies/mL are recommended for determining prolonged viral suppression and for monitoring patients who are on ART.

KEY POINT

Achieving and maintaining an undetectable viral load is always the goal of ART.

References

Baxter JD, Mayers DL, Wentworth DN, et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 2000;14(9):F83-93. [PMID: 10894268]

Behrens G, Rijnders B, Nelson M, et al. Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1-infected patients with HIV-1 RNA </=100,000 copies/mL: week 96 pooled ECHO/THRIVE subanalysis. AIDS Patient Care STDS 2014;28(4):168-175. [PMID: 24660840]

DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. 2022 Jan 20. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new-guidelines [accessed 2019 Sep 24]

Gulick RM, Meibohm A, Havlir D, et al. Six-year follow-up of HIV-1-infected adults in a clinical trial of antiretroviral therapy with indinavir, zidovudine, and lamivudine. AIDS 2003;17(16):2345-2349. [PMID: 14571186]

Haubrich RH, Riddler SA, Ribaudo H, et al. Initial viral decay to assess the relative antiretroviral potency of protease inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and nucleoside reverse transcriptase inhibitor-sparing regimens for first-line therapy of HIV infection. AIDS 2011;25(18):2269-2278. [PMID: 21941167]

HIV Surrogate Marker Collaborative Group. Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: a meta-analysis. HIV Surrogate Marker Collaborative Group. AIDS Res Hum Retroviruses 2000;16(12):1123-1133. [PMID: 10954887]

Lee PK, Kieffer TL, Siliciano RF, et al. HIV-1 viral load blips are of limited clinical significance. J Antimicrob Chemother 2006;57(5):803-805. [PMID: 16533823]

Marschner IC, Collier AC, Coombs RW, et al. Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy. J Infect Dis 1998;177(1):40-47. [PMID: 9419168]

Mellors JW, Munoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997;126(12):946-954. [PMID: 9182471]

Molina JM, Clumeck N, Redant K, et al. Rilpivirine vs. efavirenz in HIV-1 patients with baseline viral load 100,000 copies/ml or less: week 48 phase III analysis. AIDS 2013;27(6):889-897. [PMID: 23276806]

Murray JS, Elashoff MR, Iacono-Connors LC, et al. The use of plasma HIV RNA as a study endpoint in efficacy trials of antiretroviral drugs. AIDS 1999;13(7):797-804. [PMID: 10357378]

Nettles RE, Kieffer TL, Kwon P, et al. Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 2005;293(7):817-829. [PMID: 15713771]

Porter DP, Kulkarni R, Fralich T, et al. 96-week resistance analyses of the STaR study: rilpivirine/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir DF in antiretroviral-naive, HIV-1-infected subjects. HIV Clin Trials 2015;16(1):30-38. [PMID: 25777187]

Tarwater PM, Gallant JE, Mellors JW, et al. Prognostic value of plasma HIV RNA among highly active antiretroviral therapy users. AIDS 2004;18(18):2419-2423. [PMID: 15622318]

Thiebaut R, Morlat P, Jacqmin-Gadda H, et al. Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d’Epidemiologie du SIDA en Aquitaine (GECSA). AIDS 2000;14(8):971-978. [PMID: 10853978]

Townsend D, Troya J, Maida I, et al. First HAART in HIV-infected patients with high viral load: value of HIV RNA levels at 12 weeks to predict virologic outcome. J Int Assoc Physicians AIDS Care (Chic) 2009;8(5):314-317. [PMID: 19759257]

Wu H, Mellors J, Ruan P, et al. Viral dynamics and their relations to baseline factors and longer term virologic responses in treatment-naive HIV-1-infected patients receiving abacavir in combination with HIV-1 protease inhibitors. J Acquir Immune Defic Syndr 2003;33(5):557-563. [PMID: 12902798]

Immunologic Monitoring (CD4 Count)

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Lead author: Samuel T. Merrick, MD, with the Medical Care Criteria Committee (MCCC); updated June 16, 2022

Lymphocyte subsets (CD4 count): CD4 lymphocyte count is used to evaluate immunologic staging, predict the risk of clinical progression, and make decisions regarding opportunistic infection prophylaxis [Lopez Bernaldo de Quiros, et al. 2001; El-Sadr, et al. 2000]. Low CD4 counts can be seen in other disease processes and should therefore not be used to diagnose HIV infection. Although CD4 count was used historically to establish a threshold for initiating ART, current guidelines in New York State recommend ART for all patients with HIV regardless of CD4 count. For patients who may not be ready to initiate ART, CD4 count can be used to guide discussions between patient and care provider regarding the urgency of initiating ART.

Although a CD4 count should be obtained at baseline [Moore and Keruly 2007; Oldfield, et al. 1998; Havlir, et al. 1996; Schneider, et al. 1992; Fischl, et al. 1988], clinicians are unlikely to use it to guide clinical decision-making in practice for virologically suppressed patients once their CD4 count remains above 200 cells/mm³. However, for those infected with HIV-2 or HIV-1 variants that cannot be accurately quantified using viral load assays, CD4 count remains the most effective tool for monitoring disease progression (see the NYSDOH AI guideline Diagnosis and Management of HIV-2 in Adults).

Although a significant CD4 count increase often occurs among patients treated with effective ART, the absence of such an increase should not be interpreted as treatment failure if the viral load declines appropriately. ART regimens are generally not changed in patients with undetectable viral loads who experience immunologic failure, although patients should remain on appropriate prophylaxis for opportunistic infections based on CD4 count. One study of a cohort of more than 62,000 individuals in New York City over 1.9 years of observation reported that in those who entered the cohort with a CD4 count ≥350 cells/mm³, there was a >90% likelihood of sustaining a CD4 count >200 cells/mm³ during that period of time [Myers, et al. 2016]. Reassuringly, other data suggest that in patients with sustained viral suppression and CD4 counts between 100 and 200 cells/mm³, the risk of pneumocystis pneumonia is very low even in the absence of prophylaxis [Chaiwarith, et al. 2013; Mocroft, et al. 2010; D’Egidio, et al. 2007].

Lack of correlation between viral load and CD4 count response is particularly common among patients ≥50 years old [Sabin, et al. 2008; Gras, et al. 2007] and patients with low initial CD4 counts (<100 cells/mm³) [Kelley, et al. 2009; Moore and Keruly 2007; Garcia, et al. 2004].

Absolute CD4 counts are calculated values that may fluctuate widely. The calculation is made by multiplying the total white blood cell count (in thousands) by the percentage of total lymphocytes and then by the percentage of CD4 lymphocytes. Therefore, any change in one of these three parameters will cause the absolute CD4 count to vary. CD4 percentage is a direct measurement and more reliable than the calculated absolute CD4 value, especially over time. A stable CD4 percentage, even when fluctuations occur in the absolute CD4 count, can reassure both the patient and the clinician that immunologic stability is present.

Some factors that can cause these fluctuations include sex, age, race, drugs (zidovudine, cephalosporins, cancer chemotherapy, nicotine, interferon, and corticosteroids), anti-lymphocyte antibodies, and splenectomy. Differences in reagents and equipment both within a laboratory and between laboratories may further contribute to variations in CD4 counts. There is also interlaboratory variation of normal range.

References

Chaiwarith R, Praparattanapan J, Nuntachit N, et al. Discontinuation of primary and secondary prophylaxis for opportunistic infections in HIV-infected patients who had CD4+ cell count <200 cells/mm(3) but undetectable plasma HIV-1 RNA: an open-label randomized controlled trial. AIDS Patient Care STDS 2013;27(2):71-76. [PMID: 23373662]

D’Egidio GE, Kravcik S, Cooper CL, et al. Pneumocystis jiroveci pneumonia prophylaxis is not required with a CD4+ T-cell count < 200 cells/microl when viral replication is suppressed. AIDS 2007;21(13):1711-1715. [PMID: 17690568]

El-Sadr WM, Burman WJ, Grant LB, et al. Discontinuation of prophylaxis against Mycobacterium avium complex disease in HIV-infected patients who have a response to antiretroviral therapy. Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med 2000;342(15):1085-1092. [PMID: 10766581]

Fischl MA, Dickinson GM, La Voie L. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA 1988;259(8):1185-1189. [PMID: 3257532]

Garcia F, de Lazzari E, Plana M, et al. Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count. J Acquir Immune Defic Syndr 2004;36(2):702-713. [PMID: 15167289]

Gras L, Kesselring AM, Griffin JT, et al. CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater. J Acquir Immune Defic Syndr 2007;45(2):183-192. [PMID: 17414934]

Havlir DV, Dube MP, Sattler FR, et al. Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. California Collaborative Treatment Group. N Engl J Med 1996;335(6):392-398. [PMID: 8676932]

Kelley CF, Kitchen CM, Hunt PW, et al. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 2009;48(6):787-794. [PMID: 19193107]

Lopez Bernaldo de Quiros JC, Miro JM, Pena JM, et al. A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98. N Engl J Med 2001;344(3):159-167. [PMID: 11172138]

Mocroft A, Reiss P, Kirk O, et al. Is it safe to discontinue primary Pneumocystis jiroveci pneumonia prophylaxis in patients with virologically suppressed HIV infection and a CD4 cell count <200 cells/microL? Clin Infect Dis 2010;51(5):611-619. [PMID: 20645862]

Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis 2007;44(3):441-446. [PMID: 17205456]

Myers JE, Xia Q, Torian LV, et al. Implementation and operational research: CD4 count monitoring frequency and risk of CD4 count dropping below 200 cells per cubic millimeter among stable HIV-infected patients in New York City, 2007-2013. J Acquir Immune Defic Syndr 2016;71(3):e73-78. [PMID: 26536317]

Oldfield EC, 3rd, Fessel WJ, Dunne MW, et al. Once weekly azithromycin therapy for prevention of Mycobacterium avium complex infection in patients with AIDS: a randomized, double-blind, placebo-controlled multicenter trial. Clin Infect Dis 1998;26(3):611-619. [PMID: 9524832]

Sabin CA, Smith CJ, d’Arminio Monforte A, et al. Response to combination antiretroviral therapy: variation by age. AIDS 2008;22(12):1463-1473. [PMID: 18614870]

Schneider MM, Hoepelman AI, Eeftinck Schattenkerk JK, et al. A controlled trial of aerosolized pentamidine or trimethoprim-sulfamethoxazole as primary prophylaxis against Pneumocystis carinii pneumonia in patients with human immunodeficiency virus infection. The Dutch AIDS Treatment Group. N Engl J Med 1992;327(26):1836-1841. [PMID: 1360145]

All Recommendations

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Lead author: Samuel T. Merrick, MD, with the Medical Care Criteria Committee (MCCC); updated June 16, 2022

Guideline Information

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Guideline Information
Developer and Funding Source	New York State Department of Health AIDS Institute (NYSDOH AI)
Intended Users	Clinicians providing ambulatory care for patients with HIV.
Development	See Guideline Development and Recommendation Ratings Scheme, below.
Update
June 14, 2022; Samuel T. Merrick, MD, with the MCCC	Table 1 reorganized and updated.
November 2019	Recommendations for frequency of CD4 count updated.
June 2016	Original publication

Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program
Developer	New York State Department of Health AIDS Institute (NYS DOH 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. See Expert Committees
Committee Structure	Leadership: AI-appointed chair, vice chair(s), chair emeritus, clinical specialist(s), JHU Guidelines Program Director, AI Medical Director, AI Clinical Consultant, AVAC community advisor Contributing members Guideline writing groups: Lead author, coauthors if applicable, and all committee leaders
Conflicts of Interest Disclosure and Management	Annual disclosure of financial relationships with commercial entities for the 12 months prior and upcoming is required of all individuals who work with the guidelines program, and includes disclosure for partners or spouses and primary professional affiliation. The NYSDOH AI assesses all reported financial relationships to determine the potential for undue influence on guideline recommendations and, when indicated, denies participation in the program or formulates a plan to manage potential conflicts. Disclosures are listed for each committee member.
Evidence Collection and Review	Literature search and review strategy is defined by the guideline lead author based on the defined scope of a new guideline or update. A comprehensive literature search and review is conducted for a new guideline or an extensive update using PubMed, other pertinent databases of peer-reviewed literature, and relevant conference abstracts to establish the evidence base for guideline recommendations. A targeted search and review to identify recently published evidence is conducted for guidelines published within the previous 3 years. Title, abstract, and article reviews are performed by the lead author. The JHU editorial team collates evidence and creates and maintains an evidence table for each guideline.
Recommendation Development	The lead author drafts recommendations to address the defined scope of the guideline based on available published data. Writing group members review the draft recommendations and evidence and deliberate to revise, refine, and reach consensus on all recommendations. When published data are not available, support for a recommendation may be based on the committee’s expert opinion. The writing group assigns a 2-part rating to each recommendation to indicate the strength of the recommendation and quality of the supporting evidence. The group reviews the evidence, deliberates, and may revise recommendations when required to reach consensus.
Review and Approval Process	Following writing group approval, draft guidelines are reviewed by all contributors, program liaisons, and a volunteer reviewer from the AI Community Advisory Committee. Recommendations must be approved by two-thirds of the full committee. If necessary to achieve consensus, the full committee is invited to deliberate, review the evidence, and revise recommendations when required. Final approval by the committee chair and the NYSDOH AI Medical Director is required for publication.
External Reviewers	External peer reviewers recognized for their experience and expertise review guidelines for accuracy, balance, clarity, and practicality and provide feedback. Peer reviewers may include nationally known experts from outside of New York State.
Update Process	JHU editorial staff ensure that each guideline is reviewed and determined to be current upon the 3-year anniversary of publication; guidelines that provide clinical recommendations in rapidly changing areas of practice may be reviewed annually. Published literature is surveilled to identify new evidence that may prompt changes to existing recommendations or development of new recommendations. If changes in the standard of care, newly published studies, new drug approval, new drug-related warning, or a public health emergency indicate the need for immediate change to published guidelines, committee leadership will make recommendations and immediate updates. All contributing committee members review and approve substantive changes to, additions to, or deletions of recommendations; JHU editorial staff track, summarize, and publish ongoing guideline changes.

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.