Virologic and Immunologic Monitoring - AIDS Institute Clinical Guidelines

Monitoring Intervals

Medical Care Criteria Committee, updated November 2019

Periodic laboratory tests are necessary to evaluate the response to ART and its potential related side effects. In the setting of ART failure, viral resistance assays should be used.

Regular monitoring of CD4 counts 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. Monitoring of HIV RNA levels 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].

Very few studies address the appropriate frequency of viral load monitoring. A recent retrospective study noted that the strongest predictor of virologic failure at 12 months was a missed or cancelled appointment rather than the interval of follow-up [Buscher et al. 2013]. However, this and other similar studies [Reekie et al. 2008; Romih et al. 2010] have significant limitations, including their retrospective nature and short follow-up periods. Data indicate that the linked sexual transmission of HIV in sero-discordant couples in which the HIV infected partner maintains sustained viral suppression is negligible [Rodger et al. 2016]. Based on this information, persons with HIV may rely on their antiretroviral therapy as a strategy to prevent viral transmission to an uninfected partner. Studies do not indicate the appropriate interval for viral suppression monitoring for the purposes of ongoing transmission prevention. Until more definitive data are available, the decision to lengthen monitoring intervals for HIV RNA level should be individualized. Patients who are monitored at longer intervals should be carefully selected based on length of viral suppression, CD4 count, use of antiretroviral therapy 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 non-adherence, 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: Virologic and Immunologic Monitoring for Non-Pregnant Patients [a]
At Baseline	HIV RNA Levels (copies/mL)	CD4 Lymphocyte Count (cells/mm³)
All patients	Yes (A1)	Yes (A1)
Treatment Monitoring	HIV RNA Levels (copies/mL)	CD4 Lymphocyte Count (cells/mm³)
Following (1) initiation of ART or (2) a change in ART regimen after virologic failure [b] with new resistance to prior ART	Within 4 weeks of initiation of ART or change in regimen (A3) At least every 8 weeks until complete suppression [c] is documented (A3)	Repeat at 12 weeks and then every 4 months until CD4 >200 cells/mm³ on two measurements obtained at least 4 months apart (A2); then monitor as below once suppressed
Following a change in ART to simplify treatment regimen or reduce toxicity for patients with suppressed virus	Within 4 weeks after change in regimen to ensure continued suppression (A3); then monitor as below for suppressed	Monitor as below for suppressed
Patients on ART who achieve complete suppression [c]	At least every 4 months after complete suppression (A3) May extend intervals to every 6 months in selected stable patients with CD4 counts >200 cells/mm³ after 1 year of complete suppression [Buscher et al. 2013] (B2)	If CD4 count is ≤350 cells/mm³: At least every 6 months (B2) If CD4 count is >350 cells/mm³: Further monitoring is optional (B2)
Patients on previously suppressive ART with new HIV RNA [d] above the lower limit of detection using a highly sensitive assay [c]	All patients: Assess adherence (A3) Assess for drug-drug interactions (A3) Viral load ≥500 copies/mL: Have patient return within 2 weeks and: Repeat viral load (A2) and obtain resistance testing (A1) Obtain CD4 count if not done within previous 6 months (B3) Viral load <500 copies/mL: Repeat viral load test within 4 weeks to differentiate low level transient viremia (“blip”) from virologic failure [b,e]. (A2) If viral load remains detectable on repeat test: Obtain CD4 count if not done within previous 6 months (B3) Consider resistance testing [f] (B3)
Patients not on ART: According to NYSDOH recommendations, ART is recommended for all patients with HIV [g]	If CD4 ≤500 cells/mm³: At least every 4 months (A2) If CD4 >500 cells/mm³: At least every 6 months (A2) Continue to discuss ART initiation (A1)	If CD4 ≤500 cells/mm³: At least every 4 months (A3) If CD4 >500 cells/mm³: At least every 6 months (A3) Continue to discuss ART initiation (A1)
Notes: For monitoring HIV RNA levels and CD4 counts in pregnant women with HIV, see DHHS/AIDSinfo > Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Virologic failure is defined as the inability to achieve or maintain suppression of viral replication to an HIV RNA level <200 copies/mL [AIDSinfo. Adult and Adolescent 2015]. Complete suppression is generally considered below the lower limit of detection of a highly sensitive assay (<20 to <50 copies/mL). Patients with repeated intermittent low level viremia ≤200 copies/mL over a period of years without demonstrated failure may continue routine testing intervals. ART 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 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. See the NYSDOH AI guideline When to Initiate ART.

References

AIDSinfo Adult and Adolescent. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf [accessed 2015 Jun 10]

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;27:459-466. [PubMed]

Gale HB, Giettermann SR, Hoffman HJ, et al. Is frequent CD4+ T-lymphocyte count monitoring necessary for persons with counts >300 cells/mm3 and HIV-1 suppression? Clin Infect Dis 2013;56:1340-1343. [PubMed]

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;205:1230-1238. [PubMed]

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; 22:2381–2390. [PubMed]

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 Jul 12;316(2):171-81. [PubMed]

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:e15051. [PubMed]

Updates to This Guideline

November 2019

CD4 cell count monitoring interval changed as marked below:
- If CD4 ~~≤300~~ ≤350 cells/mm³: At least every 6 months ~~(B3 )~~ (B2)
- If CD4 ~~>300 to ≤500~~ >350 cells/mm³: Further monitoring is optional ~~At least every 12 months~~ (B2)
- ~~If CD4 >500 cells/mm³: further monitoring is optional (B3)~~
New evidence cited to support changes in CD4 cell count monitoring intervals. See Myers, et al. 2016; D’Egidio, et al. 2007; Mocroft, et al. 2010; Chaiwarith, et al. 2013, in Lymphocyte Subsets (CD4 Cell Count).

Viral Load

Medical Care Criteria Committee, June 2016

Plasma HIV-1 RNA Level (Viral Load)

Plasma levels of viral RNA have been shown to correlate with clinical outcome, including overall mortality, and measurement of HIV RNA levels provides the most precise means of establishing whether a response to ART has occurred [Marschner et al. 1998; HIV Surrogate Marker Collaborative Group 2000; Murray et al. 1999; Mellors et al. 1997; Thiebaut et al. 2000]. HIV RNA levels should be obtained from all patients at baseline [Tarwater et al. 2004; Guilick et al. 2003; Wu et al. 2003; Porter et al. 2015; Behrens et al. 2014; Molina et al. 2013].

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 therapy 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	66.00	3	33,000
1.0	90.00	10	10,000
2.0	99.00	100	1,000
3.0	99.99	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].

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 [Nettles et al. 2005; Lee et al. 2006]. 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 (NATs) 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 larger dynamic range of quantification than early-version viral load tests. The lower and upper limits of quantification of the currently available FDA-approved HIV-1 viral load tests are shown in Table 3. Several different HIV viral load tests have been developed, and four 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 Limits of Quantification (LOQ)
Abbott RealTime HIV-1 (Abbott Laboratories)	Real-time PCR	40* copies/mL 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
*This lower LOQ applies when 1.0 mL of plasma is used. When 0.5 mL 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 viral load 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 Panel 2016]. 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. [PubMed]

Behrens G, Rijnders B, Nelson M, et al. Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve 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):168-75. [PubMed]

DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. 2016 Jan 28. www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf

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):2345-9. [PubMed]

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;25:2269-2278. [PubMed]

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. AIDS Res Hum Retroviruses 2000;16(12):1123-33. [PubMed]

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

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):40-7. [PubMed]

Mellors JW, Muñoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997;126(12):946-54. [PubMed]

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):889-97. [PubMed]

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. [PubMed]

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

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):30-8. [PubMed]

Tarwater PM, Gallant JE, Mellors JW, et al. Prognostic value of plasma HIV RNA among highly active antiretroviral therapy users. AIDS 2004;18(18):2419-23. [PubMed]

Thiébaut 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’Epidémiologie du SIDA en Aquitaine (GECSA). AIDS 2000;14(8):971-8. [PubMed]

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;8:314-317. [PubMed]

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):557-63. [PubMed]

CD4 Cell Count

Medical Care Criteria Committee, updated November 2019

Lymphocyte Subsets (CD4 Cell Count)

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

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

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 time period [Myers, et al. 2016]. Reassuringly, other data suggest that in patients with sustained viral suppression and CD4 counts between 100 cells/mm³ and 200 cells/mm³, risk of pneumocystis pneumonia is very low even in the absence of prophylaxis [D’Egidio, et al. 2007; Mocroft, et al. 2010; Chaiwarith, et al. 2013].

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

Absolute CD4 cell 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 in the setting of fluctuations in the absolute CD4 cell 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 cell 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. [PubMed]

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. [PubMed]

El-Sadr WM, Burman WJ, Grant LB, et al. Discontinuation of prophylaxis for 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):1085-92. [PubMed]

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):1185-9. [PubMed]

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;36:702-713. [PubMed]

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;45:183-192. [PubMed]

Havlir DV, Dubé 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):392-8. [PubMed]

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;48:787-794. [PubMed]

Lopez Bernaldo de Quiros JC, Miro JM, Peña 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):159-67. [PubMed]

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. [PubMed]

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;44:441-446. [PubMed]

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. [PubMed]

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):611-9. [PubMed]

Sabin CA, Smith CJ, d’Arminio Monforte A, et al., Collaboration of Observational HIV Epidemiological Research Europe (COHERE) Study Group. Response to combination antiretroviral therapy: Variation by age. AIDS 2008;22:1463-1473. [PubMed]

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):1836-41. [PubMed]

All Recommendations

Medical Care Criteria Committee, June 2016