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HIV and cytomegalovirus viral load and clinical outcomes in AIDS and cytomegalovirus retinitis patients: Monoclonal Antibody Cytomegalovirus Retinitis Trial

Jabs, Douglas A.; Gilpin, Adele M. Kaplana; Min, Yuan-Ia; Erice, Alejob; Kempen, John H.; Quinn, Thomas C.cfor the Studies of Ocular Complications of AIDS Research Group

Clinical Science

Objective To determine the association of cytomegalovirus (CMV) viremia with mortality and CMV retinitis progression in newly diagnosed and relapsed CMV retinitis.

Design Ancillary study of a randomized, placebo-controlled, phase III clinical trial.

Patients A total of 83 patients with AIDS and CMV retinitis, enrolled during the first phase of the Monoclonal Antibody Cytomegalovirus Retinitis Trial, were administered MSL-109 or placebo as adjuvant therapy for CMV retinitis.

Main outcome measure(s) Mortality and CMV retinitis progression.

Results Treatment with MSL-109 did not predict either progression of CMV retinitis or mortality. Detection in plasma CMV DNA at baseline predicted mortality, but CMV antigenemia did not. CMV DNA was a better predictor of mortality than a high HIV viral load. Neither CMV DNA nor antigenemia predicted the progression of CMV retinitis. Among newly diagnosed patients, there was a decline in the proportion with detectable CMV viral load and CMV antigenemia in response to anti-CMV therapy. However, there was a rebound in CMV viral load to 25% and CMV antigenemia to 54.6% at 6 months. In relapsed patients, anti-CMV therapy was not associated with a change in the percentage with detectable CMV-DNA or CMV antigenemia over time.

Conclusion In patients with AIDS and CMV retinitis, the detection of plasma CMV DNA was associated with a higher risk of mortality than was a high HIV viral load. Anti-CMV therapy provided a transient reduction in CMV viremia in newly diagnosed but not relapsed patients with CMV retinitis. Adjuvant therapy with MSL-109 was ineffective in clearing CMV-DNA and CMV antigen from the plasma.

From the Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, MD21205, aCenter for Clinical Trials, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD21205, bUniversity of Minnesota, Minneapolis, MN and cThe Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Requests for reprints to: Douglas A. Jabs, MD, MBA, Department of Ophthalmology, The Johns Hopkins University School of Medicine, 550 North Broadway, Suite 700, Baltimore, MD 21205, USA.

Correspondence to: Adele Gilpin, PhD, JD, Center for Clinical Trials, The Johns Hopkins University School of Hygiene and Public Health, 615 North Wolfe Street, Room 5010, Baltimore, MD 21205, USA. Tel: +1 410 955 8175; fax: +1 410 955 0932; e-mail:

Received: 20 July 2001;

revised: 16 November 2001; accepted: 26 November 2001.

Sponsorship: This work was supported by cooperative agreements from the National Eye Institute to the Johns Hopkins University School of Medicine (U10 EY 08052), School of Hygiene and Public Health (U10 EY 08057), and the University of Wisconsin School of Medicine (U10 EY 08067). Additional support was provided by the National Center for Research Resources through General Clinical Research Center grants 5M01 RR 00350 (Baylor College of Medicine); 5M01 RR 05096 (Louisiana State University/Tulane); 5M01 RR 00096 (New York University); 5M01 RR 000865 (University of California, Los Angeles); and 5M01 RR 00046 (University of North Carolina). Support was also provided by the National Institute of Allergy and Infectious Diseases through cooperative agreements U01 AI 27668 (Johns Hopkins University); U01 AI 27674 (Louisiana State University/Tulane); U01 AI 27669 (Memorial Sloan-Kettering) and U01 AI 25917 (New York Hospital – Cornell Medical Center); U01 AI 27667 (Mount Sinai Medical Center); U01 AI 27665 (New York University); U01 AI 25915 (Northwestern University); U01 AI 27660 (University of California, Los Angeles); U01 AI 27670 (University of California, San Diego); U01 AI 27663 (University of California, San Francisco); U01AI25868 (University of North Carolina); and U01 AI27761 (University of Minnesota). Drug and additional support was provided by Protein Design Laboratories, Inc. (Mountain View, CA).

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Cytomegalovirus (CMV) is an important opportunistic pathogen in patients with AIDS [1–5]. Although CMV may affect many organs, CMV retinitis is the most commonly encountered presentation. Retinitis accounts for 75–85% of CMV disease in patients with AIDS [1,2]. Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis affected an estimated 28–45% of patients with AIDS sometime between the diagnosis of AIDS and death [2–5]. HAART has resulted in a 55–85% reduction in the incidence of CMV retinitis, presumably via the improvement in immune function after the suppression of HIV replication [6,7]. Despite a reduction in incidence, CMV retinitis continues to occur and may cause the loss of vision.

Because HIV viral load measurement has proved to be a useful clinical tool for the management of HIV disease, there has been interest in the potential clinical uses of markers of CMV viremia. In patients with advanced AIDS who have not yet developed CMV disease, studies of CMV-DNA measurement by polymerase chain reaction (PCR) have demonstrated that patients with detectable CMV DNA have a higher risk of developing CMV disease [8–12] and of mortality [8–10]. In those patients with detectable CMV DNA in their blood, a higher CMV-DNA load is associated with an increased risk of both the development of CMV disease and mortality [8–11]. In studies of anti-CMV prophylaxis in patients with advanced AIDS, patients with initially detectable CMV-DNA loads, who became non-detectable by PCR testing during treatment had a lower risk of developing CMV disease and of mortality [8,9]. One study conducted in the era of HAART [13] had similar findings for the risk of CMV disease, but not for mortality, perhaps because the benefits of HAART overshadowed the benefits of anti-CMV prophylaxis. Detectable CMV antigenemia in patients with advanced AIDS is also associated with a higher risk of the occurrence of CMV disease [12–17] and of mortality [14,17]. Antigenemia assays are more demanding technically than DNA detection assays [18].

Although the association of higher mortality with the detection of CMV-DNA or CMV antigen in the blood has been well established for patients with AIDS at risk of CMV disease, less information is available as to the meaning of these measurements in patients already diagnosed with CMV disease. In one study of 45 patients with CMV retinitis and AIDS [19], a high initial CMV-DNA load was associated with shorter survival, but not with a shorter time to progression of the retinitis. Other reports included only small numbers of patients and are difficult to interpret with respect to these questions [16,20].

In this study, we report the relationship between the longitudinal CMV viral load and CMV antigenemia measurements with the risk of mortality and CMV retinitis progression among 83 patients with AIDS participating in a clinical trial of MSL-109 as adjunctive therapy for CMV retinitis [21]. These results provide greater power for evaluating the association of CMV viral load with the risk of mortality and of disease progression than previous studies, because of the larger sample size and longer follow-up. It is also the first large study of CMV antigenemia with respect to these outcomes.

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Materials and methods

Monoclonal Antibody Cytomegalovirus Retinitis Trial

The Monoclonal Antibody Cytomegalovirus Retinitis Trial (MACRT) enrolled patients with AIDS and active CMV retinitis, either newly diagnosed or relapsed, into a randomized controlled trial of MSL-109 as adjuvant therapy for retinitis. The diagnosis of AIDS was made on the basis of the Centers for Disease Control and Prevention 1993 revised surveillance case definition [22]. Active CMV retinitis was diagnosed on the basis of the characteristic appearance of a white necrotizing retinitis observed through a dilated pupil by a SOCA-certified (Studies of Ocular Complications of AIDS) ophthalmologist. The treatment protocol and consent procedures were reviewed and approved by the Institutional Review Boards at each of the participating institutions, and all participants gave written informed consent. This trial was halted in August 1996, when the accumulating data demonstrated that MSL-109 was ineffective as adjuvant treatment for CMV retinitis, and that there was possibly increased mortality among the MSL-109-assigned patients [21].

Patients were stratified as having either newly diagnosed or relapsed CMV retinitis, and were randomly assigned within stratum to adjuvant treatment with either MSL-109 or placebo in a 1 : 1 ratio. Both patients and physicians were masked to treatment assignment. MSL-I09 is a human monoclonal antibody of the IgG l-κ subclass that recognizes the CMV surface antigen gH. The study drug (either MSL-109 at a dosage of 60 mg, or placebo) was administered by intravenous infusion every 2 weeks. Primary therapy for CMV retinitis was determined by the treating physicians at the clinical centers. Decisions concerning changes in primary therapy were made by the local treating physicians, but treatment with the study drug continued regardless of relapses or changes in primary therapy until death or common study closeout.

Data collection visits were scheduled at enrollment (baseline), every 4 weeks for 48 weeks, and every 12 weeks thereafter. At each visit, patients gave a medical and ophthalmic history, and underwent dilated ophthalmological examination, fundus photography, and phlebotomy. Further details concerning stratification, randomization, sample size, treatment administration, and data collection have been published elsewhere [21]. Blood samples for virological studies were collected in ethylenediamine tetraacetic acid tubes from 83 patients assigned to treatment between 14 September 1995 and 19 April 1996. Specimens obtained at baseline and 1, 3 and 6 months after randomization were shipped overnight to a central repository (University of Texas Medical Branch, Galveston, TX, USA) for processing and storage. The following virological studies were performed: CMV antigenemia assay, quantification of CMV-DNA level in plasma by PCR, and quantification of HIV-RNA levels in plasma.

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Measurement of cytomegalovirus and HIV

The CMV antigenemia assay was performed by using a commercial assay (CMV-vue kit; INCSTAR Corp., Stillwater, MN, USA), as previously described [23]. Quantification of CMV DNA (viral load) was performed for plasma by using the COBAS Amplicor CMV Monitor system according to the manufacturer's instructions (Roche Diagnostic Systems, Branchburg, NJ, USA) [24]. The dynamic range for quantification is approximately 3 log10 units, with 200 copies as the lower limit of detection. Plasma HIV-1 RNA was measured by a quantitative RNA PCR assay (Amplicor HIV-1 Monitor test; Roche Diagnostic Systems) as previously described [25]. Samples below the limit of quantification of the CMV and HIV assays (200 copies/ml) were assigned a value of 200 copies/ml for the purpose of statistical analysis.

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Statistical methods

Data collected on or before 13 August 1996, which were reported to the Coordinating Center by 15 November 1996, are included in these analyses. The follow-up for mortality was censored as of 30 May 1997. All analyses, unless otherwise indicated, were performed according to patients’ original treatment assignment (`intent-to-treat’ analysis). P-values for baseline comparisons were based upon the Wilcoxon rank sum test for continuous data and the χ2 test or Fisher's exact test for categorical data. Group means were calculated for continuous variables with symmetrical distributions, whereas medians were calculated for variables with asymmetric distributions. Agreement regarding the detectability of CMV based on PCR versus antigenemia measures was calculated using the kappa statistic. Time-to-event curves and percentiles were derived from the method of Kaplan and Meier [26]. P-values for these comparisons were based on the log-rank test. Relative risks were estimated by the Cox proportional hazards model [27]. Comparisons of the proportions of patients with detectable CMV DNA or positive antigenemia over time were based on logistic regression models. Variances for correlated data were estimated using generalized estimating equations [28].

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The characteristics of the study population are described in Table 1. Twenty-three patients had newly diagnosed CMV retinitis, whereas 60 patients had relapsed CMV retinitis. As anticipated, patients with relapsed CMV retinitis were more likely to have bilateral disease, zone 1 involvement, and a greater percentage of the retinal area involved with CMV. All patients had advanced HIV disease, as evidenced by the low baseline CD4 T cell counts (median 7 cells/μl). There were no significant differences in any baseline characteristics between patients assigned to MSL-109 and those assigned to placebo.

Table 1

Table 1

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Cytomegalovirus viral load and antigenemia results

CMV DNA (greater than 200 copies/ml) was detectable in nearly one-third of patients at baseline (Table 2). Among patients with newly diagnosed CMV retinitis, CMV DNA was detectable in 42.9% compared with 29.3% in those with relapsed CMV retinitis (P = 0.261). In patients with newly diagnosed CMV retinitis, the proportion with detectable CMV DNA declined from baseline to 11.1% (P = 0.01) and 6.2% (P = 0.018), at the 1 and 3 month visits, respectively. However, by 6 months of treatment, the percentage with detectable CMV DNA rebounded to 25% (P = 0.275) with respect to baseline. Conversely, among patients with relapsed retinitis, the percentage positive was similar from baseline throughout the duration of follow-up, ranging between 25 and 30%, despite anti-CMV treatment.

Table 2

Table 2

Among patients with detectable CMV DNA, the median concentration was 2284 copies/ml, and the maximum value was 176 205 copies/ml. The distribution of detectable viral loads was similar between strata for the baseline, 1 month and 3 month timepoints. The number of samples available at the 6 month timepoint was relatively small (three newly diagnosed patients and eight relapsed patients).

CMV antigenemia was detected in a greater percentage of patients (Table 3) than had detectable CMV DNA. The agreement between CMV DNA and antigenemia results was moderate, with a kappa of 0.59 [95% confidence interval (CI) 0.48, 0.71]. As with CMV DNA, there was a significant decline in the percentage of patients with positive CMV antigenemia from baseline to 1 month in patients with newly diagnosed retinitis, from 61.9 to 12.5% (P = 0.006). However, by 6 months of treatment, the percentage of patients with newly diagnosed retinitis with positive antigenemia again climbed to a level similar to that at baseline (54.6%, P = 0.680). Conversely, among patients with relapsed retinitis, the percentage of patients positive for CMV antigenemia remained similar throughout the follow-up process, ranging from 24 to 36%. The course of antigenemia during follow-up thus mirrored that observed with CMV DNA.

Table 3

Table 3

Comparisons between the percentage of MSL-109-assigned and placebo-assigned patients demonstrated no differences in the percentage with detectable CMV DNA either at baseline or during follow-up. Likewise, no difference was demonstrated in the percentage with positive CMV antigenemia either at baseline or during follow-up.

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Clinical outcomes

The median time from the date of randomization to death was 13.9 months, and 49 out of 83 patients died. As shown in Fig. 1, patients with detectable CMV-DNA levels at baseline had significantly greater mortality than those without detectable CMV DNA [relative risk (RR) = 1.96, P = 0.02]. As shown in Fig. 2, there was no significant difference in mortality between patients positive versus those negative for CMV antigenemia. The risk of mortality for those with a baseline HIV viral load above the median level was greater than for those with lower HIV-RNA levels, but this comparison did not achieve statistical significance.

Fig. 1.

Fig. 1.

Fig. 2.

Fig. 2.

The median time to the progression of retinitis was 2.1 months, and 62 out of 78 patients had retinitis progression. No significant difference in the time to progression of the retinitis was observed between patients with detectable versus those with undetectable CMV DNA at baseline; nor between those positive versus those negative for CMV antigenemia at baseline.

Among patients with initially detectable CMV DNA in peripheral blood, those who remained positive at the 1 month follow-up visit had a similar risk of mortality (RR = 1.12, P = 0.80) and retinitis progression (RR = 0.96, P = 0.94) as those who became negative. Among patients initially positive for antigenemia, those who remained positive at 1 month had a higher risk of mortality (RR = 2.17, P = 0.10) and retinitis progression (RR = 1.91, P = 0.18) than those who became negative, but the differences were not statistically significant (see Table 4).

Table 4

Table 4

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Our findings demonstrate that the detection of CMV DNA in the peripheral blood of patients with AIDS and CMV retinitis was associated with an increased risk of subsequent mortality. This result is similar to that observed by Bowen and colleagues [19] in patients with AIDS and CMV retinitis, and to several observations in patients with advanced AIDS at risk of CMV disease [8–10]. Our study also demonstrated that the detection of CMV DNA in peripheral blood was more strongly associated with the risk of mortality than was a high HIV viral load in patients with AIDS and CMV disease, similar to observations in patients with advanced AIDS without CMV disease [9,10]. Therefore, it seems reasonable to conclude that the increased risk of mortality when CMV DNA is detectable by PCR is similar whether CMV retinitis has already occurred or not. The detection of CMV antigenemia at baseline was not significantly associated with mortality in our study, a finding that differs from observations in patients with advanced AIDS but no CMV disease [14,17]. Because PCR for CMV DNA is technically more straightforward than the detection of CMV antigenemia [18], PCR may be the preferred method for studies of CMV viremia.

For anti-CMV therapy-naive patients with advanced AIDS who have PCR evidence of CMV viremia but no CMV disease, Spector and colleagues [9] demonstrated that when ganciclovir treatment is followed by a change from CMV-DNA positive to negative status, the risk of mortality is reduced. However, we did not observe a similar decline in mortality under these conditions for patients who already had CMV disease, but we did observe that newly diagnosed CMV patients often enjoyed a decline in CMV viremia with initial treatment. Our observation that a similar percentage of patients were positive for CMV DNA in peripheral blood by 6 months of follow-up as at baseline suggests that such a clearance of viremia is usually short-lived. Furthermore, anti-CMV treatment failed to improve the control of viremia in patients with relapsed retinitis, who had previously received anti-CMV therapy. A likely explanation for these observations is the development of resistance to anti-CMV therapy over time. These disappointing results suggest that the survival benefit of anti-CMV treatment in patients observed to ‘respond’ with a clearing of CMV viremia may not be long lasting, perhaps because of the development of resistance to anti-CMV therapy over time [29,30].

In our study, the time to progression of retinitis was not significantly different between patients with detectable and those with non-detectable CMV DNA in peripheral blood at baseline, as in the study by Bowen et al. [19]. Nor were there differences in the risk of progression for patients with versus those without detectable CMV antigenemia at baseline. These observations support the theory that most retinitis progressions occur as a result of limited drug delivery to the retina after restoration of the blood–retinal barrier, rather than from the re-seeding of the retina with new virus from the blood. This conclusion is consistent with clinical intuition, in that most progressions involve the movement of existing borders of CMV lesions, rather than the development of new lesions. Systemically administered anti-CMV drugs are known to have limited penetration of the blood–retinal barrier, achieving a level approximately equal to the IC50 [31].

In the MACRT [21], MSL-109 adjuvant therapy for CMV retinitis had no benefit with respect to the progression of CMV retinitis. One potential explanation for this observation is that poor penetration of the blood–ocular barrier by MSL-109 prevented it from reaching a sufficient concentration at the retina to be of benefit. However, the results reported herein demonstrate that there was no benefit of MSL-109 adjunctive therapy with respect to the clearance of CMV viremia, suggesting that MSL-109 at a dose of 60 mg intravenously every 2 weeks is not likely to be valuable for adjuvant treatment of any kind of CMV disease. On the basis of the published pharmacokinetic data [32] the expected equilibrium MSL-109 level for a 70 kg individual would be 32.9 mg/l, well above the ED90 level of 4.45 mg/l [33]. A recently published clinical trial [34] found no benefit of MSL-109 at dosages of up to 60 mg/kg for the prevention of CMV disease in hematopoietic stem cell transplant recipients, suggesting that the drug is ineffective in vivo at a wide range of dosages.

The strengths of our study include the prospective collection of specimens and clinical data, masked photographic evaluation of retinitis progression, long-term follow-up for mortality, relatively long follow-up of peripheral blood CMV-DNA results compared with previous studies, the relatively large study size compared with other studies evaluating CMV viremia in patients with AIDS and known CMV disease, and the simultaneous evaluation of CMV DNA, CMV antigenemia and HIV RNA in this patient group. In addition, our 15 center study may have provided a study population more representative of the general population than single center studies, improving generalizability. Limitations include the substantial losses to follow-up by the 6 month observation, mostly because of early mortality, non-uniform selection of anti-CMV treatment strategy, and limited sample size. Finally, this study was conducted largely in the era before HAART. HAART has resulted in improved immune function, and in many patients the improved control of retinitis, allowing selected patients to discontinue anti-CMV therapy [35–37]. How HAART will affect the relationship of CMV viral load to mortality among those with CMV retinitis remains to be determined.

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The detection of CMV DNA in the peripheral blood of patients with known CMV retinitis and AIDS was associated with poorer survival, but was not predictive of retinitis relapse. PCR testing for CMV DNA appears to have greater predictive value for mortality than testing for CMV antigenemia in this group of patients. Although the available evidence suggests that a survival benefit may be obtained when CMV viremia can be successfully cleared by anti-CMV therapy, our study raises the concern that the clearance of CMV viremia may be short-lived in a substantial number of patients, possibly because of viral resistance. MSL-109 adjuvant therapy had no effect on CMV viremia.

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The authors would like to thank Roche Molecular Systems, Inc., Pleasanton, CA, for donation of the CMV Monitor Assays. They would also like to thank INCSTAR Corporation, Stillwater, MN, for donation of CMV-vue antigenemia assays.

Conflict of interest: Financial disclosure statements are on file at the SOCA Coordinating Center, Johns Hopkins University School of Hygiene and Public Health.

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The Monoclonal Antibody Cytomegalovirus Retinitis Trial participating clinical centers

Baylor College of Medicine, Cullen Eye Institute, Houston: Richard A. Lewis, MD, MS (Director); Louise M. Carr-Holden, CRA; Kay Doyle, RN; Victor Fainstein, MD; Neal Gardner, RPh; Ronald Gross, MD; Silvia Orengo-Nania, MD; Varsha Patel, RPh; Tobias C. Samo, MD; James W. Shigley, CRA; Laura Shawver, COT; Steven S. Spencer, COMT; Mary Weinert, MD.

Emory University Clinic, Atlanta: Daniel F. Martin, MD (Director); Deborah Gibbs, COMT; John Jernigan, MD.

Johns Hopkins University School of Medicine, Baltimore: J.P. Dunn, MD (Director); John Bartlett, MD; Rebecca Becker, PA-C; Douglas A. Jabs, MD, MBA; Daniel A. Johnson, MD; John H. Kempen, MD, PhD; Susan LaSalvia, RN; Jo Leslie, PA-C; Janine Maenza, MD; Tracy Miller, LPN, COT; Laura G. Neisser, COT; Richard D. Semba, MD; Pamela Tucker, MD.

Louisiana State University Medical Center, New Orleans: Bruce Barron, MD (Director); Christine Jarrott, RN; Gholam Peyman, MD; Dennis Swenie, MD.

Memorial Sloan-Kettering Cancer Center and New York Hospital – Cornell Medical Center, New York: Murk-Hein Heinemann, MD (Director); Roberta Janis, RN; Bruce Polsky, MD; Kent Sepkowitz, MD.

Mount Sinai School of Medicine, New York: Alan H. Friedman, MD (Director); Robin Ginsburg, MD; Colette Severin, MS; Steven Teich, MD; Fran Wallach, MD.

New Jersey Medical School, New Jersey: Ronald Rescigno, MD (Director); Rosa Paez-Boham; Eileen Buroff; Patricia Kloser, MD; Maxine Wanner.

New York University Medical Center, New York: Dorothy N. Friedberg, MD, PhD (Director); Adrienne Addessi, MA, RN; Abraham Chachoua, MD; Douglas Dieterich, MD; Jason Hill; Richard Hutt, RN; Aditya Kaul, MD; Jonathan Ligh, MD; Monica Lorenzo-Latkany, MD; Maria Pei; Therese Powers, MS.

Northwestern University, Chicago: David V. Weinberg, MD, (Director); Lee M. Jampol, MD; Alice T. Lyon, MD; Annmarie Muñana, RN; Robert Murphy, MD; Frank Palella, MD; Len Richine; Zuzanna Strugala, OMA; Gloria Valadez.

University of California at Los Angeles, Los Angeles: Gary N. Holland, MD (Director); Margrit E. Carlson, MD; Suzette A. Chafey, RN, NP; W. David Hardy, MD; Ann K. Johiro, RN, MN, FNP; Lesley J. MacArthur-Chang, MEd; Maureen A. Martin, RN, MN, FNP; Ardis A. Moe, MD; Catherine A. Strong, MT, ASCP; Adnan Tufail, MB, BS, FRCOphth; Prabha S. Ugalat, BS; James M. Weisz, MD.

University of California at San Diego, San Diego: William R. Freeman, MD (Director); J. Fernando Arevalo-Colina, MD; Tom Clark, CRA; Cheryl L. Jarman; Linda Meixner, RN; Tze Chiang Meng, MD; Stephen Spector, MD; Ibrahim Taskintuna, MD; Francesca J. Torriani, MD.

University of California at San Francisco, San Francisco: James O'Donnell, MD (Director); Pierre Alfred, MD; Fermin Ballesteros; David Clay; Rebecca Coleman, PharmD; Kathleen Gordon, MD; Deborah Gumbley; Jacqueline Hoffman; Alexander Irvine, MD; Mark Jacobson, MD; James Larson, COT; Leonardo Macalalag; Michael Narahara; Mary Payne, RN; Stuart Seiff, MD; Scarlette Wilson, MD; Harlan Woodring.

University of Miami School of Medicine, Miami: Janet Davis, MD (Director); Anita Blenke; Inez Madera, RN; Paul Mendez, MD; Timothy Murray, MD.

University of North Carolina, Chapel Hill: Charles van der Horst, MD (Director); Jan Kylstra, MD; David Wohl, MD; Kimberlee Ziman, BA.

University of South Florida, Tampa: Peter Reed Pavan, MD (co-Director); W. Sanderson Grizzard, MD (co-Director); Gary A. Bergen, MD; Steven M. Cohen, MD; Jayne Ann Craig, OT; Richard L. Dehler, MD; Elizabeth Elbert, MD; Roger W. Fox, MD; Mark E. Hammer, MD; Lizette S. Hernandez, MD; Stacey Herrera; Douglas Holt, MD; Stephen Kemp, MD; Julie A. Larkin, MD; Dennis K. Ledford, MD; Richard F. Lockey, MD; Matthew M. Menosky, MD; Sharon Millard, RN, COT; Jeffrey P. Nadler, MD; Robert P. Nelson, Jr., MD; Dorece Norris, MD; L. David Ormerod, MD; Scott E. Pautler, MD; Sarah Jessica Poblete, MD; Dena Rodriguez, COT; Kevin P. Rosenbach, MD; Daniel W. Seekins, MD; John R. Toney, MD.

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Resource centers

Chairman's Office, Johns Hopkins University School of Medicine, Baltimore, MD: Douglas A. Jabs, MD, MBA (Study Chairman); Joan M. Dodge; Joan L. Klemstine; Tracey A. Schuerholtz; Maria Stevens.

Coordinating Center, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD: Curtis L. Meinert, PhD (Director); Aynur Unalp-Arida, MD, PhD; Debra Amend-Libercci; Laura Coleson-Schreur, RN, MPH; Karen L. Collins; Betty J. Collison; Chris Dawson; John Dodge; Michele Donithan, MHS; Cathleen Ewing; Nancy Fink, MPH; Charlotte Gerczak, MLA; Judith Harle; Janet T. Holbrook, MS, MPH, PhD; Robert Huffman; Milana R. Isaacson, BS; Adele M. Kaplan Gilpin, PhD, JD; John H. Kempen, MD, PhD; Madelyn Lane; Charlene R. Levine, BS; Barbara Martin, PhD; Jill Meinert; Yuan-I Min, PhD, MHS, MPH; Deborah J. Nowakowski; Rosetta M. Jackson; Maria J. Oziemkowska, MS, MPH; Bonnie Piantadosi, MSW, MPH; Alfred Saah, MD, MPH; Michael Smith; James Tonascia, PhD; Mark L. Van Natta, MHS.

Fundus Photograph Reading Center, University of Wisconsin, Madison, WI: Matthew D. Davis, MD (Director); Jane Armstrong; Judith Brickbauer; Rosemary Brothers; Marika Chop; Larry Hubbard, MAT; Dolores Hurlburt; Linda Kastorff; Michael Neider; Jim Onofrey; Vicki Stoppenbach; Marilyn Vanderhoof-Young.

Central Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD: Thomas C. Quinn, MD; Denise McNairn, MS.

Central Laboratory, University of Minnesota, Minneapolis, MN: Alejo Erice, MD; Marlene A. Holm.

Central Repository, University of Texas Medical Branch, Galveston, TX: Richard B. Pollard, MD; Pat Turk; Jason Urtis.

Drug Distribution Center, McKesson Bioservices Corporation, Rockville, MD: Mark Walls; Robert Hughes.

National Eye Institute, Bethesda, MD: Natalie Kurinij, PhD; Richard L. Mowery, PhD.

National Institute of Allergy and Infectious Diseases, Bethesda, MD: Beverly Alston, MD, Mary Foulkes, PhD.

Protein Design Laboratories, Mountain View, CA: Paul I. Nadler, MD; Debra L. Wood, MD; Marge Bladet; Nancy Wu.

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Study Committees

Officers of the Study: Douglas A. Jabs, MD, MBA (Chair); Matthew D. Davis, MD; Natalie Kurinij, PhD; Curtis L. Meinert, PhD; Richard L. Mowery, PhD; James Tonascia, PhD.

Steering Committee: Douglas A. Jabs, MD, MBA (Chair); Adrienne Addessi, MA, RN; Beverly Alston, PhD; Tom Clark, CRA; Matthew D. Davis, MD; Judith Feinberg, MD; William Freeman, MD; Janet Holbrook, MS, MPH, PhD; Gary N. Holland, MD; Larry Hubbard, MAT; Mark Jacobson, MD; Natalie Kurinij, PhD; Richard A. Lewis, MD, MS; Leslie McArthur-Chang, MEd; Curtis Meinert, PhD; Richard Mowery, PhD; Robert Murphy, MD; Bruce Polsky, MD; James Tonascia, PhD.

SOCA-ACTG Joint Executive Committee: Douglas A. Jabs, MD, MBA (Chair); Matthew D. Davis, MD; William R. Duncan, PhD; Judith Feinberg, MD; Harold Kessler, MD; Natalie Kurinij, PhD; A. Garey Lambert (deceased); Natalie Kurinij, PhD; Curtis L. Meinert, PhD; Richard L. Mowery, PhD; William Powderly, MD; Steve Schnittman, MD; Steven Spector, MD; James Tonascia, PhD.

Policy and Data Monitoring Board: Byron W. Brown, Jr., PhD (Chair); Brian Conway, MD; James Grizzle, PhD; Robert Nussenblatt, MD; John P. Phair, MD; Harmon Smith, PhD; Richard Whitley, MD.

Non-voting members: Beverly Alston, MD; Matthew D. Davis, MD; Mary Foulkes, PhD; Douglas A. Jabs, MD, MBA; Natalie Kurinij, PhD; Curtis L. Meinert, PhD; Richard L. Mowery, PhD; James Tonascia, PhD.

Community Advisory Board: Ben Cheng; Kevin Frost; A. Garey Lambert (deceased); Michael Marco.

Viral Outcomes Committee: Thomas C. Quinn, MD (Chair); Alejo Erice, MD; Adele M. Kaplan Gilpin, PhD, JD; Douglas A. Jabs, MD, MBA; Yuan-I Min, PhD, MHS, MPH; Richard B. Pollard, MD.


AIDS; antigenemia; cytomegalovirus; HIV; randomized clinical trial; viral load; viremia

© 2002 Lippincott Williams & Wilkins, Inc.