Given the differences shown in the characteristics of patients eligible for GPT during 1999 to 2002 and 2003 to 2006 (Table 1) and the substantial uptake in resistance testing, we analyzed factors associated with GPT for each period separately. In the multivariable analysis for the period 1999 to 2002, GPT was significantly less likely among women (adjusted relative risk [RR] = 0.73) and heterosexual men (RR = 0.65) versus MSM and among blacks (RR = 0.72) versus whites. Compared with other ARV-experienced patients, GPT was significantly more likely among TCE patients (RR = 1.34) and significantly less likely among ARV-naïve patients (RR = 0.47) (Table 2). In the multivariable analyses for period 2003 to 2006, we found significantly lower likelihood of undergoing GPT among older patients (RR = 0.89 for every 10 yr of age) and higher rates of testing among ARV-naïve patients (RR = 1.81) and TCE patients (RR = 1.68) compared with other ARV-experienced patients. Women tended to remain less likely to be tested (RR = 0.83, P = 0.05) than MSM during 2003 to 2006, whereas heterosexual men were as likely to have undergone testing (RR 1.04, P = 0.65). Lower CD4 cell count and higher HIV viral load were independently associated with increased likelihood of GPT in both periods. Publicly insured patients tended to have somewhat lower rates of GPT in the first period and higher rates of testing in the second period, but these findings were not statistically significant (Table 2).
The CD4 counts and HIV viral loads of patients who underwent GPT varied by calendar year. Median CD4 count at the time of GPT increased from 223 cells/mm3 in 1999, peaked at approximately 325 cells/mm3 between 2002 and 2004, and then fell to 266 cells/mm3 among patients tested in 2006 (Fig. 4). Correspondingly, the median HIV viral load fluctuated from 4.7 log10 copies/mL in 1999 to 4.3 log10 copies/mL in 2003 and 4.6 log10 copies/mL in 2006.
Our study documents increasing use of HIV resistance testing for clinical management in a demographically diverse population of ARV-naïve and -experienced patients seen at 10 public and private HIV specialty clinics in the U.S. during 1999 to 2006. Whereas the number and fraction of patients eligible for GPT (by our conservative definition) declined over time, the annual use of GPT increased and leveled at approximately 30% of eligible patients being tested in 2003. Notably, the annual rates of GPT for ARV-naïve patients not only increased over time but after 2003 exceeded the corresponding rates for ARV-experienced patients. In more recent years of 2003 to 2006, older HOPS patients remained less likely to receive GPT, but sex and racial/ethnic disparities in testing observed during 1999 to 2002 diminished or were no longer apparent.
The leveling in use of ARV resistance testing among ARV-experienced patients in the period 2003 to 2006 may reflect an overall decrease in the frequency of virologic failures that necessitated resistance testing. The finding is supported by the observed decline in the proportion of HOPS patients eligible for testing (having HIV viral load > 1000 copies/mL) over time and is consistent with previously noted improvements in morbidity and mortality in our and other HIV cohorts in the United States and other industrialized countries.1,2,4 In the HOPS, GPT was used more frequently among patients with advanced disease (lower CD4 count and higher viral load) and among ARV-experienced TCE patients. Over time, use of both genotypic and phenotypic resistance testing became more common, and genotypic testing alone became relatively less frequent. Taken together, these data suggest that HOPS physicians were more likely to fully use resistance testing options to tailor ARV regimens for their patients at higher risk of treatment failure.
Despite adjustment for clinical and treatment factors, we observed significant differences in GPT use by sociodemographic factors, but these differences were mostly period specific, more pronounced in the earlier years, and some subsided in the second time period. Although it is encouraging that racial and ethnic disparities in use of GPT were no longer apparent during 2003 to 2006, older patients remained significantly less likely to be tested than younger patients, and women still tended to be less tested than men. This observation may warrant further investigation in light of the fact that similar disparities have been observed in the delivery of other types of HIV care.24
Our study is subject to some limitations. First, our results are derived from a convenience sample of patients who were receiving care at select HIV specialty clinics staffed by experienced HIV care providers. The HOPS physicians ordered resistance testing at their discretion, and therefore it is possible that, in some cases, our criteria for patient eligibility for genotypic and phenotypic testing (e.g., documented viral load >1000 copies/mL) may not have matched the criteria used by the treating physicians. Our present definition was a conservative choice to ensure a definitive indication for GPT in patients who would have had sufficient virus present for the assay to be performed with reliable results from 1999 onward. Second, there were instances of GPT being ordered for which no preceding HIV viral load was documented in the medical records (particularly HIV viral loads measured before first HOPS visit), which could have led us to misclassify and exclude a small fraction of patients as apparently ineligible for GPT. The percentage of patients who received GPT in any given year with no baseline viral load or only viral loads 1000 copies/mL or less and whom we thus excluded from the analysis ranged from 11% to 20% during the study period. Also, the proportion of patients undergoing GPT at their initial HOPS clinic visit, when HIV viral load may not have been available or abstracted, increased steadily from 4.3% in 1999 to 18.1% in 2006.
In conclusion, this analysis documents the increasing use of GPT in a large population of HIV-infected patients receiving routine HIV care in the United States. Use of GPT increased among both ARV-experienced and ARV-naïve patients, reflecting current recommendations. The use of GPT was closely related to the severity of HIV disease. Although initial disparities in the use of GPT by race/ethnicity have waned, older patients remained significantly less likely to have undergone testing with this diagnostic procedure. Addressing remaining disparities is important in view of recent findings from our cohort that use of GPT was independently associated with improved survival among cART-experienced patients.13
The authors thank the thousands of HOPS subjects across the United States for their continued support and participation in the study. They also thank anonymous reviewers for their thoughtful feedback on the analyses and Marcus Durham for assistance in preparation of the figures.
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Appendix. The HIV Outpatient Study (HOPS) Investigators, 2009
The HOPS Investigators currently include the following investigators and sites: John T. Brooks, Kate Buchacz, Marcus Durham, Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention (NCHSTP), Centers for Disease Control and Prevention (CDC), Atlanta, GA; Kathleen C. Wood, Rose K. Baker, James T. Richardson, Darlene Hankerson, and Carl Armon, Cerner Corporation, Vienna, VA; Frank J. Palella, Joan S. Chmiel, Carolyn Studney, and Onyinye Enyia, Feinberg School of Medicine, Northwestern University, Chicago, IL; Kenneth A. Lichtenstein and Cheryl Stewart, National Jewish Medical and Research Center Denver, CO; John Hammer, Benjamin Young, Kenneth S. Greenberg, Barbara Widick, and Joslyn D. Axinn, Rose Medical Center, Denver, CO; Bienvenido G. Yangco and Kalliope Halkias, Infectious Disease Research Institute, Tampa, FL; Douglas J. Ward and Jay Miller, Dupont Circle Physicians Group, Washington, DC; Jack Fuhrer, Linda Ording-Bauer, Rita Kelly, and Jane Esteves, State University of New York (SUNY), Stony Brook, NY; Ellen M. Tedaldi, Ramona A. Christian, Faye Ruley and Dania Beadle, Temple University School of Medicine, Philadelphia, PA; Richard M. Novak and Andrea Wendrow, University of Illinois at Chicago, Chicago, IL. Cited Here...