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U.S. Trends in Antiretroviral Therapy Use, HIV RNA Plasma Viral Loads, and CD4 T-Lymphocyte Cell Counts Among HIV-Infected Persons, 2000 to 2008

Keri N. Althoff, PhD, MPH; Kate Buchacz, PhD, MPH; H. Irene Hall, PhD, MPH; Jinbing Zhang, MS; David B. Hanna, MS; Peter Rebeiro, ScM; Stephen J. Gange, PhD; Richard D. Moore, MD, MHS; Mari M. Kitahata, MD, MPH; Kelly A. Gebo, MD, MPH; Jeffrey Martin, MD; Amy C. Justice, MD, PhD; Michael A. Horberg, MD; Robert S. Hogg, PhD; Timothy R. Sterling, MD; Angela Cescon, MPH; Marina B. Klein, MD; Jennifer E. Thorne, MD, PhD; Heidi M. Crane, MD, MPH; Michael J. Mugavero, MD; Sonia Napravnik, PhD; Gregory D. Kirk, MD, PhD; Lisa P. Jacobson, ScD; John T. Brooks, MD, for the North American AIDS Cohort Collaboration on Research and Design
[+] Article and Author Information

From Johns Hopkins University, Baltimore, Maryland; Centers for Disease Control and Prevention, Atlanta, Georgia; University of Washington, Seattle, Washington; University of California, San Francisco, San Francisco, California; Yale University and the Veterans Affairs Connecticut Healthcare System, New Haven, Connecticut; Mid-Atlantic Permanente Research Institute, Rockville, Maryland; British Columbia Centre for Excellence in HIV/AIDS and Simon Fraser University, Vancouver, British Columbia, Canada; Vanderbilt University, Nashville, Tennessee; McGill University, Montreal, Quebec, Canada; University of Alabama, Birmingham, Birmingham, Alabama; and University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Disclaimer: Dr. Althoff and Mr. Zhang had full access to all of the NA-ACCORD data in the study; they take responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Buchacz and Hall had full access to the HARS data in the study; they take responsibility for the integrity of the data and the accuracy of the data analysis. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC.

Grant Support: By grants U01-AI069918, U10-AA13566, U01-AI31834, U01-AI34989, U01-AI34993, U01-AI34994, U01-AI35004, U01-AI35039, U01-AI35040, U01-AI35041, U01-AI35042, U01-AI35043, U01-AI37613, U01-AI37984, U01-AI38855, U01-AI38858, U01-AI42590, U01-AI68634, U01-AI68636, U01-HD32632, U10-EY08057, U10-EY08052, U10-EY08067, UL1-RR024131, UL1-RR024131, M01-RR-00052, M01-RR00071, M01-RR00079, M01-RR00083, M01-RR00722, M01-RR025747, P30-AI27757, P30-AI27767, P30-AI27763, P30-AI50410, P30-AI54999, R01-DA04334, R01-DA12568, R01-DA11602, R01-AA16893, R24-AI067039, Z01-CP010176, AHQ290-01-0012, N02-CP55504, AI-69432, AI-69434, K01-AI071725, K23-AI610320, K23-EY013707, K24-DA00432, K01-AI093197 (Dr. Althoff) and F31-DA30254 (Mr. Hanna) from the National Institutes of Health; contract CDC200-2006-18797 from the CDC; grants TGF-96118, HCP-97105, CBR-86906, CBR-94036, KRS-86251, and 169621 from the Canadian Institutes of Health Research; the Canadian HIV Trials Network, project 24; and the government of British Columbia. The CDC funds all U.S. states and the District of Columbia to conduct HIV surveillance and provides technical assistance to all funded areas. Participating investigators and contributors are CDC employees. Employees of the CDC conducted the surveillance data analyses, and the report was reviewed and approved by the CDC.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-0355.

Reproducible Research Statement:Study protocol: For more information about the NA-ACCORD, please go to http://statepiaps.jhsph.edu/naaccord/. Statistical code and data set: Available from Dr. Althoff (e-mail, kalthoff@jhsph.edu).

Requests for Single Reprints: Keri N. Althoff, PhD, MPH, 615 North Wolfe Street, Room E-7142, Baltimore, MD 21231; e-mail, kalthoff@jhsph.edu.

Current Author Addresses: Dr. Althoff: Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 North Wolfe Street, Room E-7142, Baltimore, MD 21205.

Drs. Buchacz, Hall, and Brooks: Centers for Disease Control and Prevention, Divisions of HIV/AIDS Prevention, 1600 Clifton Road Northeast, MS E-45, Atlanta, GA 30333.

Mr. Zhang: Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 111 Market Place, Suite 906, Baltimore, MD 21202.

Mr. Hanna and Mr. Rebeiro: Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 North Wolfe Street, Baltimore, MD 21205.

Dr. Gange: Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 North Wolfe Street, Room E-7638, Baltimore, MD 21205.

Dr. Moore: Johns Hopkins School of Medicine, 1830 East Monument Street, Room 8059, Baltimore, MD 21205.

Drs. Kitahata and Crane: University of Washington, Harborview Medical Center, 325 9th Avenue, Seattle, WA 98104.

Dr. Gebo: Johns Hopkins School of Medicine, Division of Infectious Diseases, 1830 East Monument Street, Room 432, Baltimore, MD 21205.

Dr. Martin: University of California, San Francisco, 185 Berry Street 5700, Box 0560, San Francisco, CA 94143.

Dr. Justice: Veterans Affairs Connecticut Healthcare System, 950 Campbell Avenue, 11-ACSLG, West Haven, CT 06516.

Dr. Horberg: Mid-Atlantic Permanente Research Institute, 2101 East Jefferson Street, 3 West, Rockville, MD 20852.

Dr. Hogg and Ms. Cescon: British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, 608-1081 Burrard Street, Vancouver, British Columbia V6Z 1Y6, Canada.

Dr. Sterling: Vanderbilt University School of Medicine, Division of Infectious Disease, 1161 21st Avenue A 2200 MCN, Nashville, TN 37232.

Dr. Klein: McGill University Health Centre, Division of Infectious Disease and Immunodeficiency Service, 3650 Rue Saint Urbain J9.01d, Montreal, Quebec H2X 2P4, Canada.

Dr. Thorne: Wilmer Eye Institute, Division of Ocular Immunology, 600 North Wolfe Street, Maumenee 119, Baltimore, MD 21287.

Dr. Mugavero: University of Alabama, Birmingham, 1917 Clinic Cohort, CCB 178, 1530 3rd Avenue South, Birmingham, AL 35294.

Dr. Napravnik: The University of North Carolina at Chapel Hill, 130 Mason Farm Road, 2101 Bioinformatics Building, CB 7215, Chapel Hill, NC 27599.

Dr. Kirk: Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 North Wolfe Street, Room E-6533, Baltimore, MD 21205.

Ms. Jacobson: Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, 615 North Wolfe Street, Room E-7646, Baltimore, MD 21205.

Author Contributions: Conception and design: K.N. Althoff, K. Buchacz, D.B. Hanna, S.J. Gange, R.D. Moore, M. Kitahata, J. Thorne, H. Crane, J.T. Brooks.

Analysis and interpretation of the data: K.N. Althoff, K. Buchacz, H.I. Hall, J. Zhang, D.B. Hanna, P. Rebeiro, S.J. Gange, R.D. Moore, M. Kitahata, A.C. Justice, M. Horberg, R.S. Hogg, T.R. Sterling, A. Cescon, J. Thorne, M.J. Mugavero, G.D. Kirk, L.P. Jacobson, J.T. Brooks.

Drafting of the article: K.N. Althoff, H.I. Hall, P. Rebeiro, S.J. Gange, J. Martin, J.T. Brooks.

Critical revision of the article for important intellectual content: K.N. Althoff, K. Buchacz, H.I. Hall, D.B. Hanna, S.J. Gange, R.D. Moore, M. Kitahata, K.A. Gebo, J. Martin, A.C. Justice, M. Horberg, R.S. Hogg, T.R. Sterling, A. Cescon, M.B. Klein, J. Thorne, M.J. Mugavero, S. Napravnik, G.D. Kirk, L.P. Jacobson, J.T. Brooks.

Final approval of the article: K.N. Althoff, K. Buchacz, H.I. Hall, D.B. Hanna, P. Rebeiro, S.J. Gange, R.D. Moore, M. Kitahata, K.A. Gebo, J. Martin, A.C. Justice, M. Horberg, R.S. Hogg, T.R. Sterling, A. Cescon, M.B. Klein, J. Thorne, H. Crane, M.J. Mugavero, S. Napravnik, G.D. Kirk, L.P. Jacobson, J.T. Brooks.

Provision of study materials or patients: K. Buchacz, R.D. Moore, K.A. Gebo, A.C. Justice, T.R. Sterling, J. Thorne, S. Napravnik, G.D. Kirk, J.T. Brooks.

Statistical expertise: K.N. Althoff, J. Zhang, D.B. Hanna, S.J. Gange, J. Martin, A.C. Justice, L.P. Jacobson.

Obtaining of funding: R.D. Moore, M. Kitahata, J. Martin, L.P. Jacobson.

Administrative, technical, or logistic support: H.I. Hall, R.D. Moore, J. Thorne.

Collection and assembly of data: H.I. Hall, P. Rebeiro, S.J. Gange, R.D. Moore, M. Kitahata, A.C. Justice, M. Horberg, R.S. Hogg, H. Crane, M.J. Mugavero, S. Napravnik, GD. Kirk, J.T. Brooks.


Ann Intern Med. 2012;157(5):325-335. doi:10.7326/0003-4819-157-5-201209040-00005
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Background: The U.S. National HIV/AIDS Strategy targets for 2015 include “increasing access to care and improving health outcomes for persons living with HIV in the United States” (PLWH-US).

Objective: To demonstrate the utility of the NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) for monitoring trends in the HIV epidemic in the United States and to present trends in HIV treatment and related health outcomes.

Design: Trends from annual cross-sectional analyses comparing patients from pooled, multicenter, prospective, clinical HIV cohort studies with PLWH-US, as reported to national surveillance systems in 40 states.

Setting: U.S. HIV outpatient clinics.

Patients: HIV-infected adults with 1 or more HIV RNA plasma viral load (HIV VL) or CD4 T-lymphocyte (CD4) cell count measured in any calendar year from 1 January 2000 to 31 December 2008.

Measurements: Annual rates of antiretroviral therapy use, HIV VL, and CD4 cell count at death.

Results: 45 529 HIV-infected persons received care in an NA-ACCORD–participating U.S. clinical cohort from 2000 to 2008. In 2008, the 26 030 NA-ACCORD participants in care and the 655 966 PLWH-US had qualitatively similar demographic characteristics. From 2000 to 2008, the proportion of participants prescribed highly active antiretroviral therapy increased by 9 percentage points to 83% (P < 0.001), whereas the proportion with suppressed HIV VL (≤2.7 log10 copies/mL) increased by 26 percentage points to 72% (P < 0.001). Median CD4 cell count at death more than tripled to 0.209 × 109 cells/L (P < 0.001).

Limitation: The usual limitations of observational data apply.

Conclusion: The NA-ACCORD is the largest cohort of HIV-infected adults in clinical care in the United States that is demographically similar to PLWH-US in 2008. From 2000 to 2008, increases were observed in the percentage of prescribed HAART, the percentage who achieved a suppressed HIV VL, and the median CD4 cell count at death.

Primary Funding Source: National Institutes of Health; Centers for Disease Control and Prevention; Canadian Institutes of Health Research; Canadian HIV Trials Network; and the government of British Columbia, Canada.

Figures

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Figure 1.

Unadjusted percentages of persons living with HIV infection in the 50 states and the District of Columbia who were alive and in care among U.S. clinical cohorts participating in NA-ACCORD (n  = 23 884), by state, year-end 2008.

Data from the multicenter Veterans Aging Cohort Study are excluded because residency information was not available for participants or for their site of clinical care. Two additional cohorts, the HIV Research Network and the HIV Outpatient Study, report residency by the location of clinical care. As of 2008, stable, confidential, name-based systems for reporting persons living with HIV infection to the Centers for Disease Control and Prevention were used in Alabama, Alaska, Arizona, Arkansas, Colorado, Connecticut, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maine, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Hampshire, New Jersey, New Mexico, New York, Nevada, North Carolina, North Dakota, Ohio, Oklahoma, Pennsylvania, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, West Virginia, Wisconsin, and Wyoming. Estimated totals from these states were adjusted for reporting delays and missing risk factors. The remaining 10 states (California, Delaware, Hawaii, Maryland, Massachusetts, Montana, Oregon, Rhode Island, Vermont, and Washington) and the District of Columbia reported only unadjusted estimates for year-end 2008. NA-ACCORD = North American AIDS Cohort Collaboration on Research and Design.

* No NA-ACCORD participants eligible for this analysis were known to be living in the state.

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Figure 2.

Trends in prescribed ART for HIV infection among participants in U.S. clinical cohort studies in NA-ACCORD, 2000 to 2008.

Proportions are noted in the horizontal bars if >1%. P values for the top and middle panels were calculated by using general linear models with generalized estimating equations for repeated measures; for values in the bottom panel, the Cochran–Armitage test of trend was used. ART = antiretroviral therapy; HAART = highly active antiretroviral therapy; NA-ACCORD = North American AIDS Cohort Collaboration on Research and Design; NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor. Top. ART status among all participants. P for trend <0.001 for HAART, ART, off ART, and treatment-naive; P for trend = 0.137 for off HAART. Middle. Prescribed HAART, by drug class. P for trend <0.001 for all groups. Bottom. Prescribed therapy, by drug class, among treatment-naive participants initiating HAART. P for trend <0.001 for all groups.

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Figure 3.

Trends in the proportion of participants with suppressed HIV VL (≤2.7 log10 copies/mL [≤500 copies/mL]) and midyear HIV VL, by ART status, among participants in U.S. clinical cohort studies in NA-ACCORD, from 2000 to 2008.

For midyear HIV VL, we used the measurement obtained closest to 30 June (P for trend <0.001 for overall suppressed HIV VL, missing HIV VL, and mean HIV VL [overall and for HAART recipients]; P values for trends in median HIV VL are not reported). ART = antiretroviral therapy; HAART = highly active antiretroviral therapy; NA-ACCORD = North American AIDS Cohort Collaboration on Research and Design; VL = RNA plasma viral load.

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Figure 4.

Median CD4 cell count within 18 months before death among participants in U.S. clinical cohort studies in NA-ACCORD, 2000 to 2008.

Among the 5144 decedents, 4417 had a CD4 cell count measured at or within 18 months before death. Lines represent 95% CIs, estimated by using bootstrapping with 2000 repeats. NA-ACCORD = North American AIDS Cohort Collaboration on Research and Design.

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Appendix Figure 1.

Age distribution of study population, by year.

NA-ACCORD = North American AIDS Cohort Collaboration on Research and Design.

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Appendix Figure 2.

Mortality rates per 1000 person-years, by CD4 cell count and age group.

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