CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection

Background:Reductions in AIDS-related morbidity and mortality following the advent of combination antiretroviral therapy have coincided with relative increases in chronic non-AIDS end-organ diseases among HIV+ patients. Objective:To examine the association of latest CD4+ counts with risk of non-AIDS diseases in a cohort of 1397 patients who initiate antiretroviral therapy. Methods:CD4+ counts and HIV RNA levels along with fatal, and non-fatal, AIDS and non-AIDS diseases (liver, cardiovascular, renal, and cancer) were assessed over a median follow-up of 5 years. Cox proportional regression models were used to study risk associations. Results:A total of 227 patients experienced an AIDS event and 80 patients developed a non-AIDS disease event. Both AIDS and non-AIDS diseases rates (events/100 person-years), respectively, declined with higher latest CD4+ counts: 13.8 and 2.1 with latest CD4+ counts less than 200 cells/μl; 2.0 and 1.7 for counts of 200–350 cells/μl; and 0.7 and 0.7 for counts greater than 350 cells/μl. After adjusting for baseline covariates and the latest HIV RNA level, risk of AIDS and non-AIDS diseases were lowered by 44% (95% confidence interval for hazard ratio 0.50–0.62, P < 0.01) and 14% (95% confidence interval for hazard ratio 0.77–0.96, P = 0.01), respectively, for each 100 cell/μl higher latest CD4+ count. Conclusion:Higher CD4+ counts on antiretroviral therapy are associated with lower rates of non-AIDS diseases and AIDS. These findings expand our understanding of the implications of HIV-related immunodeficiency and motivate randomized studies to evaluate the effects of antiretroviral therapy on a broad set of clinical outcomes at CD4+ counts greater than 350 cells/μl.

[1]  J. Neaton,et al.  Risk of cancers during interrupted antiretroviral therapy in the SMART study , 2007, AIDS.

[2]  M. Falster,et al.  Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis , 2007, The Lancet.

[3]  O. Kirk,et al.  Class of antiretroviral drugs and the risk of myocardial infarction. , 2007, The New England journal of medicine.

[4]  R. Weber,et al.  HIV-induced immunodeficiency and Risk of Fatal AIDS-defining and non-AIDS-defining Malignancies: Results from the D:A:D Study , 2007 .

[5]  B. McGovern,et al.  The impact of cirrhosis on CD4+ T cell counts in HIV-seronegative patients. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  J. Goedert,et al.  Elevated risk of lung cancer among people with AIDS , 2007, AIDS.

[7]  J. Kaldor,et al.  Cancer incidence before and after kidney transplantation. , 2006, JAMA.

[8]  M. Kozal,et al.  A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST Study): a long-term randomised trial , 2006, The Lancet.

[9]  M. Markowitz,et al.  Lack of Mucosal Immune Reconstitution during Prolonged Treatment of Acute and Early HIV-1 Infection , 2006, PLoS medicine.

[10]  J Darbyshire,et al.  CD4+ count-guided interruption of antiretroviral treatment. , 2006, The New England journal of medicine.

[11]  Melissa R Pfeiffer,et al.  Causes of Death among Persons with AIDS in the Era of Highly Active Antiretroviral Therapy: New York City , 2006, Annals of Internal Medicine.

[12]  John T Brooks,et al.  Mortality in the Highly Active Antiretroviral Therapy Era: Changing Causes of Death and Disease in the HIV Outpatient Study , 2006, Journal of acquired immune deficiency syndromes.

[13]  O. Kirk,et al.  Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. , 2006, Archives of internal medicine.

[14]  J. Kovacs,et al.  Metabolic and skeletal complications of HIV infection: the price of success. , 2006, JAMA.

[15]  E. Bini,et al.  Use of flexible sigmoidoscopy to screen for colorectal cancer in HIV-infected patients 50 years of age and older. , 2006, Archives of internal medicine.

[16]  Milton C Weinstein,et al.  The survival benefits of AIDS treatment in the United States. , 2006, The Journal of infectious diseases.

[17]  Kholoud Porter,et al.  Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion , 2006, AIDS.

[18]  B. Lau,et al.  C-reactive protein is a marker for human immunodeficiency virus disease progression. , 2006, Archives of internal medicine.

[19]  E. Stier,et al.  A Population-Based Analysis of Temporal Trends in the Incidence of Squamous Anal Canal Cancer in Relation to the HIV Epidemic , 2005, Journal of acquired immune deficiency syndromes.

[20]  A. Mocroft,et al.  Is there evidence for an increase in the death rate from liver-related disease in patients with HIV? , 2005, AIDS.

[21]  M. Wallace,et al.  Incidence and risk factors for the occurrence of non‐AIDS‐defining cancers among human immunodeficiency virus‐infected individuals , 2005, Cancer.

[22]  J. Palefsky,et al.  Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men , 2005, AIDS.

[23]  L. Szczech,et al.  Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease. , 2005, Journal of the American Society of Nephrology : JASN.

[24]  A. Varin,et al.  HIV and inflammation. , 2005, Current HIV research.

[25]  J. Kramer,et al.  Does HIV infection independently increase the incidence of lung cancer? , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  D. Price,et al.  CD4+ T Cell Depletion during all Stages of HIV Disease Occurs Predominantly in the Gastrointestinal Tract , 2004, The Journal of experimental medicine.

[27]  T. Erlinger,et al.  C-reactive protein and the risk of incident colorectal cancer. , 2004, JAMA.

[28]  Jiirgen Kurt Rockstroh.  Management of Hepatitis B and C in HIV Co-Infected Patients , 2003, Journal of acquired immune deficiency syndromes.

[29]  Laurence L. George,et al.  The Statistical Analysis of Failure Time Data , 2003, Technometrics.

[30]  J. Palefsky,et al.  Natural history and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency virus. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[31]  A. Mocroft,et al.  Changes in the cause of death among HIV positive subjects across Europe: results from the EuroSIDA study , 2002, AIDS.

[32]  J. Goedert,et al.  Association of cancer with AIDS-related immunosuppression in adults. , 2001, JAMA.

[33]  R D MacArthur,et al.  The rationale and design of the CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 058 FIRST (Flexible Initial Retrovirus Suppressive Therapies) trial. , 2001, Controlled clinical trials.

[34]  C. Tetta,et al.  C REACTIVE PROTEIN IN PATIENTS WITH CHRONIC RENAL DISEASES , 2001, Renal failure.

[35]  P. Kissinger,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. , 1998, The New England journal of medicine.

[36]  G. Satten,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. , 1998, The New England journal of medicine.

[37]  J Leibowitch,et al.  Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. , 1997, Science.

[38]  Roger Detels,et al.  Plasma Viral Load and CD4+ Lymphocytes as Prognostic Markers of HIV-1 Infection , 1997, Annals of Internal Medicine.

[39]  John W. Ward,et al.  1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. , 1993, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[40]  J. Rockstroh.  Influence of viral hepatitis on HIV infection. , 2006, Journal of hepatology.

[41]  Rodolphe Thiébaut,et al.  Combination antiretroviral therapy and the risk of myocardial infarction , 2003 .

[42]  Ose,et al.  Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events* , 2002 .

[43]  Update: AIDS--United States, 2000. , 2002, MMWR. Morbidity and mortality weekly report.

[44]  F. Miedema,et al.  T cell dynamics in HIV-1 infection. , 1999, Advances in immunology.