JAIDS Journal of Acquired Immune Deficiency Syndromes:
Mortality in the Highly Active Antiretroviral Therapy Era: Changing Causes of Death and Disease in the HIV Outpatient Study
Palella, Frank J. Jr MD*; Baker, Rose K. MA†; Moorman, Anne C. BSN, MPH‡; Chmiel, Joan S. PhD*; Wood, Kathleen C. BSN†; Brooks, John T. MD‡; Holmberg, Scott D. MD, MPH‡; HIV Outpatient Study Investigators
From the *Feinberg School of Medicine, Northwestern University, Chicago, IL; †Cerner Corporation, Vienna, VA; and ‡Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.
Received for publication January 20, 2006; accepted June 9, 2006.
This work was supported by Centers for Disease Control and Prevention.
The HIV Outpatient Study investigators are listed in Appendix A.
Reprints: Frank Palella, Jr., MD, Division of Infectious Diseases, Northwestern University Feinberg School of Medicine, Suite 200, 676 North Saint Clair, Chicago, IL 60611 (e-mail: firstname.lastname@example.org).
Background: AIDS-related death and disease rates have declined in the highly active antiretroviral therapy (HAART) era and remain low; however, current causes of death in HAART-treated patients remain ill defined.
Objective: To describe mortality trends and causes of death among HIV-infected patients in the HAART era.
Design: Prospective, multicenter, observational cohort study of participants in the HIV Outpatient Study who were treated from January 1996 through December 2004.
Measurements: Rates of death, opportunistic disease, and other non-AIDS-defining illnesses (NADIs) determined to be primary or secondary causes of death.
Results: Among 6945 HIV-infected patients followed for a median of 39.2 months, death rates fell from 7.0 deaths/100 person-years of observation in 1996 to 1.3 deaths/100 person-years in 2004 (P = 0.008 for trend). Deaths that included AIDS-related causes decreased from 3.79/100 person-years in 1996 to 0.32/100 person-years in 2004 (P = 0.008). Proportional increases in deaths involving liver disease, bacteremia/sepsis, gastrointestinal disease, non-AIDS malignancies, and renal disease also occurred (P = <0.001, 0.017, 0.006, <0.001, and 0.037, respectively.) Hepatic disease was the only reported cause of death for which absolute rates increased over time, albeit not significantly, from 0.09/100 person-years in 1996 to 0.16/100 person-years in 2004 (P = 0.10). The percentage of deaths due exclusively to NADI rose from 13.1% in 1996 to 42.5% in 2004 (P < 0.001 for trend), the most frequent of which were cardiovascular, hepatic, and pulmonary disease, and non-AIDS malignancies in 2004. Mean CD4 cell counts closest to death (n = 486 deaths) increased from 59 cells/μL in 1996 to 287 cells/μL in 2004 (P < 0.001 for trend). Patients dying of NADI causes were more HAART experienced and initiated HAART at higher CD4 cell counts than those who died with AIDS (34.5% vs 16.8%, respectively, received HAART for 4 of more years, P < 0.0001; 22.4% vs 7.8%, respectively, initiated HAART with CD4 cell counts of more than 350 cells/μL, P < 0.001).
Conclusions: Although overall death rates remained low through 2004, the proportion of deaths attributable to non-AIDS diseases increased and prominently included hepatic, cardiovascular, and pulmonary diseases, as well as non-AIDS malignancies. Longer time spent receiving HAART and higher CD4 cell counts at HAART initiation were associated with death from non-AIDS causes. CD4 cell count at time of death increased over time.
Marked and sustained reductions in AIDS-related death and opportunistic disease have been observed as a consequence of the extensive use of highly active antiretroviral therapy (HAART) since 1996 in the United States and Europe.1-7 These benefits have been observed across diverse patient populations and have resulted in prolonged disease-free survival, durable HIV virologic suppression, immunologic (CD4 cell) repletion, and reductions in hospitalization rates.8 During this time, new morbidities have been observed among HAART-treated persons that have been variably ascribed to specific antiretroviral therapy (ART) received9,10 and to factors other than treatment such as stage of underlying HIV disease, baseline host (patient age, race, and sex), and other factors.11,12 Although AIDS-related death and opportunistic disease rates have remained low, increased attention has been paid to the treatment and consequences of important comorbidities such as lipoatrophy, lipoaccumulation, insulin resistance with consequent hyperglycemia, hyperlipidemia, cardiovascular disease, osteopenia, and, less commonly, symptomatic hyperlactatemia.11-18 Another consequence of improved long-term management of HIV infection has been recognition of the increased importance of providing effective treatment of chronic coinfections such as hepatitis B and C.19-21
Detailed descriptions of the spectrum of illnesses encountered among HAART-treated persons whose HIV infection is under control and of the conditions that are likely to result in death in such persons are lacking, although there are some reports profiling causes of death among person-with-AIDS diagnoses early in the HAART era,22 among non-US populations that were less extensively HAART-treated,23,24 and among women only.25 We sought to evaluate the most recent trends in mortality and morbidity among mostly HAART-treated persons in the HIV Outpatient Study (HOPS), a large geographically and ethnically diverse cohort of HIV-infected persons in the United States. We present data profiling rates and causes of death and disease (both opportunistic and nonopportunistic) over time among HOPS participants treated since 1996.
The HIV Outpatient Study
The HOPS is an ongoing prospective observational cohort study into which patients have been continuously recruited and followed since 1993.26 Study sites are 12 clinics (7 university, 3 public, and 2 private) in 10 US cities that provide care for about 3000 HIV-infected patients per year. More than 8000 HOPS patients have been seen in more than 30,000 person-years of observation since 1993. All HOPS clinicians have extensive experience treating HIV-infected patients. Information is abstracted from outpatient charts at each visit and entered electronically by trained staff, compiled centrally, then reviewed and edited before being analyzed. Information abstracted includes demographic characteristics and risk factors for HIV infection, symptoms, diagnosed diseases (both definitive and presumptive), medications prescribed, including dose and duration, and laboratory values, including CD4 cell counts and measurements of plasma HIV-1 RNA (viral load).
Since 2000, HOPS sites have used a standardized mortality data entry template designed to capture patient information near the time of death, including primary, secondary, and contributing causes of death, hospitalization chart information, and antiretroviral drug use. This mortality data template was used to collect information for deaths that occurred from January 1, 1996, to the end of the observation period (December 31, 2004) analyzed. As sites identified and recorded known deaths among their HIV-infected patient population, trained data abstractors completed the mortality form using data available from sources, including one or more of the following: death certificates, medical charts, discharge summaries, autopsy reports, and direct discussion with clinicians who had cared for the deceased. Whenever possible, any additional information available from clinicians (physicians and nurses) involved with the care of the deceased was used.
Selection of Patients for Analysis
We analyzed data from 6945 participants in the HOPS who were seen at least twice from January 1, 1996, to December 31, 2004, using HOPS data updated as of December 31, 2005. Data were censored at the end of 2004 to allow adequate time for data entry lag that occurs in the identification and documentation of deaths. End of follow-up was defined as the date of first occurrence of the following: (1) last patient contact (physician/clinic visit, hospitalization, home nursing visit, or telephone contact) plus 180 days, (2)date of death, or (3) December 31, 2004. Only deaths that occurred during follow-up were included in this analysis.
We calculated the annual number of deaths per 100 person-years between 1996 and 2004. Up to 5 primary and secondary causes of death could be entered for each patient, and all documented death causes were analyzed. Causes of death that were non-AIDS-defining illnesses (NADIs) were classified by the first author into the following disease categories for analysis: bacteremia/sepsis, central nervous system disorders, pulmonary diseases, hepatic diseases, renal diseases, cardiovascular diseases, gastrointestinal diseases, and nonopportunistic malignancies. We calculated annual death rates that involved at least one of these disease categories and annual death rates involving AIDS.
We also evaluated HAART use over time in relation to death rates. The HAART definition used for this analysis included antiretroviral regimens that fell into one of the following categories: (a) 3 antiretrovirals, one of which was either a protease inhibitor (PI) or a nonnucleoside reverse-transciptase inhibitor; (b) 3 nucleoside reverse-transciptase inhibitors, one of which was abacavir or tenofovir (TDF) (except for the regimens abacavir + TDF + lamivudine (3TC) and didanosine + TDF + 3TC; (c) 2 full-dose PIs; and (d) a boosted PI with an nonnucleoside reverse-transciptase inhibitor.
We evaluated CD4 cell counts within 6 months of death by year of death, by duration of time spent receiving HAART, and by CD4 cell count at HAART initiation, all stratified by cause of death. If a patient's ART discontinuation date was not known at the time of death, this date was imputed to be 90 days after the last visit with a HOPS clinician.
All analyses were done using a standard statistical package (SAS version 8.2, SAS Institute, Cary, NC). Tests for trend in death rates were done using log-linear modeling of death rates over time assuming a Poisson distribution where rates were calculated based upon numbers of deaths divided by 100 person-years.27 Tests for trend by age over time were done using general linear modeling. Reported P values are not adjusted for multiple comparisons.
The 6945 patients analyzed had a median follow-up of 39.2 months. From 1996 through 2004, we identified 702 deaths. Death rates declined from 7.0 deaths per 100 person-years in 1996 to 1.3 deaths per 100 person-years in 2004 (P = 0.008 for trend; Fig. 1) and stabilized at approximately 2.0 deaths per 100 person-years between 1999 and 2002, after which little further decline was noted. Over this same period, HAART utilization rates rose from 43% of patients in 1996 to 82% in 2004. Since 1999, about 78% of HOPS participants received HAART.
Characterization of those who died by age, sex, race, HIV risk, and insurance status (Table 1) revealed that death rates dropped for all groups of patients. However, death rates were higher among African Americans, those who were publicly insured, and those with a history of injection drug use. Median age at death increased from 39 years in 1996 to 49 years in 2004 (P < 0.001), as did the median age of HOPS participants overall (from 38 to 44 years), although not as steeply.
We were able to obtain at least one primary and/or secondary cause of death for 554 (79%) of the 702 deaths. We compared patients for whom causes of death were known versus not known. We found no significant differences with respect to sex, age, HIV risk behavior, months of HAART use, CD4 cell counts, or plasma HIV viral loads within 6 months ofdeath. Persons for whom no cause of death information wasavailable were more likely to be African American (P = 0.011), have public insurance (P = 0.011), and have had shorter lengths of follow-up (P = 0.0009) than those for whom cause of death information was known.
Deaths for which AIDS-related causes were included among reported death causes decreased from 3.79 per 100 person-years in 1996 to 0.32 per 100 person-years in 2004 (Table 2A). Deaths for which no primary or secondary causes were available also significantly decreased over time from 2.28 per 100 person-years to 0.42 per 100 person-years (P < 0.0001). We observed significant reductions over time in deaths for which neurologic, cardiovascular, and pulmonary disorders were cited as death causes with or without a concurrent opportunistic infection (Table 2A). Hepatic disease was the only reported cause of death that increased in rate over time (albeit not significantly), from 0.09 per 100 person-years in 1996 to 0.16 per 100 person-years in 2004 (P = 0.100), peaking in 2002 (0.53 per 100 person-years). Among patients dying of hepatic disease, the proportion who were coinfected with hepatitis B or C increased from 50% in 1996 to 80% in 2004 (P = 0.079 for trend). If deaths that included an AIDS-related cause were excluded, a significant decrease in NADI-associated deaths was observed for deaths associated with pulmonary disease from 0.37 per 100 person-years in 1996 to 0.13 per 100 person-years in 2004 (P = 0.038).
Evaluation of cause-specific deaths as a proportion of all deaths in a given year (Table 2B) revealed decreases over time in the proportion of deaths due to AIDS (P = 0.008) and unknown causes (P = 0.021), with concomitant increases in the proportion of deaths associated exclusively with NADIs from 13.1% in 1996 to 42.5% in 2004 (P < 0.001). More specifically, proportional increases in deaths caused by bacteremia/sepsis, gastrointestinal disease, hepatic disease, non-AIDS malignancies, and renal disease were observed. When specific NADI death causes were evaluated as a proportion of deaths for which only NADI causes were documented, we noted no significant trends except for a decrease in pulmonary illness-related deaths, decreasing from 40% in 1996 to 23.5% in 2004 (P = 0.039 for trend). The most frequently reported NADI causes in 2004 (regardless of trend) were cardiovascular, hepatic and pulmonary disease, and non-AIDS malignancies.
CD4 cell counts nearest to time of death were known for 486 (69%) of deaths. Mean CD4 cell count values increased over time from 59 cells/μL in 1996 to 287 cells/μL in 2004 (P < 0.001 for trend) for all observed deaths. This increase was greater for deaths due exclusively to NADI causes (Fig. 2) for which mean CD4 cell counts closest to death rose from 76 cells/μL in 1996 to 354 cells/μL in 2004 (P < 0.0001 for trend). In comparison, among AIDS-related deaths, CD4 cell counts closest to death increased from 42 cells/μL in 1996 to 130 cells/μL in 2004 (P = 0.014 for trend).
Complete ART history was known for 569 (81%) of the 702 deaths. CD4 cell counts at time of HAART initiation and overall HAART use duration were significantly associated with cause of death category (AIDS- vs NADI-associated cause of death; Table 3). Among exclusively NADI-associated deaths, 34.7% had received HAART for 4 or more years compared with 16.8% of patients dying with AIDS-related diseases (overall P < 0.0001). CD4 cell count measurements documented within 6 months before HAART initiation were available for 334 of the deceased. Evaluation of these revealed that 22.4% of patients dying of NADI causes versus 7.8% of patients dying of AIDS-related illness initiated HAART with CD4 more than 350 cells/μL (P = 0.001). Patients who died exclusively from NADI causes were also more likely to have been receiving ART at the time of death (51.8%) compared with 40.4% of patients with AIDS death causes (P = 0.015). However, knowledge of ART receipt status at the time of death was known for more persons with exclusively NADI causes of death than those with AIDS-related death causes.
Our review of causes of death among a large and demographically diverse population of HIV-infected persons in the post-HAART era revealed several major findings. First, while overall death rates remained quite low through the ninth year of highly prevalent HAART use in the HOPS, the annual percentage of deaths with at least one non-AIDS cause of death increased progressively over time, accounting for well over half of all deaths by the end of 2004. During the period 2000 to 2004, non-AIDS death causes prominently included hepatic, pulmonary, and cardiovascular illnesses. Compared with persons dying from AIDS-related conditions, persons with exclusively non-AIDS death causes initiated ART at higher CD4 cell counts, were more HAART experienced, and were more likely to have received HAART near the time of death. Consonant with these findings, mean CD4 cell counts proximal to the time of death and age at death increased significantly over time. Long-term HIV suppression, CD4 cell count stability or improvement, and clinical benefits provided by ART increasingly allowed HOPS participants to avoid AIDS-defining illnesses and delay death even if they had a history of a prior AIDS-defining illness. As a result, more prolonged survival allowed chronic underlying comorbid conditions or risks for such conditions to become more clinically relevant, particularly liver disease (especially chronic coinfection with viral hepatitis), hypertension, diabetes, cardiovascular illness, pulmonary disease, and non-AIDS malignancies.
HIV treatments themselves may have resulted in conditions that contributed to an increased likelihood of certain deaths. Our data can be interpreted to imply that the increased proportion of non-AIDS-related causes of death (from multiple illness categories) can be attributed to longer ART treatment (eg, PI use and myocardial infarctions as seen in this cohort),13 but those with longer ART treatment histories also were living longer with comorbid illnesses and chronic risks for illnesses other than AIDS. Likewise, recent reports from this cohort and others demonstrate mortality benefits of initiating ART earlier in the course of HIV infection (ie, at higher CD4 cell counts)28 and the survival benefits of maintaining continuous HAART even when higher CD4 cell counts have been achieved.29 Thus, while appreciating the shift in spectrum of illnesses contributing to death among those living longer in the HAART era, it is important to emphasize that any contributions of ART to the risk for NADIs are clearly outweighed by the benefits consequent to HAART's use in reducing overall mortality and AIDS-related morbidity. These benefits are dramatic, durable, and unequivocal.1-7
It is also possible that HAART-associated immune reconstitution may have increased the risk for NADIs via chronic immune activation and upregulation of proinflammatory cytokines. This has been suggested in recent analyses from this cohort and others profiling increased rates of specific non-AIDS-related morbidities.30-32
Given that our findings show increasing mean CD4 values at death among HIV-infected HAART-treated persons, are CD4 cell counts losing their predictive value in the assessment of death risk in this population? Although this seems to be true for both those dying with or those dying without AIDS-defining illnesses, it needs to be interpreted in light of our central findings-that AIDS-associated death rates remained durably low among HAART-treated persons, and such deaths are increasingly likely to occur as a consequence of NADIs, particularly among persons with higher CD4 cell counts and those who were receiving HAART near the time of death. There was no evidence that AIDS-associated opportunistic diseases occurred and contributed to death despite increasing CD4 counts (particularly among those with CD4 counts approximately >150 cells/μL) nearest to time of death, nor that there was an overt dissociation between CD4 counts and opportunistic infection risk. However, we did not undertake a formal predictor analysis to assess the ability of CD4 cell counts measured near the time of death to predict death risk. This has been done in other studies.33
There are unavoidable limitations in an analysis of an observational cohort of HIV-infected ambulatory outpatients. First, we lack a readily available age- and risk-matched HIV-seronegative population to whom we can easily compare our death rates from non-AIDS-related illnesses. As successfully treated HIV patients survive longer with higher CD4 cell counts, it is reasonable to anticipate that their diseases will more closely resemble those of comparable non-HIV-infected persons. Second, the HOPS is a dynamic cohort in which all patients are not necessarily followed continuously throughout the course of their HIV infection (ie, patients may enter or leave the cohort any time during the observation period). However, we believe that a major strength of this analysis is that it profiles mortality rates and causes among a heterogeneous and representative group of HIV-infected persons who received care from their own HIV clinicians. Third, discernment of precise causes of death is always a challenge. We gathered cause of death information from meticulous review of medical records with input from clinicians caring for patients near the time of death. Moreover, the proportion of deaths for which there was no death cause information available decreased over time. Because many of the deceased died while hospitalized, and we were able to undertake systematic and careful review of inpatient as well as outpatient records, we may have better classification of death causes than other published reports. Short of the routine performance of autopsies, we believe we thoroughly accessed available clinical data from existing sources. Finally, some recent reports have discussed the role of more optimal medication adherence upon improved survival among HAART-treated persons with advanced HIV infection.34 Although we did not have precise measurements of medication adherence for all of the deceased profiled in this report, a recent report from the HOPS suggests a very high rate of HAART medication adherence in our cohort.35
In conclusion, in an era during which HIV-infected persons routinely live longer as a result of timely intervention with HAART, it is important for clinicians to be aware that other underlying, nontraditionally HIV-related conditions are ever more likely to figure prominently in the risk for death and disease. These conditions should be aggressively screened for, monitored, and treated. Chronic liver disease (especially in chronic viral hepatitis-coinfected persons), cardiovascular and pulmonary disease, and non-AIDS malignancies loom particularly large among these nontraditionally HIV-related morbidities that usually require specific ongoing targeted therapy. Although HIV-infected persons are clearly living longer as a consequence of effective HAART, they may be dying earlier than those in the general population, albeit not from traditionally HIV-associated conditions. These observations underscore the need for improved vigilance on the part of clinicians in maintaining proactive and preventive medical care and routine screening for all HIV-infected persons receiving HAART.
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The HOPS Investigators include the following investigators and sites: Anne C. Moorman, Tony Tong, Scott D. Holmberg (currently at Research Triangle Institute, Atlanta), John T. Brooks, and Kate Buchacz, Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA; Kathleen C. Wood, Rose K. Baker, and Carl Armon, Cerner Corporation, Vienna, VA; Frank J. Palella, Joan S. Chmiel, Katharine A. Kirby, Janet Cheley, and Tiffany Murphy, Feinberg School of Medicine, Northwestern University, Chicago, IL; Kenneth A. Lichtenstein, University of Colorado Health Sciences Center, Denver, CO; Kenneth S. Greenberg, Benjamin Young, Barbara Widick, Cheryl Stewart, and Peggy Zellner, Rose Medical Center, Denver, CO; Bienvenido G. Yangco, Kalliope Halkias, and Arletis Lay, Infectious Disease Research Institute, Tampa, FL; Douglas J. Ward and Charles A. Owen, Dupont Circle Physicians Group, Washington, DC; Jack Fuhrer, Linda Ording-Bauer, Rita Kelly, and Jane Esteves, State University of New York, Stony Brook, NY; Ellen M. Tedaldi, Ramona A. Christian, and Linda Walker-Kornegay, Temple University School of Medicine, Philadelphia, PA; Joseph B. Marzouk, Roger T. Phelps, and Mark Rachel, Adult Immunology Clinic, Oakland, CA; Silver Sisneros and Mark Rachel, Fairmont Hospital, San Leandro, CA; Richard M. Novak, Jonathan P. Uy, and Andrea Wendrow, University of Illinois at Chicago, Chicago, IL.
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Current Hiv Research, 8(4):
Plos OneIncrease in Non-AIDS Related Conditions as Causes of Death among HIV-Infected Individuals in the HAART Era in BrazilPlos One
Clinical Infectious DiseasesMissed Visits and Mortality among Patients Establishing Initial Outpatient HIV TreatmentClinical Infectious Diseases
American Journal of EpidemiologyThe Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study)American Journal of Epidemiology
AIDS Patient Care and StdsGenital and Perianal Herpes Simplex Simulating Neoplasia in Patients with AIDSAIDS Patient Care and Stds
New England Journal of MedicineEffect of Early versus Deferred Antiretroviral Therapy for HIV on SurvivalNew England Journal of Medicine
International Journal of Infectious DiseasesChronic viral hepatitis may diminish the gains of HIV antiretroviral therapy in sub-Saharan AfricaInternational Journal of Infectious Diseases
Janac-Journal of the Association of Nurses in AIDS CareProcess and contents of telephone consultations between registered nurses and clients with HIV/AIDS in JapanJanac-Journal of the Association of Nurses in AIDS Care
Clinical Infectious DiseasesThe effect of highly active antiretroviral therapy on mortality among HIV-infected former plasma donors in ChinaClinical Infectious Diseases
Clinical Infectious DiseasesRate of comorbidities not related to HIV infection or AIDS among HIV infected patients, by CD4 cell count and HAART use statusClinical Infectious Diseases
Clinical Infectious DiseasesHospitalization for Pneumonia among Individuals With and Without HIV Infection, 1995-2007: A Danish Population-Based, Nationwide Cohort StudyClinical Infectious Diseases
HIV-Related Lipodystrophy in Africa and Asia
AIDS Reader, 19(4):
AIDS Education and Prevention
Review: the Need for Smoking Cessation Among Hiv-Positive Smokers
AIDS Education and Prevention, 21(3):
AIDS Patient Care and StdsRace, Outpatient Mental Health Service Use, and Survival After an AIDS Diagnosis in the Highly Active Antiretroviral Therapy EraAIDS Patient Care and Stds
Journal of NeurovirologyHuman immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brainJournal of Neurovirology
Trends in perimortal conditions and mortality rates among HIV-infected patients
American Journal of PsychiatryRelation of lifetime trauma and depressive symptoms to mortality in HIVAmerican Journal of Psychiatry
British Journal of Clinical PharmacologyAdverse drug reactions in adult medical inpatients in a South African hospital serving a community with a high HIV/AIDS prevalence: prospective observational studyBritish Journal of Clinical Pharmacology
Hiv Clinical TrialsDetermination of the underlying cause of death in three multicenter international HIV clinical trialsHiv Clinical Trials
Rates of hospitalizations and associated diagnoses in a large multisite cohort of HIV patients in the United States, 1994-2005
Attitudes towards vaccines and infectious disease risk among U. S. troops
Human Vaccines, 4(4):
Journal of Managed Care Pharmacy
The HIV landscape in a managed care environment: Current challenges and potential solutions
Journal of Managed Care Pharmacy, 12(7):
Medizinische KlinikHIV infection 2007Medizinische Klinik
MitochondrionNucleoside reverse transcriptase inhibitors (NRTIs)-induced expression profile of mitochondria-related genes in the mouse liverMitochondrion
Plos OneExtensive HIV-1 Intra-Host Recombination Is Common in Tissues with Abnormal HistopathologyPlos One
Science in China Series C-Life SciencesHigh level HIV-1 DNA concentrations in brain tissues differentiate patients with post-HAART AIDS dementia complex or cardiovascular disease from those with AIDSScience in China Series C-Life Sciences
AIDS Patient Care and StdsPrevalence and Impact of Body Physical Changes in HIV Patients Treated with Highly Active Antiretroviral Therapy: Results from a Study on Patient and Physician PerceptionsAIDS Patient Care and Stds
Hiv MedicineCauses of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapyHiv Medicine
Clinical Infectious DiseasesHIV care and the incidence of acute renal failureClinical Infectious Diseases
Journal of Managed Care Pharmacy
Strategies to enhance adherence, reduce costs, and improve patient quality of life
Journal of Managed Care Pharmacy, 14(5):
Journal of InfectionAssociation of non-HDL cholesterol with subclinical atherosclerosis in HIV-positive patientsJournal of Infection
PharmacogenomicsPharmacogenetics of tenofovir treatmentPharmacogenomics
Clinical Infectious DiseasesAIDS Drug Assistance Programs in the era of routine HIV testingClinical Infectious Diseases
Clinical Infectious DiseasesAre All Subtypes Created Equal? The Effectiveness of Antiretroviral Therapy against Non-Subtype B HIV-1Clinical Infectious Diseases
Medicina ClinicaNeoplasms and HIV in the epidemic's third decadeMedicina Clinica
Strategies to Optimize HIV Treatment Outcomes in Resource-Limited Settings
AIDS Reviews, 11(4):
International Journal of Infectious DiseasesFactors associated with mortality among HIV-infected patients in the era of highly active antiretroviral therapy in southern IndiaInternational Journal of Infectious Diseases
Journal of Infectious DiseasesCurrent CD4 cell count and the short-term risk of AIDS and death before the availability of effective antiretroviral therapy in HIV-infected children and adultsJournal of Infectious Diseases
Cadernos De Saude Publica
AIDS mortality, "race or color", and social inequality in a context of universal access to highly active antiretroviral therapy (HAART) in Brazil, 1999-2004
Cadernos De Saude Publica, 23():
Insulin resistance, hepatic lipid and adipose tissue distribution in HIV-infected men
Antiviral Therapy, 13(3):
National review of deaths among HIV-infected adults
Clinical Medicine, 8(3):
Ciencia & Saude Coletiva
"Get back to where you once belonged": monitoring the AIDS pandemic in the 21st century
Ciencia & Saude Coletiva, 13(6):
InfectionItalian Consensus Statement on Management of HIV-Infected Individuals with Advanced Disease Na < ve to Antiretroviral TherapyInfection
Journal of Antimicrobial ChemotherapyHIV/hepatitis B virus co-infection: current challenges and new strategiesJournal of Antimicrobial Chemotherapy
Journal of the National Medical Association
HIV/AIDS Disparities: The Mounting Epidemic Plaguing US Blacks
Journal of the National Medical Association, 101():
Emergency Medicine Clinics of North AmericaMetabolic and Hepatobiliary Side Effects of Antiretroviral Therapy (ART)Emergency Medicine Clinics of North America
Clinics in Chest MedicineTuberculosis-associated Immune Reconstitution Inflammatory Syndrome and Unmasking of Tuberculosis by Antiretroviral TherapyClinics in Chest Medicine
OphthalmologyLongitudinal study of the ocular complications of AIDS - 1. Ocular diagnoses at enrollmentOphthalmology
Transactions of the Royal Society of Tropical Medicine and HygieneDeclining incidence of intestinal microsporidiosis and reduction in AIDS-related mortality following introduction of HAART in Sydney, AustraliaTransactions of the Royal Society of Tropical Medicine and Hygiene
Journal of Medicinal ChemistryDesign and synthesis of human immunodeficiency virus entry inhibitors: Sulfonamide as an isostere for the alpha-ketoamide groupJournal of Medicinal Chemistry
Non-AIDS-defining cancers: Should antiretroviral therapy be initiated earlier?
AIDS Reader, 18(1):
Diagnosis and Management of Common Chronic Metabolic Complications in HIV-Infected Patients
Postgraduate Medicine, 120(4):
Plos OneInteractive "Video Doctor" Counseling Reduces Drug and Sexual Risk Behaviors among HIV-Positive Patients in Diverse Outpatient SettingsPlos One
European Journal of Medical Research
Switch From A Zdv/3Tc-Based Regimen to A Completely Once Daily (Qd) Regimen of Emtricitabine/Tenofovir Df Fixed Dose Combination Plus A Third Qd Agent (Sonett)
European Journal of Medical Research, 14(5):
Current Hiv Research
The Changing Face of HIV/AIDS in Treated Patients
Current Hiv Research, 7(4):
American Journal of EpidemiologyCopy-Years Viremia as a Measure of Cumulative Human Immunodeficiency Virus Viral BurdenAmerican Journal of Epidemiology
Clinical Infectious DiseasesTransmission of HIV-1 Drug-Resistant Variants: Prevalence and Effect on Treatment OutcomeClinical Infectious Diseases
Social Science & MedicineRace, place and AIDS: The role of socioeconomic context on racial disparities in treatment and survival in San FranciscoSocial Science & Medicine
Journal of Medicinal ChemistryHeterobiaryl Human Immunodeficiency Virus Entry InhibitorsJournal of Medicinal Chemistry
International Journal of EpidemiologyCauses of death in HIV-infected women: persistent role of AIDS. The 'Mortalite 2000 & 2005' Surveys (ANRS EN19)International Journal of Epidemiology
Cadernos De Saude Publica
Twenty-five years of the AIDS epidemic in Brazil: principal epidemiological findings, 1980-2005
Cadernos De Saude Publica, 23():
Clinical Infectious DiseasesLong-term prognosis of HIV-infected patients with Kaposi sarcoma treated with pegylated liposomal doxorubicinClinical Infectious Diseases
Expert Opinion on PharmacotherapyAccess denied? The status of co-receptor inhibition to counter HIV entryExpert Opinion on Pharmacotherapy
Future VirologyAtazanavir/ritonavir: a valuable once-daily HIV protease inhibitor with little impact on lipid profileFuture Virology
Journal of Medical VirologyCurrent HIV epidemiology and revised recommendations for HIV testing in health-care settingsJournal of Medical Virology
Drug interactions between HIV protease inhibitors and acid-reducing agents
Clinical Pharmacokinetics, 47(2):
Impact of lipoatrophy on patient-reported outcomes in antiretroviral-experienced patients
AIDS Reader, 18(5):
HepatologyHepatitis B and Human Immunodeficiency Virus CoinfectionHepatology
American Journal of TransplantationSuccessful Lung Transplantation in an HIV- and HBV-Positive Patient with Cystic FibrosisAmerican Journal of Transplantation
Hiv Clinical TrialsCost-effectiveness of Raltegravir in Antiretroviral Treatment-Experienced HIV-1-Infected Patients in SwitzerlandHiv Clinical Trials
AIDS Patient Care and StdsHigh-Volume Rapid HIV Testing in an Urban Emergency DepartmentAIDS Patient Care and Stds
AIDS Research and Human RetrovirusesPredictors of Success with Highly Active Antiretroviral Therapy in an Antiretroviral-Naive Urban PopulationAIDS Research and Human Retroviruses
AIDS Patient Care and StdsThe effects of smoking abstinence on symptom burden and quality of life among persons living with HIV/AIDSAIDS Patient Care and Stds
Seminars in NephrologyAcute Kidney Injury in HIV-Infected PatientsSeminars in Nephrology
Journal of Antimicrobial ChemotherapyInfluence of liver fibrosis stage on plasma levels of efavirenz in HIV-infected patients with chronic hepatitis B or CJournal of Antimicrobial Chemotherapy
Canadian Journal of Infectious Diseases & Medical Microbiology
Tuberculosis screening and active tuberculosis among HIV-infected persons in a Canadian tertiary care centre
Canadian Journal of Infectious Diseases & Medical Microbiology, 20(2):
Plos OneFertility Desires and Intentions of HIV-Positive Women of Reproductive Age in Ontario, Canada: A Cross-Sectional StudyPlos One
AIDS Patient Care and StdsIntegrating Smoking Cessation into HIV CareAIDS Patient Care and Stds
Clinical Infectious DiseasesCauses of Death in HIV-1-Infected Patients Treated with Antiretroviral Therapy, 1996-2006: Collaborative Analysis of 13 HIV Cohort StudiesClinical Infectious Diseases
Emergency Medicine Clinics of North AmericaRenal and Urologic Emergencies in the HIV-infected PatientEmergency Medicine Clinics of North America
Deutsche Medizinische WochenschriftHIV-infectionDeutsche Medizinische Wochenschrift
Revista DO Instituto De Medicina Tropical De Sao Paulo
Clinical and histological characteristics of HIV and hepatitis C virus-co-infected patients in Brazil: A case series study
Revista DO Instituto De Medicina Tropical De Sao Paulo, 50(4):
Chinese Medical JournalImproving China's antiretroviral treatment program: assessing current and future performance using the principals of ethicsChinese Medical Journal
Journal of the American Geriatrics SocietyPrediction of Cardiorespiratory Fitness in Older Men Infected with the Human Immunodeficiency Virus: Clinical Factors and Value of the Six-Minute Walk DistanceJournal of the American Geriatrics Society
Reviews in Medical VirologySolid organ transplantation in HIV-infected individuals: an updateReviews in Medical Virology
Clinical Infectious DiseasesHuman T lymphotropic virus type 1 - Associated myelopathy/tropical spastic paraparesis in an HIV-Positive patient coinfected with human T lymphotropic virus type 2 following initiation of Antiretroviral therapyClinical Infectious Diseases
Clinical Infectious DiseasesUniversal HIV testing: Is it enough?Clinical Infectious Diseases
AIDS Patient Care and StdsIncidence and predictors of severe liver fibrosis in HIV-infected patients with chronic hepatitis C in BrazilAIDS Patient Care and Stds
Annals of PharmacotherapyIntegrase Inhibitors: A Novel Class of Antiretroviral AgentsAnnals of Pharmacotherapy
Plos OneEarly Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy TrialPlos One
Hiv MedicineCryptogenic liver disease in HIV-seropositive menHiv Medicine
AIDS Research and Human RetrovirusesCost-Effectiveness Analysis of Raltegravir in Treatment-Experienced HIV Type 1-Infected Patients in SpainAIDS Research and Human Retroviruses
AIDS Patient Care and StdsPrevalence and Factors Associated with Renal Dysfunction Among HIV-Infected PatientsAIDS Patient Care and Stds
International Review of PsychiatryTreatment of depression in HIV positive individuals: A critical reviewInternational Review of Psychiatry
Hiv MedicineHepatitis C virus antibody-positive patients with HIV infection have a high risk of insulin resistance: a cross-sectional studyHiv Medicine
Clinical Pharmacology & TherapeuticsLopinavir-Ritonavir dramatically affects the pharmacokinetics of irinotecan in HIV patients with Kaposi's sarcomaClinical Pharmacology & Therapeutics
Jama-Journal of the American Medical Association
Antiretroviral treatment of adult HIV infection - 2008 recommendations of the International AIDS Society USA panel
Jama-Journal of the American Medical Association, 300(5):
Brazilian Journal of Infectious Diseases
Survival of AIDS Patients and Characteristics of Those Who Died Over Eight Years of Highly Active Antiretroviral Therapy, at a Referral Center in Northeast Brazil
Brazilian Journal of Infectious Diseases, 12(4):
Ciencia & Saude Coletiva
From "acute AIDS" to "chronic AIDS": body perception and surgical interventions in people living with HIV and AIDS
Ciencia & Saude Coletiva, 13(6):
AIDS and BehaviorDepression Symptoms and Treatment Among HIV Infected and Uninfected VeteransAIDS and Behavior
Hiv MedicineHospitalization risk following initiation of highly active antiretroviral therapyHiv Medicine
Clinical Gastroenterology and HepatologyPrevalence and Factors Associated With Liver Test Abnormalities Among Human Immunodeficiency Virus-Infected PersonsClinical Gastroenterology and Hepatology
European Journal of Health EconomicsDeterminants of health care costs of HIV-positive patients in the Canary Islands, SpainEuropean Journal of Health Economics
Role of Interleukin-2 in Patients with HIV Infection
AIDS and BehaviorSmoking Among HIV Positive New Yorkers: Prevalence, Frequency, and Opportunities for CessationAIDS and Behavior
NefrologiaTemporal evolution of renal involvement in a necropsy study of HIV patients from the pre and HAART erasNefrologia
Clinical Infectious DiseasesTest and Treat DC: Forecasting the Impact of a Comprehensive HIV Strategy in Washington DCClinical Infectious Diseases
AIDSAntiretroviral drugs and liver injuryAIDS
AIDSMetabolic bone disease in HIV infectionAIDS
Current Opinion in Infectious DiseasesShould HIV therapy be started at a CD4 cell count above 350 cells/μl in asymptomatic HIV-1-infected patients?Current Opinion in Infectious Diseases
JAIDS Journal of Acquired Immune Deficiency SyndromesDeclines in Mortality Rates and Changes in Causes of Death in HIV-1-Infected Children During the HAART EraJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesAssociation of HIV Infection, Demographic and Cardiovascular Risk Factors With All-Cause Mortality in the Recent HAART EraJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesNonalcoholic Fatty Liver Disease Among HIV-Infected PersonsJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesTrends in Mortality and Causes of Death Among Women With HIV in the United States: A 10-Year StudyJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesTemporal Changes in Causes of Death Among HIV-Infected Patients in the HAART Era in Rio de Janeiro, BrazilJAIDS Journal of Acquired Immune Deficiency Syndromes
JAIDS Journal of Acquired Immune Deficiency SyndromesSurvival After AIDS Diagnosis in Italy, 1999-2006: A Population-Based StudyJAIDS Journal of Acquired Immune Deficiency Syndromes
mortality; opportunistic infection; liver; cause of death; trends; HAART
© 2006 Lippincott Williams & Wilkins, Inc.
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