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Epidemiology

Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis

Grover, Surbhi MD, MPH*; Desir, Fidel MPH; Jing, Yuezhou MS; Bhatia, Rohini K. BA; Trifiletti, Daniel M. MD§; Swisher-McClure, Samuel MD*; Kobie, Julie PhD; Moore, Richard D. MD, MHS; Rabkin, Charles S. MD, MSc#; Silverberg, Michael J. PhD, MPH**; Salters, Kate PhD††; Mathews, William Christopher MD, MSPH‡‡; Gill, Michael John MB, ChB, MS§§; Thorne, Jennifer E. MD, PhD†,║║; Castilho, Jessica MD, MPH¶¶; Kitahata, Mari M. MD, MPH##; Justice, Amy MD, PhD***; Horberg, Michael A. MD†††; Achenbach, Chad J. MD, MPH‡‡‡; Mayor, Angel M. MD§§§; Althoff, Keri N. PhD, MPH; for the North American AIDS Cohort Collaboration on Research and Design

Author Information
JAIDS Journal of Acquired Immune Deficiency Syndromes: December 1, 2018 - Volume 79 - Issue 4 - p 421-429
doi: 10.1097/QAI.0000000000001842

Abstract

INTRODUCTION

Although rates of certain AIDS-defining cancers, such as Kaposi sarcoma and non-Hodgkin lymphoma, have declined with the introduction of modern antiretroviral therapy (ART), rates of other cancers, such as anal, cervical, lung, oropharynx, and Hodgkin lymphoma, have remained elevated, or increased, among persons with HIV (PWH) in the modern ART era.1–3 Furthermore, cancer is an increasingly common cause of death among PWH in the modern ART era in the United States.4,5

AIDS-defining illnesses (ADIs) are 26 diagnoses identified by the Centers for Disease Control and Prevention (CDC) that serve as an international guideline for diagnosis of AIDS.6 They are indicative of clinical progression, advanced HIV disease, and a higher degree of systemic immune dysfunction.7,8 In the modern ART era, ADIs occur both in those with low (<500 cells/μL) and high (≥500 cells/μL) CD4 cell counts, suggesting that ADIs may provide clinically meaningful indices of immune dysfunction that are not fully captured by CD4 count alone.9,10 Indeed, despite the effectiveness of ART in suppressing viral replication, immunologic abnormalities persist and levels of immune activation may remain elevated compared to people without HIV.11

It is hypothesized, but currently unknown, whether immune suppression enables more aggressive malignancies, which may lead to an increased risk of diagnosis at a later cancer stage. Previous studies comparing PWH with those in the general population have reported a later stage at cancer diagnosis for colorectal, breast, and prostate cancer; the studies focused on lung cancer have produced conflicting results.12–17 Surveillance for cancer is an important factor when considering the stage at cancer diagnosis. Previous studies have shown that those with less access to care and cancer screening are more likely to be diagnosed at a more distant stage of disease.18 Potential differences in access to care (and subsequently differential surveillance for cancer), as well as important differences in risk factors for cancer in PWH and the general population are present in these previous studies.10–15

Previous studies have reported poorer survival after cancer diagnosis in PWH compared with the general population, possibly because of (1) a later cancer stage at diagnosis and/or (2) greater immune dysfunction among PWH.17,19 ADIs have been associated with increased mortality in PWH. In the ART Cohort Collaboration, those with an ADI had a 3.45-fold increase in the rate of death compared to those without an ADI.20 Although ADIs are associated with increased mortality in PWH, it is unknown whether a history of an ADI at cancer diagnosis influences the mortality rate (MR) after cancer diagnosis.

The objective of this study was to compare cancer stage at diagnosis, MRs, and survival after cancer diagnosis among PWH with and without a history of ADI who have successfully linked into HIV care. To the best of our knowledge, there are no studies that report on differences in type-specific cancer stage at diagnosis among PWH by a history of severe immune suppression at cancer diagnosis.

METHODS

Study Population

The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) is a consortium of >20 clinical and interval HIV cohorts in the United States and Canada and has been described elsewhere.21 Using standardized cohort-specific methods, each contributing cohort collects demographic, clinical, and laboratory data on HIV-infected individuals who successfully engaged in care (defined as ≥2 clinical visits within 12 months). At regularly scheduled intervals, the data are submitted to the NA-ACCORD central Data Management Core at the University of Washington, where they are harmonized after undergoing quality control procedures for accuracy. The data are then securely transferred to the Epidemiology/Biostatistics Core for additional quality control procedures. Institutional Review Board approval for the human subject activities of the NA-ACCORD was obtained from each participating cohort and the Johns Hopkins University School of Medicine.

The study population for this analysis included PWH aged 18 years and older receiving HIV care in 1 of 12 clinical cohorts in the NA-ACCORD (10 in the United States and 2 in Canada) who had an incident cancer diagnosis between January 2000 and December 2009.

In supplemental analyses, the National Cancer Database (NCDB) was used as a comparison group for PWH with and without ADI. The NCDB is a nationwide, facility-based, comprehensive clinical surveillance oncology dataset established in 1989 that collects demographic and oncological patient data from more than 1500 hospital-based cancer registries in the United States.22 Please see the Supplement for more information on the NCDB and the findings comparing mortality among PWH with and without a history of an ADI to that among individuals in the general population represented in the NCDB.

Outcomes: Cancer Stage at Diagnosis and Death

We examined cancer stage at diagnosis for the following 5 types of incident cancer: anal, lung, cervical, oropharynx cancers, and Hodgkin lymphoma. We chose these cancers given their high incidence among PWH in the modern ART era.22 We analyzed only the first cancer diagnosis of any of the 5 cancer types if more than one type of cancer occurred. We did not exclude individuals with previous cancer diagnoses that did not match the 5 specific cancers included in this analysis. Cancer diagnoses in the NA-ACCORD were validated through a web-based standardized abstraction protocol that included manual review of medical records and pathology reports or linkage to cancer registries to collect cancer site and staging information for each case. Data abstractors and reviewers were overseen by physicians and abstracted data on cancer site, diagnosis date, histopathology, grade, stage, and risk factors. Reviewers were provided detailed instructions and examples based on SEER cancer data collection instructions to determine the most accurate cancer diagnosis category and date. Further details of this process have been validated and previously described.23 NA-ACCORD data have TNM and summary stage available. For our analysis, we used summary stage when available. If summary stage was unavailable, we used TNM data to deduce summary stage using the American Joint Committee on Cancer seventh edition.

All-cause mortality after type-specific cancer diagnosis was also an outcome of interest. Cohorts in the NA-ACCORD have previously demonstrated good ascertainment of deaths using active and passive methods.24 Deaths were ascertained using medical record abstraction and linkage to the National Death Index, the Social Security Death Index, as well as Canadian provincial death registries.

Exposure

NA-ACCORD participants were classified as having had a history of an ADI if one was diagnosed at, or before, cancer diagnosis. ADI was defined by the 26 diagnoses that designated a person as having high risk of immunosuppression and morbidity according to the expanded surveillance criteria established by the CDC in 1993, including invasive cervical cancer and tuberculosis, among other diagnoses.6 As cervical cancer is an ADI, those with a previous ADI at cervical cancer diagnosis were classified as having a previous ADI; those without a previous ADI at the time of cervical cancer diagnosis were classified as not having a history of ADI at cervical cancer diagnosis.

Covariates

Covariates were measured as close to cancer diagnosis as possible, within the window of 6 months before 3 months after cancer diagnosis. Self-reported race was categorized as white, black, or other/unknown. CD4 cell count was categorized as <200, 200–349, 350–499, or ≥500 cells per microliter. Viral suppression was defined as plasma HIV RNA ≤200 copies per microliter. ART was defined as a combination of ART agents from ≥2 classes with an identified anchor agent that suggested the specific regimen class.25 Cigarette smoking was measured as ever having evidence of cigarette smoking while under observation in the NA-ACCORD (through medical record or data collected through substance surveys; multiple imputation was used for missing smoking status only among cohorts with at least 70% of participants having an observed smoking status. The analysis of covariates is disproportionately representative of the male sex because of unequal sample sizes. A subgroup analysis performed noted differences in the prevalence rates of smoking and ADI, but it was not statistically significant.

Statistical Analyses

Person-time accrual began on the observed incident cancer diagnosis date. Each participant was followed until death date, date of loss to follow-up (defined as 18 months after the date of last HIV RNA or CD4 measurement), December 31, 2009, or the cohort-specific end of the observation window of validated cancer diagnosis (if it was before December 31, 2009).

All analyses were stratified by cancer type. Among NA-ACCORD participants, the distribution of cancer stage at diagnosis was compared between PWH with and without an ADI for each cancer type through the χ2 test statistic. Kaplan–Meier curves with the log-rank test were used to compare overall survival between PWH with and without an ADI. We calculated crude MRs after cancer diagnosis by ADI status. Poisson regression models estimated crude [MR ratio (MRR)] and adjusted MRRs (aMRRs) and 95% confidence intervals (CIs) for ADI status, controlling for cancer stage, age, sex, race, cigarette smoking, ART, and CD4 count. Age was the only time-varying variable; all other covariates were time-fixed at cancer diagnosis.

The analyses were conducted by the NA-ACCORD Epidemiology/Biostatistics Core. SAS software, version 9.4 (SAS Institute, Inc., Cary, NC), was used to conduct analyses, and a P value <0.05 guided statistical interpretation.

RESULTS

Among 81,865 PWH observed for cancer outcomes between January 1, 2000, and December 31, 2009, 814 were diagnosed with the type-specific cancers of interest. These included cancers of the anus (162, 20%), lung (444, 55%), oropharynx (114, 14%), cervix (5, 0.6%), and Hodgkin lymphoma (89, 11%; Table 1). Because of the small number of cervical cancers (n = 5), stage at cancer diagnosis was compared by ADI status, but MRs and survival after cervical cancer diagnosis were not estimated. Among the 162 anal cancer cases, 18 (11%) had a cancer diagnosis with another cancer type before anal cancer diagnosis; 8/114 (7%) oropharynx cancer cases, 7/89 (8%) Hodgkin lymphoma cases, and 36/444 (8%) lung cancer cases had a different cancer diagnosis before a first diagnosis with the type-specific cancer. After diagnosis with the type-specific cancers of interest, 9/162 (6%) of participants with anal cancer, 8/114 (7%) of participants with oropharynx cancer, 4/89 (4%) of participants with Hodgkin lymphoma, and 5/444 (1%) of participants with lung cancer had a subsequent cancer diagnosis. The median [interquartile range (IQR)] follow-up time for each cancer type (from cancer diagnosis until death or censoring) was 7.2 (4.8–9.0) years for anal, 9.0 (6.6–9.0) years for cervical, 4.6 (2.2–7.1) years for lung, 6.6 (3.6–8.9) years for oropharynx, and 6.1 (3.8–8.8) years for Hodgkin lymphoma.

TABLE 1.
TABLE 1.:
Characteristics of HIV-Infected Adults at Cancer Diagnosis in the NA-ACCORD, by Cancer Type

Of the 814 PWH diagnosed with cancer, 96% were men, 97% resided in the United States, and 85% were ever smokers. Eighty-four percent of participants were on ART at the time of cancer diagnosis. Median (IQR) CD4 count at cancer diagnosis was 328 (187–515) cells per microliter for anal cancer, 372 (160–491) cells per microliter for cervical cancer, 247 (102–434) cells per microliter for oropharynx cancer, 204 (112–340) cells per microliter for Hodgkin lymphoma, and 288 (158–482) cells per microliter for lung cancer. Median (IQR) time from ART initiation to cancer diagnosis was 5.3 (3.3–7.9) years for anal, 1.2 (0.3–3.7) years for cervical, 4.8 (2.2–7.3) years for oropharynx, 4.6 (2.6–7.1) years for lung cancer, and 3.7 (2.1–5.5) years for Hodgkin lymphoma.

Thirty-nine percent of those with a cancer diagnosis had a history of ADI at cancer diagnosis. The most common ADIs at or before cancer diagnosis were as follows: anal cancer, Pneumocystis carinii pneumonia (PCP) n = 18 or 25%, and tuberculosis n = 14 or 20%; none of the 5 women with cervical cancer had an ADI before cervical cancer; oropharynx cancer, tuberculosis n = 9 or 27%, and PCP n = 7 or 21%; Hodgkin lymphoma, PCP n = 6 or 23%, candidiasis n = 4 or 15%, and tuberculosis n = 5 or 15%; and lung cancer, tuberculosis n = 45 or 24%, and recurrent pneumonia n = 45 or 24% as noted in Table S2, Supplemental Digital Content http://links.lww.com/QAI/B210.

The longest median (IQR) time from diagnosis of ADI to diagnosis of cancer was 5.2 (3.1–7.5) years for anal cancer, followed by 4.4 years for oropharynx (1.8–8.0), 3.3 (0.9–5.8) years for lung, and 2.8 (0.2–4.5) years for Hodgkin lymphoma.

Cancer Stage at Diagnosis, by ADI

At diagnosis, the majority of lung (75%), oropharynx (69%), and Hodgkin lymphoma (65%) cases had either locally advanced or metastasized disease at diagnosis, whereas the majority of anal cancer cases were classified as stage I (22%) or stage II (46%). Of the 5 cervical cancer cases, 4 were stage I and 1 was stage III. The distribution of cancer stage at diagnosis did not differ significantly by history of ADI for any cancer type (all P values >0.05; Fig. 1). At diagnosis, the percentage with cancer in stages III–IV for those with vs. without previous ADI was 33% vs. 30% for anal cancers, 66% vs. 70% for oropharynx cancers, 66% vs. 65% for Hodgkin lymphoma, and 73% vs. 77% for lung cancers.

FIGURE 1.
FIGURE 1.:
Stage at cancer diagnosis for anal, cervical, oropharynx cancers, Hodgkin lymphoma, and lung cancer, by ADI status at cancer diagnosis in the NA-ACCORD. As cervical cancer is an ADI, those with a previous ADI at cervical cancer diagnosis were classified as having a previous ADI; those without a previous ADI at the time of cancer diagnosis are classified as not having a previous ADI.

Crude Mortality Rates After Cancer Diagnosis, by Stage and ADI at Cancer Diagnosis

For anal, lung, oropharynx cancer, and Hodgkin lymphoma, we observed an increase in all-cause mortality with increasing stage of cancer diagnosis (Fig. 2A). PWH with a history of ADI at lung cancer diagnosis had a higher mortality than those without an ADI; mortality among PWH with anal, oropharynx cancer, and Hodgkin lymphoma diagnoses was similar with vs. without an ADI (Fig. 2B).

FIGURE 2.
FIGURE 2.:
Crude MRs, stratified by (A) stage at cancer diagnosis, and (B) ADI at, or before, cancer diagnosis in the NA-ACCORD. A, Crude MRs and 95% CI, by stage at cancer diagnosis. B, Crude MRs and 95% CI, by ADI at, or before, cancer diagnosis. Hodgkin, Hodgkin lymphoma; OP, oropharynx cancer.

Adjusted Mortality Rate Ratios for ADI

In crude analyses, we observed a higher MR among PWH with an ADI (vs. without) after anal [MRR = 1.6 (1.0–2.7)], Hodgkin lymphoma [MRR = 1.3 (0.6–2.7)], and lung [MRR = 1.6 (1.3–2.0)] cancer diagnoses, but there was no difference in the MRs by ADI status for oropharynx cancer [MRR = 1.0 (0.6–1.8)] (Table 2). After accounting for confounders of the association between a history of ADI at cancer diagnosis and death, the association remained statically significant for lung cancer only [aMRR = 1.6 (1.3–2.1)], but the association was consistent for anal cancer [aMRR = 1.5 (0.9–2.8)] and Hodgkin lymphoma [aMRR = 1.3 (0.5–3.3)]. The adjusted estimate for oropharynx cancer showed an increased MR in those with (vs. without) ADI [aMRR = 1.7 (0.9–3.3)] (Table 2).

TABLE 2.
TABLE 2.:
Crude MRs and Crude (MRR) and aMRR After Type-Specific Cancer Diagnosis, by ADI at, or Before, Cancer Diagnosis, the NA-ACCORD

Survival by ADI

Survival curves depicted an overall survival advantage among those without a history of ADI (vs. with a history of ADI) at anal and lung cancer diagnoses with supporting evidence from the log-rank test of a statistical difference in survival for these cancers (Figs. 3A, D). Although the log-rank test did not demonstrate statistical evidence of a difference in survival by a history of ADI for oropharynx cancer and Hodgkin lymphoma, the survival curves show that the probability of survival was greater in the first 2 years after oropharynx cancer and Hodgkin lymphoma diagnosis among those who had no history of ADI (Figs. 3B, C).

FIGURE 3.
FIGURE 3.:
Kaplan–Meier survival estimates and log-rank test for a difference in survival after type-specific cancer diagnosis, by history of ADI at cancer diagnosis in the NA-ACCORD. A, Anal cancer (P = 0.08). B, Oropharynx cancer (P = 0.92). C, Hodgkin lymphoma (P = 0.45). D, Lung cancer (P = 0.0001).

Comparison of Mortality After Type-Specific Cancer Diagnosis Among PWH With the General Population (Supplemental Analysis)

In Table S1, Supplemental Digital Content http://links.lww.com/QAI/B210 MRs (and 95% CI) after type-specific cancer diagnoses are presented among (1) the general population in the NCDB, (2) PWH without a history of ADI at cancer diagnosis, and (3) PWH with a history of ADI at cancer diagnosis, by stage. Age-standardized mortality ratios comparing PWH with and without a history of ADI vs. the general population show a dose–response relationship for all type-specific cancers; the standardized mortality ratio for PWH with a history of ADI at oropharynx cancer diagnosis was not statistically significant (Figure S1, Supplemental Digital Content http://links.lww.com/QAI/B210).

DISCUSSION

Our study findings suggest that no difference in cancer stage at diagnosis for anal, lung, cervical, oropharynx cancers, and Hodgkin lymphoma by ADI at, or before, cancer diagnosis. Holding cancer stage at diagnosis constant, there was a difference in the MR after lung cancer diagnosis by ADI status, and a suggestion of a difference after anal cancer diagnosis with borderline statistical significance. Advanced immunosuppression, immune activation, and/or chronic inflammation at, or before, cancer diagnosis may be playing an independent role in survival after some type-specific cancer diagnoses.26–29

We believe our study is among the first to compare stage at diagnosis by ADI status among PWH. We hypothesized that those with a history of ADI at cancer diagnosis would be more likely to have an advanced stage at cancer diagnosis; however, we did not find a difference. Differential cancer surveillance by ADI status is possible, but we think that it is likely minimized among our study population of adults who have all linked into care. This lack of a difference in stage by a history of ADI at cancer diagnosis is similar to studies that have found no difference in stage at cancer diagnosis by HIV status. A population-based study on lung cancer found similar proportions of cancer stages III and IV in patients with and without HIV.30 Similarly, other studies found no difference in cancer stage at diagnosis with anal cancer31 or cervical cancer32 by HIV status. An additional study found that stage was similar by HIV status for anal, colorectal, and lung cancers; however, compared to patients without HIV, PWH presented with more advanced stages of Hodgkin lymphoma.19 Finding no difference in cancer stage at diagnosis by a history of ADI status builds on similar findings of no difference in stage by HIV status, but also reduces the impact of differences in stage at diagnosis on death.

Previous studies have suggested that HIV-induced immune suppression, chronic inflammation, and the virus itself may be contributing to the increased lung cancer incidence in PWH (after accounting for the competing risk of death and the higher prevalence of smoking in PWH).33–36 Immune dysfunction is believed to enable tumor growth and lead to a reduction in tumor surveillance.35,37 Immune dysfunction at, and before, cancer diagnosis is likely influencing the risk of death. Immunosuppressive agents used to treat cancer may compound HIV-related immune dysfunction. It is currently unknown how many PWH are not able to complete cancer treatments because of life-threatening complications of immunosuppressive treatments. Additional studies are needed to separate out the effects of HIV-related immune dysfunction on tumor biology vs. treatment incompletion on mortality after cancer diagnosis, particularly for lung and anal cancer. Prospective studies comparing tumor biology between patients with or without ADI with complete cancer treatment information and cancer risk factor information will be critical to answer this question. With NA-ACCORD adding cancer treatment information in future data collection, we plan to study rates of cancer treatment completion in patients with or without ADI. Furthermore, studying the impact of ADIs on the cancer will provide further evidence to support “treat-all” strategy for HIV globally. Also, for patients diagnosed in pre–“treat-all” era, it would provide support for more aggressive cancer screening strategies for these patients.

There are several strengths to our study, the 2 most important being the careful validation of cancer cases that included collection of staging information at diagnosis, and a sample size to investigate survival after cancer diagnosis. Another strength includes the previously demonstrated demographic similarities between adults in the NA-ACCORD and people living with HIV according to CDC surveillance data.38 The distribution of demographic characteristics among NA-ACCORD participants is also similar to a nationally representative sample of PWH who are in care (described by the Medical Monitoring Project, for comparison, www.naaccord.org).

An important limitation to our study is that we were unable to account for the role of cancer treatment (and completion of treatment) on mortality; cancer treatment data collection is currently underway in the NA-ACCORD. In addition, we did not investigate cause-specific mortality after cancer diagnosis. It should be noted, however, that the predominant causes of death among PWH with access to ART beyond AIDS-related deaths are also predominant causes of death in the general population (namely, cardiovascular disease and cancer).39–43 Residual confounding by smoking status is likely, and smokeless tobacco use was not available. Cancer screening data were also not available in the NA-ACCORD. Finally, ADIs are a heterogeneous mix of infections and diseases that do not signal a single type of immune dysfunction; however, ADIs are a good marker of a history of severe immune dysfunction and are often associated with an increased risk of age-related comorbidities among PWH.9,10,35,44

In conclusion, there is no difference by a history of ADI in stage at diagnosis for anal, lung, cervical, oropharynx cancers and Hodgkin lymphoma among PWH. However, there was increased mortality and reduced survival among PWH with a history of ADI (vs. those without) for lung, anal, and oropharynx cancers, and Hodgkin lymphoma, although not all the estimates were statistically significant. Higher mortality and reduced survival after cancer diagnosis among those with an ADI may suggest a more aggressive biology of disease in patients with more severe immune dysfunction or inability to receive complete cancer treatment; further studies of the cumulative immune dysfunction during the natural and treated histories of HIV and comorbidity outcomes, such as cancer stage and mortality after cancer diagnosis, are needed with complete cancer treatment information. In the current “treat-all” era, it is possible that the proportion of PWH who have an ADI at, or before, cancer diagnosis may decrease; monitoring of the effect of the “treat-all” era on cancer outcomes and mortality after diagnosis is needed.

ACKNOWLEDGMENTS

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

APPENDIX 1. NA-ACCORD Collaborating Cohorts and Representatives

AIDS Clinical Trials Group Longitudinal Linked Randomized Trials: Constance A. Benson and Ronald J. Bosch; AIDS Link to the IntraVenous Experience: Gregory D. Kirk; Fenway Health HIV Cohort: Stephen Boswell, Kenneth H. Mayer, and Chris Grasso; HAART Observational Medical Evaluation and Research: Robert S. Hogg, P. Richard Harrigan, Julio S. G. Montaner, Benita Yip, Julia Zhu, Kate Salters, and Karyn Gabler; HIV Outpatient Study: Kate Buchacz and John T. Brooks; HIV Research Network: Kelly A. Gebo and Richard D. Moore; Johns Hopkins HIV Clinical Cohort: Richard D. Moore; John T. Carey Special Immunology Unit Patient Care and Research Database, Case Western Reserve University: Benigno Rodriguez; Kaiser Permanente Mid-Atlantic States: Michael A. Horberg; and Kaiser Permanente Northern California: Michael J. Silverberg; Longitudinal Study of Ocular Complications of AIDS: Jennifer E. Thorne; Multicenter Hemophilia Cohort Study–II: Charles Rabkin; Multicenter AIDS Cohort Study: Joseph B. Margolick, Lisa P. Jacobson, and Gypsyamber D'Souza; Montreal Chest Institute Immunodeficiency Service Cohort: Marina B. Klein; Ontario HIV Treatment Network Cohort Study: Abigail Kroch, Anita R. Rachlis, and Patrick Cupido; Retrovirus Research Center, Bayamon Puerto Rico: Robert F. Hunter-Mellado and Angel M. Mayor; Southern Alberta Clinic Cohort: M. John Gill; Study of the Consequences of the Protease Inhibitor Era: Steven G. Deeks and Jeffrey N. Martin; Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy: Pragna Patel and John T. Brooks; University of Alabama at Birmingham 1917 Clinic Cohort: Michael S. Saag, Michael J. Mugavero, and James Willig; University of California at San Diego: William C. Mathews; University of North Carolina at Chapel Hill HIV Clinic Cohort: Joseph J. Eron and Sonia Napravnik; University of Washington HIV Cohort: Mari M. Kitahata, Heidi M. Crane, and Daniel R. Drozd; Vanderbilt Comprehensive Care Clinic HIV Cohort: Timothy R. Sterling, David Haas, Peter Rebeiro, Megan Turner, Sally Bebawy, and Ben Rogers; Veterans Aging Cohort Study: Amy C. Justice, Robert Dubrow, and David Fiellin; and Women's Interagency HIV Study: Stephen J. Gange and Kathryn Anastos.

NA-ACCORD Study Administration

Executive Committee: Richard D. Moore, Michael S. Saag, Stephen J. Gange, Mari M. Kitahata, Keri N. Althoff, Michael A. Horberg, Marina B. Klein, Rosemary G. McKaig, and Aimee M. Freeman; Administrative Core: Richard D. Moore, Aimee M. Freeman, and Carol Lent; Data Management Core: Mari M. Kitahata, Stephen E. Van Rompaey, Heidi M. Crane, Daniel R. Drozd, Liz Morton, Justin McReynolds, and William B. Lober; and Epidemiology and Biostatistics Core: Stephen J. Gange, Keri N. Althoff, Jennifer S. Lee, Bin You, Brenna Hogan, Jinbing Zhang, Jerry Jing, Bin Liu, Fidel Desir, Mark Riffon, Elizabeth Humes, and Sally Coburn.

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Keywords:

HIV; AIDS; anal cancer; oropharynx cancer; cervical cancer; lung cancer; Hodgkin lymphoma; survival; mortality

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