John T. Brooks

Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study.

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/&mgr;L in 1996 to 287 cells/&mgr;L 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/&mgr;L, 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.

Antiretroviral Preexposure Prophylaxis for Heterosexual HIV Transmission in Botswana

BACKGROUND Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival

BACKGROUND The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy.

Incidence of Types of Cancer among HIV-Infected Persons Compared with the General Population in the United States, 1992–2003

BACKGROUND Persons who are HIV-infected may be at higher risk for certain types of cancer than the general population. OBJECTIVE To compare cancer incidence among HIV-infected persons with incidence in the general population from 1992 to 2003. DESIGN Prospective observational cohort studies. SETTING United States. PATIENTS 54,780 HIV-infected persons in the Adult and Adolescent Spectrum of HIV Disease Project (47,832 patients) and the HIV Outpatient Study (6948 patients), who contributed 157,819 person-years of follow-up from 1992 to 2003, and 334,802,121 records from the Surveillance, Epidemiology, and End Results program of 13 geographically defined, population-based, central cancer registries. MEASUREMENTS Standardized rate ratios (SRRs) to compare cancer incidence in the HIV-infected population with standardized cancer incidence in the general population. RESULTS The incidence of the following types of non-AIDS-defining cancer was significantly higher in the HIV-infected population than in the general population: anal (SRR, 42.9 [95% CI, 34.1 to 53.3]), vaginal (21.0 [CI, 11.2 to 35.9]), Hodgkin lymphoma (14.7 [CI, 11.6 to 18.2]), liver (7.7 [CI, 5.7 to 10.1]), lung (3.3 [CI, 2.8 to 3.9]), melanoma (2.6 [CI, 1.9 to 3.6]), oropharyngeal (2.6 [CI, 1.9 to 3.4]), leukemia (2.5 [CI, 1.6 to 3.8]), colorectal (2.3 [CI, 1.8 to 2.9]), and renal (1.8 [CI, 1.1 to 2.7]). The incidence of prostate cancer was significantly lower among HIV-infected persons than the general population (SRR, 0.6 [CI, 0.4 to 0.8]). Only the relative incidence of anal cancer increased over time. LIMITATIONS Lower ascertainment of cancer in the HIV cohorts may result in a potential bias to underestimate rate disparities. Tobacco use as a risk factor and the effect of changes in cancer screening practices could not be evaluated. CONCLUSION The incidence of many types of non-AIDS-defining cancer was higher among HIV-infected persons than among the general population from 1992 to 2003.

Non-O157 Shiga Toxin–Producing Escherichia coli Infections in the United States, 1983–2002

BACKGROUND Shiga toxin-producing Escherichia coli (STEC) O157:H7 is a well-recognized cause of bloody diarrhea and hemolytic-uremic syndrome (HUS). Non-O157 STEC contribute to this burden of illness but have been underrecognized as a result of diagnostic limitations and inadequate surveillance. METHODS Between 1983 and 2002, 43 state public health laboratories submitted 940 human non-O157 STEC isolates from persons with sporadic illnesses to the Centers for Diseases Control and Prevention reference laboratory for confirmation and serotyping. RESULTS The most common serogroups were O26 (22%), O111 (16%), O103 (12%), O121 (8%), O45 (7%), and O145 (5%). Non-O157 STEC infections were most frequent during the summer and among young persons (median age, 12 years; interquartile range, 3-37 years). Virulence gene profiles were as follows: 61% stx(1) but not stx(2); 22% stx(2) but not stx(1); 17% both stx(1) and stx(2); 84% intimin (eae); and 86% enterohemolysin (E-hly). stx(2) was strongly associated with an increased risk of HUS, and eae was strongly associated with an increased risk of bloody diarrhea. STEC O111 accounted for most cases of HUS and was also the cause of 3 of 7 non-O157 STEC outbreaks reported in the United States. CONCLUSIONS Non-O157 STEC can cause severe illness that is comparable to the illness caused by STEC O157. Strains that produce Shiga toxin 2 are much more likely to cause HUS than are those that produce Shiga toxin 1 alone. Improving surveillance will more fully elucidate the incidence and pathological spectrum of these emerging agents. These efforts require increased clinical suspicion, improved clinical laboratory isolation, and continued serotyping of isolates in public health laboratories.

Guidelines for preventing opportunistic infections among HIV-infected persons - 2002

Introduction In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV) (1-3). These guidelines, which are intended for clinicians and health-care providers and their HIV-infected patients, were revised in 1997 (4) and again in 1999 (5), and have been published in MMWR (1, 4, 5), Clinical Infectious Diseases (2, 6, 7), Annals of Internal Medicine (3, 8), American Family Physician (9, 10), and Pediatrics (11); accompanying editorials have appeared in JAMA (12, 13). Response to these guidelines (e.g., a substantial number of requests for reprints, website contacts, and observations from health-care providers) demonstrates that they have served as a valuable reference for HIV health-care providers. Because the 1995, 1997, and 1999 guidelines included ratings indicating the strength of each recommendation and the quality of supporting evidence, readers have been able to assess the relative importance of each recommendation. Since acquired immunodeficiency syndrome (AIDS) was first recognized 20 years ago, remarkable progress has been made in improving the quality and duration of life for HIV-infected persons in the industrialized world. During the first decade of the epidemic, this improvement occurred because of improved recognition of opportunistic disease processes, improved therapy for acute and chronic complications, and introduction of chemoprophylaxis against key opportunistic pathogens. The second decade of the epidemic has witnessed extraordinary progress in developing highly active antiretroviral therapies (HAART) as well as continuing progress in preventing and treating OIs. HAART has reduced the incidence of OIs and extended life substantially (14-16). HAART is the most effective approach to preventing OIs and should be considered for all HIV-infected persons who qualify for such therapy (14-16). However, certain patients are not ready or able to take HAART, and others have tried HAART regimens but therapy failed. Such patients will benefit from prophylaxis against OIs (15). In addition, prophylaxis against specific OIs continues to provide survival benefits even among persons who are receiving HAART (15). Clearly, since HAART was introduced in the United States in 1995, chemoprophylaxis for OIs need not be lifelong. Antiretroviral therapy can restore immune function. The period of susceptibility to opportunistic processes continues to be accurately indicated by CD4+ T lymphocyte counts for patients who are receiving HAART. Thus, a strategy of stopping primary or secondary prophylaxis for certain patients whose immunity has improved as a consequence of HAART is logical. Stopping prophylactic regimens can simplify treatment, reduce toxicity and drug interactions, lower cost of care, and potentially facilitate adherence to antiretroviral regimens. In 1999, the USPHS/IDSA guidelines reported that stopping primary or secondary prophylaxis for certain pathogens was safe if HAART has led to an increase in CD4+ T lymphocyte counts above specified threshold levels. Recommendations were made for only those pathogens for which adequate clinical data were available. Data generated since 1999 continue to support these recommendations and allow additional recommendations to be made concerning the safety of stopping primary or secondary prophylaxis for other pathogens. For recommendations regarding discontinuing chemoprophylaxis, readers will note that criteria vary by such factors as duration of CD4+ T lymphocyte count increase, and, in the case of secondary prophylaxis, duration of treatment of the initial episode of disease. These differences reflect the criteria used in specific studies. Therefore, certain inconsistencies in the format of these criteria are unavoidable. Although considerable data are now available concerning discontinuing primary and secondary OI prophylaxis, essentially no data are available regarding restarting prophylaxis when the CD4+ T lymphocyte count decreases again to levels at which the patient is likely to again be at risk for OIs. For primary prophylaxis, whether to use the same threshold at which prophylaxis can be stopped (derived from data in studies addressing prophylaxis discontinuation) or to use the threshold below which initial prophylaxis is recommended, is unknown. Therefore, in this revision of the guidelines, in certain cases, ranges are provided for restarting primary or secondary prophylaxis. For prophylaxis against Pneumocystis carinii pneumonia (PCP), the indicated threshold for restarting both primary and secondary prophylaxis is 200 cells/L. For all these recommendations, the Roman numeral ratings reflect the lack of data available to assist in making these decisions (Box). Table. System Used to Rate the Strength of Recommendations and Quality of Supporting Evidence During the development of these revised guidelines, working group members reviewed published manuscripts as well as abstracts and material presented at professional meetings. Periodic teleconferences were held to develop the revisions. Major Changes in These Recommendations Major changes in the guidelines since 1999 include the following: Higher level ratings have been provided for discontinuing primary prophylaxis for PCP and Mycobacterium avium complex (MAC) when CD4+ T lymphocytes have increased to >200 cells/L and >100 cells/L, respectively, for 3 months in response to HAART (AI), and a new recommendation to discontinue primary toxoplasmosis prophylaxis has been provided when the CD4+ T lymphocyte count has increased to >200 cells/L for 3 months (AI). Secondary PCP prophylaxis should be discontinued among patients whose CD4+ T lymphocyte counts have increased to >200 cells/L for 3 months as a consequence of HAART (BII). Secondary prophylaxis for disseminated MAC can be discontinued among patients with a sustained (e.g., 6-month) increase in CD4+ count to >100 cells/L in response to HAART, if they have completed 12 months of MAC therapy and have no symptoms or signs attributable to MAC (CIII). Secondary prophylaxis for toxoplasmosis and cryptococcosis can be discontinued among patients with a sustained increase in CD4+ counts (e.g. 6 months) to >200 cells/L and >100200 cells/L, respectively, in response to HAART, if they have completed their initial therapy and have no symptoms or signs attributable to these pathogens (CIII). The importance of screening all HIV-infected persons for hepatitis C virus (HCV) is emphasized (BIII). Additional information concerning transmission of human herpesvirus 8 infection (HHV-8) is provided. New information regarding drug interactions is provided, chiefly related to rifamycins and antiretroviral drugs. Revised recommendations for vaccinating HIV-infected adults and HIV-exposed or infected children are provided. Using the Information in This Report For each of the 19 diseases covered in this report, specific recommendations are provided that address 1) preventing exposure to opportunistic pathogens, 2) preventing first episodes of disease, and 3) preventing disease recurrences. Recommendations are rated by a revised version of the IDSA rating system (17). In this system, the letters AE signify the strength of the recommendation for or against a preventive measure, and Roman numerals IIII indicate the quality of evidence supporting the recommendation (Box). Because of their length and complexity, tables in this report are grouped together and follow the references. Tables appear in the following order: Table 1 Dosages for prophylaxis to prevent first episode of opportunistic disease among infected adults and adolescents; Table 1. Prophylaxis to Prevent First Episode of Opportunistic Disease among Adults and Adolescents Infected with Human Immunodeficiency Virus (HIV) Table 2 Dosages for prophylaxis to prevent recurrence of opportunistic disease among HIV-infected adults and adolescents; Table 2. Prophylaxis to Prevent Recurrence of Opportunistic Disease, after Chemotherapy for Acute Disease, among Adults and Adolescents Infected with Human Immunodeficiency Virus (HIV) Table 3 Effects of food on drugs used to treat OIs; Table 3. Effects of Food on Drugs Used to Prevent Opportunistic Infections Table 4 Effects of medications on drugs used to treat OIs; Table 4. Effects of Medications on Drugs Used to Prevent Opportunistic Infections Table 5 Effects of OI medications on drugs commonly administered to HIV-infected persons; Table 5. Effects of Opportunistic Infection Medications on Antiretroviral Drugs Commonly Administered to Persons Infected with Human Immunodeficiency Virus (HIV) Table 6 Adverse effects of drugs used to prevent OIs; Table 6. Adverse Effects of Drugs Used in Preventing Opportunistic Infections Table 7 Dosages of drugs for preventing OIs for persons with renal insufficiency; Table 7. Dosing of Drugs for Primary Prevention of or Maintenance Therapy for Opportunistic Infections Related to Renal Insufficiency Table 8 Costs of agents recommended for preventing OIs among adults with HIV infection; Table 8. Wholesale Acquisition Costs of Agents Recommended for Preventing Opportunistic Infections among Adults Infected with Human Immunodeficiency Virus Table 9 Immunologic categories for HIV-infected children; Table 9. Immunologic Categories for Human Immunodeficiency Virus-Infected Children, Based on Age-Specific CD4+ T Lymphocyte Counts and Percentage of Total Lymphocytes Table 10 Immunization schedule for HIV-infected children; Table 10. Recommended Immunization Schedule for Human Immunodeficiency Virus (HIV)-Infected Children Table 11 Dosages for prophylaxis to prevent first episode of opportunistic disease among HIV-infected infants and children; Table 11. Prophylaxis to Prevent First Episode of Opportunistic Disease among Infants and Children Infected with Human Immunodeficiency Virus Tabl

Risk of Anal Cancer in HIV-Infected and HIV-Uninfected Individuals in North America

BACKGROUND Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends. METHODS In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men). RESULTS Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7-151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5-61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8-6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5-2.2). In comparison with the period 2000-2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3-.9) in 1996-1999 and 0.9 (95% CI, .6-1.2) in 2004-2007. CONCLUSIONS Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.

Estimating per-act HIV transmission risk: a systematic review

Background:Effective HIV prevention programs rely on accurate estimates of the per-act risk of HIV acquisition from sexual and parenteral exposures. We updated the previous risk estimates of HIV acquisition from parenteral, vertical, and sexual exposures, and assessed the modifying effects of factors including condom use, male circumcision, and antiretroviral therapy. Methods:We conducted literature searches to identify new studies reporting data regarding per-act HIV transmission risk and modifying factors. Of the 7339 abstracts potentially related to per-act HIV transmission risk, three meta-analyses provided pooled per-act transmission risk probabilities and two studies provided data on modifying factors. Of the 8119 abstracts related to modifying factors, 15 relevant articles, including three meta-analyses, were included. We used fixed-effects inverse-variance models on the logarithmic scale to obtain updated estimates of certain transmission risks using data from primary studies, and employed Poisson regression to calculate relative risks with exact 95% confidence intervals for certain modifying factors. Results:Risk of HIV transmission was greatest for blood transfusion, followed by vertical exposure, sexual exposures, and other parenteral exposures. Sexual exposure risks ranged from low for oral sex to 138 infections per 10 000 exposures for receptive anal intercourse. Estimated risks of HIV acquisition from sexual exposure were attenuated by 99.2% with the dual use of condoms and antiretroviral treatment of the HIV-infected partner. Conclusion:The risk of HIV acquisition varied widely, and the estimates for receptive anal intercourse increased compared with previous estimates. The risk associated with sexual intercourse was reduced most substantially by the combined use of condoms and antiretroviral treatment of HIV-infected partners.

AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study.

Objectives:To assess the incidence and spectrum of AIDS-defining opportunistic illnesses in the highly active antiretroviral therapy (cART) era. Design:A prospective cohort study of 8070 participants in the HIV Outpatient Study at 12 U.S. HIV clinics. Methods:We calculated incidence rates per 1000 person-years of observation for the first opportunistic infection, first opportunistic malignancy, and first occurrence of each individual opportunistic illness during 1994–2007. Using stratified Poisson regression models, and adjusting for sex, race, and HIV risk category, we modeled annual percentage changes in opportunistic illness incidence rates by calendar period. Results:Eight thousand and seventy patients (baseline median age 38 years; median CD4 cell count 298 cells/μl) experienced 2027 incident opportunistic illnesses during a median of 2.9 years of observation. During 1994–1997, 1998–2002, and 2003–2007, respectively, rates of opportunistic infections (per 1000 person-years) were 89.0, 25.2 and 13.3 and rates of opportunistic malignancies were 23.4, 5.8 and 3.0 (P for trend <0.001 for both). Opportunistic illness rate decreases were similar for the subset of patients receiving cART. During 2003–2007, there were no significant changes in annual rates of opportunistic infections or opportunistic malignancies; the leading opportunistic illnesses (rate per 1000 person-years) were esophageal candidiasis (5.2), Pneumocystis pneumonia (3.9), cervical cancer (3.5), Mycobacterium avium complex infection (2.5), and cytomegalovirus disease (1.8); 36% of opportunistic illness events occurred at CD4 cell counts at least 200 cells/μl. Conclusions:Opportunistic illness rates declined precipitously after introduction of cART and stabilized at low levels during 2003–2007. In this contemporary cART era, a third of opportunistic illnesses were diagnosed at CD4 cell counts at least 200 cells/μl.

Low Vitamin D among HIV-Infected Adults: Prevalence of and Risk Factors for Low Vitamin D Levels in a Cohort of HIV-Infected Adults and Comparison to Prevalence among Adults in the US General Population

BACKGROUND we explored serum 25-hydroxyvitamin D (25[OH]D) levels and associated factors for insufficiency or deficiency in an adult human immunodeficiency virus (HIV) cohort and compared 25(OH)D levels with those in the general US population. METHODS using baseline data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN), a prospective, observational cohort study of HIV-infected adults enrolled at 7 HIV specialty clinics in 4 US cities from March 2004 to June 2006, we estimated the prevalence of vitamin D insufficiency or deficiency (defined as 25(OH)D levels <30 ng/mL), standardized by age, race, and sex. Using multiple logistic regression, we examined risk factors for vitamin D insufficiency or deficiency. RESULTS among 672 SUN participants with baseline serum 25(OH)D determinations who were not receiving vitamin D supplements, 70.3% (95% confidence interval [CI], 68.1%-74.9%) were vitamin D insufficient or deficient, compared with 79.1% (95% CI, 76.7-81.3) of US adults. Factors associated with vitamin D insufficiency or deficiency included black race (adjusted odds ratio [aOR], 4.51; 95% CI, 2.59-7.85), Hispanic ethnicity (aOR, 2.78; 95% CI, 1.31-5.90), higher body mass index (aOR, 1.04; 95% CI, 1.00-1.09), hypertension (aOR, 1.88; 95% CI, 1.10-3.22), lack of exercise (aOR, 3.14; 95% CI, 1.80-5.47), exposure to efavirenz (aOR, 1.98; 95% CI, 1.18-3.34), higher exposure to ultraviolet light (aOR, .78; 95% CI, .71-.86), renal insufficiency (aOR, .55; 95% CI, .36-.83), and exposure to ritonavir (aOR, .56; 95% CI, .35-0.89). CONCLUSIONS similar to findings in US adults generally, vitamin D insufficiency or deficiency is highly prevalent among HIV-infected adults and is associated with known risk factors. Observed associations of vitamin D levels with renal insufficiency and with use of ritonavir- and efavirenz-containing regimens are consistent with both HIV-related and therapy-mediated alterations in vitamin D metabolism. Clinicians should consider screening all patients for vitamin D insufficiency or deficiency.