Lucia V. Torian

Causes of Death among Persons with AIDS in the Era of Highly Active Antiretroviral Therapy: New York City

Context As HIV treatment becomes more effective, AIDS-related deaths are decreasing and HIV-infected patients are dying of other causes. Better information about these other causes will help to determine appropriate health care for this population. Contribution The authors used death certificates to identify the causes of death in 68669 residents of New York City reported with AIDS. The percentage of deaths from nonHIV-related causes increased from 19.8% to 26.3% between 1999 and 2004. The principal causes of nonHIV-related deaths were cardiovascular disease, substance abuse, and nonAIDS-defining cancer. Cautions Death certificates are an imperfect way to identify cause of death. Implications Health care for HIV-infected patients must include prevention and management of common diseases as well as HIV-focused care. The Editors Over the past 20 years, AIDS has been transformed from a disease that was almost inevitably fatal to a chronic condition that is manageable for many people in the United States (1). The evolution began modestly in the early 1990s with prophylaxis against common opportunistic illnesses and accelerated in the mid-1990s with the introduction of protease inhibitors and highly active antiretroviral therapy (HAART). Between 1996 and 1998, HIV-related morbidity and mortality decreased by 60% in the United States (24). Along with increases in survival, the spectrum of underlying causes of death among persons with AIDS has gradually shifted. Between 1987 and 1999, the proportion of deaths due to nonHIV-related causes increased from 10.6% to 22.9% in 2 U.S. metropolitan areas (5). The most common nonHIV-related causes of death reported in the literature are alcohol and drug dependence, cardiovascular disease, and nonHIV-related cancer (69). The distribution of these causes varies with the sociodemographic characteristics of the persons studied, notably the prevalence of injection drug use (1012). In recognition of the increasing importance of nonHIV-related causes of death, the Infectious Diseases Society of America (IDSA) has argued that health care for people with HIV infection should expand from a primary focus on HIV-related illnesses to include preventable conditions that account for an increasing proportion of deaths (13). Thus, analyses that contribute to a fuller understanding of the underlying causes of death in subpopulations of persons with AIDS are needed. Many previous analyses are limited by small sample size, lack of generalizability, a focus on specific causes of death, and a failure to distinguish between deaths of persons with AIDS and deaths of persons with HIV infection (non-AIDS) (8, 1419). New York City is the single largest HIV/AIDS-reporting jurisdiction in the United States, accounting for 15.3% of AIDS cases and 16.4% of deaths among persons with AIDS (20). Thus, we had a unique opportunity to conduct a population-based analysis of the spectrum of underlying causes of death in a large and heterogeneous population. The data are drawn from 2 population-based registries, the New York City HIV/AIDS Reporting System and Vital Statistics Registry, and cover the period of 1999 through 2004. Methods Population The population was made up of persons 13 years of age or older who received; a diagnosis of AIDS; were alive at any time between 1999 and 2004; were reported to the New York City HIV/AIDS Reporting System as of 30 September 2005; were residents of New York City at the time of diagnosis; and, among those who died, had a known underlying cause of death (98.2% of all deaths). Data Sources The New York City HIV/AIDS Reporting System is a population-based registry of persons who received a diagnosis of AIDS (beginning in 1981), as defined by the Centers for Disease Control and Prevention (CDC), or HIV infection (non-AIDS) (beginning in 2000) (21). The current AIDS case definition includes a positive test result for HIV plus 1 or more of 26 opportunistic illnesses or a CD4+ lymphocyte count less than 0.200109 cells/L or less than 14% of total lymphocytes. The New York City HIV/AIDS Reporting System receives reports of possible AIDS diagnoses through an electronic laboratory reporting system or physician reports and investigates them by chart review. Reporting of AIDS in New York City is estimated to be 95% complete (22). The vital status of persons with AIDS is ascertained by semiannual matches between the HIV/AIDS Reporting System and the Vital Statistics Registry. The underlying cause of death is coded at the New York City Department of Health and Mental Hygiene (DOHMH) Office of Vital Statistics by a nosologist who is certified by the National Center for Health Statistics. The nosologist codes the cause of death using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) (23). We classified persons as living in an area of poverty if they lived in a ZIP codetabulation area with more than 20% of the population below the 1999 federal poverty level or if they were homeless (24). All other variables were patient-level and were collected as part of routine surveillance. We derived demographic data from medical record reviews and provider reports and computed age at the end of 2004 or at the time of death for persons who died. We classified race or ethnicity as Hispanic, black (non-Hispanic), white (non-Hispanic), or other or unknown. The HIV transmission categories were injection drug use, men who have sex with men, and high-risk heterosexual sex. The high-risk heterosexual category included heterosexual sex with a partner who had HIV infection, with an injection drug user, or with a bisexual man. We classified men who were injection drug users and who had sex with men as injection drug users. Otherwise, when more than 1 risk factor was reported, we classified persons on the basis of the CDC hierarchy of transmission categories (25). We defined borough as the borough of residence at the time of AIDS diagnosis. We grouped the year of the AIDS diagnosis into 3 periods: pre-HAART (before 1996), early HAART (19961998), and late HAART (19992004). We obtained CD4+ lymphocyte counts primarily through an electronic laboratory reporting system. The CD4+ lymphocyte count used in the analysis was the lowest count in the second half of 2004 or within 6 months of death. Outcome The outcome was the underlying cause of death. Persons with an unknown underlying cause of death (n= 233 [1.8%]) were excluded from cause-specific analyses. HIV-Related Underlying Causes of Death We classified deaths as HIV-related if the ICD-10 code for the underlying cause of death was between B20 and B24 (HIV disease) or if the ICD-10 code was for an opportunistic illness in the CDC case definition. The latter criterion ensured that we did not misclassify deaths of people with AIDS as nonHIV-related because HIV was not mentioned on the death certificate (26). We did not further categorize these deaths in the main analysis because 70.9% of deaths were assigned a nonspecific underlying cause, for example, HIV disease resulting in other specified conditions (ICD-10 code B23.8) (Appendix Table 1). Appendix Table 1. Categories of Underlying Causes of HIV-Related Deaths in Persons with AIDS in New York City, 19992004* NonHIV-Related Underlying Causes of Death We classified deaths with a known underlying cause that did not meet the criteria described earlier as nonHIV-related. We further classified underlying causes into 9 major categories based on those used by the New York City DOHMH Office of Vital Statistics (27). Appendix Table 2 shows these categories and their associated ICD-10 codes. The substance abuse category included heterogeneous conditions that were associated with alcohol and drug abuse, including drug dependence (that is, overdose), alcoholic liver disease, cirrhosis, hepatitis C, and liver cancer (2732). The cardiovascular disease category comprised all ICD-10 codes between I00 and I78, except cardiac arrest codes. The cancer category comprised malignant types of cancer, except liver cancer and neoplasms that are part of the CDC case definition. We further classified nonHIV-related causes into 16 specific subcategories to better characterize the cause of death. Appendix Table 2. Codes for Major Categories of NonHIV-Related Causes of Death and Selected Specific Causes within Categories* Statistical Analysis We calculated the age-adjusted mortality rates per 10000 persons with AIDS for each year from 1999 to 2004 and for the entire time period. Mortality rates were age-standardized to the U.S. Census population in New York City in 2000 (33). We tested trends in rates of HIV-related deaths, nonHIV-related deaths, and specific nonHIV-related causes by using linear regression models. The model that tested trends in HIV-related and nonHIV-related deaths pooled all deaths to allow for differential trends and an explicit statistical test of whether they differed. We compared crude and age-standardized mortality rates by using methods developed for mortality vital statistics (34). We tested the association between time to death and patient characteristics in separate Cox proportional hazards regression models for HIV-related and nonHIV-related deaths. Independent variables in the model were age, sex, race or ethnicity, HIV transmission category, borough, residence in an area of poverty, year of AIDS diagnosis, and lowest CD4+ lymphocyte count. Date of cohort entry was 1 January 1999 or the date of AIDS diagnosis if diagnosis was after this date. We followed cases until death or we censored cases on 31 December 2004 if patients were still alive on that date. Those who died of a nonHIV-related cause were censored on the date of death in the model that assessed time to HIV-related death. Similarly, those who died of an HIV-related cause were censored at death in the model that assessed time to nonHIV-related death. We verified the proportional hazards assumption by

The Epidemiology of Antiretroviral Drug Resistance among Drug-Naive HIV-1-Infected Persons in 10 US Cities

BACKGROUND The prevalence and characteristics of persons with newly diagnosed human immunodeficiency virus (HIV) infections with or without evidence of mutations associated with drug resistance have not been well described. METHODS Drug-naive persons in whom HIV had been diagnosed during the previous 12 months and who did not have acquired immune deficiency syndrome were sequentially enrolled from 39 clinics and testing sites in 10 US cities during 1997-2001. Genotyping was conducted from HIV-amplification products, by automated sequencing. For specimens identified as having mutations previously associated with reduced antiretroviral-drug susceptibility, phenotypic testing was performed. RESULTS Of 1311 eligible participants, 1082 (83%) were enrolled and successfully tested; 8.3% had reverse transcriptase or major protease mutations associated with reduced antiretroviral-drug susceptibility. The prevalence of these mutations was 11.6% among men who had sex with men but was only 6.1% and 4.7% among women and heterosexual men, respectively. The prevalence was 5.4% and 7.9% among African American and Hispanic participants, respectively, and was 13.0% among whites. Among persons whose sexual partners reportedly took antiretroviral medications, the prevalence was 15.2%. CONCLUSIONS Depending on the characteristics of the patients tested, HIV-genotype testing prior to the initiation of therapy would identify a substantial number of infected persons with mutations associated with reduced antiretroviral-drug susceptibility.

Associations of Race/Ethnicity With HIV Prevalence and HIV-Related Behaviors Among Young Men Who Have Sex With Men in 7 Urban Centers in the United States

Abstract:Using data from a multisite venue-based survey of male subjects aged 15 to 22 years, we examined racial/ethnic differences in demographics, partner type, partner type-specific condom use, drug use, and HIV prevalence in 3316 US black, multiethnic black, Latino, and white men who have sex with men (MSM). We further estimated associations of these factors with HIV infection and their influence on racial/ethnic disparities in HIV prevalence. HIV prevalences were 16% for both black and multiethnic black participants, 6.9% for Latinos, and 3.3% for whites. Paradoxically, potentially risky sex and drug-using behaviors were generally reported most frequently by whites and least frequently by blacks. In a multiple logistic regression analysis, positive associations with HIV included older age, being out of school or work, sex while on crack cocaine, and anal sex with another male regardless of reported condom use level. Differences in these factors did not explain the racial/ethnic disparities in HIV prevalence, with both groups of blacks experiencing more than 9 times and Latinos experiencing approximately twice the fully adjusted odds of infection compared with whites. Understanding racial/ethnic disparities in HIV risk requires information beyond the traditional risk behavior and partnership type distinctions. Prevention programs should address risks in steady partnerships, target young men before sexual initiation with male partners, and tailor interventions to men of color and of lower socioeconomic status.

Unrecognized HIV infection, risk behaviors, and perceptions of risk among young men who have sex with men: opportunities for advancing HIV prevention in the third decade of HIV/AIDS.

This study evaluated the magnitude and distribution of unrecognized HIV infection among young men who have sex with men (MSM) and of those with unrecognized infection, the prevalence and correlates of unprotected anal intercourse (UAI), perceived low risk for infection, and delayed HIV testing. MSM aged 15-29 years were approached, interviewed, counseled, and tested for HIV at 263 randomly sampled venues in 6 US cities from 1994-2000. Of 5649 MSM participants, 573 (10%) tested positive for HIV. Of these, 91% of black, 69% of Hispanic, and 60% of white MSM (77% overall) were unaware of their infection. The 439 MSM with unrecognized infection reported a total of 2253 male sex partners in the previous 6 months; 51% had UAI; 59% perceived that they were at low risk for being infected; and 55% had not tested in the previous year. The HIV epidemic among MSM in the United States continues unabated, in part, because many young HIV-infected MSM are unaware of their infection and unknowingly expose their partners to HIV. To advance HIV prevention in the third decade of HIV/AIDS, prevention programs must reduce unrecognized infection among young MSM by increasing the demand for and availability of HIV testing services.

Regional Patterns and Correlates of Substance Use Among Young Men Who Have Sex With Men in 7 US Urban Areas

OBJECTIVES We sought to characterize substance use patterns in young men who have sex with men (MSM) in 7 US urban areas and sociodemographic characteristics and history associated with such use. METHODS We examined data collected from 1994 through 1998 in a venue-based, cross-sectional survey. RESULTS Among the 3492 participants, 66% reported use of illicit drugs; 28%, use of 3 or more drugs; 29%, frequent drug use (once a week or more); and 4%, injection drug use. These practices were more common among participants who were White, self-identified as bisexual or heterosexual, had run away, or had experienced forced sex. CONCLUSIONS Effective drug prevention and treatment programs addressing local drug-use patterns and associated factors are urgently needed for young MSM, a population with a high rate of illicit drug use.

HIV Incidence Among Injection Drug Users in New York City, 1990 to 2002: Use of Serologic Test Algorithm to Assess Expansion of HIV Prevention Services

OBJECTIVES We sought to estimate HIV incidence among injection drug users (IDUs) in New York City from 1990 to 2002 to assess the impact of an expansion of syringe exchange services. Syringe exchange increased greatly during this period, from 250,000 to 3,000,000 syringes exchanged annually. METHODS Serum samples were obtained from serial cross-sectional surveys of 3,651 IDUs. HIV-positive samples were tested with the Serologic Test Algorithm for Recent HIV Seroconversion (STARHS) assay to identify recent HIV infections and to estimate HIV incidence. Consistency with other incidence studies was used to assess strengths and limitations of STARHS. RESULTS HIV incidence declined from 3.55/100 person-years at risk (PYAR) from 1990-1992, to 2.63/100 PYAR from 1993-1995, to 1.05/100 PYAR from 1996-1998, and to 0.77/100 PYAR from 1999-2002 (P<.001). There was a very strong negative linear relationship (r= -.99, P<.005) between the annual numbers of syringes exchanged and estimated HIV incidence. These results were highly consistent with a large number of shorter incidence studies among IDUs conducted during the time period. CONCLUSIONS STARHS testing of samples from large serial cross-sectional surveys can provide important data for the assessment of community-level HIV prevention.

Risk Factors for Delayed Initiation of Medical Care After Diagnosis of Human Immunodeficiency Virus

BACKGROUND The full benefit of timely diagnosis of human immunodeficiency virus (HIV) infection is realized only if there is timely initiation of medical care. We used routine surveillance data to measure time to initiation of care in New York City residents diagnosed as having HIV by positive Western blot test in 2003. METHODS The time between the first positive Western blot test and the first reported viral load and/or CD4 cell count or percentage was used to indicate the interval from initial diagnosis of HIV (non-AIDS) to first HIV-related medical care visit. Using Cox proportional hazards regression, we identified variables associated with delayed initiation of care and calculated their hazard ratios (HRs). RESULTS Of 1928 patients, 1228 (63.7%) initiated care within 3 months of diagnosis, 369 (19.1%) initiated care later than 3 months, and 331 (17.2%) never initiated care. Predictors of delayed care were as follows: diagnosis at a community testing site (HR, 1.9; 95% confidence interval [CI], 1.5-2.3), the city correctional system (HR, 1.6; 95% CI, 1.2-2.0), or Department of Health sexually transmitted diseases or tuberculosis clinics (HR, 1.3; 95% CI, 1.1-1.6) vs a site with colocated primary medical care; nonwhite race/ethnicity (HR, 1.8; 95% CI, 1.5-2.0); injection drug use (HR, 1.3; 95% CI, 1.1-1.5); and location of birth outside the United States (HR, 1.1; 95% CI, 1.0-1.2). CONCLUSIONS A total of 1597 persons (82.8%) diagnosed as having HIV in 2003 ever initiated care, most within 3 months of diagnosis. Initiation of care was most timely when diagnosis occurred at a testing site that offered colocated medical care. Improving referrals by nonmedical sites is critical. However, because most diagnoses occur in medical sites, improving linkage in these sites will have the greatest effect on timely initiation of care.

Associations between substance use and sexual risk among very young men who have sex with men.

Objective: To determine if an association exists in young men who have sex with men (MSM) between being under the influence of alcohol or drugs during sex and participation in sexual behaviors which increase the risk of human immunodeficiency virus (HIV). Study Design: A total of 3492 young MSM were interviewed through the Young Men’s Survey, an anonymous, cross-sectional, multisite, venue-based survey conducted from 1994 through 1998 at 194 public venues frequented by MSM aged 15 to 22 years in 7 US cities. Results: The majority of young MSM reported both receptive and insertive anal intercourse, and of these, approximately half reported not using condoms. Report of unprotected receptive anal intercourse at least once in the prior 6 months was associated with being under the influence of alcohol (adjusted odds ratio [AOR] = 1.5; 95% confidence interval [CI] = 1.2–1.8), cocaine (AOR = 1.6; 95% CI = 1.1–2.2), amphetamines (AOR = 1.5; 95% CI = 1.1–2.0) or marijuana during sex (AOR = 1.3; 95% CI = 1.1–1.6). Report of unprotected insertive anal intercourse at least once in the prior 6 months was associated with being under the influence of alcohol (AOR = 1.2; 95% CI = 1.0–1.5), cocaine (AOR = 1.5; 95% CI = 1.1–2.0) or amphetamines (AOR = 1.9; 95% CI = 1.4–2.6). Conclusions: HIV prevention strategies for young MSM need to incorporate substance use risk reduction.

Convergence of HIV seroprevalence among injecting and non-injecting drug users in New York City.

Objective:To compare HIV prevalence among injecting and non-injecting heroin and cocaine users in New York City. As HIV is efficiently transmitted through the sharing of drug-injecting equipment, HIV infection has historically been higher among injecting drug users. Design:Two separate cross-sectional surveys, both with HIV counseling and testing and drug use and HIV risk behavior questionnaires. Methods:Injecting and non-injecting heroin and cocaine users recruited at detoxification and methadone maintenance treatment from 2001–2004 (n = 2121) and recruited through respondent-driven sampling from a research storefront in 2004 (n = 448). Results:In both studies, HIV prevalence was nearly identical among current injectors (injected in the last 6 months) and heroin and cocaine users who had never injected: 13% [95% confidence interval (CI), 12–15%] among current injectors and 12% (95% CI, 9–16%) among never-injectors in the drug treatment program study, and 15% (95% CI, 11–19%) among current injectors and 17% (95% CI, 12–21%) among never injectors in the respondent driven sampling storefront study. The 95% CIs overlapped in all gender and race/ethnicity subgroup comparisons of HIV prevalence in both studies. Conclusions:The very large HIV epidemic among drug users in New York City appears to be entering a new phase, in which sexual transmission is of increasing importance. Additional prevention programs are needed to address this transition.

Declining seroprevalence in a very large HIV epidemic: injecting drug users in New York City, 1991 to 1996.

OBJECTIVES This study assessed recent trends in HIV seroprevalence among injecting drug users in New York City. METHODS We analyzed temporal trends in HIV seroprevalence from 1991 through 1996 in 5 studies of injecting drug users recruited from a detoxification program, a methadone maintenance program, research storefronts in the Lower East Side and Harlem areas, and a citywide network of sexually transmitted disease clinics. A total of 11,334 serum samples were tested. RESULTS From 1991 through 1996, HIV seroprevalence declined substantially among subjects in all 5 studies: from 53% to 36% in the detoxification program, from 45% to 29% in the methadone program, from 44% to 22% at the Lower East Side storefront, from 48% to 21% at the Harlem storefront, and from 30% to 21% in the sexually transmitted disease clinics (all P < .002 by chi 2 tests for trend). CONCLUSIONS The reductions in HIV seroprevalence seen among injecting drug users in New York City from 1991 through 1996 indicate a new phase in this large HIV epidemic. Potential explanatory factors include the loss of HIV-seropositive individuals through disability and death and lower rates of risk behavior leading to low HIV incidence.