Judith E. Sackoff

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

Severity of 2009 pandemic influenza A (H1N1) virus infection in pregnant women.

OBJECTIVE: To examine 2009 H1N1 influenza illness severity and the effect of antiviral treatment on the severity of illness among pregnant women. METHODS: We abstracted medical records from hospitalized pregnant (n=62) and nonpregnant (n=74) women with laboratory-confirmed 2009 H1N1 influenza in New York City, May through June 2009. We compared characteristics of pregnant and nonpregnant women and of severe and moderate influenza illness among pregnant women, with severe defined as illness resulting in intensive care admission or death. RESULTS: The 2009 H1N1 hospitalization rate was significantly higher among pregnant than nonpregnant women (55.3 compared with 7.7 per 100,000 population). Eight pregnant (including two deaths) and 16 nonpregnant (including four deaths) cases were severe. Pregnant women represented 6.4% of hospitalized cases and 4.3% of deaths caused by 2009 H1N1 influenza. Only 1 in 30 (3.3%) pregnant women who received oseltamivir treatment within 2 days of symptom onset had severe illness compared with 3 of 14 (21.4%) and four of nine (44.4%) pregnant women who started treatment 3–4 days and 5 days or more after symptom onset, respectively (P=.002 for trend). Severe and moderate 2009 H1N1 influenza illness occurred in all pregnancy trimesters, but most women (54.8%) were in the third trimester. Twenty-two women delivered during their influenza hospitalization, and severe neonatal outcomes (neonatal intensive care unit admission or death) occurred among five of six (83.3%) women with severe illness compared with 2 of 16 (12.5%) women with moderate illness (P=.004). CONCLUSION: Our findings highlight the potential for severe illness and adverse neonatal outcomes among pregnant 2009 H1N1 influenza-infected women and suggest the benefit of early oseltamivir treatment. LEVEL OF EVIDENCE: II

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.

Relapse and Acquired Rifampin Resistance in HIV-Infected Patients with Tuberculosis Treated with Rifampin- or Rifabutin-Based Regimens in New York City, 1997–2000

BACKGROUND The relationship between rifamycin use and either relapse or treatment failure with acquired rifampin resistance (ARR) among human immunodeficiency virus (HIV)-infected patients with tuberculosis (TB) is not well understood. METHODS We conducted a retrospective cohort study of HIV-infected and HIV-uninfected persons with rifampin-susceptible TB, (1) to compare relapse rates, ARR, and treatment failure, according to HIV serostatus; and (2) to examine whether and how use of rifamycin was associated with clinical outcomes of interest among HIV-infected patients with TB. RESULTS HIV-infected patients were more likely to have ARR than were HIV-uninfected patients (0.9% vs. 0.1%; P = .007), and the association remained significant in multivariate analysis (adjusted odds ratio [OR], 5.5; 95% confidence interval [CI], 1.4-21.5). Among HIV-infected patients with TB, none of 57 patients treated with rifabutin-based regimens alone had ARR, and only 1 of 395 patients treated with rifabutin given in combination with a rifampin-based regimen had ARR, whereas 6 of 355 patients treated with a rifampin-based regimen alone had relapse and ARR. HIV-infected patients treated with rifampin-based regimens alone had a higher risk for relapse and development of rifampin resistance if intermittent dosing of rifampin was started during the intensive phase of treatment, compared with patients who did not receive intermittent dosing (hazard ratio [HR] for relapse, 6.7 [95% CI, 1.1-40.1]; HR for ARR, 6.4 [95% CI, 1.1-38.4]). This association remained when confined to patients with a CD4+ T lymphocyte count of < 100 lymphocytes/mm3. Intermittent dosing started only after the intensive phase of treatment did not increase the risks of relapse and ARR among HIV-infected patients with TB. CONCLUSION The risk for ARR among HIV-infected persons with TB did not depend on the rifamycin used but, rather, on the rifampin dosing schedule in the intensive phase of treatment.

Validation of selected items on the 2003 U.S. standard certificate of live birth: New York City and Vermont.

Objective. We assessed the validity of selected items on the 2003 revised U.S. Standard Certificate of Live Birth to understand the accuracy of new and existing items. Methods. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of select variables reported on the birth certificate using the medical record as the gold standard for a representative sample of live births in New York City (n=603) and Vermont (n=664) in 2009. Results. In both sites, sensitivity was excellent (>90%) for Medicaid coverage at delivery, any previous live births, and current method of delivery; sensitivity was moderate (70%–90%) for gestational diabetes; and sensitivity was poor (<70%) for premature rupture of the membranes and gestational hypertension. In both sites, PPV was excellent for Medicaid coverage, any previous live births, previous cesarean delivery, and current method of delivery, and poor for premature rupture of membranes. In both sites, almost all items had excellent (>90%) specificity and NPV. Conclusion. Further research is needed to determine how best to improve the quality of data on the birth certificate. Future revisions of the birth certificate may consider removing those items that have consistently proven difficult to report accurately.

AIDS-defining opportunistic illnesses in the HAART era in New York City

Abstract Despite widespread availability of HAART, opportunistic illnesses (OIs) still occur and result in an increased risk of mortality among persons with AIDS. We estimated the incidence of OIs among all new adult AIDS cases in New York City in 2000 overall and in demographic and clinical subgroups and identified factors associated with occurrence of an AIDS-defining OI versus AIDS diagnosis based on low CD4+ values only. In 2000, 5,451 new AIDS cases were reported to the New York City Department of Health and Mental Hygiene. Of these 27.4% (95% CI: 22.8–32.6) had at least one OI, most frequent being Pneumocystis jiroveci pneumonia (12.2%) and M. tuberculosis (5.3%); 47.1% (41.7–52.5) had a late HIV diagnosis (i.e.≤6 months before AIDS diagnosis). Persons with a late HIV diagnosis not in recent care had a 3.5-fold increased odds (1.29–9.63) of an OI, compared to non-late testers in care. Other predictors of an OI were injection drug use and older age. We conclude that OIs remain prevalent in the HAART era and late testers not in care are especially likely to develop an OI. Our results support comprehensive HIV programs promoting early HIV testing and linkage to care to prevent OI-related morbidity and mortality.

Comparing the National Death Index and the Social Security Administration's Death Master File to Ascertain Death in HIV Surveillance

Objectives. New York City (NYC) maintains a population-based registry of people with human immunodeficiency virus (HIV) infection to monitor the epidemic and inform resource allocation. We evaluated record linkages with the National Death Index (NDI) and the Social Security Administrations Death Master File (SSDMF) to find deaths occurring from 2000 through 2004. Methods. We linked records from 32,837 people reported with HIV and not previously known to be dead with deaths reported in the NDI and the SSDMF. We calculated the kappa statistic to assess agreement between data sources. We performed subgroup analyses to assess differences within demographic and transmission risk subpopulations. We quantified the benefit of linkages with each data source beyond prior death ascertainment from local vital statistics data. Results. We discovered 1,926 (5.87%) deaths, which reduced the HIV prevalence estimate in NYC by 2.03%, from 1.19% to 1.16%. Of these, 458 (23.78%) were identified only from NDI, and 305 (15.84%) only from SSDMF. Agreement in ascertainment between sources was substantial (kappa = [K] 0.74, 95% confidence interval [CI] 0.72, 0.76); agreement was lower among Hispanic people (K=0.65, 95% CI 0.62, 0.69) and people born outside the U.S. (K=0.60, 95% CI 0.52, 0.68). We identified an additional 13.62% of deaths to people reported with HIV in NYC; white people and men who have sex with men were disproportionately likely to be underascertained without these linkages (p<0.0001). Conclusion. Record linkages with national databases are essential for accurate prevalence estimates from disease registries, and the SSDMF is an inexpensive means to supplement linkages with the NDI to maximize death ascertainment.

Incident sexually transmitted infections among persons living with diagnosed HIV/AIDS in New York City, 2001-2002 : A population-based assessment

Objective/Goal: To describe the incidence of 3 bacterial sexually transmitted infections (STIs) among persons living with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) (PLWHA) in New York City (NYC) and to identify predictors for STI acquisition. Study Design: The surveillance registry of PLWHA diagnosed with HIV through December 31, 2000, and reported to the NYC Department of Health and Mental Hygiene was matched with the surveillance registry of persons diagnosed with other STIs during 2001–2002. Incident STIs were defined as cases of gonorrhea, chlamydia, or early syphilis acquired after HIV diagnosis. Results: Among 62,264 NYC PLWHA, 1466 (2.4%) had an incident STI diagnosed during 2001–2002. Two-year cumulative STI incidence was highest among PLWHA who were men (2.6%), non-Hispanic white (3.2%), aged 13–24 years (8.4%), men who have sex with men (4.5%), and persons living with HIV (non–AIDS) (4.1%). Predictors of STI acquisition among PLWHA varied substantially by STI type. Conclusions: This population-based surveillance registry cross-match reveals that high-risk sexual practices occur among specific segments of the NYC PLWHA population. To decrease associated morbidity and prevent the secondary spread of HIV and STIs, prevention efforts should focus on PLWHA who continue to engage in high-risk sexual activity.

Pregnancy Risk among Black, White, and Hispanic Teen Girls in New York City Public Schools

Disparities in teen pregnancy rates are explained by different rates of sexual activity and contraceptive use. Identifying other components of risk such as race/ethnicity and neighborhood can inform strategies for teen pregnancy prevention. Data from the 2005 and 2007 New York City Youth Risk Behavior Surveys were used to model demographic differences in odds of recent sexual activity and birth control use among black, white, and Hispanic public high school girls. Overall pregnancy risk was calculated using pregnancy risk index (PRI) methodology, which estimates probability of pregnancy based on current sexual activity and birth control method at last intercourse. Factors of race/ethnicity, grade level, age, borough, and school neighborhood were assessed. Whites reported lower rates of current sexual activity (23.4%) than blacks (35.4%) or Hispanics (32.7%), and had lower predicted pregnancy risk (PRI = 5.4% vs. 9.0% and 10.5%, respectively). Among sexually active females, hormonal contraception use rates were low in all groups (11.6% among whites, 7.8% among blacks, and 7.5% among Hispanics). Compared to white teens, much of the difference in PRI was attributable to poorer contraceptive use (19% among blacks and 50% among Hispanics). Significant differences in contraceptive use were also observed by school neighborhood after adjusting for age group and race/ethnicity. Interventions to reduce teen pregnancy among diverse populations should include messages promoting delayed sexual activity, condom use and use of highly effective birth control methods. Access to long-acting contraceptive methods must be expanded for all sexually active high school students.

Purified protein derivative testing and tuberculosis preventive therapy for HIV-infected patients in New York City.

Objective:To determine whether Centers for Disease Control and Prevention recommendations for purified protein derivative (PPD) testing and tuberculosis (TB) preventive therapy for PPD-positive patients are implemented in HIV clinics. Design:Retrospective medical chart review. Setting:Ten hospital-based HIV clinics in New York City. Participants:A total of 2397 patients with a first clinic visit in 1995. Outcome measures:PPD testing of eligible patients, and recommendation of preventive therapy and completion of regimen in PPD-positive patients. Method:Outpatient medical records were abstracted for TB history, PPD testing, TB preventive therapy, and patient demographic, social and clinical characteristics. Multivariate analyses were performed using logistic regression. Results:Of 1342 patients with an indication for a PPD test, 865 (64%) were PPD tested in the clinic and 757 (88%) returned to have it read. Factors strongly associated with PPD testing in the clinic were number of visits, same sex behavior with men, and CD4+ lymphocyte count above 200 × 106/l. Preventive therapy was recommended for 80% of newly identified PPD-positive patients and 22% of previously identified PPD-positive patients. Of 119 patients on preventive therapy in the clinic, 49 (41%) completed the regimen, 50 (42%) were lost to follow-up, and 20 (17%) discontinued therapy or their status could not be determined. Conclusion:A significant number of missed opportunities to implement TB prevention practices were identified in HIV clinics. Focused attention in HIV clinics, and increased collaboration between HIV clinics and TB control programs may be needed to increase adherence to prevention guidelines.