Sharon K. Melville

Trends in antiretroviral therapy use and survival rates for a large cohort of HIV-infected children and adolescents in the United States, 1989-2001.

Background:In the United States, HIV-infected children and adolescents are aging and using antiretroviral (ARV) therapy for extended periods of time. Objective:To assess trends in ARV use and long-term survival in an observational cohort of HIV-infected children and adolescents in the United States. Methods:The Pediatric Spectrum of HIV Disease Study (PSD) is a prospective chart review of more than 2000 HIV-infected children and adolescents. Patients were included in the analysis from enrollment until last follow-up. Results:Triple-ARV therapy use (for 6 months or more) increased from 27% to 66% during 1997 to 2001 (P < 0.0001, χ2 for trend). The proportion of patients receiving 3 or more sequential triple-therapy regimens also increased from 4% to 17% during 1997 to 2001 (P < 0.0001, χ2 for trend), however, and the durability of triple-therapy regimens decreased from 13 to 7 months from the first to third regimen. Survival rates for the 1997 to 2001 birth cohorts were significantly better than for the 1989 to 1993 and 1994 to 1996 cohorts (P < 0.0001). Conclusions:Survival rates in the PSD cohort have increased in association with triple-ARV therapy use. With continued changes in ARV regimens, effective modifications in ARV therapy and the sustainability of gains in survival need to be determined.

Differences in prescription of antiretroviral therapy in a large cohort of HIV-infected patients.

The objective of this study was to determine factors associated with prescription of highly active antiretroviral therapy (HAART). The authors observed 9530 patients eligible for antiretroviral therapy (ART) in more than 100 hospitals and clinics in 10 US cities. Multiple logistic regression analysis was used to assess factors associated with HAART prescription, stratifying patients by no history versus history of ART to assess the association between prescription and CD4, viral load, and outpatient visits. Overall, female gender (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.60–0.76) and alcoholism (OR, 0.85; 95% CI, 0.74–0.99) were associated with decreased likelihood of HAART prescription. Enrollment at a private facility (OR, 1.33; 95% CI, 1.14–1.56), heterosexual exposure (OR, 1.34; 95% CI, 1.13–1.58), and Hispanic ethnicity (OR, 1.19; 95% CI, 1.04–1.37) were associated with prescription. For patients with no history of prescribed ART, CD4 <500 cells/&mgr;L (OR, 3.94; 95% CI, 2.02–7.66), and high viral load were associated with increased likelihood of prescription; for patients with history of ART prescription, those whose outpatient visits averaged ≥2 per 6-month interval (OR, 1.30; 95% CI, 1.10–1.54) were more likely and those with high viral load were less likely to be prescribed HAART (OR, 0.50; 95% CI, 0.44–0.56). The authors found differences in HAART prescription by gender, race, exposure mode, alcoholism, and provider type for all patients, by CD4 and viral load for patients with no history of ART prescription, and by average number of outpatient visits and viral load for patients with history of ART prescription.

Performance of Premarket Rapid Hepatitis C Virus Antibody Assays in 4 National Human Immunodeficiency Virus Behavioral Surveillance System Sites

SUMMARY Performance characteristics of rapid assays for hepatitis C virus antibody were evaluated in 4 National HIV Behavioral Surveillance System injection drug use sites. The highest assay-specific sensitivities achieved for the Chembio, MedMira and OraSure tests were 94.0%, 78.9%, and 97.4%, respectively; the highest specificities were 97.7%, 83.3%, and 100%, respectively. BACKGROUND The Centers for Disease Control and Prevention (CDC) estimates that 4.1 million Americans have been infected with hepatitis C virus (HCV) and 75%-80% of them are living with chronic HCV infection, many unaware of their infection. Persons who inject drugs (PWID) account for 57.5% of all persons with HCV antibody (anti-HCV) in the United States. Currently no point-of-care tests for HCV infection are approved for use in the United States. METHODS Surveys and testing for human immunodeficiency virus (HIV) and anti-HCV were conducted among persons who reported injection drug use in the past 12 months as part of the National HIV Behavioral Surveillance System in 2009. The sensitivity and specificity of point-of-care tests (finger-stick and 2 oral fluid rapid assays) from 3 manufacturers (Chembio, MedMira, and OraSure) were evaluated in field settings in 4 US cities. RESULTS Sensitivity (78.9%-97.4%) and specificity (80.0%-100.0%) were variable across assays and sites. The highest assay-specific sensitivities achieved for the Chembio, MedMira, and OraSure tests were 94.0%, 78.9% and 97.4%, respectively; the highest specificities were 97.7%, 83.3%, and 100%, respectively. In multivariate analysis, false-negative anti-HCV results were associated with HIV positivity for the Chembio oral assay (adjusted odds ratio, 8.4-9.1; P < .01) in 1 site (New York City). CONCLUSIONS Sensitive rapid anti-HCV assays are appropriate and feasible for high-prevalence, high-risk populations such as PWID, who can be reached through social service settings such as syringe exchange programs and methadone maintenance treatment programs.

Disparities in the treatment and outcomes of lung cancer among HIV-infected individuals

Objectives:HIV-infected people have elevated risk for lung cancer and higher mortality following cancer diagnosis than HIV-uninfected individuals. It is unclear whether HIV-infected individuals with lung cancer receive similar cancer treatment as HIV-uninfected individuals. Design/methods:We studied adults more than 18 years of age with lung cancer reported to the Texas Cancer Registry (N = 156 930) from 1995 to 2009. HIV status was determined by linkage with the Texas enhanced HIV/AIDS Reporting System. For nonsmall cell lung cancer (NSCLC) cases, we identified predictors of cancer treatment using logistic regression. We used Cox regression to evaluate effects of HIV and cancer treatment on mortality. Results:Compared with HIV-uninfected lung cancer patients (N = 156 593), HIV-infected lung cancer patients (N = 337) were more frequently young, non-Hispanic black, men, and with distant stage disease. HIV-infected NSCLC patients less frequently received cancer treatment than HIV-uninfected patients [60.3 vs. 77.5%; odds ratio 0.39, 95% confidence interval (CI) 0.30–0.52, after adjustment for diagnosis year, age, sex, race, stage, and histologic subtype]. HIV infection was associated with higher lung cancer-specific mortality (hazard ratio 1.34, 95% CI 1.15–1.56, adjusted for demographics and tumor characteristics). Inclusion of cancer treatment in adjusted models slightly attenuated the effect of HIV on lung cancer-specific mortality (hazard ratio 1.25; 95% CI 1.06–1.47). Also, there was a suggestion that HIV was more strongly associated with mortality among untreated than among treated patients (adjusted hazard ratio 1.32 vs. 1.16, P-interaction = 0.34). Conclusion:HIV-infected NSCLC patients were less frequently treated for lung cancer than HIV-uninfected patients, which may have affected survival.

Cancer Treatment Disparities in HIV-Infected Individuals in the United States

PURPOSE HIV-infected individuals with cancer have worse survival rates compared with their HIV-uninfected counterparts. One explanation may be differing cancer treatment; however, few studies have examined this. PATIENTS AND METHODS We used HIV and cancer registry data from Connecticut, Michigan, and Texas to study adults diagnosed with non-Hodgkins lymphoma, Hodgkins lymphoma, or cervical, lung, anal, prostate, colorectal, or breast cancers from 1996 to 2010. We used logistic regression to examine associations between HIV status and cancer treatment, adjusted for cancer stage and demographic covariates. For a subset of local-stage cancers, we used logistic regression to assess the relationship between HIV status and standard treatment modality. We identified predictors of cancer treatment among individuals with both HIV and cancer. RESULTS We evaluated 3,045 HIV-infected patients with cancer and 1,087,648 patients with cancer without HIV infection. A significantly higher proportion of HIV-infected individuals did not receive cancer treatment for diffuse large B-cell lymphoma (DLBCL; adjusted odds ratio [aOR], 1.67; 95% CI, 1.41 to 1.99), lung cancer (aOR, 2.18; 95% CI, 1.80 to 2.64), Hodgkins lymphoma (aOR, 1.77; 95% CI, 1.33 to 2.37), prostate cancer (aOR, 1.79; 95% CI, 1.31 to 2.46), and colorectal cancer (aOR, 2.27; 95% CI, 1.38 to 3.72). HIV infection was associated with a lack of standard treatment modality for local-stage DLBCL (aOR, 2.02; 95% CI, 1.50 to 2.72), non-small-cell lung cancer (aOR, 2.43; 95% CI, 1.46 to 4.03), and colon cancer (aOR, 4.77; 95% CI, 1.76 to 12.96). Among HIV-infected individuals, factors independently associated with lack of cancer treatment included low CD4 count, male sex with injection drug use as mode of HIV exposure, age 45 to 64 years, black race, and distant or unknown cancer stage. CONCLUSION HIV-infected individuals are less likely to receive treatment for some cancers than uninfected people, which may affect survival rates.

Lack of Definitive Severe Mitochondrial Signs and Symptoms among Deceased HIV-Uninfected and HIV-Indeterminate Children ≤ 5 Years of Age, Pediatric Spectrum of HIV Disease Project (PSD), USA

Abstract: Background: In response to recent reports of mitochondrial dysfunction in HIV‐uninfected infants exposed to antiretroviral (ARV) prophylaxis, the Perinatal Safety Review Working Group reviewed deaths in five large HIV‐exposed perinatal cohorts in the United States to determine if similar cases of severe mitochondrial toxicity could be detected. We describe the results of this review for the PSD cohort.

Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000.

Background: Meta‐analysis and randomized clinical trial results reported in June 1998 indicated a significant reduction in perinatal HIV transmission rates among mothers undergoing a cesarean section (C‐section). Objective: The objective of this study was to examine recent trends in and factors associated with C‐section deliveries among HIV‐infected women in the United States. Design: A multisite pediatric medical record review of a cohort of HIV‐exposed and HIV‐infected infants in the Pediatric Spectrum of HIV Disease (PSD) Cohort study (n = 6467) and the national Pediatric HIV/AIDS Reporting System (HARS) (n = 8,306) was conducted. Setting/Patients: All infants born between 1994 and 2000 to HIV‐positive mothers referred to the PSD study or to a Pediatric HARS hospital or clinic site were enrolled. Results: The proportion of deliveries by C‐section was steady at about 20% from 1994 through June 1998. From July 1998 through December 2000, this proportion increased to 44% in the PSD study and to nearly 50% in the Pediatric HARS. On analysis by multiple logistic regression, delivery of infants by C‐section was associated with the release of study results (OR = 2.83), delivery in four PSD sites in reference to Texas (OR: 2.02‐1.43), having private medical care reimbursement (OR = 1.62), and having maternal prenatal care (OR = 1.43). Conclusions: The PSD and Pediatric HARS data demonstrate a sharp increase in C‐section rates mainly among HIV‐infected women in the United States after the release of the meta‐analysis and randomized clinical trial results in 1998. This finding highlights the rapid impact of study results on obstetric practice. It underscores the critical role of prenatal care in offering perinatal interventions such as scheduled C‐section when indicated to reduce the likelihood of HIV transmission.

Health Care Providers’ Perspectives on Patient Delay for Seeking Care for Symptoms of Acute Myocardial Infarction

To inform intervention development in a multisite randomized community trial, the Rapid Early Action for Coronary Treatment (REACT) project formative research was undertaken for the purpose of investigating the knowledge, beliefs, perceptions, and usual practice of health care professionals. A total of 24 key informant interviews of cardiologists and emergency physicians and 15 focus groups (91 participants) were conducted in five major geographic regions: Northeast, Northwest, Southeast, Southwest, and Midwest. Transcript analyses revealed that clinicians are somewhat unaware of the empirical evidence related to the problem of patient delay, are concerned about the practice constraints they face, and would benefit from concrete suggestions about how to improve patient education and encourage fast action. Findings provide guidance for selection of educational strategies and messages for health providers as well as patients and the public.

Hospitalization trends among children and youths with perinatal human immunodeficiency virus infection, 1990-2002.

Background: Major improvements in disease progression among HIV-infected children have followed the adoption of combination antiretroviral therapy. Methods: We examined trends in hospitalization rates between 1990–2002 among 3927 children/youths with perinatal HIV infection, ranging in age from newborn to 21 years. We used Poisson regression to test for trends in hospitalization rates by age and year; binomial regression to test for trends in intensive care unit (ICU) admissions and hospitalization at least once and more than once, by age and year; and multivariate logistic regression to examine factors associated with hospitalization, ICU admission, and hospitalization longer than 10 days. Results: Statistically significant downward trends in hospitalization rates and multiple hospitalizations were observed in all age groups from 1990–2002. The proportion of HIV-infected children/youths who were hospitalized at least once declined from 30.4% in 1990 to 12.9% in 2002, with a steady decline occurring after 1996, when the U.S. Public Health Service issued guidelines recommending triple-drug antiretroviral therapy (triple therapy) for HIV-infected children. ICU admissions declined significantly in all age groups except among children younger than 2 years. Logistic regression results indicated that black and Hispanic children/youths were significantly more likely to be hospitalized than white children/youths and that children/youths receiving triple therapy were significantly more likely to be hospitalized than therapy-naive children; the latter association was not observed among children monitored from 1997–2002. Conclusions: Substantial reductions in rates of hospitalization, multiple hospitalizations, and ICU admission have occurred among HIV-infected children/youths from 1990–2002, particularly after 1996, with increased use of triple therapy.

Mother-to-child transmission of the human immunodeficiency virus in Texas

Background. The Pediatric Spectrum of HIV Diseases (PSD) project has been collecting data on HIV-exposed children in Texas since 1989. These data have now been analyzed to describe mother-to-child transmission in Texas and to provide much needed information on the magnitude of the pediatric HIV epidemic in the state. Methods. We examined trends in the numbers of perinatally exposed children and perinatally acquired cases of HIV in the Texas PSD cohort. We calculated transmission rates and relative risks for 656 children born from January, 1995, to July, 1998, that received all or part of the ACTG 076 regimen. Results. Only a small proportion (38%) of pairs of an HIV-infected mother and her HIV-exposed child received the full AIDS Clinical Trial Group 076 (ACTG 076) regimen; only 73% of the mothers received at least some prenatal care. In recent years, however, the numbers of perinatally exposed children and perinatally acquired cases of HIV have decreased in Texas. Univariate analyses showed that a reduction in the vertical transmission of HIV was associated with receipt of a full ACTG 076 regimen, receipt of a partial ACTG 076 regimen and residence in Dallas County. Conclusions. Findings identify a gap in meeting the health care needs of pregnant HIV-infected women and suggest missed opportunities to prevent mother-to-child transmission of HIV. At the same time this study confirms progress in prevention efforts to reduce mother-to-child transmission of HIV in Texas.