Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.

BACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS: Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. RESULTS: 184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. CONCLUSIONS: The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. TRIAL REGISTRATION: ClinicalTrials.gov NCT01418235.

Subtype C gp140 Vaccine Boosts Immune Responses Primed by the South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More than a 2-Year Gap.

A phase I safety and immunogenicity study investigated South African AIDS Vaccine Initiative (SAAVI) HIV-1 subtype C (HIV-1C) DNA vaccine encoding Gag-RT-Tat-Nef and gp150, boosted with modified vaccinia Ankara (MVA) expressing matched antigens. Following the finding of partial protective efficacy in the RV144 HIV vaccine efficacy trial, a protein boost with HIV-1 subtype C V2-deleted gp140 with MF59 was added to the regimen. A total of 48 participants (12 U.S. participants and 36 Republic of South Africa [RSA] participants) were randomized to receive 3 intramuscular (i.m.) doses of SAAVI DNA-C2 of 4 mg (months 0, 1, and 2) and 2 i.m. doses of SAAVI MVA-C of 1.45 × 10(9) PFU (months 4 and 5) (n = 40) or of a placebo (n = 8). Approximately 2 years after vaccination, 27 participants were rerandomized to receive gp140/MF59 at 100 µg or placebo, as 2 i.m. injections, 3 months apart. The vaccine regimen was safe and well tolerated. After the DNA-MVA regimen, CD4(+) T-cell and CD8(+) T-cell responses occurred in 74% and 32% of the participants, respectively. The protein boost increased CD4(+) T-cell responses to 87% of the subjects. All participants developed tier 1 HIV-1C neutralizing antibody responses as well as durable Env binding antibodies that recognized linear V3 and C5 peptides. The HIV-1 subtype C DNA-MVA vaccine regimen showed promising cellular immunogenicity. Boosting with gp140/MF59 enhanced levels of binding and neutralizing antibodies as well as CD4(+) T-cell responses to HIV-1 envelope. (This study has been registered at ClinicalTrials.gov under registration no. NCT00574600 and NCT01423825.).

Race, socioeconomic status, and the use of bariatric surgery in Michigan.

Studies examining the characteristics of patients undergoing bariatric surgery in the USA have concluded that the procedure is not being used equitably. We used population-based data from Michigan to explore disparities in the use of bariatric surgery by gender, race, and socioeconomic status. We constructed a summary measure of socioeconomic status (SES) for Michigan postal ZIP codes using data from the 2000 census and divided the population into quintiles according to SES. We then used data from the state drivers' license list and 2004-2005 state inpatient and ambulatory surgery databases to examine population-based rates of morbid obesity and bariatric surgery in adults according to gender, race, and socioeconomic status. There is an inverse linear relationship between SES and morbid obesity. In the lowest SES quintile, 13% of females and 7% of males have a body mass index >40 compared to 4% of females and males in the highest SES quintile. Overall rates of bariatric surgery were highest for black females (29.4/10,000), followed by white (21.3/10,000), and other racial minority (8.6/10,000) females. Rates of bariatric surgery were low (<6/10,000) for males of all racial groups. An inverse linear relationship was observed between SES and rates of bariatric surgery among whites. However, for racial minorities, rates of surgery are lower in the lowest SES quintiles with the highest rates of bariatric surgery in the medium or highest SES quintiles. In contrast with prior studies, we do not find evidence of wide disparities in the use of bariatric surgery.

Hospital factors and racial disparities in mortality after surgery for breast and colon cancer.

PURPOSE: Black patients have worse prognoses than whites with breast or colorectal cancer. Mechanisms underlying such disparities have not been fully explored. We examined the role of hospital factors in racial differences in late mortality after surgery for breast or colon cancer. METHODS: Patients undergoing surgery after new diagnosis of breast or colon cancer were identified using the Surveillance Epidemiology and End Results-Medicare linked database (1995 to 2005). The main outcome measure was mortality at 5 years. Proportional hazards models were used to assess relationships between race and late mortality, accounting for patient factors, socioeconomic measures, and hospital factors. Fixed and random effects models were used to account for quality differences across hospitals. RESULTS: Black patients, compared with white patients, had lower 5-year overall survival rates after surgery for breast (62.1% v 70.4%, respectively; P < .001) and colon cancer (41.3% v 45.4%, respectively; P < .001). After controlling for age, comorbidity, and stage, black race remained an independent predictor of mortality for breast (adjusted hazard ratio [HR] = 1.25; 95% CI, 1.16 to 1.34) and colon cancer (adjusted HR = 1.13; 95% CI, 1.07 to 1.19). After risk adjustment, hospital factors explained 36% and 54% of the excess mortality for black patients with breast cancer and colon cancer, respectively. Hospitals with large minority populations had higher late mortality rates independent of race. CONCLUSION: Hospital factors, including quality, are important mediators of the association between race and mortality for breast and colon cancer. Hospital-level quality improvement should be a major component of efforts to reduce disparities in cancer outcomes.

Socioeconomic status and surgical mortality in the elderly.

BACKGROUND: Although racial disparities in the quality of surgical care are well described, the impact of socioeconomic status on operative mortality is relatively unexplored. METHODS: We used Medicare data to identify all patients undergoing 1 of 6 common, high risk surgical procedures between 1999 and 2003. We constructed a summary measure of socioeconomic status for each US ZIP code using data from the 2000 US Census linked to the patient's ZIP code of residence. We assessed the effects of socioeconomic status on operative mortality rates while controlling for other patient characteristics and then examined the extent to which disparities in operative mortality could be attributed to differences in hospital factors. RESULTS: Socioeconomic status was a significant predictor of operative mortality for all 6 procedures in crude analyses and in those adjusted for patient characteristics. Comparing the lowest quintile of socioeconomic status to the highest, the adjusted odds ratios (OR) and 95% confidence intervals (CI) ranged from OR = 1.17; 95% CI: 1.10-1.25 for colectomy to OR = 1.39; 95% CI: 1.18-1.65 for gastrectomy. After further adjustment for hospital factors, the odds ratio associated with socioeconomic status for coronary artery bypass (OR = 1.14; 95% CI: 1.09-1.19), aortic valve replacement (OR = 1.13; 95% CI: 1.04-1.23), and mitral valve replacement (OR = 1.11; 95% CI: 1.00-1.23) were diminished, and those for lung resection (OR = 0.93; 95% CI: 0.81-1.07), colectomy (OR = 1.04; 95% CI: 0.98-1.12), and gastrectomy (OR = 1.11; 95% CI: 0.90-1.38) were reduced and also were no longer statistically significant. Within hospitals, there were only small differences in adjusted operative mortality by patient socioeconomic status. CONCLUSIONS: Patients with lower socioeconomic status have higher rates of adjusted operative mortality than patients with higher socioeconomic status across a wide range of surgical procedures. These disparities in surgical outcomes are largely attributable to differences between the hospitals where patients of higher and lower socioeconomic status tend to receive surgical treatment.