Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America.

BACKGROUND: Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined. METHODS: Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level >1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure. RESULTS: Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P < .001). The cumulative mortality after onset of second virologic failure was 26% at 5 years and decreased over time. A history of AIDS, a lower CD4(+) T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patients CONCLUSIONS: Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4(+) T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.

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.

Progressive periodontal disease and risk of very preterm delivery.

OBJECTIVE: The goal was to estimate whether maternal periodontal disease was predictive of preterm (less than 37 weeks) or very preterm (less than 32 weeks) births. METHODS: A prospective study of obstetric outcomes, entitled Oral Conditions and Pregnancy (OCAP), was conducted with 1,020 pregnant women who received both an antepartum and postpartum periodontal examination. Predictive models were developed to estimate whether maternal exposure to either periodontal disease at enrollment (less than 26 weeks) and/or periodontal disease progression during pregnancy, as determined by comparing postpartum with antepartum status, were predictive of preterm or very preterm births, adjusting for risk factors including previous preterm delivery, race, smoking, social domain variables, and other infections. RESULTS: Incidence of preterm birth was 11.2% among periodontally healthy women, compared with 28.6% in women with moderate-severe periodontal disease (adjusted risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1-2.3). Antepartum moderate-severe periodontal disease was associated with an increased incidence of spontaneous preterm births (15.2% versus 24.9%, adjusted RR 2.0, 95% CI 1.2-3.2). Similarly, the unadjusted rate of very preterm delivery was 6.4% among women with periodontal disease progression, significantly higher than the 1.8% rate among women without disease progression (adjusted RR 2.4, 95% CI 1.1-5.2). CONCLUSION: The OCAP study demonstrates that maternal periodontal disease increases relative risk for preterm or spontaneous preterm births. Furthermore, periodontal disease progression during pregnancy was a predictor of the more severe adverse pregnancy outcome of very preterm birth, independently of traditional obstetric, periodontal, and social domain risk factors. LEVEL OF EVIDENCE: II-2.

Association between herpes simplex virus type 1 and Helicobacter pylori in US adolescents.

OBJECTIVE: To understand how Helicobacter pylori infection is acquired and the role that herpes simplex virus type 1 (HSV-1) may have, we determined whether an association between HSV and H pylori exists at the individual level and for what reason. STUDY DESIGN: Data were collected from 1,090 participants aged 12-19 years during phase 1 (1988-1991) of the NHANES III. Generalized estimating equations were used to estimate prevalence ratios (PR). RESULTS: The crude overall PR and 95% CI for H pylori seropositivity comparing HSV+ to HSV- individuals was 2.20 (1.69-2.85). In large urban households the PR adjusted for poverty level and race/ethnicity was twice that in small nonurban households (2.27 versus 1.15, respectively). CONCLUSIONS: Overall, HSV-1 seropositivity is associated with a higher H pylori seroprevalence. The negligible association found in some strata suggests that shared environmental factors or routes of transmission rather than biologic reasons may be primarily responsible for this association.

Education in HIV risk screening, counseling, testing, and referral: survey of U.S. dental schools.

According to Centers for Disease Control and Prevention estimates, thousands of Americans are infected with HIV but are unaware of their infection status. National disease prevention goals to identify and treat these individuals will benefit from HIV risk screening, counseling, testing, and referral services conducted in nontraditional settings and the use of alternative diagnostic methods such as oral fluid-based HIV antibody testing. Using a mail survey of the fifty-four U.S. dental schools (85 percent response rate), this study assessed the teaching and practice of HIV risk screening, as well as the opinions of dental educators regarding HIV counseling and testing and a possible role for oral fluid-based HIV antibody testing in dental offices. All responding dental schools have curriculum and clinical education training regarding HIV behavioral risks, medical history, and use of oral manifestations as indicators of HIV Educators felt risk screening and referral for HIV counseling and testing was part of a dentist's professional role. One-third of respondents indicated they might include HIV counseling and testing using a rapid oral fluid-based HIV antibody test in their clinics. However, these respondents lacked confidence that graduating dentists have the skills and willingness to conduct HIV counseling and testing in dental practice. Lack of training in prevention counseling was seen as a primary barrier.