Risk factors for tuberculosis after highly active antiretroviral therapy initiation in the United States and Canada: implications for tuberculosis screening.

BACKGROUND: Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts. METHODS: Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995-August 2009. Parametric survival models identified factors associated with tuberculosis occurrence. RESULTS: Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131-333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk. CONCLUSIONS: Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm³ or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.

CD4 count at presentation for HIV care in the United States and Canada: are those over 50 years more likely to have a delayed presentation?

We assessed CD4 count at initial presentation for HIV care among ≥50-year-olds from 1997-2007 in 13 US and Canadian clinical cohorts and compared to <50-year-olds. 44,491 HIV-infected individuals in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included in our study. Trends in mean CD4 count (measured as cells/mm³) and 95% confidence intervals ([,]) were determined using linear regression stratified by age category and adjusted for gender, race/ethnicity, HIV transmission risk and cohort. From 1997-2007, the proportion of individuals presenting for HIV care who were ≥50-years-old increased from 17% to 27% (p-value < 0.01). The median CD4 count among ≥50 year-olds was consistently lower than younger adults. The interaction of age group and calendar year was significant (p-value <0.01) with both age groups experiencing modest annual improvements over time (< 50-year-olds: 5 [4 , 6] cells/mm3; ≥50-year-olds: 7 [5 , 9] cells/mm³), after adjusting for sex, race/ethnicity, HIV transmission risk group and cohort; however, increases in the two groups were similar after 2000. A greater proportion of older individuals had an AIDS-defining diagnosis at, or within three months prior to, first presentation for HIV care compared to younger individuals (13% vs. 10%, respectively). Due to the increasing proportion, consistently lower CD4 counts, and more advanced HIV disease in adults ≥50-year-old at first presentation for HIV care, renewed HIV testing efforts are needed.

Late presentation for human immunodeficiency virus care in the United States and Canada.

BACKGROUND. Initiatives to improve early detection and access to human immunodeficiency virus (HIV) services have increased over time. We assessed the immune status of patients at initial presentation for HIV care from 1997 to 2007 in 13 US and Canadian clinical cohorts. METHODS. We analyzed data from 44,491 HIV-infected patients enrolled in the North American-AIDS Cohort Collaboration on Research and Design. We identified first presentation for HIV care as the time of first CD4(+) T lymphocyte (CD4) count and excluded patients who prior to this date had HIV RNA measurements, evidence of antiretroviral exposure, or a history of AIDS-defining illness. Trends in mean CD4 count (measured as cells/mm(3)) and 95% confidence intervals were determined using linear regression adjusted for age, sex, race/ethnicity, HIV transmission risk, and cohort. RESULTS. Median age at first presentation for HIV care increased over time (range, 40-43 years; P < .01), whereas the percentage of patients with injection drug use HIV transmission risk decreased (from 26% to 14%; P < .01) and heterosexual transmission risk increased (from 16% to 23%; P < .01). Median CD4 count at presentation increased from 256 cells/mm(3) (interquartile range, 96-455 cells/mm(3)) to 317 cells/mm(3) (interquartile range, 135-517 cells/mm(3)) from 1997 to 2007 (P < .01). The percentage of patients with a CD4 count > or = 350 cells/mm(3) at first presentation also increased from 1997 to 2007 (from 38% to 46%; P < .01). The estimated adjusted mean CD4 count increased at a rate of 6 cells/mm(3) per year (95% confidence interval, 5-7 cells/mm(3) per year). CONCLUSION. CD4 count at first presentation for HIV care has increased annually over the past 11 years but has remained <350 cells/mm(3), which suggests the urgent need for earlier HIV diagnosis and treatment.

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.

Factors associated with fewer visits for HIV primary care at a tertiary care center in the Southeastern U.S.

In this study we sought to evaluate sociodemographic and clinical characteristics associated with decreased access to HIV outpatient care in a University-based clinic in the Southeastern U.S. The number of HIV outpatient clinic visits per person-year was estimated among 1,404 HIV-infected individuals participating in a large observational clinical cohort study. On average, participants attended 3.38 visits per person-year (95% CI = 3.32, 3.44), with 71% attending fewer than 4 visits per year. Younger persons, of Black race/ethnicity, with less advanced HIV disease, and a shorter time from entry to HIV care, had poorer access to care, as did participants without health insurance and residing a greater distance from care. Vulnerable subgroups of HIV-infected patients in the South have decreased access to ongoing HIV health care. Interventions including more intensive counseling and active outreach for newly HIV diagnosed individuals and support with obtaining health insurance and transportation may lead to improved outcomes.

Effectiveness of highly-active antiretroviral therapy by race/ethnicity.

OBJECTIVE: To determine the effectiveness of HAART by race/ethnicity. DESIGN: Prospective multicenter cohort study. METHODS: We studied 991 African-Americans and 911 European-Americans enrolled in the United States Military's Tri-Service AIDS Clinical Consortium Natural History Study who had dates of HIV seroconversion known within 5 years and followed between 1990 and 2002. We determined the rate of disease progression to AIDS and death for subjects in this cohort. Multivariable models evaluated race, pre-HAART (1990-1995) and HAART (1996-2002) eras, age, gender and military service. RESULTS: In the pre-HAART era, African-Americans had a statistically nonsignificant trend towards better outcomes: the relative hazards (RH) of AIDS and death for African-Americans compared to European-Americans were 0.85 [95% confidence interval (CI), 0.68-1.05] and 0.77 (95% CI, 0.55-1.08), respectively. In the HAART era, outcomes were similar by race: 1.17 (95% CI, 0.86-1.61) for AIDS and 1.11 (95% CI, 0.81-1.53) for death with overlapping Kaplan-Meier curves. Relative to the pre-HAART era, the adjusted RH of AIDS in the HAART era was 0.41 (95% CI, 0.31-0.54) and 0.30 (95% CI, 0.22-0.40) for African-American and European-American participants, respectively. Analogous RH for death were 0.55 (95% CI, 0.38-0.80) and 0.38 (95% CI, 0.27-0.54). The precipitous declines in AIDS and death in the HAART era were not statistically different by race. CONCLUSIONS: : In a large multi-racial cohort with equal access to health care, HIV treatment outcomes by race/ethnicity were similar.

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.

Social development of commercial sex workers in India: an essential step in HIV/AIDS prevention.

India has the highest number of HIV/AIDS cases in the world. Current HIV/AIDS prevention strategies are based on regular and appropriate condom use. However, most commercial sex workers (CSWs), who form the core/high-risk groups toward whom the prevention strategy is directed, are disempowered and socioeconomically marginalized. This does not allow them to insist on condom use by the client, especially in absence of governmental structural support. This paper discusses HIV/AIDS prevention issues that relate to CSWs in India; issues that play a vital role in initiation, perpetuation, and expansion of economic activity of CSWs; and those factors that influence the HIV/AIDS preventive practices of CSWs. This paper argues that CSWs can be empowered and emancipated; that HIV/AIDS control and prevention efforts in India must recognize that ad hoc promotion of condom use or similar such programs will not be effective to control HIV/AIDS; and that more extensive developmental work aimed at betterment of living conditions of CSWs is required for effective HIV/AIDS prevention.

Perceived oral health status, unmet needs, and barriers to dental care among HIV/AIDS patients in a North Carolina cohort: impacts of race.

OBJECTIVE: This prospective observational study examined differences in perceived oral health status, treatment needs, dental care utilization patterns, and barriers to care between HIV-infected non-Hispanic blacks and whites in North Carolina. METHODS: 632 adult HIV-infected medical clinic attendees provided information on their oral health status and dental care history during face-to-face interviews with a trained interviewer. RESULTS: Compared to whites, blacks were significantly more likely to be female, older, less educated, have lower income, and have acquired HIV by heterosexual sex or injecting drug use. Although two-thirds of patients reported good oral health, blacks were significantly more likely to have loose teeth, need extractions, and be episodic dental care utilizers. Primary barriers to dental care were cost (30%), fear (19%), and low motivation (13%). Sixty-five percent of patients had unmet dental needs in the last three years. Race, cost, fear, and immune competence were significantly associated with unmet dental need in a multivariable model. CONCLUSIONS: Disparities exist within this HIV-infected population in oral symptoms, utilization patterns, and perceived unmet dental need. Targeted interventions that address barriers to care are needed to help establish preventive dental care patterns in this region, especially among blacks.

A comparison of slide/audiotape and Web-based instructional formats for teaching normal intraoral radiographic anatomy.

PURPOSE: The purpose of this study was to evaluate the relationship between individual learning styles, test performance, and attitudes toward the use of Web-based self-instruction and slide/audiotape self-instruction METHODS: Participants consisted of 33 junior, first-year dental hygiene students enrolled in a university-based dental hygiene program. A stratified random allocation (by gender, English as a second language, and prior dental experience) and random number table were used to assign participants into one of two groups. Group one studied the mandibular arch using the slide/audiotape format and the maxillary arch using the Web-based format, and group two studied the mandibular arch using the Web-based format and the maxillary arch using the slide/audiotape format. A post-test was taken at the completion of each instructional format. The Kolb Learning Style Inventory was used to assess preferred learning styles, and a written survey was used for instructional format preference. Descriptive analyses, Pearson correlations, and unpaired t-tests were used to analyze the data. RESULTS: Thirty-one subjects completed the study. By group, no difference in mean post-test performance was seen based on the sequence or order of instructional method (P > 0.05) or by arch (P > 0.05). No difference in post-test performance based on Web-based and slide-tape instructional methods was seen. Predominate learning style did not predict preference of instructional format nor were they correlated with post-test scores. However, almost 70% of all participants reported that they preferred using the Web-based format to the slide/audiotape. CONCLUSIONS: A variety of learning styles and preferences may be accommodated when substituting Web-based self-instruction for slide/audiotape self-instruction in normal radiographic anatomy.

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.