Sharon Perry

Non-adherence to highly active antiretroviral therapy predicts progression to AIDS

The introduction of highly active antiretroviral therapy (HAART) has produced a dramatic reduction in mortality among HIV-infected individuals [1–4]. Whereas the level of adherence to HAART is closely associated with suppression of the HIV viral load in plasma [5–14], a relationship between adherenc

Emergency department use among the homeless and marginally housed: Results from a community-based study

OBJECTIVES This study examined factors associated with emergency department use among homeless and marginally housed persons. METHODS Interviews were conducted with 2578 homeless and marginally housed persons, and factors associated with different patterns of emergency department use were assessed in multivariate models. RESULTS Findings showed that 40.4% of respondents had 1 or more emergency department encounters in the previous year; 7.9% exhibited high rates of use (more than 3 visits) and accounted for 54.5% of all visits. Factors associated with high use rates included less stable housing, victimization, arrests, physical and mental illness, and substance abuse. Predisposing and need factors appeared to drive emergency department use. CONCLUSIONS Efforts to reduce emergency department use among the homeless should be targeted toward addressing underlying risk factors among those exhibiting high rates of use.

High levels of adherence do not prevent accumulation of HIV drug resistance mutations.

Objectives: To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence. Methods: Adherence was measured with unannounced pill counts performed at the participants usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2. Results: High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92–100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79–100%). Conclusion: Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.

Adherence to Highly Active Antiretroviral Therapy in the Homeless Population in San Francisco: A Prospective Study

BACKGROUND We examined adherence to highly active antiretroviral therapy (HAART) in the homeless population, a population thought to be at high risk for poor adherence to therapy and for development of drug-resistant strains of human immunodeficiency virus (HIV). METHODS We performed a 12-month prospective study of 148 persons receiving HAART who were identified in a stratified screening of the homeless and marginally housed. We sampled in lunch lines, shelters, and hotels in 3 neighborhoods of San Francisco, California. We used pill counts at unannounced home visits as the primary measure of adherence. RESULTS Of 148 individuals sampled, 46 (31%) discontinued HAART during the study. Average adherence in the group of those who discontinued HAART was 51%, and 9% of these subjects had undetectable virus loads (i.e., <400 copies/mL) at the last follow-up visit. Predictors of discontinuation of therapy were depressive symptoms, injection drug use, African American ethnicity, and early poor adherence. Of 148 subjects, 102 (69%) continued to receive HAART throughout the study period. Average adherence in the group of those who continued to receive HAART was 74%, and 55% of these subjects had undetectable virus loads at the last follow-up visit. Predictors of lower average adherence in this group were African American ethnicity and use of crack cocaine; men who had sex with men had higher adherence. CONCLUSIONS One-third of homeless and marginally housed persons receiving HAART discontinued therapy during the follow-up period and would benefit from adherence interventions directed at sustaining therapy; two-thirds continued to receive therapy at adherence levels comparable to those found with other clinical populations.

Clinical Application and Limitations of Interferon-γ Release Assays for the Diagnosis of Latent Tuberculosis Infection

Interferon-release assays (IGRAs) represent advances in tuberculosis immunology and evolutionary biology. IGRAs were designed to replace tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection because of their logistical advantages and enhanced specificity over TST. Although IGRAs and TST have been useful in epidemiologic studies, they lack the sensitivity and reproducibility normally expected from diagnostic tests in clinical practice. In this review, we present an overview of the current recommendations and knowledge in the field and discuss practical approaches in areas of uncertainty related to discordant IGRA results.

Vitamin D Deficiency and Tuberculosis Progression

To assess the association between vitamin D deficiency and tuberculosis disease progression, we studied vitamin D levels in a cohort of tuberculosis patients and their contacts (N = 129) in Pakistan. Most (79%) persons showed deficiency. Low vitamin D levels were associated with a 5-fold increased risk for progression to tuberculosis.

Infection with Helicobacter pylori is associated with protection against tuberculosis.

Background Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings We first examined M. tuberculosis-specific IFN-γ and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-γ responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases were significantly less likely to be H. pylori infected (AOR: 0.55, 95% CI 0.0.36–0.83, p = 0.005), though seroprevalence was not significantly different from non-progressors in 37 incident TB cases (AOR: 1.35 [95% CI 0.63–2.9] p = 0.44). Cynomolgus macaques with natural H. pylori infection were significantly less likely to progress to TB 6 to 8 months after M. tuberculosis challenge (RR: 0.31 [95% CI 0.12–0.80], p = 0.04). Conclusions/Significance H. pylori infection may induce bystander effects that modify the risk of active TB in humans and non-human primates. That immunity to TB may be enhanced by exposure to other microbial agents may have important implications for vaccine development and disease control.

Gastroenteritis and Transmission of Helicobacter pylori Infection in Households

In northern California homes, exposure to gastroenteritis in an H. pylori–infected contact markedly increased H. pylori infection.

Reproducibility of QuantiFERON-TB Gold In-Tube Assay

ABSTRACT Studies are needed to characterize the reproducibility of QuantiFERON-TB Gold (QFT-G) for targeted U.S. screening populations. Members of northern California households were tested with the QFT-G in-tube assay (QFT-G-IT) at two home visits 3 months apart. Reproducibility and agreement with the tuberculin skin test (TST) were assessed. Monte Carlo simulation was used to evaluate the role of test-related error. Of 63 individuals (49 adults and 14 children) completing QFT-G-IT at both time points, 79% were foreign-born (98% from Latin America) and 68% reported Mycobacterium bovis BCG vaccination. At the baseline visit, 23 (37%) were TST positive and 15 (24%) were QFT-G-IT positive (κ = 0.48 [± 0.11]). At 3 months, 3/48 (6.3%; 95% confidence interval [95CI], 2 to 17) of those initially QFT-G-IT negative converted, and 5/15 (33%; 95CI, 15 to 58) of those initially QFT-G-IT positive reverted. Among the 8 individuals with inconsistent QFT-G-IT results, the maximum gamma interferon response at either visit was 0.68 IU/ml versus means of 4.99 (± 3.74) and 6.95 (± 5.6) for 10 persistent positives at the first and second visits, respectively. Expected false-reversion and -conversion rates were 32% (90CI, 25 to 39%) and 6.95% (90CI, 4.6 to 9.8%) when the sensitivity and specificity were assumed to average 70% and 98%, respectively. Transient responses to QFT-G-IT are common, and low positive results need to be interpreted with caution. Further studies are needed to characterize the predictive value of the test for U.S. foreign-born and other targeted screening populations.

Use of insecticide-treated nets (ITNs) following a malaria education intervention in Piron, Mali: a control trial with systematic allocation of households

BackgroundInsecticide-treated nets (ITNs) reduce malaria morbidity and mortality, but use is limited. A barrier to ITN use may be lack of knowledge regarding malaria transmission and prevention. This study is a controlled trial comparing ITN use and malaria knowledge levels between households in Piron, Mali, undertaken in 2003.MethodsHouseholds received net impregnation services either with or without antecedent education. The main outcome measure was ITN use, defined as impregnation of at least one of the households existing bednets with insecticide during the study. Knowledge about malaria and prevention practices was assessed pre- and post- educational intervention. Results were analysed by household and by individual.ResultsForty-nine percent (34/70) of households who received the educational component impregnated their nets in comparison to 35% (22/62) of households who did not (OR = 1.6 CI = 0.8–3.3, P = 0.19). In individual analysis, ITN use was significantly greater in participants who had received the educational intervention (48%) vs. individuals who did not (33%, OR = 1.9, P = 0.012). Knowledge levels about malaria significantly increased for each individual pre- versus post- educational intervention (average change score = 2.13, standard deviation = 1.97, t = -17.78, P < 0.001), although there was no difference found between educational (change score = 2.14) and control groups (change score = 2.12).ConclusionIt is possible to educate individuals about malaria and to implement net impregnation services with limited resources. Greater accessibility to net-impregnation services is necessary but not sufficient to increase ITN use.