Individual and poly-substance use and condomless sex among HIV-uninfected adults reporting heterosexual sex in a multi-site cohort.

BACKGROUND: We analyzed the association between substance use (SU) and condomless sex (CS) among HIV-negative adults reporting heterosexual sex in the Seek, Test, Treat, and Retain (STTR) consortium. We describe the impact of SU as well as person/partner and context-related factors on CS, identifying combinations of factors that indicate the highest likelihood of CS. METHODS: We analyzed data from four US-based STTR studies to examine the effect of SU on CS using two SU exposures: 1) recent SU (within 3 months) and 2) SU before/during sex. Behavioral data were collected via 1:1 or self-administered computerized interviews. Adjusted individual-study, multivariable relative risk regression was used to examine the relationship between CS and SU. We also examined interactions with type of sex and partner HIV status. Pooled effect estimates were calculated using traditional fixed-effects meta-analysis. We analyzed data for recent SU (n = 6781; 82% men, median age = 33 years) and SU before/during sex (n = 2915; 69% men, median age = 40 years). RESULTS: For both exposure classifications, any SU other than cannabis increased the likelihood of CS relative to non-SU (8-16%, p-values< 0.001). In the recent SU group, however, polysubstance use did not increase the likelihood of CS compared to single-substance use. Cannabis use did not increase the likelihood of CS, regardless of frequency of use. Type of sex was associated with CS; those reporting vaginal and anal sex had a higher likelihood of CS compared to vaginal sex only for both exposure classifications (18-21%, p < 0.001). Recent SU increased likelihood of CS among those reporting vaginal sex only (9-10%, p < 0.001); results were similar for those reporting vaginal and anal sex (5-8%, p < 0.01). SU before/during sex increased the likelihood of CS among those reporting vaginal sex only (20%; p < 0.001) and among those reporting vaginal and anal sex (7%; p = 0.002). Single- and poly-SU before/during sex increased the likelihood of CS for those with exclusively HIV-negative partners (7-8%, p ≤ 0.02), and for those reporting HIV-negative and HIV-status unknown partners (9-13%, p ≤ 0.03). CONCLUSION: Except for cannabis, any SU increased the likelihood of CS. CS was associated with having perceived HIV-negative partners and with having had both anal/vaginal sex.

Adherence to Pre-exposure Prophylaxis in Black Men Who Have Sex with Men and Transgender Women in a Community Setting in Harlem, NY.

While oral pre-exposure prophylaxis (PrEP) has proven efficacious for HIV prevention, consistent use is necessary to achieve its intended impact. We compared effectiveness of enhanced PrEP (enPrEP) adherence support to standard of care (sPrEP) among Black MSM and TGW attending a community clinic in Harlem, NY. EnPrEP included peer navigation, in-person/online support groups, and SMS messages. Self-reported adherence over previous 30 days, collected in quarterly interviews, was defined as ≥ 57%. Crude and adjusted analyses examined factors associated with adherence. A total of 204 participants were enrolled and randomized; 35% were lost to follow-up. PrEP adherence was 30% at 12-months; no intervention effect was observed (p = 0.69). Multivariable regression analysis found that lower adherence was associated with low education and depressive symptoms. We found that an enhanced adherence intervention did not improve PrEP adherence. Findings point to the need for innovative methods to improve PrEP adherence among Black MSM and TGW.Clinical Trial Registration NCT02167386, June 19, 2014.

Association between exposure to antiretroviral drugs and the incidence of hypertension in HIV-positive persons: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

OBJECTIVES: Previous studies have suggested that hypertension in HIV-positive individuals is associated primarily with traditional risk factors such as older age, diabetes and dyslipidaemia. However, controversy remains as to whether exposure to antiretroviral (ARV) drugs poses additional risk, and we investigated this question in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort. METHODS: The incidence of hypertension [systolic blood pressure (BP) > 140 and/or diastolic BP > 90 mmHg and/or initiation of antihypertensive treatment] was determined overall and in strata defined by demographic, metabolic and HIV-related factors, including cumulative exposure to each individual ARV drug. Predictors of hypertension were identified using uni- and multivariable Poisson regression models. RESULTS: Of 33 278 included persons, 7636 (22.9%) developed hypertension over 223 149 person-years (PY) [incidence rate: 3.42 (95% confidence interval (CI) 3.35-3.50) per 100 PY]. In univariable analyses, cumulative exposure to most ARV drugs was associated with an increased risk of hypertension. After adjustment for demographic, metabolic and HIV-related factors, only associations for nevirapine [rate ratio 1.07 (95% CI: 1.04-1.13) per 5 years] and indinavir/ritonavir [rate ratio 1.12 (95% CI: 1.04-1.20) per 5 years] remained statistically significant, although effects were small. The strongest independent predictors of hypertension were male gender, older age, black African ethnicity, diabetes, dyslipidaemia, use of lipid-lowering drugs, high body mass index (BMI), renal impairment and a low CD4 count. CONCLUSIONS: We did not find evidence for any strong independent association between exposure to any of the individual ARV drugs and the risk of hypertension. Findings provide reassurance that screening policies and preventative measures for hypertension in HIV-positive persons should follow algorithms used for the general population.

Sexual Behaviors of US Women at Risk of HIV Acquisition: A Longitudinal Analysis of Findings from HPTN 064.

We describe the sexual behaviors of women at elevated risk of HIV acquisition who reside in areas of high HIV prevalence and poverty in the US. Participants in HPTN 064, a prospective HIV incidence study, provided information about individual sexual behaviors and male sexual partners in the past 6 months at baseline, 6- and 12-months. Independent predictors of consistent or increased temporal patterns for three high-risk sexual behaviors were assessed separately: exchange sex, unprotected anal intercourse (UAI) and concurrent partnerships. The baseline prevalence of each behavior was >30 % among the 2,099 participants, 88 % reported partner(s) with >1 HIV risk characteristic and both individual and partner risk characteristics decreased over time. Less than high school education and food insecurity predicted consistent/increased engagement in exchange sex and UAI, and partner's concurrency predicted participant concurrency. Our results demonstrate how interpersonal and social factors may influence sustained high-risk behavior by individuals and suggest that further study of the economic issues related to HIV risk could inform future prevention interventions.

Increased risk of cardiovascular disease (CVD) with age in HIV-positive men: a comparison of the D:A:D CVD risk equation and general population CVD risk equations.

OBJECTIVES: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. RESULTS: A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.

'There's no place like home': perceptions of home-based HIV testing in Lesotho.

HIV testing has the potential to reduce HIV transmission by identifying and counseling individuals with HIV, reducing risk behaviors, linking persons with HIV to care and earlier treatment, and reducing perinatal transmission. In Lesotho, a high HIV prevalence country in which a large proportion of the population has never tested for HIV, home-based testing (HBT) may be an important strategy to increase HIV testing. We identified factors influencing acceptability of HIV prevention strategies among a convenience sample of 200 pregnant or post-partum Basotho women and 30 Basotho men. We first conducted cross-sectional surveys, followed by key informant interviews with all 30 men and focus group discussions with a sub-set of 62 women. In total, 82% of women reported positive perceptions of HBT; women and men viewed HBT as a potential way to increase testing among men and saw the home as a comfortable, supportive environment for testing and counseling couples and families together. Potential barriers to HBT uptake included concerns about confidentiality, privacy, coercion to test, conflict within the family and fear of HIV/AIDS-associated stigma. Participants emphasized community mobilization and education as important elements of HBT.

Evaluation of HIV protease inhibitor use and the risk of sudden death or nonhemorrhagic stroke.

Concerns have arisen about possible effects of protease inhibitors (PIs) on cardiac conductivity. We found no significant association between current or recent PI exposure and sudden death or nonhemorrhagic stroke (adjusted rate ratio, 1.22; 95% confidence interval, .95-1.57), whereas cumulative exposure to PIs was associated with an increased risk (adjusted rate ratio, 1.06 per year of exposure; 95% confidence interval, 1.01-1.11).

Effectiveness of a community-based intervention to prevent childhood TB in Lesotho.

BACKGROUND: Child contact management (CCM) is a recognized strategy to prevent TB; however, implementation is suboptimal. PREVENT was a cluster-randomized trial that evaluated the effectiveness and acceptability of a community-based intervention (CBI) to improve CCM in Lesotho.METHODS: Ten health facilities (HFs) were randomized to CBI or standard-of-care (SOC). CBI included nurse training/mentorship, health education by village health workers (VHW), adherence support, and multidisciplinary team meetings. Information on TB cases registered from February 2016 to June 2018 and their child contacts was abstracted. Outcomes were TB preventive treatment (TPT) initiation, TPT completion, and CBI acceptability. Generalized linear mixed models were used to test for differences between study arms and qualitative interview thematic analysis for acceptability.RESULTS: Among 547 registered children (CBI: n = 399; SOC: n = 148) of 426 adult TB patients, 46% were <2 years, 48% female, and 3% HIV-exposed/positive, with no significant differences between study arms. A total of 501 children initiated TPT-98% at CBI and 88% at SOC HFs (P < 0.0001). TPT completion was 82% in CBI vs. 59% in SOC sites (P = 0.048). Caregivers and providers reported that CBI was acceptable.CONCLUSION: The CBI was acceptable and significantly improved TPT initiation and completion in Lesotho, offering the opportunity to mitigate the threat of TB among children.

Rates of cardiovascular disease following smoking cessation in patients with HIV infection: results from the D:A:D study(*).

OBJECTIVES: The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection. METHODS: Patients who reported smoking status and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow-up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all-cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow-up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment. RESULTS: A total of 27 136 patients had smoking status reported, with totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow-up decreased from 2.32 within the first year of stopping to 1.49 after >3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all-cause mortality. CONCLUSION: The risk of CVD events in HIV-positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV-positive patients.

Leveraging differentiated HIV service delivery to expand tuberculosis preventive treatment: a call to action.

Tuberculosis (TB) is the leading cause of death among people living with human immunodeficiency virus (PLHIV), and sub-Saharan Africa has a particularly heavy burden of HIV-associated TB. Although effective TB preventive treatment (TPT) has been available for decades and shorter regimens are newly available in some settings, TPT coverage among PLHIV is suboptimal, leading to preventable illness and death. In 2018, the United Nations High-Level Meeting on Ending Tuberculosis called for ambitious new targets for TPT coverage among PLHIV and many countries in sub-Saharan Africa have redoubled their efforts to take TPT to scale. Importantly, however, this push to expand TPT among PLHIV is taking place in the context of a changing HIV treatment delivery landscape. Countries in sub-Saharan Africa are at the forefront of innovative changes in HIV program design, including a shift towards less-intensive differentiated service delivery (DSD) models for stable patients doing well on antiretroviral therapy. Understanding the opportunities and challenges that DSD presents for TB diagnosis, prevention and linkage to care among PLHIV will be critical to success.

CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS: A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

Implementing family-focused HIV care and treatment: the first 2 years' experience of the mother-to-child transmission-plus program in Abidjan, Côte d'Ivoire.

OBJECTIVES: To describe a family-focused approach to HIV care and treatment and report on the first 2 years experience of implementing the mother-to-child transmission (MTCT)-plus program in Abidjan, Côte d'Ivoire. PROGRAM: The MTCT-plus initiative aims to enroll HIV-infected pregnant and postpartum women in comprehensive HIV care and treatment for themselves and their families. MAIN OUTCOMES: Between August 2003 and August 2005, 605 HIV-infected pregnant or postpartum women and 582 HIV-exposed infants enrolled. Of their 568 male partners reported alive, 52% were aware of their wife's HIV status and 30% were tested for HIV; 53% of these tested partners were found to be HIV-infected and 78% enrolled into the program. Overall only 10% of the women enrolled together with their infected partner. On the other hand, the program involved half of the seronegative men who came for voluntary counselling and testing (VCT) in the care of their families. Of 1624 children <15 years reported alive by their mothers (excluding the last newborn infants of the most recent pregnancy systematically screened for HIV), only 10.8% were brought in for HIV testing, of whom 12.3% were found to be HIV-infected. LESSONS LEARNED AND CHALLENGES: The family-focused model of HIV care pays attention to the needs of families and household members. The program was successful in enrolling HIV women, their partners and infants in continuous follow-up. However engaging partners and family members of newly enrolled women into care involves numerous challenges such as disclosure of HIV status by women to their partners and family members. Further efforts are required to understand barriers for families accessing HIV services as strategies to improve partner involvement and provide access to care for other children in the households are needed in this West African urban setting.

Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial.

BACKGROUND: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. OBJECTIVE: To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease or death. DESIGN: Randomized, controlled trial. SETTING: Sites in 33 countries. PATIENTS: 5472 HIV-infected individuals with CD4(+) cell counts greater than 0.350 x 10(9) cells/L enrolled from January 2002 to January 2006. INTERVENTION: Episodic or continuous antiretroviral therapy initially, followed by continuous therapy in participants previously assigned to episodic treatment. MEASUREMENTS: Opportunistic disease or death was the primary outcome. RESULTS: Eighteen months after the recommendation to reinitiate continuous therapy, mean CD4+ cell counts were 0.152 x 10(9) cells/L (95% CI, 0.136 to 0.167 x 10(9) cells/L) less in participants previously assigned to episodic treatment (P < 0.001). The proportion of follow-up time spent with CD4+ cell counts of 0.500 x 10(9) cells/L or more and HIV RNA levels of 400 copies/mL or less was 29% for participants initially assigned to episodic therapy and 66% for those assigned to continuous therapy. Participants who reinitiated continuous therapy experienced rapid suppression of HIV RNA levels (89.7% with HIV RNA levels < or =400 copies/mL after 6 months), but CD4+ cell counts after 6 months remained 0.140 x 10(9) cells/L below baseline. The hazard ratio (episodic versus continuous treatment) for opportunistic disease or death decreased after the recommendation to reinitiate continuous therapy (from 2.5 [CI, 1.8 to 3.5] to 1.4 [CI, 1.0 to 2.0]; P = 0.033 for difference). The residual excess risk was attributable to failure to reinitiate therapy by some participants and slow recovery of CD4+ cell counts for those who reinitiated therapy. LIMITATION: Follow-up was too short to assess the full effect of switching from episodic to continuous antiretroviral therapy. CONCLUSION: Reinitiating continuous antiretroviral therapy in patients previously assigned to episodic treatment reduced excess risk for opportunistic disease or death, but excess risk remained. Episodic antiretroviral therapy, as used in the SMART study, should be avoided.

Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction.

BACKGROUND: Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. METHODS: The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow-up for 33,389 HIV-infected patients from December 1999 through February 2006. RESULTS: The proportion of patients at high risk of CVD increased from 35.3% during 1999-2000 to 41.3% during 2005-2006. Of 28,985 patients, 2801 (9.7%) initiated lipid-lowering therapy; initiation of lipid-lowering therapy was more common for those with abnormal lipid values and those with traditional risk factors for CVD (male sex, older age, higher body mass index [calculated as the weight in kilograms divided by the square of the height in meters], family and personal history of CVD, and diabetes mellitus). After controlling for these, use of lipid-lowering drugs became relatively less common over time. The incidence of myocardial infarction (0.32 cases per 100 person-years [PY]; 95% confidence interval [CI], 0.29-0.35 cases per 100 PY) appeared to remain stable. However, after controlling for changes in risk factors for CVD, the rate decreased over time (relative rate in 2003 [compared with 1999-2000], 0.73 cases per 100 PY [95% CI, 0.50-1.05 cases per 100 PY]; in 2004, 0.64 cases per 100 PY [95% CI, 0.44-0.94 cases per 100 PY]; in 2005-2006, 0.36 cases per 100 PY [95% CI, 0.24-0.56 cases per 100 PY]). Further adjustment for lipid levels attenuated the relative rates towards unity (relative rate in 2003 [compared with 1999-2000], 1.06 cases per 100 PY [95% CI, 0.63-1.77 cases per 100 PY]; in 2004, 1.02 cases per 100 PY [95% CI, 0.61-1.71 cases per 100 PY]; in 2005-2006, 0.63 cases per 100 PY [95% CI, 0.36-1.09 cases per 100 PY]). CONCLUSIONS: Although the CVD risk profile among patients in the Data Collection on Adverse Events of Anti-HIV Drugs Study has decreased since 1999, rates have remained relatively stable, possibly as a result of a more aggressive approach towards managing the risk of CVD.

Integrating tuberculosis and HIV care in rural Rwanda.

SETTING: Rwanda has generalised human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics. The Rwandan Ministry of Health approved a policy on TB-HIV collaborative activities in 2005. The present study is a report on the results of the integrated TB and HIV activities at a rural health care site between July 2005 and June 2006. METHODS: Activities included provider-initiated HIV testing and counselling (PITC) of TB patients and the implementation of a standardised TB screening questionnaire for in-patients on medical wards and HIV-infected out-patients. RESULTS: Of a total 259 TB patients registered, 87% with unknown HIV status or who were HIV-negative accepted PITC. Overall, 48% (125/259) of TB patients were HIV-infected. The proportion of TB patients ever tested for HIV increased from 82% (138/169) in 2004-2005 to 93% (240/259) in 2005-2006 (P < 0.001). Of the 770 in-patients screened for TB, 162 (21%) tested positive, of whom 53 (33%) were diagnosed with TB; 39 (76%) of these were HIV co-infected. Three hundred out-patients with HIV were screened for TB; 80 (27%) tested positive, of whom 11 (14%) were diagnosed with TB. DISCUSSION: Activities integrating TB and HIV were feasible in a rural health care setting. PITC was successful in TB patients and unrecognised TB was common, particularly among HIV-infected in-patients.

Tuberculosis preventive treatment preferences among care givers of children in Lesotho: a pilot study.

BACKGROUND: Shorter-duration regimens for preventing drug-susceptible tuberculosis (TB) have been shown to be safe and efficacious in children, and may improve acceptability, adherence, and treatment completion. While these regimens have been used in children in low TB burden countries, they are not yet widely used in high TB burden countries. SETTING: Five health facilities in one district in Lesotho, a high TB burden country. OBJECTIVE: Assess the preventive treatment preferences of care givers of child TB contacts. DESIGN: Qualitative data were collected using in-depth interviews with 12 care givers whose children completed preventive treatment, and analyzed using grounded theory. FINDINGS: Care givers were interested in being involved in the children's treatment decisions. Pill burden, treatment duration and related frequency of dosing were identified as important factors that influenced preventive treatment preferences among care givers. CONCLUSION: Understanding care giver preferences and involving them in treatment decisions may facilitate efforts to implement successful preventive treatment for TB among children in high TB burden countries.

Frequency, severity and duration of immune reconstitution events in HIV-related tuberculosis.

SETTING: Patients were enrolled in a prospective trial of rifabutin-based tuberculosis (TB) treatment for human immunodeficiency virus related TB. Antiretroviral therapy (ART) was encouraged, but not required. OBJECTIVE: To evaluate the frequency, risk factors and duration of immune reconstitution events. DESIGN: Patients were prospectively evaluated for immune reconstitution events, and all adverse event reports were reviewed to identify possible unrecognized events. RESULTS: Of 169 patients, 25 (15%) developed immune reconstitution events related to TB. All 25 were among the 137 patients who received ART during TB treatment, so the frequency in this subgroup was 18% (25/137). Risk factors for an immune reconstitution event in multivariate analysis were Black race, the presence of extra-pulmonary TB and a shorter interval from initiation of TB treatment to initiation of ART. The most common clinical manifestations were fever (64%), new or worsening adenopathy (52%) and worsening pulmonary infiltrates (40%). Twelve patients (48%) were hospitalized for a median of 7 days, six underwent surgery and 11 had needle aspiration. The median duration of events was 60 days (range 11-442). CONCLUSION: Immune reconstitution events were common among patients receiving ART during TB treatment, produced substantial morbidity and had a median duration of 2 months.

Help-seeking behavior of marginalized groups: a study of TB patients in Harlem, New York.

SETTING: Harlem Hospital Directly Observed Therapy (DOT) Program, New York City. OBJECTIVE: To identify various pathways to tuberculosis (TB) diagnosis, and determine time to diagnosis and reasons for delay, to ensure rapid diagnosis of TB and prompt initiation of appropriate treatment. DESIGN: Cross-sectional survey of the help-seeking behavior of TB patients within 2 months of their enrollment into DOT from May 2001 to December 2004. RESULTS: The average total delay between symptom onset and a patient's diagnosis of TB was 18 weeks among 39 patients. The average delay to diagnosis attributed to patient delay and health care system delay were 10.5 and 7.5 weeks, respectively. Patients visited on average 1.6 sources of care prior to receiving a TB diagnosis. Foreign-born patients in particular were found to have more complex paths to diagnosis. The most common reason for delaying seeking care reported by patients was that they didn't think it was serious' (29.1%). CONCLUSION: There was a substantial time interval between the onset of symptoms and TB diagnosis due to both patient and health care system delay. Foreign-born status, economic and social factors, and missed opportunities for diagnosis by the health care system played important roles in delaying TB diagnoses for the marginalized patients in this study.

Results of a tuberculosis-specific IFN-gamma assay in children at high risk for tuberculosis infection.

The specificity of the tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) is adversely affected by bacille Calmette-Guérin (BCG) vaccination and infection with non-tuberculous mycobacteria. Interferon-gamma release assays (IGRAs) using TB-specific antigens promise higher specificity. We compared a new IGRA and TST in 184 schoolchildren at high risk for LTBI. The IGRA and TST were positive in 33.2% and 43.5% of the children, respectively (P < 0.001). If studies confirm that this difference is due to higher specificity of this IGRA, it may have an important role to play in the diagnosis of LTBI and identification of children at true risk for TB.

Physician attitudes regarding latent tuberculosis infection: international vs. U.S. medical graduates.

Tuberculosis in the U.S. is increasingly noted among the foreign-born, with many individuals at risk being managed by international medical graduates (IMGs). We utilized anonymous surveys using hypothetical scenarios to assess and compare the attitudes of IMGs and U.S. medical graduates regarding the treatment of latent tuberculosis infection (LTBI) to identify how attitudes and intentions may influence physician behavior. IMGs were less likely to treat LTBI in almost all scenarios. Educational efforts should focus on IMGs to encourage attitudes more consistent with U.S. guidelines.