Expanding Hospital Human Immunodeficiency Virus Testing in the Bronx, New York and Washington, District of Columbia: Results From the HPTN 065 Study.

Background: Human immunodeficiency virus (HIV) testing is critical for both HIV treatment and prevention. Expanding testing in hospital settings can identify undiagnosed HIV infections. Methods: To evaluate the feasibility of universally offering HIV testing during emergency department (ED) visits and inpatient admissions, 9 hospitals in the Bronx, New York and 7 in Washington, District of Columbia (DC) undertook efforts to offer HIV testing routinely. Outcomes included the percentage of encounters with an HIV test, the change from year 1 to year 3, and the percentages of tests that were HIV-positive and new diagnoses. Results: From 1 February 2011 to 31 January 2014, HIV tests were conducted during 6.5% of 1621016 ED visits and 13.0% of 361745 inpatient admissions in Bronx hospitals and 13.8% of 729172 ED visits and 22.0% of 150655 inpatient admissions in DC. From year 1 to year 3, testing was stable in the Bronx (ED visits: 6.6% to 6.9%; inpatient admissions: 13.0% to 13.6%), but increased in DC (ED visits: 11.9% to 15.8%; inpatient admissions: 19.0% to 23.9%). In the Bronx, 0.4% (408) of ED HIV tests were positive and 0.3% (277) were new diagnoses; 1.8% (828) of inpatient tests were positive and 0.5% (244) were new diagnoses. In DC, 0.6% (618) of ED tests were positive and 0.4% (404) were new diagnoses; 4.9% (1349) of inpatient tests were positive and 0.7% (189) were new diagnoses. Conclusions: Hospitals consistently identified previously undiagnosed HIV infections, but universal offer of HIV testing proved elusive.

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings.

BACKGROUND: The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. METHODS: Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. RESULTS: Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB(-)), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. CONCLUSIONS: In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation.

Costs of Expanded Rapid HIV Testing in Four Emergency Departments.

OBJECTIVE: The HIV Prevention Trials Network (HPTN) 065 trial sought to expand HIV screening of emergency department (ED) patients in Bronx, New York, and Washington, D.C. This study assessed the testing costs associated with different expansion processes and compared them with costs of a hypothetical optimized process. METHODS: Micro-costing studies were conducted in two participating EDs in each city that switched from point-of-care (POC) to rapid-result laboratory testing. In three EDs, laboratory HIV testing was only conducted for patients having blood drawn for clinical reasons; in the other ED, all HIV testing was conducted with laboratory testing. Costs were estimated through direct observation and interviews to document process flows, time estimates, and labor and materials costs. A hypothetical optimized process flow used minimum time estimates for each process step. National wage and fringe rates and local reagent costs were used to determine the average cost (excluding overhead) per completed nonreactive and reactive test in 2013 U.S. dollars. RESULTS: Laboratory HIV testing costs in the EDs ranged from $17.00 to $23.83 per completed nonreactive test, and POC testing costs ranged from $17.64 to $37.60; cost per completed reactive test ranged from $89.29 to $123.17. Costs of hypothetical optimized HIV testing with automated process steps were approximately 45% lower for nonreactive tests and 20% lower for reactive tests. The cost per ED visit to conduct expanded HIV testing in each hospital ranged from $1.21 to $3.96. CONCLUSION: An optimized process could achieve additional cost savings but would require an investment in electronic system interfaces to further automate testing processes.

Factors associated with adherence amongst 5295 people receiving antiretroviral therapy as part of an international trial.

BACKGROUND: We assessed factors associated with antiretroviral therapy (ART) adherence, including specific ART medications. METHODS: The Strategies for Management of Antiretroviral Therapy study was an international antiretroviral therapy (ART) strategy trial that compared intermittent ART, using CD4(+) T-cell count as a guide, to continuous ART. Adherence during the 7 days before each visit was measured using self-report. We defined high adherence as self-report of taking "all" pills for each prescribed ART medication; all other reports were defined as suboptimal adherence. Factors associated with adherence were assessed using logistic regression with generalized estimating equations. RESULTS: Participants reported suboptimal adherence at 6016 of 35 695 study visits (17%). Factors independently associated with suboptimal adherence were black race, protease inhibitor-containing regimens, greater pill burden, higher maximum number of doses per day, and smoking. Factors independently associated with higher adherence were older age, higher education, region of residence, episodic treatment, higher latest (at the time of adherence) CD4(+) T-cell count, and being prescribed concomitant drugs (ie, medications for comorbidities). Of specific drugs investigated, atazanavir, atazanavir/ritonavir, fosamprenavir, indinavir, indinavir/ritonavir, and lopinavir/ritonavir were associated with suboptimal adherence, and tenofovir disoproxil fumarate/emtricitabine was associated with higher adherence. CONCLUSIONS: In this, the largest analysis of ART adherence to date, some protease inhibitor-containing regimens and regimens with >1 dose per day were associated with suboptimal adherence.

Antiretroviral medication adherence and class- specific resistance in a large prospective clinical trial.

OBJECTIVE: To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance. DESIGN: Secondary analysis of prospective clinical trial data. METHODS: Participants randomized to the protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA more than 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis. RESULTS: Included were 457 and 446 antiretroviral-naive participants on the protease inhibitor and NNRTI strategies, respectively. The median time to initial virological failure in the protease inhibitor strategy was 1.2 years; 135 (30%) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28%) failed with resistance. No association was found between cumulative adherence and protease inhibitor resistance [hazard ratio 1.1, 95% confidence interval (CI) 0.9-1.4 per 10% lower adherence]. However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (hazard ratio 1.2, 95% CI 1.1-1.3 per 10% lower adherence). In both strategies, lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure. CONCLUSION: Adherence-resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence.

Episodic antiretroviral therapy increases HIV transmission risk compared with continuous therapy: results of a randomized controlled trial.

OBJECTIVE: To compare the HIV transmission risk among patients randomized to episodic versus continuous antiretroviral therapy. DESIGN: This was a substudy of the Strategies of Management of Antiretroviral Therapy study, in which patients were randomized to continuous versus CD4-guided episodic antiretroviral therapy. Participants were surveyed about sexual activity and needle sharing and had laboratory testing for gonorrhea, chlamydia, and syphilis. RESULTS: A total of 883 patients were enrolled in this study, the mean age of the patients was 45 years, 25% were women, and 78% were on antiretroviral therapy. At baseline, 136 participants (15.4%) had high-risk behavior (vaginal or anal sex without a condom, needle sharing, or incident bacterial sexually transmitted infection). After randomization, the proportion of participants reporting high-risk behavior was stable and did not differ by randomized arm (P = 0.39). Among participants off therapy at baseline, high-risk behavior was less common 4 months after randomization among those who were randomized to start antiretroviral therapy (P = 0.03). HIV transmission risk (high-risk behavior while HIV RNA level >1500 copies/mL) with partners perceived to be HIV uninfected was higher in the episodic therapy arm (P = 0.02). CONCLUSIONS: Patients on episodic antiretroviral therapy did not decrease high-risk behavior, and because HIV RNA levels were higher, this strategy may result in increased HIV transmission.

Mild-to-moderate symptoms during the first year of antiretroviral therapy worsen quality of life in HIV-infected individuals.

Symptoms and quality of life were assessed among human immunodeficiency virus (HIV)-infected individuals initiating their first course of antiretroviral therapy. Symptoms, which were mostly mild or moderate, were common in the first year and significantly affected the patients' quality of life. Quality of life was inversely related to the number of symptoms and in the change in the number of symptoms from baseline.

Differential adherence to combination antiretroviral therapy is associated with virological failure with resistance.

OBJECTIVES: To investigate the occurrence of differential adherence to components of combination antiretroviral therapy and assess its predictors and association with virological failure and antiretroviral medication resistance. DESIGN: A secondary analysis of prospective clinical trial data. METHODS: The Flexible Initial Retrovirus Suppressive Therapies study (Community Programs for Clinical Research on AIDS 058) was a randomized trial comparing non-nucleoside reverse transcriptase inhibitor (NNRTI) versus protease inhibitor (PI) versus NNRTI plus PI-based (three-class) antiretroviral therapy in treatment-naive HIV-1-infected individuals. Adherence was assessed at months 1 and 4, and then every 4 months. Differential adherence, defined as any difference in self-reported level of adherence to individual antiretroviral medications at the same timepoint, was evaluated as a binary time-updated variable in multivariate Cox regression analyses of time to initial virological failure (HIV-RNA > 1000 copies/ml) and initial virological failure with genotypic antiretroviral resistance. RESULTS: Differential adherence was reported at least once by 403 of 1379 participants (29%), over 60 months median follow-up. Differential adherence was more commonly reported by participants randomly assigned to the three-class strategy (35%) than the NNRTI (28%) or PI (25%) strategies (P = 0.005), but was not associated with demographic or baseline disease-specific factors. Of those reporting differential adherence, 146 (36%) reported it before initial virological failure. These participants had an increased risk of initial virological failure and initial virological failure with antiretroviral resistance compared with participants without differential adherence before initial virological failure. CONCLUSION: Differential adherence was commonly reported and was associated with an increased risk of initial virological failure and initial virological failure with antiretroviral resistance.

The Incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naïve participants started on three different antiretroviral therapy strategies.

BACKGROUND: Treatment-naïve participants were randomized to three antiretroviral strategies (all with nucleoside reverse transcriptase inhibitor [NRTI] background): protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or PI+NNRTI. The strategies were compared for drug resistance at first virologic failure (VF; HIV RNA >1000 copies/mL). The impact of resistance on AIDS or death was determined. METHOD: Drug resistance was determined by genotype. Cox models were used to compare the strategies for VF with resistance and to determine the impact of resistance on AIDS or death. RESULTS: Of 1,360 participants, 866 experienced VF; 226 experienced AIDS or death (median follow-up 5 years). Rates (per 100 personyears) for VF with resistance were 14.9 (PI), 10.8 (NNRTI), and 11.5 (PI+NNRTI); hazard ratio (HR) was 0.78 (95% CI 0.61-0.99) for NNRTI versus PI. Compared to those with no VF, there was a significantly increased risk of AIDS or death for participants with solitary NNRTI resistance (HR 2.31, 95% CI 1.46-3.66) and for those failing with no known resistance (HR 1.78, 95% CI 1.18-2.68). Participants failing with solitary NNRTI resistance and with no resistance had the lowest percent of time on antiretroviral treatment (ART) and the lowest cumulative mean adherence scores. CONCLUSION: For treatment-naïve participants, the risk of AIDS or death is increased for those who failed virologically with solitary NNRTI resistance and those who failed with no known drug resistance compared to those with no virologic failure. Both the lack of ART exposure in nonadherent participants and the development of NNRTI resistance among those who take and fail their ART regimen predict poor clinical outcomes.

Seroprevalence of HTLV-I and HTLV-II among a cohort of HIV-infected women and women at risk for HIV infection. Women's Interagency HIV Study

OBJECTIVES: To determine the seroprevalence of, and risk factors for, HTLV-I and HTLV-II infection among HIV-infected women and women at high risk for HIV infection. DESIGN: Cross-sectional analysis of baseline data for women enrolled in the prospective Women's Interagency HIV Study (WIHS). METHODS: From October 1994 through November 1995, 2657 women from five metropolitan areas in the United States (Chicago, Los Angeles, New York City [two sites], Northern California, and Washington DC) were enrolled in WIHS. An interview-based survey collected data on demographics, behavior, and medical history. HTLV-I and HTLV-II determinations were made using a combined HTLV-I/HTLV-II indirect immunofluorescent antibody (IFA) screening test, an IFA titration specificity test, and individual HTLV-I and HTLV-II confirmatory Western blots. Fisher's exact tests and logistic regression were used to determine univariate and multi variate independent predictors for HTLV-II infection. RESULTS: Of 2625 women enrolled in WIHS with confirmed HIV results, 2487 (95 percent) were tested for HTLV-I and HTLV-II. Of these, 241 (10 percent) HTLV-II-seropositive and 13 (0.5 percent) were HTLV-I-seropositive. On multivariate analysis, independent predictors of HTLV-II infection included injection drug use (OR = 5.2; p < .001), black race (OR = 3.6; p < 0.001), age > 35 years (OR = 3.3; p < .001) and a history of sex with a male injecting drug user (OR = 1.9; p < .001). Among women injected with HIV, the seroprevalence of HTLV-II was 11 percent compared infected with HIV, the seroprevalence of HTLV-II was 11 percent compared with 6 percent for women at risk for HIV but not infected (p < .001). However, HIV was not an independent predictor of HTLV-II infection in multivariate analysis. CONCLUSIONS: This cross sectional analysis confirms that HTLV-II is found commonly in HIV-infected women at risk for HIV in major urban areas throughout the United States and that HTLV-II is far more common than HTLV-I in these populations. Although injecting drug use is most strongly associated with HTLV-II infection, sexual transmission likely contributes to the high HTLV-II seroprevalence in this cohort.(AU)