Taraz Samandari

HIV Infection Linked to Injection Use of Oxymorphone in Indiana, 2014-2015.

BACKGROUND In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent and cause of the outbreak and implemented control measures. METHODS We identified an outbreak-related case as laboratory-confirmed HIV infection newly diagnosed after October 1, 2014, in a person who either resided in Scott County, Indiana, or was named by another case patient as a syringe-sharing or sexual partner. HIV polymerase (pol) sequences from case patients were phylogenetically analyzed, and potential risk factors associated with HIV infection were ascertained. RESULTS From November 18, 2014, to November 1, 2015, HIV infection was diagnosed in 181 case patients. Most of these patients (87.8%) reported having injected the extended-release formulation of the prescription opioid oxymorphone, and 92.3% were coinfected with hepatitis C virus. Among 159 case patients who had an HIV type 1 pol gene sequence, 157 (98.7%) had sequences that were highly related, as determined by phylogenetic analyses. Contact tracing investigations led to the identification of 536 persons who were named as contacts of case patients; 468 of these contacts (87.3%) were located, assessed for risk, tested for HIV, and, if infected, linked to care. The number of times a contact was named as a syringe-sharing partner by a case patient was significantly associated with the risk of HIV infection (adjusted risk ratio for each time named, 1.9; P<0.001). In response to this outbreak, a public health emergency was declared on March 26, 2015, and a syringe-service program in Indiana was established for the first time. CONCLUSIONS Injection-drug use of extended-release oxymorphone within a network of persons who inject drugs in Indiana led to the introduction and rapid transmission of HIV. (Funded by the state government of Indiana and others.).

Differences in Response to a Hepatitis B Vaccine Booster Dose Among Alaskan Children and Adolescents Vaccinated During Infancy

BACKGROUND. The duration of protection provided by hepatitis B vaccination is unknown, but the presence of immune memory can be evaluated indirectly by measuring the immune response to a booster dose of vaccine. METHODS. Participants included 74 adolescents (aged 11.7–14.9 years) who had received a plasma-derived 3-dose primary vaccine series and 138 adolescents (aged 10.0–14.7 years) and 166 children (aged 5.0–7.0 years) who received a recombinant 3-dose primary vaccine series. All were born to hepatitis B surface antigen–negative mothers and had received the first dose of hepatitis B vaccine within 7 days of birth. The proportion of participants with serologic evidence of protective immunity (antibody to hepatitis B surface antigen ≥10 mIU/mL) at baseline (prebooster), the proportion who developed an anamnestic response (increase to ≥10 mIU/mL or at or more than fourfold increase in antibody to hepatitis B surface antigen to >10 mIU/mL), and the geometric mean concentration by 1, 2, and 4 weeks after a 5-μg recombinant vaccine booster dose were determined. RESULTS. No participant had evidence of chronic hepatitis B virus infection. Overall, 99% of the group of children who received recombinant hepatitis B vaccine, 83% of the group of adolescents who received recombinant hepatitis B vaccine, and 69% of the group of adolescents who received the plasma-derived vaccine had an anamnestic response to a booster dose; among responders, the geometric mean concentration at 2 weeks postbooster was 3360 and 128 mIU/mL among adolescents who received plasma-derived vaccine with antibodies to hepatitis B surface antigen ≥10 and <10 mIU/mL at baseline, respectively, compared with 1283 and 369 mIU/mL among adolescents who received recombinant hepatitis B vaccine and 5091 and 696 mIU/mL for children who received recombinant hepatitis B vaccine. The anamnestic response rate at 2 weeks postbooster among participants with antibodies to hepatitis B surface antigen <10 mIU/mL at baseline was inversely associated with age; 97% of 5-year-olds responded compared with 60% of 14-year-olds. CONCLUSIONS. Although most participants responded to a booster dose of hepatitis B vaccine, the significance of the increased proportion of nonresponses among older adolescents might indicate waning immune memory.

A large outbreak of hepatitis B virus infections associated with frequent injections at a physician's office.

OBJECTIVES To determine whether hepatitis B virus (HBV) transmission occurred among patients visiting a physicians office and to evaluate potential transmission mechanisms. DESIGN Serologic survey, retrospective cohort study, and observation of infection control practices. SETTING Private medical office. PATIENTS Those visiting the office between March 1 and December 26, 2001. RESULTS We identified 38 patients with acute HBV infection occurring between February 2000 and February 2002. The cohort study, limited to the 10 months before outbreak detection, included 91 patients with serologic test results and available charts representing 18 case-patients and 73 susceptible patients. Overall, 67 patients (74%) received at least one injection during the observation period. Case-patients received a median of 14 injections (range, 2-25) versus 2 injections (range, 0-17) for susceptible patients (P < .001). Acute infections occurred among 18 (27%) of 67 who received at least one injection versus none of 24 who received no injections (RR, 13.6; CI95, 2.4-undefined). Risk of infection increased 5.2-fold (CI95, 0.6-47.3) for those with 3 to 6 injections and 20.0-fold (CI95, 2.8-143.5) for those with more than 6 injections. Typically, injections consisted of doses of atropine, dexamethasone, vitamin B12, or a combination of these mixed in one syringe. HBV DNA genetic sequences of 24 patients with acute infection and 4 patients with chronic infection were identical in the 1,500-bp region examined. Medical staff were seronegative for HBV infection markers. The same surface was used for storing multidose vials, preparing injections, and dismantling used injection equipment. CONCLUSION Administration of unnecessary injections combined with failure to separate clean from contaminated areas and follow safe injection practices likely resulted in patient-to-patient HBV transmission in a private physicians office.

Persistence of long-term immunity to hepatitis B among adolescents immunized at birth.

The long-term duration of recombinant hepatitis B vaccine-induced immunity among persons vaccinated starting at birth is still not well understood. Waning of vaccine-induced immunity could leave young adults at risk of hepatitis B virus infection due to behavioral or occupational exposures. We followed a cohort of children immunized starting at birth with a 3-dose regimen of recombinant hepatitis B vaccine (5 mcg, 2.5 mcg, 2.5 mcg). They were challenged with a booster dose of the hepatitis B vaccine 10 and 15 years after vaccination to assess anamnestic response as a measure of persistence of protection. Among 108 participants who had lost protective antibody levels against hepatitis B, the majority (>70%) had an anamnestic response to the booster dose; response rates did not decline significantly between 10 and 15 years follow-up periods. A high antibody concentration following primary vaccination was independently associated with an anamnestic response later on in life. Nonetheless, ~20-30% of participants were unable to mount an immune response after boosting. Hepatitis B revaccination might be required for persons vaccinated starting at birth if opportunities for hepatitis B virus exposure exist. Future vaccine recommendations should be based on studies ascertaining protection against clinically significant disease.

Isoniazid tuberculosis preventive therapy in HIV-infected adults accessing antiretroviral therapy: a Botswana Experience, 2004-2006.

Objectives:To describe reasons for exclusion from isoniazid tuberculosis preventive therapy (IPT) and outcomes of persons living with HIV (PLWH) during 6 months of IPT. Methods:In a clinical trial conducted in government clinics, first screening (screen 1) used National IPT Program guidelines and a second screening (screen 2) was trial specific. Adherence was defined as attending 6 monthly visits. Results:Between 2004 and 2006, at 4018 screening visits, 2934 (73%) PLWH met screen 1 criteria; 1995 (68%) met screen 2 criteria and were enrolled. Major reasons for exclusion were illness (66%) at screen 1 and abnormal chest radiographs (36%) at screen 2. Tuberculin skin tests were ≥5 mm in 24% of those enrolled and 31% had CD4 lymphocyte counts <200 cells/mm3. During the 6 months, 8 (0.40%) developed tuberculosis disease, 28 (1.4%) had severe adverse events (19/28 were hepatitis including one death probably isoniazid-associated), 20 others died, and 22% initiated antiretroviral therapy (ART). Although adherence was 86%, being on ART improved adherence: relative risk 1.41 (95% confidence limits 1.04-1.91). In multivariate analysis, ART was associated with a 4.38 greater odds of adherence to IPT. Conclusions:Six months of IPT was relatively safe and well-tolerated by PLWH. Adherence to IPT was significantly better among those receiving ART with IPT.

Isoniazid-associated Hepatitis and Antiretroviral Drugs during Tuberculosis Prophylaxis in HIV-infected Adults in Botswana

RATIONALE Little is known about the incidence of isoniazid-associated hepatitis in HIV-infected Africans who receive both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART). OBJECTIVES To assess the rate of and risk factors for isoniazid (INH)-associated hepatitis in persons living with HIV (PLWH) during IPT. METHODS PLWH recruited for a clinical trial received 6 months of open-label, daily, self-administered INH at public health clinics. At screening PLWH were excluded if they had any cough, weight loss, night sweats, or other illness. Alcohol abuse was defined as meeting any CAGE criterion. INH-associated hepatitis (INH-hepatitis) was defined as having either alanine or aspartate aminotransferase greater than 5.0 times the upper limit of normal regardless of symptoms when INH was not excluded as the cause. MEASUREMENTS AND MAIN RESULTS Of 1,995 PLWH enrolled between 2004 and 2006, 1,762 adhered to at least 4 months of IPT and were analyzed. Nineteen (1.1%) developed hepatitis probably or possibly associated with INH including one death at month 6; 14 of 19 (74%) occurred in months 1-3. Antiretroviral therapy (ART) was received by 480 participants but was not statistically associated with INH-hepatitis (relative risk [RR], 1.56; 95% confidence intervals [CI], 0.62-3.9); those receiving nevirapine had a higher rate (2.0%) than those receiving efavirenz (0.9%; P = 0.34). Although alcohol use did not reach significance (RR, 1.42; 95% CI, 0.57-3.51), meeting at least one CAGE criterion approached statistical significance (RR, 2.37; 95% CI, 0.96-5.84). Neither age greater than 35 years nor the presence of hepatitis B virus core antibody was associated with INH-hepatitis. CONCLUSIONS The observed rates of INH-hepatitis were similar to published data. Six months of IPT, which is recommended by the World Health Organization, was relatively safe in this, the largest cohort of African PLWH. Clinical trial registered with www.clinicaltrials.gov (NCT 00164281).

Risk Factors for Non-Adherence and Loss to Follow-Up in a Three-Year Clinical Trial in Botswana

Background Participant non-adherence and loss to follow-up can compromise the validity of clinical trial results. An assessment of these issues was made in a 3-year tuberculosis prevention trial among HIV-infected adults in Botswana. Methods and Findings Between 11/2004–07/2006, 1995 participants were enrolled at eight public health clinics. They returned monthly to receive bottles of medication and were expected to take daily tablets of isoniazid or placebo for three years. Non-adherence was defined as refusing tablet ingestion but agreeing to quarterly physical examinations. Loss to follow-up was defined as not having returned for appointments in ≥60 days. Between 10/2008–04/2009, survey interviews were conducted with 83 participants identified as lost to follow-up and 127 identified as non-adherent. As a comparison, 252 randomly selected adherent participants were also surveyed. Multivariate logistic regression analysis was used to identify associations with selected risk factors. Men had higher odds of being non-adherent (adjusted odds ratio (AOR), 2.24; 95% confidence interval [95%CI] 1.24–4.04) and lost to follow-up (AOR 3.08; 95%CI 1.50–6.33). Non-adherent participants had higher odds of reporting difficulties taking the regimen or not knowing if they had difficulties (AOR 3.40; 95%CI 1.75–6.60) and lower odds associated with each year of age (AOR 0.95; 95%CI 0.91–0.98), but other variables such as employment, distance from clinic, alcohol use, and understanding study requirements were not significantly different than controls. Among participants who were non-adherent or lost to follow-up, 40/210 (19.0%) reported that they stopped the medication because of work commitments and 33/210 (15.7%) said they thought they had completed the study. Conclusions Men had higher odds of non-adherence and loss to follow-up than women. Potential interventions that might improve adherence in trial participants may include:targeting health education for men, reducing barriers, clarifying study expectations, educating employers about HIV/AIDS to help reduce stigma in the workplace, and encouraging employers to support employee health. Trial Registration ClinicalTrials.gov NCT00164281

Temporal trends in HIV-1 incidence and risk behaviours in men who have sex with men in Bangkok, Thailand, 2006-13: An observational study

BACKGROUND HIV-1 incidence in men who have sex with men (MSM) is often difficult to estimate. We therefore assessed temporal trends in HIV-1 incidence and behavioural risk factors in MSM in Bangkok, Thailand, from 2006 to 2013. METHODS In this observational study, we used data for clients attending the Silom Community Clinic for voluntary counselling and testing (VCT) services and from the Bangkok MSM Cohort Study (BMCS) to investigate trends in HIV incidence per 100 person-years per quarter in both cohorts. During VCT, basic demographic data were gathered at registration. However, no behavioural risk data were gathered. In the BMCS, we gathered demographic and behavioural data at baseline and at regular study visits using audio computer-assisted self-interviewing. Questions were included about potential risk factors such as drug use, sexual practices, and how often condoms were used. We also analysed behavioural risk factors in the BMCS cohort, using a restricted cubic spline function for time. FINDINGS From 2006 to 2013, 8176 MSM came for VCT; 1999 (24%) clients were initially seronegative and returned for another test. 235 (12%) individuals seroconverted. The overall HIV-1 incidence was 5.5 per 100 person-years (95% CI 4.8-6.3), with an increasing trend (adjusted p=0.02). In the BMCS, 1372 people were seronegative at baseline; 1259 (92%) had more than one follow-up test and 238 (17%) seroconverted. The overall HIV-1 incidence was 5.3 per 100 person-years (95% CI 4.7-6.1), with an increase and then a decline (inverted U-shaped curve, p=0.0001). Individuals aged 21 years and younger were at significantly higher risk of HIV infection than were those aged 30 years and older in the in the VCT (rate ratio 2.29, 95% CI 1.88-2.78, p<0.0001) and BMCS cohorts (1.99, 1.50-2.65, p<0.0001). Overall, drug use (p=0.03), drug use to enhance sex (p=0.0006), use of drugs for erectile dysfunction (p<0.0001), and 100% condom use (p<0.0001) increased over time, whereas the proportion of individuals reporting receptive anal intercourse decreased (p=0.004). INTERPRETATION With a sustained high HIV-1 incidence and increasing drug use in MSM in Bangkok, we urgently need innovative and acceptable HIV prevention interventions, especially for young MSM. FUNDING US Centers for Disease Control and Prevention.

Screening Yield of HIV Antigen/Antibody Combination and Pooled HIV RNA Testing for Acute HIV Infection in a High-Prevalence Population

IMPORTANCE Although acute HIV infection contributes disproportionately to onward HIV transmission, HIV testing has not routinely included screening for acute HIV infection. OBJECTIVE To evaluate the performance of an HIV antigen/antibody (Ag/Ab) combination assay to detect acute HIV infection compared with pooled HIV RNA testing. DESIGN, SETTING, AND PARTICIPANTS Multisite, prospective, within-individual comparison study conducted between September 2011 and October 2013 in 7 sexually transmitted infection clinics and 5 community-based programs in New York, California, and North Carolina. Participants were 12 years or older and seeking HIV testing, without known HIV infection. EXPOSURES All participants with a negative rapid HIV test result were screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled human immunodeficiency virus 1 (HIV-1) RNA testing. HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. MAIN OUTCOMES AND MEASURES Number and proportion with acute HIV infections detected. RESULTS Among 86,836 participants with complete test results (median age, 29 years; 75.0% men; 51.8% men who have sex with men), established HIV infection was diagnosed in 1158 participants (1.33%) and acute HIV infection was diagnosed in 168 participants (0.19%). Acute HIV infection was detected in 134 participants with HIV Ag/Ab combination testing (0.15% [95% CI, 0.13%-0.18%]; sensitivity, 79.8% [95% CI, 72.9%-85.6%]; specificity, 99.9% [95% CI, 99.9%-99.9%]; positive predictive value, 59.0% [95% CI, 52.3%-65.5%]) and in 164 participants with pooled HIV RNA testing (0.19% [95% CI, 0.16%-0.22%]; sensitivity, 97.6% [95% CI, 94.0%-99.4%]; specificity, 100% [95% CI, 100%-100%]; positive predictive value, 96.5% [95% CI, 92.5%-98.7%]; sensitivity comparison, P < .001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone, HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% (95% CI, 8.8%-12.2%) and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4% (95% CI, 10.7%-14.3%). CONCLUSIONS AND RELEVANCE In a high-prevalence population, HIV screening using an HIV Ag/Ab combination assay following a negative rapid test detected 82% of acute HIV infections detectable by pooled HIV RNA testing, with a positive predictive value of 59%. Further research is needed to evaluate this strategy in lower-prevalence populations and in persons using preexposure prophylaxis for HIV prevention.

Tuberculosis incidence after 36 months’ isoniazid prophylaxis in HIV-infected adults in Botswana: a posttrial observational analysis

Objective:Thirty-six months of isoniazid preventive therapy (36IPT) was superior to 6 months of IPT (6IPT) in preventing tuberculosis (TB) among HIV-infected adults in Botswana. We assessed the posttrial durability of this benefit. Design:A 36-month double-blind placebo controlled trial (1 : 1 randomization) with recruitment between November 2004 and July 2006 and observation until June 2011. Methods:One thousand, nine hundred and ninety-five participants were followed in eight public health clinics. Twenty-four percent had a tuberculin skin test ≥5 mm (TST-positive). A minimum CD4+ lymphocyte count was not required for enrolment. Antiretroviral therapy (ART) was provided in accordance with Botswana guidelines; 72% of participants retained by June 2011 had initiated ART. Multivariable analysis using Cox regression analysis included treatment arm, TST status, ART as a time-dependent variable and CD4+ cell count at baseline and updated at 36 months. Results:In the posttrial period, 2.13 and 2.14 per 100 person-years accumulated, whereas 0.93 and 1.13% TB incidence rates were observed in the 36IPT and 6IPT arms, respectively (P = 0.52). The crude hazard ratio of TB during the trial and posttrial was 0.57 [95% confidence intervals (CI) 0.33, 0.99] and 0.82 (95% CI 0.46, 1.49), and when restricted to TST-positive participants was 0.26 (95% CI 0.08, 0.80) and 0.40 (95% CI 0.15, 1.08), respectively. Multivariable analysis showed that ART use was associated with reduced death (adjusted hazard ratio 0.36, 95% CI 0.17–0.75) but not TB (0.92, 95% CI 0.55–1.53) in the posttrial period. Conclusion:The benefit of 36IPT for TB prevention declined posttrial in this cohort. Adjunctive measures are warranted to prevent TB among HIV-infected persons receiving long-term ART in TB-endemic settings.