Illicit drug users continue to be a group at high risk for tuberculosis (TB) infection and disease. In this article, we present an updated review on the relationship between TB and drug use, summarizing more than a decade of new research. Drug users, and injection drug users in particular, have driven TB epidemics in a number of countries. The successful identification and treatment of TB among drug users remains an important component of a comprehensive TB strategy, but drug users present a unique set of challenges for TB diagnosis and control. New diagnostic modalities, including interferon-γ release assays (IGRAs), offer potential for improved diagnosis and surveillance among this group, alongside proven treatment strategies which incorporate the use of directly-observed therapy (DOT) with treatment for drug abuse. Special considerations, including co-infection with viral hepatitis and the Rifampin/methadone drug interaction, warrant clinical attention and are also updated here.

SummaryBackgroundInfluenza causes significant morbidity and mortality despite currently available treatments. Anecdotal reports suggest plasma with high antibody titers towards influenza may be of benefit in the treatment of severe influenza.MethodsWe conducted a randomized, open-label, multicenter phase 2 trial at 29 academic medical centers in the United States to assess the safety and efficacy of anti-influenza plasma with hemagglutination inhibition (HAI) antibody titers of ≥ 1:80 to the infecting strain. Hospitalized children and adults (including pregnant women) with severe influenza A or B (defined as hypoxia or tachypnea) were randomly assigned to receive either 2 units (or pediatric equivalent) of anti-influenza plasma plus standard care (P+S), versus standard care alone (S), and were followed for 28 days. The primary endpoint was time to normalization of patients’ respiratory status (respiratory rate of ≤ 20 for adults or age defined thresholds of 20–38 for children), and a room air saturation of oxygen ≥ 93%. ClinicalTrials.gov Identifier: NCT01052480FindingsBetween January 13, 2011 and March 2, 2015, 113 participants were screened, and 98 were randomized. Of the participants with confirmed influenza, 28 of 42 (67%) of P+S participants normalized their respiratory status by Day 28, as compared to 24 of 45 (53%) of S participants (p=0·069). The estimated hazard ratio comparing P+S to S was 1·71 (95% CI: 0·96 to 3·06). Six participants died, 1 (2%) and 5 (10%) from the P+S and S arms respectively (p=0·093). P+S participants had non-significant reductions in days in hospital (median 6 vs. 11 days, p=0·13) and days on mechanical ventilation (median 0 vs. 3 days, p=0·14), and significantly improved clinical status at Day 7 (p=0·020). Fewer P+S participants experienced SAEs compared to S recipients (20% vs. 38%, p= 0·041), the most frequent of which were acute respiratory distress syndrome (1 [2%] vs 2 [4%]) and stroke (1 [2%] vs 2 [4%]).InterpretationResults from this Phase II randomized trial of immune plasma for the treatment of severe influenza provides support for a possible benefit of immunotherapy across the primary and secondary endpoints. A Phase III randomized trial is now underway to further evaluate this intervention.

Background Whether persistent low-level viremia (pLLV) predicts virologic failure (VF) is unclear. We used data from the US Military HIV Natural History Study (NHS), to examine the association of pLLV and VF. Methods NHS subjects who initiated combination antiretroviral therapy (ART) after 1996 were included if they had 2 or more VLs measured with a lower limit of detection of ≤50 copies/mL. VF was defined as a confirmed VL ≥200 copies/mL or any VL >1000 copies/mL. Participants were categorized into mutually exclusive virologic categories: intermittent LLV (iLLV) (VL of 50–199 copies/mL on <25% of measurements), pLLV (VL of 50–199 copies/mL on ≥25% of measurements), high-level viremia (hLV) (VL of 200–1000 copies/mL), and continuous suppression (all VL <50 copies/mL). Cox proportional hazards models were used to evaluate the association between VF and LLV; hazard ratios and 95% confidence interval (CI) are presented. Results Two thousand six subjects (median age 29.2 years, 93% male, 41% black) were included; 383 subjects (19%) experienced VF. After adjusting for demographics, VL, CD4 counts, ART regimen, prior use of mono or dual antiretrovirals, and time to ART start, pLLV (3.46 [2.42–4.93]), and hLV (2.29 [1.78–2.96]) were associated with VF. Other factors associated with VF include black ethnicity (1.33 [1.06–1.68]) and antiretroviral use prior to ART (1.79 [1.34–2.38]). Older age at ART initiation (0.71 [0.61–0.82]) and non-nucleoside reverse transcriptase inhibitor (0.68 [0.51–0.90]) or integrase strand transfer inhibitor use (0.26 [0.13–0.53]) were protective. Conclusion Our data add to the body of evidence that suggests persistent LLV is associated with deleterious virologic consequences.

Methamphetamine (meth) abuse is increasingly of public health concern and has been associated with neurocognitive dysfunction. Some previous studies have been hampered by background differences between meth users and comparison subjects, as well as unknown HIV and hepatitis C (HCV) status, which can also affect brain functioning. We compared the neurocognitive functioning of 54 meth dependent (METH+) study participants who had been abstinent for an average of 129 days, to that of 46 demographically comparable control subjects (METH-) with similar level of education and reading ability. All participants were free of HIV and HCV infection. The METH+ group exhibited higher rates of neuropsychological impairment in most areas tested. Among meth users, neuropsychologically normal (n=32) and impaired (n=22) subjects did not differ with respect to self-reported age at first use, total years of use, route of consumption, or length of abstinence. Those with motor impairment had significantly greater meth use in the past year, but impairment in cognitive domains was unrelated to meth exposure. The apparent lack of correspondence between substance use parameters and cognitive impairment suggests the need for further study of individual differences in vulnerability to the neurotoxic effects of methamphetamine.

BackgroundIncreased HIV testing frequency among high-risk populations such as men who have sex with men (MSM) and male-to-female transgender women (TW) can lead to earlier treatment and potentially reduce HIV transmission.MethodsWe analyzed baseline survey data from 718 high-risk, young (median age 29 [interquartile range 23–35]) MSM/TW enrolled in a community-based HIV prevention trial between 2008–2009. Participants were recruited from 24 neighborhoods in and around Lima, Peru. We assessed HIV testing frequency, testing behaviour, and motivations and barriers to testing. Multivariate analysis identified correlates to prior HIV testing.ResultsOverall, 79.6% reported HIV testing within their lifetimes, however, only 6.2% reported an average of two tests per year, as per Peruvian Ministry of Health guidelines. The most commonly reported motivators for testing were to check one’s health (23.3%), lack of condom use (19.7%), and availability of free testing (14.0%), while low self-perceived risk for HIV (46.9%), fear of a positive result (42.0%), and lack of access to testing services (35.7%) were the most frequently reported barriers. In multivariate analysis, factors independently associated with HIV testing included age [adjusted prevalence ratio (APR) 1.00, 95% CI (1.00-1.01)], transgender-identification vs. gay-identification [APR 1.11, 95% CI (1.03-1.20)], history of transactional sex [APR 1.16, 95% CI (1.07-1.27)], and prior sexually transmitted infection diagnosis [APR 1.15, 95% CI (1.07-1.24)].ConclusionsAn overwhelming majority of participants did not meet the standard-of-care for testing frequency. The reported motivations and barriers to testing highlight issues of risk perception and accessibility. Our findings suggest utilizing non-traditional outreach methods and promoting HIV testing as a routine part of healthcare in Peru to encourage testing and knowledge of HIV serostatus.

IntroductionHIV controllers (HICs) experience relatively low-level viraemia and CD4 preservation without antiretroviral therapy (ART), but also immune activation that may predispose to adverse clinical events such as cardiovascular disease and hospitalization. The objective of this study was to characterize the rates and reasons for hospitalization among HICs and persons with medically controlled HIV.MethodsSubjects with consistently well-controlled HIV were identified in the U.S. Military HIV Natural History Study. ART prescription and HIV-1 RNA data were used to categorize subjects as HICs or medically controlled as defined by ≥3 HIV-1 RNA measurements ≤2000 or ≤400 copies/mL, respectively, representing the majority of measurements spanning ≥12 months. Hospitalizations were tallied and assigned diagnostic categories. All-cause hospitalization rates were compared between groups using negative binomial regression.Results and discussionOf 3106 subjects followed from 2000 to 2013, 221 were HICs, including 33 elite (1.1%) and 188 viraemic (6.0%) controllers, who contributed 882 person-years (PY) of observation time. An additional 870 subjects with medically controlled HIV contributed 4217 PY. Mean hospitalization rates were 9.4/100 PY among HICs and 8.8/100 PY among medically controlled subjects. Non-AIDS-defining infections were the most common reason for hospitalization (2.95/100 PY and 2.70/100 PY, respectively) and rates of cardiovascular hospitalization were similar in both groups (0.45/100 PY and 0.76/100 PY). There was no difference in hospitalization rate for HICs compared with subjects with medically controlled HIV (adjusted incidence rate ratio 1.15 [95% confidence interval 0.80 to 1.65]).ConclusionsAll-cause and cardiovascular hospitalization rates did not differ between HICs and persons with medically controlled HIV. Non-AIDS defining infections were common in this young, healthy, predominantly male cohort of military personnel and beneficiaries.

Objectives-The population of Latino men who have sex with men (MSM) and who are also injection drug users (IDUs) is understudied. We explored risk behaviors of MSM/IDUs compared with other male IDUs in 2 Mexican border cities.Study Design-In 2005, IDUs who had injected within the previous 30 days were recruited using respondent-driven sampling (RDS) in Tijuana and Ciudad Juárez. They underwent antibody testing for HIV, HCV, and syphilis and interviewer-administered surveys. Men were categorized as MSM if they reported ≥1 lifetime male partners. Logistic regression was used to compare MSM/IDUs with non-MSM/IDUs.Results-A third (31%) of 377 male IDUs were categorized as MSM (47% in Tijuana and 13% in Ciudad Juárez, P <0.01). Combined RDS-adjusted prevalence of HIV and Hepatitis C was 3% (95% CI: 1, 5) and 96%, (95% CI: 94, 99) respectively, while 17% (95% CI: 2, 36) of MSM and 8% (95% CI: 3,12) of non-MSM tested positive for syphilis antibody. In multivariate logistic regression adjusted for site, MSM/IDUs were more likely than non-MSM/IDUs to have ever used inhalants (OR: 3.4; 95% CI: 1.8, 6.2) or oral tranquilizers (OR: 2.4; 95% CI: 1.3, 4.6), received treatment for a drug problem (OR:1.9; 95% CI: 1.1, 3.2) shared needles in the last six months (OR: 2.1; 95% CI: 1.0, 4.2) and also had higher numbers of lifetime female partners (log-transformed continuous variable, OR: 1.6; 95% CI: 1.2, 2.1).Conclusions-In these Mexican cities, the proportion of MSM among male IDUs was high. Compared with other male IDUs, MSM/IDUs were more likely to engage in behaviors placing them at risk of acquiring HIV/STIs. Culturally appropriate interventions targeting Latino MSM/IDUs are warranted.The profile of Latino injection drug users (IDUs) who are also men who have sex with other men (MSM) has been understudied. Two US studies found that homosexual/bisexual behavior This study sought to characterize and compare the sexual and drug use behaviors and prevalence of HIV, syphilis, and hepatitis C among male IDUs who reported sex with other males versus those who did not in 2 Mexico-US border cities. An advantage of the current study was the use of respondent-driven sampling (RDS), 21 which facilitated the rapid recruitment of the "hidden" IDUs population and enabled the calculation of less biased estimates of self-reported homosexual/bisexual activity and risk behaviors in this study. Materials and MethodsWe conducted a cross-sectional study of behavioral and contextual factors associated with HIV, HCV, and syphilis infections among IDUs in the Mexican border cities of Tijuana (population 1.3 million) and Ciudad Juárez, México (population 1.2 million). 22 Both cities are located on major drug trafficking routes and have large, predominantly male IDUs populations. 23 Eligibility criteria for the study included having injected illicit drugs within the past 30 days, confirmed by inspection of injection stigmata (track marks); aged 18 years or older; willing and able to provide informed consent; and not having previously been inte...

Background Infectious diarrhea is a common problem among travelers. Expert guidelines recommend the prompt use of antibiotics for self-treatment of moderate or severe traveler’s diarrhea (TD). There is limited data on whether travelers follow these self-treatment guidelines. We evaluated the risk factors associated with TD, use of TD self-treatment, and risk of irritable bowel syndrome (IBS) during travel. Methods Department of Defense beneficiaries traveling outside the US for ≤ 6.5 months were enrolled in a prospective cohort study. Participants received pre- and post-travel surveys, and could opt into a travel illness diary and follow-up surveys for symptoms of IBS. Standard definitions were used to assess for TD and IBS. Sub-optimal self-treatment was defined as use of antibiotics (with or without antidiarrheal agents) for mild TD, or use of antidiarrheals alone or no self-treatment in cases of moderate or severe TD. Results Twenty-four percent of participants (270/1120) met criteria for TD. The highest incidence was recorded in Africa (8.6 cases/100 person-weeks, 95% CI: 6.7–10.5). Two hundred and twelve TD cases provided information regarding severity and self-treatment: 89 (42%) had mild TD and 123 (58%) had moderate or severe TD. Moderate or severe TD was independently associated with suboptimal self-treatment (OR 10.4 [95% CI: 4.92–22.0]). Time to last unformed stool did not differ between optimal and suboptimal self-treatment. IBS occurred in 4.5% (7/154) of TD cases and 3.1% (16/516) of patients without TD (p=0.39). Among TD cases, a lower incidence of IBS was noted in participants who took antibiotics (4.8% (5/105) vs. 2.2% (1/46)), but the difference did not reach statistical significance (p=0.60). Conclusions Our results suggest the underutilization of antibiotics in travelers with moderate or severe TD. Further studies are needed to systematically evaluate pre-travel instruction and traveler adherence to self-treatment guidelines, and the impact of suboptimal self-treatment on outcomes.