Kelsey B. Loeliger

Enhanced Survival of Plasmodium-Infected Mosquitoes during Starvation

Plasmodium spp. are pathogenic to their vertebrate hosts and also apparently, impose a fitness cost on their insect vectors. We show here, however, that Plasmodium-infected mosquitoes survive starvation significantly better than uninfected mosquitoes. This survival advantage during starvation is associated with higher energy resource storage that infected mosquitoes accumulate during period of Plasmodium oocyst development. Microarray analysis revealed that the metabolism of sated mosquitoes is altered in the presence of rapidly growing oocysts, including the down-regulation of several enzymes involved in carbohydrate catabolism. In addition, enhanced expression of several insulin-like peptides was observed in Plasmodium-infected mosquitoes. Blocking insulin-like signaling pathway resulted in impaired Plasmodium development. We conclude that Plasmodium infection alters metabolic pathways in mosquitoes, epitomized by enhanced insulin-like signaling – thereby conferring a survival advantage to the insects during periods of starvation. Manipulation of this pathway might provide new strategies to influence the ability of mosquitoes to survive and transmit the protozoa that cause malaria.

Tuberculosis screening in a novel substance abuse treatment center in Malaysia: Implications for a comprehensive approach for integrated care

People who use drugs (PWUD) represent a key high risk group for tuberculosis (TB). The prevalence of both latent TB infection (LTBI) and active disease in drug treatment centers in Malaysia is unknown. A cross-sectional convenience survey was conducted to assess the prevalence and correlates of LTBI among attendees at a recently created voluntary drug treatment center using a standardized questionnaire and tuberculin skin testing (TST). Participants (N=196) were mostly men (95%), under 40 (median age=36 years) and reported heroin use immediately before treatment entry (75%). Positive TST prevalence was 86.7%. Nine (4.6%) participants were HIV-infected. Previous arrest/incarcerations (AOR=1.1 for every entry, p<0.05) and not being HIV-infected (AOR=6.04, p=0.03) were significantly associated with TST positivity. There is an urgent need to establish TB screening and treatment programs in substance abuse treatment centers and to tailor service delivery to the complex treatment needs of patients with multiple medical and psychiatric co-morbidities.

Patterns of substance use and correlates of lifetime and active injection drug use among women in Malaysia

ABSTRACT Background: While drug use is associated with HIV risk in Southeast Asia, little is known about substance use behaviors among women, including drug injection. Objectives: To describe patterns of substance use among women using alcohol and drugs in Malaysia and identify correlates of lifetime and active drug injection, a risk factor for HIV transmission. Methods: A survey of 103 women who used drugs in the last 12 months assessed drug use history and frequency, including drug injection and drug use during pregnancy, self-reported HIV-status, childhood and adulthood physical and sexual abuse, and access to and utilization of harm reduction services, including needle-syringe exchange programs (NSEP) and opioid agonist maintenance therapy (OAT). Principal component analyses (PCA) were conducted to assess drug use grouping. Results: Amphetamine-type substances (ATS; 82.5%), alcohol (75.7%) and heroin (71.8%) were the most commonly used drugs across the lifetime. Drug injection was reported by 32.0% (n = 33) of participants with 21.4% (n = 22) having injected in the last 30 days. PCA identified two groups of drug users: opioids/benzodiazepines and club drugs. Lifetime drug injection was significantly associated with lower education, homelessness, prior criminal justice involvement, opioid use, polysubstance use, childhood physical and sexual abuse, and being HIV-infected, but not with prior OAT. Conclusion: Women who use drugs in Malaysia report high levels of polysubstance use and injection-related risk behaviors, including sharing of injection equipment and being injected by others. Low OAT utilization suggests the need for improved access to OAT services and other harm reduction measures that prioritize women.

The syndemic of HIV, HIV-related risk and multiple co-morbidities among women who use drugs in Malaysia: Important targets for intervention

BACKGROUND Substance use and HIV are syndemic public health problems in Malaysia. Harm reduction efforts to reduce HIV transmission have primarily focused on men with substance use disorders. OBJECTIVES To explore HIV risk behaviors, substance use, and social factors associated with poor health outcomes among women who use drugs in Malaysia. METHODS A cross-sectional survey of 103 drug-using women in Kuala Lumpur, Malaysia were recruited to assess their medical, psychiatric and social comorbidity as well as their engagement in nationally recommended HIV testing and monitoring activities. RESULTS One-third reported having ever injected drugs, with most (68.2%) having recently shared injection paraphernalia. Sex work (44.7%) and infrequent condom use (42.4%) were common as was underlying psychiatric illness and physical and sexual violence during childhood and adulthood. Most women (62.1%) had unstable living situations and suffered from an unmet need for social support and health services. HIV prevalence was high (20%) with only two thirds of women eligible for antiretroviral therapy having received it. Suboptimal HIV testing and/or monitoring was positively associated with interpersonal violence (AOR 2.73; 95% CI 1.04-7.14) and negatively associated with drug injection (AOR 0.28; 95% CI 0.10-0.77). CONCLUSIONS/IMPORTANCE Women who use drugs in Malaysia demonstrate considerable medical, psychiatric and social co-morbidity, which negatively contributes to optimal and crucial engagement in HIV treatment-as-prevention strategies. Mental health and social support may be key targets for future public health interventions aimed at drug-using women in Malaysia.

Gender Differences in HIV Risk Behaviors Among Persons Involved in the U.S. Criminal Justice System and Living with HIV or at Risk for HIV: A “Seek, Test, Treat, and Retain” Harmonization Consortium

The U.S. female criminal justice (CJ) population is rapidly growing, yet large-scale studies exploring gender-specific HIV risk behaviors in the CJ population are lacking. This analysis uses baseline data on adults with a CJ history from eight U.S. studies in an NIH-funded “Seek, Test, Treat, Retain” harmonization consortium. Data were collected using a standardized HIV risk behavior assessment tool and pooled across studies to describe participants’ characteristics and risk behaviors. Multilevel mixed-effects logistic regression models were used to test for gender-based behavior differences. Among 784 HIV-positive (21.4% female) and 5521 HIV-negative (8.5% female) participants, HIV-positive women had higher odds than HIV-positive men of engaging in condomless sexual intercourse (AOR 1.84 [1.16–2.95]) with potentially sero-discordant partners (AOR 2.40 [1.41–4.09]) and of sharing injection equipment (AOR 3.36 [1.31–8.63]). HIV risk reduction interventions targeting CJ-involved women with HIV are urgently needed as this population may represent an under-recognized potential source of HIV transmission.ResumenLa población femenina del Sistema de justicia penal (JP) de EEUU está creciendo rápidamente, sin embargo, hacen falta estudios de gran escala que exploren conductas de alto riesgo de VIH, género específicas, en la población de JP. Este análisis usa datos de referencia de adultos con historia de JP, extraídos de ocho estudios de EEUU parte de un consorcio de armonización de “Buscar, Evaluar, Tratar, Retener”, financiado por el Instituto Nacional de Salud. Usando una herramienta estandarizada de evaluación de conductas de riesgo en VIH, los datos recopilados de los estudios fueron combinados para describir las características de los participantes y las conductas de riesgo. Se usaron modelos de regresión logística multinivel de efectos mixtos para evaluar diferencias en las conductas según el género. De 784 participantes VIH positivo (21.4% mujeres) y 5521 VIH negativo (8.5% mujeres), las mujeres VIH positivas tuvieron mayor probabilidad que los hombres VIH positivos de tener relaciones sexuales sin condón (AOR 1.84 [1.16–2.95]), con parejas potencialmente serodiscordantes (AOR 2.40 [1.41–4.09]) y de compartir equipos de inyección (AOR 3.36 [1.31–8.63]). Se necesitan urgentemente intervenciones dirigidas a mujeres VIH positivas del sistema de JP para la reducción del riesgo de VIH, ya que esta población puede representar una fuente potencial y poco conocida de VIH.

All-cause mortality among people with HIV released from an integrated system of jails and prisons in Connecticut, USA, 2007–14: a retrospective observational cohort study

BACKGROUND People transitioning from prisons or jails have high mortality, but data are scarce for people with HIV and no studies have integrated data from both criminal justice and community settings. We aimed to assess all-cause mortality in people with HIV released from an integrated system of prisons and jails in Connecticut, USA. METHODS We linked pharmacy, custodial, death, case management, and HIV surveillance data from Connecticut Departments of Correction and Public Health to create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut between 2007 and 2014. We compared the mortality rate of adults with HIV released from incarceration with the general US and Connecticut populations, and modelled time-to-death from any cause after prison release with Cox proportional hazard models. FINDINGS We identified 1350 people with HIV who were released after 24 h or more of incarceration between 2007 and 2014, of whom 184 (14%) died after index release; median age was 45 years (IQR 39-50) and median follow-up was 5·2 years (IQR 3·0-6·7) after index release. The crude mortality rate for people with HIV released from incarceration was 2868 deaths per 100 000 person-years, and the standardised mortality ratio showed that mortality was higher for this cohort than the general US population (6·97, 95% CI 5·96-7·97) and population of Connecticut (8·47, 7·25-9·69). Primary cause of death was reported for 170 individuals; the most common causes were HIV/AIDS (78 [46%]), drug overdose (26 [15%]), liver disease (17 [10%]), cardiovascular disease (16 [9%]), and accidental injury or suicide (13 [8%]). Black race (adjusted hazard ratio [HR] 0·52, 95% CI 0·34-0·80), having health insurance (0·09, 0·05-0·17), being re-incarcerated at least once for 365 days or longer (0·41, 0·22-0·76), and having a high percentage of re-incarcerations in which antiretroviral therapy was prescribed (0·08, 0·03-0·21) were protective against mortality. Positive predictors of time-to-death were age (≥50 years; adjusted HR 3·65, 95% CI 1·21-11·08), lower CD4 count (200-499 cells per μL, 2·54, 1·50-4·31; <200 cells per μL, 3·44, 1·90-6·20), a high number of comorbidities (1·86, 95% CI 1·23-2·82), virological failure (2·76, 1·94-3·92), and unmonitored viral load (2·13, 1·09-4·18). INTERPRETATION To reduce mortality after release from incarceration in people with HIV, resources are needed to identify and treat HIV, in addition to medical comorbidities, psychiatric disorders, and substance use disorders, during and following incarceration. Policies that reduce incarceration and support integrated systems of care between prisons and communities could have a substantial effect on the survival of people with HIV. FUNDING US National Institutes of Health.

Risk behaviors and HIV care continuum outcomes among criminal justice-involved HIV-infected transgender women and cisgender men: Data from the Seek, Test, Treat, and Retain Harmonization Initiative

Background Transgender persons are highly victimized, marginalized, disproportionately experience incarceration, and have alarmingly increased rates of HIV infection compared to cis-gender persons. Few studies have examined the HIV care continuum outcomes among transgender women (TW), particularly TW who are involved with the criminal justice (CJ) system. Methods To improve our understanding of HIV care continuum outcomes and risk behaviors among HIV-infected TW who are involved with the CJ system, we analyzed data from the National Institute on Drug Abuse-supported Seek, Test, Treat, Retain (STTR) Data Harmonization Initiative. Baseline data were pooled and analyzed from three U.S. STTR studies to examine HIV risk and care continuum indicators among CJ-involved HIV-infected TW compared to cisgender men (CM), matched on age (within 5 years) and study at a ratio of 1:5. Results Eighty-eight TW and 440 CM were included in the study. Among matched participants, TW were more likely to report crack and cocaine use compared to CM (40%,16% respectively, p<0.001); both TW and CM reported high rates of condomless sex (58%, 64%, respectively); TW were more likely than CM to have more than one sexual partner (OR = 2.9, 95% CI: 1.6, 5.2; p<0.001) and have engaged in exchange sex (OR = 3.9, 95% CI: 2.3, 6.6; p<0.001). There were no significant differences between TW and CM in the percentage currently taking ART (52%, 49%, respectively), the mean percent adherence to ART (77% for both groups), and the proportion who achieved viral suppression (61%, 58%, respectively). Conclusions HIV-infected CJ-involved TW and CM had similar use of ART and viral suppression but TW were more likely than matched CM to engage in exchange sex, have multiple sexual partners, and use crack/cocaine. TW and CM had similarly high rates of condomless sex and use of other drugs. TW require tailored risk reduction interventions, however both CJ-involved TW and CM require focused attention to reduce HIV risk and improve HIV continuum of care outcomes.

Retention in HIV care during the 3 years following release from incarceration: A cohort study

Background Sustained retention in HIV care (RIC) and viral suppression (VS) are central to US national HIV prevention strategies, but have not been comprehensively assessed in criminal justice (CJ) populations with known health disparities. The purpose of this study is to identify predictors of RIC and VS following release from prison or jail. Methods and findings This is a retrospective cohort study of all adult people living with HIV (PLWH) incarcerated in Connecticut, US, during the period January 1, 2007, to December 31, 2011, and observed through December 31, 2014 (n = 1,094). Most cohort participants were unmarried (83.7%) men (77.0%) who were black or Hispanic (78.1%) and acquired HIV from injection drug use (72.6%). Prison-based pharmacy and custody databases were linked with community HIV surveillance monitoring and case management databases. Post-release RIC declined steadily over 3 years of follow-up (67.2% retained for year 1, 51.3% retained for years 1–2, and 42.5% retained for years 1–3). Compared with individuals who were not re-incarcerated, individuals who were re-incarcerated were more likely to meet RIC criteria (48% versus 34%; p < 0.001) but less likely to have VS (72% versus 81%; p = 0.048). Using multivariable logistic regression models (individual-level analysis for 1,001 individuals after excluding 93 deaths), both sustained RIC and VS at 3 years post-release were independently associated with older age (RIC: adjusted odds ratio [AOR] = 1.61, 95% CI = 1.22–2.12; VS: AOR = 1.37, 95% CI = 1.06–1.78), having health insurance (RIC: AOR = 2.15, 95% CI = 1.60–2.89; VS: AOR = 2.01, 95% CI = 1.53–2.64), and receiving an increased number of transitional case management visits. The same factors were significant when we assessed RIC and VS outcomes in each 6-month period using generalized estimating equations (for 1,094 individuals contributing 6,227 6-month periods prior to death or censoring). Additionally, receipt of antiretroviral therapy during incarceration (RIC: AOR = 1.33, 95% CI 1.07–1.65; VS: AOR = 1.91, 95% CI = 1.56–2.34), early linkage to care post-release (RIC: AOR = 2.64, 95% CI = 2.03–3.43; VS: AOR = 1.79; 95% CI = 1.45–2.21), and absolute time and proportion of follow-up time spent re-incarcerated were highly correlated with better treatment outcomes. Limited data were available on changes over time in injection drug use or other substance use disorders, psychiatric disorders, or housing status. Conclusions In a large cohort of CJ-involved PLWH with a 3-year post-release evaluation, RIC diminished significantly over time, but was associated with HIV care during incarceration, health insurance, case management services, and early linkage to care post-release. While re-incarceration and conditional release provide opportunities to engage in care, reducing recidivism and supporting community-based RIC efforts are key to improving longitudinal treatment outcomes among CJ-involved PLWH.