Network-based strategies to combat HCV: Examining social and spatial drivers of transmission among PWID in New Delhi.

People who inject drugs (PWID) account for some of the fastest-growing HCV epidemics globally. While individual risk factors for infection are understood, less is known about network and spatial factors critical for elimination strategies. Two thousand five hundred twelve PWID in New Delhi, India, were recruited (2017-19) through network referrals. Biometrics identified duplicates and cross-network linkages. Participants completed semi-annual surveys and blood tests for HCV antibodies and RNA. Poisson regression and network analyses identified predictors of incident HCV and compared network-based intervention approaches. Baseline HCV antibody prevalence was 65.1%, of whom 79.6% were HCV RNA-positive. We observed 92 HCV seroconversions over 382.25 person-years (incidence: 24.1 per 100 person-years). Of the 92 seroconverters, 67% (62) were directly connected to an RNA-positive participant, and all were within one degree of separation from an RNA-positive participant. Individual-level factors associated with seroconversion included age, sexual activity, and injection behaviours. After adjusting for individual-level factors, seroconversion was significantly associated with number of RNA-positive partners (adjusted incidence rate ratio [AIRR] = 1.30) and injecting at a particular venue (AIRR = 2.53). This association extended to indirect ties, with 17% reduced odds of seroconversion for each degree of separation from the venue (AIRR = 0.83). Network analyses comparing intervention strategies found that targeting venues identified more cases compared to a treat-a-friend approach. We observed a fast-growing HCV epidemic driven by viremia within individuals' immediate networks and indirect social and spatial ties, demonstrating the importance of achieving broad, sustained virologic response and rethinking network-based interventions to include venues.

Expanding single-venue services to better engage young people who inject drugs: insights from India.

BACKGROUND: Over the last decade, India has had an alarming rise in injection of opioids across several cities. Although scale-up of public sector services for people who inject drugs (PWID) in India has occurred over decades, accessibility has been diminished by fragmented services across physical locations. To circumvent this barrier, and in alignment with the World Health Organization's guidelines to provide comprehensive care to key populations, Integrated Care Centers (ICCs) were established across 8 Indian cities as a public-private service delivery model for providing free single-venue services to PWID. ICCs have been very successful in expanding service availability and convenience for PWID generally. However, few studies from low- and middle-income countries (LMIC) have evaluated how well young PWID (defined as those ≤ 29 years of age) engage with single-venue service models like ICCs or specific services provided in such models. Young PWID are an important subpopulation in India, as they bear a disproportionate burden of new HIV infections because of greater risk and evidence of lower receipt of HIV testing and harm reduction services compared to older PWID. In this comment, we offer insights specific to young PWID drawn from multiple quantitative and qualitative studies examining the reach and effectiveness of ICCs, which may provide generalizable insights into limitations of services for young PWID more broadly in India and globally. FINDINGS: Our studies suggest that while ICCs have expanded service availability, particularly in cities with emerging injection drug use epidemics, population-level reach to foster initial engagement among young PWID can be optimized. Additionally, young PWID who do engage with ICCs experience gaps in substance use treatment receipt and retention, and experience barriers to receipt of ICC services that are distinct from those experienced by older PWID. Notably, HIV incidence among ICC clients is concentrated in young PWID. Finally, ICCs were not intended to reach adolescent PWID, and new services are needed for this subpopulation. CONCLUSIONS: In addition to co-locating services, iterative optimization of models such as ICCs should incorporate youth-specific differentiated interventions and be accompanied by policy changes that are critical to improving the reach and effectiveness of harm reduction and HIV services among young PWID in India.

Effect of Adopting the New Race-Free 2021 Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate Creatinine Equation on Racial Differences in Kidney Disease Progression Among People With Human Immunodeficiency Virus: An Observational Study.

BACKGROUND: The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. METHODS: We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. RESULTS: With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], .73-.82), an equal risk of progressing from stage 2 to 3 (1.00; .92-.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60-3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. CONCLUSIONS: The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD.

Changes in HIV care continuum indicators among community-based samples of HIV-infected people who inject drugs and men who have sex with men across 21 cities in India.

Monitoring key populations' progress towards UNAIDS 90-90-90 targets is essential to achieving HIV/AIDS epidemic control. Using serial cross-sectional data, we evaluated changes in HIV care continuum among people who inject drugs(PWID) and men who have sex with men(MSM) in India. Cross-sectional baseline (2012/2013) and follow-up (2016/2017) samples were recruited using respondent-driven sampling across 21 cities. All participants were tested for HIV and RNA measured in HIV-positive participants. Linear regression was used to model temporal site-level changes in continuum indicators in MSM versus PWID. At baseline, we recruited 2,544 HIV-infected PWID and 1,086 HIV-infected MSM. At follow-up, we recruited 2,517 HIV-infected PWID and 1,763 HIV-infected MSM. At baseline, there were no significant differences in continuum indicators between MSM and PWID. At follow-up, compared to PWID, the proportion of MSM reaching each care continuum indicator-awareness of status, receipt of care, ART use, viral suppression-increased by 15-33 percentage points: 78% of MSM versus 49% of PWID were aware of their status (p < 0.01); 56% of MSM versus 32% of PWID were virologically suppressed (p = 0.05). MSM showed marked improvements across the care continuum, whereas PWID lagged and may require additional intervention. Differential improvement in HIV engagement may necessitate population-specific interventions and routine surveillance to facilitate HIV elimination.

Exploring multilevel determinants of co-occurring violence, HIV, mental health and substance use problems.

Multiple factors contribute to co-occurring issues such as violence, HIV, and mental disorders among people who inject drugs (PWID), particularly those residing in limited resource settings. Using an ecological framework, this study explored multilevel determinants of co-occurring violence, HIV, mental health, and substance use issues among PWID. Data were collected via semi-structured in-depth interviews with 31 men and women PWID in India. Findings revealed factors at the community (e.g., stigma), interpersonal (e.g., abusive partners), and individual (e.g., financial stress) levels. Findings highlight the need for prevention and intervention programs addressing factors at multiple ecological levels to reduce comorbidity among PWID.

Spatiotemporal Phylodynamics of Hepatitis C Among People Who Inject Drugs in India.

BACKGROUND AND AIMS: Implementing effective interventions for HCV requires a detailed understanding of local transmission dynamics and geospatial spread. Little is known about HCV phylodynamics, particularly among high-burden populations, such as people who inject drugs (PWID). APPROACH AND RESULTS: We used 483 HCV sequences and detailed individual-level data from PWID across four Indian cities. Bayesian phylogeographic analyses were used to evaluate transmission hotspots and geospatial diffusion of the virus. Phylogenetic cluster analysis was performed to infer epidemiologic links and factors associated with clustering. A total of 492 HIV sequences were used to draw comparisons within the same population and, in the case of coinfections, evaluate molecular evidence for shared transmission pathways. Overall, 139/483 (28.8%) of HCV sequences clustered with a median cluster size of 3 individuals. Genetically linked participants with HCV were significantly younger and more likely to be infected with HCV subtype 3b as well as to live and inject close to one another. Phylogenetic evidence suggests likely ongoing HCV infection/reinfection with limited support for shared HIV/HCV transmission pathways. Phylogeographic analyses trace historic HCV spread back to Northeastern India and show diffusion patterns consistent with drug trafficking routes. CONCLUSIONS: This study characterizes HCV phylodynamics among PWID in a low and middle-income country setting. Heterogeneity and recent genetic linkage of HCV across geographically disparate Indian states suggest that targeted interventions could help prevent reimportation of virus through drug trafficking routes.

Substance use is associated with condomless anal intercourse among men who have sex with men in India: a partner-level analysis.

BACKGROUND: Men who have sex with men (MSM) bear a disproportionately high burden of new HIV infections while lagging behind other populations with respect to engagement across the HIV care continuum. General risk factors for condomless anal intercourse (CAI) among MSM are well studied but there is a paucity of partner-level data, where emerging evidence suggests that much of the variation in condom use occurs. METHODS: MSM were recruited across 10 cities in India using respondent-driven sampling (RDS) from 2016-17. Among the individuals who reported sexual intercourse in the prior 6 months, condom use and partner characteristics of the last 4 partners were captured. Correlates of CAI at the individual and partner level were determined using Poisson regression models using generalized estimating equations and incorporating RDS-II weights, which weights estimates for the participant's network size. RESULTS: Among the 8,086 individuals, 21,723 sexual partnerships were analyzed. The prevalence of CAI was 46.9% and most partners were casual or one-time (70.7%) with partner HIV status reported as unknown in 42.6% of the sexual encounters. In multivariable analyses, partner-level characteristics associated with higher likelihood of CAI included unknown partner HIV status (aPR vs. known HIV negative partner: 1.34; 95% confidence interval (CI): 1.27-1.43) and use of alcohol/ drugs prior to intercourse either sometimes (aPR 1.42; 95% CI: 1.33-1.51) or always (aPR 1.31; 95% CI: 1.23-1.41). At an individual level, any HIV treatment literacy was associated with a lower likelihood of CAI (aPR 0.80; 95% CI: 0.74-0.86). CONCLUSIONS: To reduce HIV transmission among this population of MSM across India, combination interventions are likely needed. Interventions targeting substance use and education as well as initiatives to increase self-testing are urgently needed among MSM in India and have the potential to reduce HIV transmission in this high-risk population. Trial registration ClinicalTrials.gov Identifier: NCT01686750. Date of Registration: September 18, 2012.

Initiation of Antiretroviral Therapy in the Hospital Is Associated With Linkage to Human Immunodeficiency Virus (HIV) Care for Persons Living With HIV and Substance Use Disorder.

BACKGROUND: Studies have demonstrated benefits of antiretroviral therapy (ART) initiation on the day of human immunodeficiency virus (HIV) testing or at first clinical visit. The hospital setting is understudied for immediate ART initiation. METHODS: CTN0049, a linkage-to-care randomized clinical trial, enrolled 801 persons living with HIV (PLWH) and substance use disorder (SUD) from 11 hospitals across the United States. This secondary analysis examined factors related to initiating (including reinitiating) ART in the hospital and its association with linkage to HIV care, frequency of outpatient care visits, retention, and viral suppression. RESULTS: Of 801 participants, 124 (15%) initiated ART in the hospital, with more than two-thirds of these participants (80/124) initiating ART for the first time. Time to first HIV care visit among those who initiated ART in the hospital and those who did not was 29 and 54 days, respectively (P = .0145). Hospital initiation of ART was associated with increased frequency of HIV outpatient care visits at 6 and 12 months. There was no association with ART initiation in the hospital and retention and viral suppression over a 12-month period. Participants recruited in Southern hospitals were less likely to initiate ART in the hospital (P < .001). CONCLUSIONS: Previous research demonstrated benefits of immediate ART initiation, yet this approach is not widely implemented. Research findings suggest that starting ART in the hospital is beneficial for increasing linkage to HIV care and frequency of visits for PLWH and SUD. Implementation research should address barriers to early ART initiation in the hospital.

Syringe Coverage Among People Who Inject Drugs in West Virginia, USA.

Ensuring people who inject drugs (PWID) have ≥ 100% sterile syringe coverage (i.e., persons have access to a sterile syringe for all injections) is optimal for HIV prevention. Existing syringe coverage literature is informative, yet little work has examined syringe coverage among PWID in rural communities. Using data from a 2018 PWID population estimation study conducted in a rural county in West Virginia, we used logistic regression to identify correlates of adequate sterile syringe coverage (at least 100%). A minority (37%) of PWID reported having adequate syringe coverage. Factors inversely associated with adequate syringe coverage included having recently (past 6 months): engaged in transactional sex work, shared syringes, and injected fentanyl. Having exclusively acquired syringes from a syringe services program was associated with increased odds of adequate syringe coverage. Rural PWID may benefit from tailored interventions designed to increase sterile syringe access.

Psychosocial Barriers to Viral Suppression in a Community-based Sample of Human Immunodeficiency Virus-infected Men Who Have Sex With Men and People Who Inject Drugs in India.

BACKGROUND: Little is known about the impact of psychosocial factors and substance use on viral suppression among human immunodeficiency virus (HIV)-infected key populations in resource-limited settings. Accordingly, we examined the association and interactions between depression, alcohol use, and recreational drug use on viral suppression among men who have sex with men (MSM) and people who inject drugs (PWID) in India. METHODS: MSM and PWID were recruited across India using respondent-driven sampling (RDS). Correlates of viral suppression were determined using Poisson regression models incorporating RDS-II weights. Two-way multiplicative interactions were assessed with separate models of all combinations of the 3 variables of interest using interaction terms; 3-way interactions were evaluated by stratifying 2-way interactions by the third variable. RESULTS: Among 1454 treatment-eligible HIV-infected MSM and 1939 PWID, older age (adjusted prevalence ratio [aPR], 1.14 for MSM; 1.41 for PWID) and higher HIV treatment literacy (aPR, 1.58 for MSM; 3.04 for PWID) were positively associated with viral suppression. Among MSM, there was evidence of a synergistic negative association between severe depression and recreational drug use (aPR, 0.37 [95% confidence interval {CI}, .16-.84]), alcohol dependence and recreational drug use (aPR, 0.45 [95% CI, .20-.99]), and severe depression, alcohol dependence, and recreational drug use (aPR, 0.23 [95% CI, .09-.57]). Among PWID, daily injection (aPR, 0.51 [95% CI, .31-.82]) was the primary barrier to suppression. CONCLUSIONS: Incorporating psychosocial and harm-reduction services into differentiated care models targeting MSM and PWID in low-resource settings is critical to achieving the 90-90-90 HIV/AIDS targets.

Integrating HCV testing with HIV programs improves hepatitis C outcomes in people who inject drugs: A cluster-randomized trial.

BACKGROUND & AIMS: There have been calls to integrate HCV testing into existing services, including harm reduction and HIV prevention and treatment, but there are few empirical trials to date. We evaluated the impact of integrating HCV testing/education into integrated care centers (ICCs) delivering HIV services to people who inject drugs (PWID) across India, using a cluster-randomized trial. METHODS: We compared ICCs with usual care in the PWID stratum (12 sites) of a 22-site cluster-randomized trial. In 6 sites, ICCs delivering HIV testing, harm reduction, other preventive services and linkage to HIV treatment were scaled from opioid agonist therapy centers and operated for 2 years. On-site rapid HCV antibody testing was integrated after 1 year. To assess impact, we conducted baseline and evaluation surveys using respondent-driven sampling (RDS) across the 12 sites (n = 11,993 recruited at baseline; n = 11,721 recruited at evaluation). The primary outcome was population-level self-reported HCV testing history. RESULTS: At evaluation, HCV antibody prevalence ranged from 7.2-76.6%. Across 6 ICCs, 5,263 ICC clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were 4-fold more likely to report being tested for HCV than in usual care clusters, adjusting for baseline testing (adjusted prevalence ratio [aPR] 3.69; 95% CI 1.34-10.2). PWID in ICC clusters were also 7-fold more likely to be aware of their HCV status (aPR 7.11; 95% CI 1.14-44.3) and significantly more likely to initiate treatment (aPR 9.86; 95% CI 1.52-63.8). CONCLUSIONS: We provide among the first empirical data supporting the integration of HCV testing into HIV/harm reduction services. To achieve elimination targets, programs will need to scale-up such venues to deliver comprehensive HCV services. CLINICALTRIALS. GOV IDENTIFIER: NCT01686750. LAY SUMMARY: Delivering hepatitis C virus (HCV) testing to people who inject drugs (PWID) in places where they also have access to HIV prevention and treatment services is an effective way to improve uptake of HCV testing among communities of PWID. To achieve the World Health Organization's ambitious elimination targets, integrated programs will need to be scaled up to deliver comprehensive HCV services.

Barriers and Facilitators to PrEP Use Among People Who Inject Drugs in Rural Appalachia: A Qualitative Study.

The opioid crisis has increased risks for injection drug use-associated HIV outbreaks in rural communities throughout the United States. Existing research has examined pre-exposure prophylaxis (PrEP) utilization among people who inject drugs (PWID); however, no studies have been conducted to explore barriers and facilitators of PrEP use among rural PWID in Appalachia. We conducted qualitative interviews with PWID (n = 48) in two rural counties in West Virginia to explore barriers and facilitators of PrEP use. Among our participants, the majority (68.8%) had never heard of PrEP. Upon learning about PrEP, most participants expressed willingness to use it. Rural PWID described several factors that may impede PrEP utilization (e.g., housing instability, forgetting to take PrEP). Participants also identified practical strategies to support sustained PrEP utilization, such as integrating PrEP services into venues PWID access. This research provides important insights into the barriers and facilitators of PrEP utilization among rural PWID.

The North-South Divide: Substance Use Risk, Care Engagement, and Viral Suppression Among Hospitalized Human Immunodeficiency Virus-Infected Patients in 11 US Cities.

Regional variability in human immunodeficiency virus (HIV) care engagement remains underexplored. Multiple logistic models compared HIV outcomes for participants from 5 Southern (n = 557) and 6 non-Southern (n = 670) sites. Southern participants were less likely to experience viral suppression (adjusted odds ratio [aOR], 0.52; 95% confidence interval [CI], .37-.72) and had a higher likelihood of a CD4+ count <200 cells/µL (aOR, 1.53; 95% CI, 1.17-2.00). HIV intervention and social safety net programs should be expanded. Clinical Trials Registration: NCT01612169.

A systematic review of comprehensive interventions for substance abuse: Focus on victimization.

Violence victimization is common among men and women who use substances and is associated with co-occurring health issues such as PTSD, depression and HIV. Substance use interventions, therefore, should include integrated components that are designed to address co-occurring health issues among victimized substance-using individuals. This systematic review synthesized the evidence on efficacy of comprehensive, integrated, multicomponent interventions for victimized substance-using individuals. The efficacy of integrated multicomponent intervention strategies was assessed for the following syndemic conditions: mental health, substance misuse, violence, and HIV risk. Seventeen studies were identified. Examples of effective components were empowerment strategies for violence, mindfulness-based stress reduction for mental health, social cognitive skill building for addressing HIV risk and psychoeducation for substance misuse. Although in this review, some components were found to be effective, we identified methodological limitations of included studies which calls for more rigorous research in this area. Further, there is lack of evidence base for multicomponent interventions for victimized substance-using individuals in developing countries. Additional studies are needed to establish rigorous evidence base for multicomponent interventions for victimized substance using individuals that help them cope effectively with their trauma of violence and address their needs.

Psychosocial Factors Associated with Problem Drinking Among Substance Users with Poorly Controlled HIV Infection.

AIMS: We aimed to identify psychosocial factors related to problem drinking among patients with poorly controlled human immunodeficiency virus (HIV) infection. SHORT SUMMARY: We aimed to identify psychosocial factors related to problem drinking among those with poorly controlled HIV infection. Increased levels of interpersonal conflict were associated with greater severity of alcohol problems. Poorer mental health, medical mistrust and less satisfaction with one's physician related to excessive drinking. METHODS: This secondary analysis used baseline data from a large multisite randomized controlled trial of substance users whose HIV infection was currently poorly controlled, from 11 urban hospitals across the USA. Participants were HIV-infected adult inpatients (n = 801; 67% male, 75% African American) with substance use histories. Participants self-reported on their drinking, perceived health, mental health, social relationships and patient-provider relationship. Structural equation models examined psychosocial factors associated with problem drinking, controlling for demographic covariates. RESULTS: Increased levels of interpersonal conflict were associated with greater severity of alcohol problems. Poorer mental health, medical mistrust and less satisfaction with one's physician were associated with excessive drinking. CONCLUSIONS: Several psychosocial factors, including interpersonal conflict, poor mental health (i.e. anxiety, depression and somatization), medical mistrust and less satisfaction with one's provider, were associated with problem drinking among HIV-infected substance users with poorly controlled HIV infection. The co-occurrence of these concerns highlights the need for comprehensive services (including attention to problem drinking, social services, mental health and quality medical care) in this at-risk group.

Respondent-driven sampling for identification of HIV- and HCV-infected people who inject drugs and men who have sex with men in India: A cross-sectional, community-based analysis.

BACKGROUND: A major barrier to achieving ambitious targets for global control of HIV and hepatitis C virus (HCV) is low levels of awareness of infection among key populations such as men who have sex with men (MSM) and people who inject drugs (PWID). We explored the potential of a strategy routinely used for surveillance in these groups, respondent-driven sampling (RDS), to be used as an intervention to identify HIV- and HCV-infected PWID and MSM who are unaware of their status and those who are viremic across 26 Indian cities at various epidemic stages. METHODS AND FINDINGS: Data were collected as part of the baseline assessment of an ongoing cluster-randomized trial. RDS was used to accrue participants at 27 sites (15 PWID sites and 12 MSM sites) selected to reflect varying stages of the HIV epidemic among MSM and PWID in India. A total of 56 seeds recruited a sample of 26,447 persons (approximately 1,000 participants per site) between October 1, 2012, and December 19, 2013. Across MSM sites (n = 11,997), the median age was 25 years and the median number of lifetime male partners was 8. Across PWID sites (n = 14,450), 92.4% were male, the median age was 30 years, and 87.5% reported injection in the prior 6 months. RDS identified 4,051 HIV-infected persons, of whom 2,325 (57.4%) were unaware of their HIV infection and 2,816 (69.5%) were HIV viremic. It also identified 5,777 HCV-infected persons, of whom 5,337 (92.4%) were unaware that they were infected with HCV and 4,728 (81.8%) were viremic. In the overall sample (both MSM and PWID), the prevalence of HIV-infected persons who were unaware of their status increased with sampling depth, from 7.9% in participants recruited in waves 1 through 5 to 12.8% among those recruited in waves 26 and above (p-value for trend < 0.001). The overall detection rate of people unaware of their HIV infection was 0.5 persons per day, and the detection rate of HIV-infected persons with viremia (regardless of their awareness status) was 0.7 per day. The detection rate of HIV viremic individuals was positively associated with underlying HIV prevalence and the prevalence of HIV viremia (linear regression coefficient per 1-percentage-point increase in prevalence: 0.05 and 0.07, respectively). The median detection rate of PWID who were unaware of their HCV infection was 2.5 per day. The cost of identifying 1 unaware HIV-infected individual ranged from US$51 to US$2,072 across PWID sites and from US$189 to US$5,367 across MSM sites. The mean additional cost of identifying 1 unaware HCV-infected PWID was US$13 (site range: US$7-US$140). Limitations of the study include the exclusivity of study sites to India, lack of prior HIV/HCV diagnosis confirmation with clinic records, and lack of cost data from other case-finding approaches commonly used in India. CONCLUSIONS: In this study, RDS was able to rapidly identify at nominal cost a substantial number of unaware and viremic HIV-infected and HCV-infected individuals who were currently not being reached by existing programs and who were at high risk for transmission. Combining RDS (or other network-driven recruitment approaches) with strategies focused on linkage to care, particularly in high-burden settings, may be a viable option for achieving the 90-90-90 targets in key populations in resource-limited settings.

Association between hepatitis C virus and chronic kidney disease: heterogeneity begets heterogeneity.

Epidemiologic studies examining the association between hepatitis C virus and chronic kidney disease have yielded conflicting findings. Analyzing data from a Taiwanese cohort, Lai and colleagues report a novel finding that the odds of chronic kidney disease were nearly 3-fold higher in hepatitis C virus-infected persons with genotype 2 compared with genotype 1. Hepatitis C virus genotype distributions differ in regions around the world. Can genotypic differences in chronic kidney disease risk explain some of the heterogeneity in prior studies?

HIV, Cocaine Use, and Hepatitis C Virus: A Triad of Nontraditional Risk Factors for Subclinical Cardiovascular Disease.

OBJECTIVE: We assessed cross-sectional and longitudinal associations of 3 nontraditional cardiovascular disease risk factors-HIV, cocaine use, and chronic hepatitis C virus infection-with 3 validated markers of subclinical cardiovascular disease: carotid artery plaque, albuminuria, and aortic pulse wave velocity in a well-characterized cohort. APPROACH AND RESULTS: We measured carotid plaque at baseline and after 24 months, urine albumin/creatinine ratio every 6 months, and pulse wave velocity annually for up to 36 months in a predominantly black cohort of 292 participants (100 HIV negative and 192 HIV positive). Thirty-nine percent had chronic hepatitis C virus infection and 20%, 28%, and 52% were never, past, and current cocaine users, respectively. Sixteen percent, 47%, and 64% of those with none, 1 or 2, or all 3 nontraditional risk factors had ≥2 abnormal cardiovascular disease risk markers (P=0.001). In fully adjusted models that included all 3 nontraditional risk factors, HIV infection was independently associated with carotid plaque progression (increase in the number of anatomic segments with plaque), albuminuria (albumin-creatinine ratio >30 mg/g), albuminuria progression (doubling of albumin-creatinine ratio from baseline to a value >30 mg/g), and pulse wave velocity. Cocaine use was associated with an ≈3-fold higher odds of carotid plaque at baseline, and hepatitis C virus infection was significantly associated with a higher risk of carotid plaque progression. CONCLUSIONS: These results suggest that HIV infection, cocaine use, and hepatitis C virus infection are important nontraditional risk factors for cardiovascular disease and highlight the need to understand the distinct and overlapping mechanisms of the associations.

Rhabdomyolysis in an HIV cohort: epidemiology, causes and outcomes.

BACKGROUND: The Literature on rhabdomyolysis in the HIV-positive population is sparse and limited. We aimed to explore the incidence, patient characteristics, etiologies and outcomes of rhabdomyolysis in a cohort of HIV-positive patients identified through the Johns Hopkins HIV clinical registry between June 1992 and April 2014. METHODS: A retrospective analysis of 362 HIV-positive patients with non-cardiac CK elevation ≥1000 IU/L was performed. Both inpatients and outpatients were included. Incidence rate and potential etiologies for rhabdomyolysis were ascertained. The development of acute kidney injury (AKI, defined as doubling of serum creatinine), need for dialysis, and death in the setting of rhabdomyolysis were determined. Logistic regression was used to evaluate the association of peak CK level with the development of AKI. RESULTS: Three hundred sixty two cases of rhabdomyolysis were identified in a cohort of 7079 patients with a 38,382 person years follow-up time. The incidence rate was nine cases per 1000 person-years (95% CI: 8.5-10.5). Infection was the most common etiology followed by compression injury and drug/alcohol use. One-third of cases had multiple potential etiologies. AKI developed in 46% of cases; 20% of which required dialysis. Thirteen percent died during follow-up. After adjustment, AKI was associated with higher CK (OR 2.05 for each 1-log increase in CK [95% CI: 1.40-2.99]), infection (OR 5.48 [95% CI 2.65-11.31]) and higher HIV viral load (OR 1.22 per 1-log increase [95% CI: 1.03-1.45]). CONCLUSION: Rhabdomyolysis in the HIV-positive population has many possible causes and is frequently multifactorial. HIV-positive individuals with rhabdomyolysis have a high risk of AKI and mortality.