Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections affect millions of persons around the globe and cause profound morbidity and mortality. A major intersection exists between these two epidemics, with HCV infection being more common in persons with HIV than in the general population, largely due to shared routes of transmission. HCV co-infection increases risk for liver- and non-liver-related morbidity and mortality, making HCV treatment a priority in HIV co-infected persons, but the treatment of HCV in co-infected patients has been daunting for multiple reasons. Until recently, HCV treatment has frequently been deferred due to the low rates of cure, significant adverse effects, burdensome duration of therapy and drug-drug interactions with HIV antiretroviral medications. Untreated HCV has resulted in significant health consequences for the millions of those infected and has led to multiple downstream impacts on our healthcare systems around the world. The development of a remarkable number of new HCV direct-acting agents (DAAs) that are significantly more efficacious and tolerable than the previous interferon-based regimens has transformed this important field of medicine, with the potential to dramatically reduce the burden of infection and improve health outcomes in this population. This review will summarize the epidemiology and clinical impact of HIV/HCV co-infection and current approaches to the treatment of HCV in HIV/HCV co-infected patients.

Background

We implemented and evaluated a large health system-wide hepatitis C virus (HCV) screening and linkage to care program for persons born between 1945 and 1965 ("baby boomers").

Methods

An electronic health record (EHR) clinical decision support (CDS) tool for HCV screening for baby boomers was introduced in August 2015 for patients seen in the outpatient University of California, Los Angeles healthcare system setting. An HCV care coordinator was introduced in January 2016 to facilitate linkage to HCV care. We compared HCV testing in the year prior (August 2014-July 2015) to the year after (August 2015-July 2016) implementation of the CDS tool. Among patients with reactive HCV antibody testing, we compared outcomes related to the care cascade including HCV ribonucleic acid (RNA) testing, HCV RNA positivity, and linkage to HCV specialty care.

Results

During the study period, 19606 participants were screened for HCV antibody. Hepatitis C virus antibody screening increased 145% (from 5676 patients tested to 13930 tested) after introduction of the CDS intervention. Screening increased across all demographic groups including age, sex, and race/ethnicity, with the greatest increases among those in the older age groups. The addition of an HCV care coordinator increased follow-up HCV RNA testing for HCV antibody positive patients from 83% to 95%. Ninety-four percent of HCV RNA positive patients were linked to care postimplementation.

Conclusions

Introduction of an EHR CDS tool and care coordination markedly increased the number of baby boomers screened for HCV, rates of follow-up HCV RNA testing, and linkage to specialty HCV care for patients with chronic HCV infection.

Objectives

HIV-1-infected persons spontaneously controlling viremia without treatment (SCV) are rare. Sex and race effects on prevalence and outcome are poorly defined, and it is unclear whether SCV qualitatively or quantitatively differs from typical infection. These issues are examined in this article.

Design

Medical records of 46 524 persons receiving outpatient care for HIV-1 infection were reviewed. Of these, 29 811 had adequate viremia testing for SCV screening.

Methods

SCV was defined as at least three consecutive plasma viremia measurements <50 RNA copies/ml spanning at least 1 year without treatment. SCV loss was defined as at least three consecutive viremia measurements ≥50 RNA copies/ml or one ≥1000 RNA copies/ml. Demographics of persons with SCV were compared with the total population. Viremia and blood CD4 T-cell levels during SCV were compared between demographic subgroups and persons who maintained or lost SCV during observation.

Results

In total, 53 persons (0.18%) met SCV criteria. Prevalence was higher for women versus men and blacks versus whites; these appeared independent. Loss of SCV was observed at 1.22% per year, and significantly associated with viremia 'blips'. Blip magnitudes fit log-normal distributions with means below 50 RNA copies/ml.

Conclusion

Our novel observation of higher SCV prevalence in women and blacks is consistent with prior studies of typical chronic infection. Viremia blips correspond to greater risk of loss of SCV, likely reflecting higher set-point viremia under the limit of detection. Our findings suggest that SCV represents an extreme along a continuum of HIV-1 infection, and not qualitative difference.

Rates of aging-related comorbidities, which require targeted medications to treat, have been shown to be increased among persons living with HIV compared with uninfected counterparts. Polypharmacy is generally defined as the concurrent use of 5 or more medications. We investigated polypharmacy prevalence for non-HIV medications over a 12-year period among HIV-positive and -negative participants in the Multicenter AIDS Cohort Study. Information regarding non-HIV medication use, HIV status, age, race/ethnicity, enrollment period, and medication insurance was obtained on 3,160 participants from semiannual visits between 2004 and 2016. Polypharmacy was defined as taking 5 or more non-HIV medications since the last health care visit. Generalized estimating equation models with repeated measures were produced overall and by HIV status to examine polypharmacy. The unadjusted prevalence of polypharmacy across all study visits was 18.6% and was higher among HIV-positive participants (24.4%) compared with HIV-negative participants (11.6%) (P < .0001). Among the 50 years and older age group, HIV-positive and HIV-negative participants had increases in polypharmacy over the observation period, from 38.4% to 46.8% (P = .0081) and from 16.7% to 46.0% (P < .0001), respectively. Among participants younger than 50, polypharmacy among HIV-positive participants remained stable (18.9% in 2004 to 17.3% in 2016; P = .5374) but increased among HIV-negative men (5.6% to 20.4%; P < .0001). After adjusting for age, race/ethnicity, and medication insurance, HIV-positive participants had a higher prevalence of polypharmacy than HIV-negative participants (25.3% vs 18.7%; P < .0001). Older age, white race, and having medication insurance coverage were also associated with greater polypharmacy. A convergence of polypharmacy prevalence was observed between HIV-positive and -negative participants at the end of observation. HIV-positive status was associated with an increased likelihood of polypharmacy, after adjusting for age, race/ethnicity, enrollment period, medication insurance, and study visit. Over time, polypharmacy prevalence increased among all participants, with converging rates between HIV-positive and -negative participants by the end of the observation period.

Background

Successful hepatitis C virus (HCV) treatment may reduce cardiovascular disease (CVD) risk and improve levels of CVD biomarkers produced outside the liver (nonhepatic biomarkers).

Methods

Stored serum or plasma from before and 24 weeks after end of HCV treatment (EOT) from human immunodeficiency virus (HIV)/HCV-coinfected subjects who received up to 72 weeks of peginterferon/ribavirin, 27 with and 27 without sustained virologic response (SVR) matched by race, ethnicity and sex, were tested for nonhepatic (soluble intercellular adhesion molecule-1 [sICAM-1], soluble P-selectin [sP-selectin], interleukin [IL]-6, d-dimer, and lipoprotein-associated phospholipase A2 [Lp-PLA2]) and hepatic (cholesterol and high-sensitivity C-reactive protein) CVD and macrophage activation markers (soluble CD163 [sCD163] and soluble CD14). Changes in biomarkers and their association with SVR were examined by t tests or Wilcoxon tests and regression models.

Results

Of the 54 subjects, 30 were white, 24 were black, and 44 were male. Pretreatment levels of nonhepatic biomarkers were high: sICAM-1 overall median, 439.2 ng/mL (interquartile range [IQR], 365.6-592.8]; sP-selectin, 146.7 ng/mL (IQR, 94.1-209.9), and IL-6, 2.32 pg/mL (IQR, 1.61-3.49). Thirty-seven of 52 (71%) subjects had Lp-PLA2 >235 ng/mL. Sustained virologic response was associated with decrease in sICAM-1 (P = .033) and sCD163 (P = .042); this result was attenuated after controlling for changes in the alanine aminotransferase level. At 24 weeks after EOT, 17 (63%) SVRs had Lp-PLA2 >235 ng/mL vs 25 (93%) non-SVRs (P = .021).

Conclusions

Hepatitis C virus clearance may reduce hepatic and, subsequently, systemic inflammation and CVD risk in HIV/HCV coinfection.

Background and aim

Direct-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States.

Methods

The AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription.

Results

Of 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm³ (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m² (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA.

Conclusions

In addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today.

Polypharmacy is the concurrent use of five or more medications. We used group-based trajectory analysis to identify groups of non-HIV medication polypharmacy and investigate associated risk factors among HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study (MACS) from 2004 to 2016. Each participant was assigned to mutually exclusive groups based on their observed patterns of polypharmacy over time. Risk factors associated with membership with resulting groups were investigated using a multinomial generalized logit model with repeated measures. There were 3160 participants (54.3% HIV positive) included in the study. The overall prevalence of polypharmacy was 33.1% and was higher in HIV-positive than HIV-negative participants (36.2% vs. 30.0%; p < 0.001). Four distinct groups of polypharmacy emerged over time among all participants and among HIV-positive participants only: (1) nonpolypharmacy, (2) slow increasing polypharmacy, (3) rapid increasing polypharmacy, and (4) sustained polypharmacy. Being HIV positive, being 50 years of age or older, having medication insurance coverage, and having increased health care use were positively associated with membership in groups with sustained or increasing polypharmacy. Half of participants in each analysis had membership in one of the three high polypharmacy groups. This study revealed that access to care, through medication insurance coverage and health care use, was a key driver of polypharmacy in this cohort. Further exploration of medically appropriate and inappropriate prescribing practices in the context of polypharmacy and its impact on health outcomes in this and other populations is warranted.

We compared the Framingham risk score (FRS) for 10-year coronary heart disease (CHD) risk in age- and race-matched hepatitis C virus (HCV)-infected and HCV-uninfected persons: 114,073 HCV-infected (111,436 HCV-monoinfected and 2,637 HIV/HCV-coinfected) and 122,996 HCV-uninfected (121,380 HIV and HCV-uninfected and 1,616 HIV-monoinfected) males without cardiovascular disease, diabetes, or hepatitis B. In unadjusted analyses, FRS was similar between the HCV-infected and HCV-uninfected groups [median (interquartile range, IQR) risk points 13 (10-14) vs. 13 (10-14), p=0.192]. Cholesterol levels were lower and current smoking more prevalent in the HCV groups (both HCV and HIV/HCV) compared with the uninfected groups (p<0.001 for both). Prevalence of non-FRS CHD risk factors, such as substance abuse and chronic kidney disease, in the cohort was high, and differed by HCV and HIV status. Adjusting for age, race/ethnicity, body mass index, chronic kidney disease, drug and alcohol use, and HIV status, HCV infection was associated with minimally lower FRS (β=-0.095 risk points, p<0.001), suggesting a small but significant difference in 10-year CHD risk estimation in HCV-infected as compared to HCV-uninfected persons when measuring risk by FRS. Given the complex relationship between HCV, HIV, and CHD risk factors, some of which are not captured by the FRS, the FRS may underestimate CHD risk in HCV-monoinfected and HIV/HCV-coinfected persons. HCV- and HIV/HCV-specific risk scores may be needed to optimize CHD risk stratification.

Nonalcoholic fatty liver disease (NAFLD) affects 25% of adults in the general population and is a disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) to end-stage liver disease. NAFLD is an independent risk factor for cardiovascular disease, diabetes mellitus, and all-cause mortality, and NASH cirrhosis is a frequent indication for liver transplantation. In persons with human immunodeficiency virus (PWH), chronic liver disease is the second leading cause of non-human immunodeficiency virus-related mortality. Between 20% and 63% of PWH have NASH, and 14% to 63% have NASH with fibrosis. However, little is known about the optimal diagnostic strategies, risk factors for, and treatment of NAFLD in PWH. Here, we review current data on and identify knowledge gaps in the epidemiology, pathophysiology, diagnosis, and management of NAFLD in PWH and highlight priorities for research.