Coinfection

ICAAC 2015: Comorbidities and Mortality Among HIV-Positive and HIV/HCV Coinfected People

alt

While illness and death due to opportunistic illnesses has declined, people living with HIV remain prone to comorbidities that contribute to hospitalization and reduced survival, according to presentations at the 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) last weekin San Diego. Mortality is higher among HIV-positive people coinfected with hepatitis C virus (HCV), and is associated with liver fibrosis progression, offering further evidence supporting prompt hepatitis C treatment.

People with HIV/HCV coinfection experience more rapid liver disease progression, on average, than HIV-negative people with hepatitis C. As effective antiretroviral therapy (ART) has dramatically reduced the risk of AIDS-related conditions, liver disease has become a leading cause of illness and death for people with HIV.

Vladimir Berthaud from Meharry Medical College in Nashville and colleagues looked at factors predicting survival among people with HIV at a clinic in Tennessee.

The researchers analyzed medical records of 745 patients seen at the clinic from 2004 through 2014. About two-thirds were men, most (80%) were African American, 16% had a history of injection drug use, and 14% were homeless. Overall, 24% had HIV/HCV coinfection, but the rate rose to 54% among patients who died, according to the study abstract.

Just over three-quarters of participants were retained in care, 76% were prescribed ART, and 64% achieved undetectable HIV viral load. Hepatitis C treatment was less common: about a quarter of coinfected people received interferon-based therapy, with a cure rate of 68%.

Shorter survival was associated with HIV/HCV coinfection, fewer clinic visits, last viral load measurement >75 copies/mL, CD4 count <200 cells/mm3, and older age. The researchers concluded that HCV coinfection plays a major role in survival of people with HIV -- even more so than detectable HIV viral load.

"In the context of HIV plasma viral load suppression, scale-up of hepatitis C treatment will further reduce mortality among medically underserved minority communities disproportionately impacted by HIV/HCV coinfection in the Deep South," they concluded.

In a related study from Spain, researchers from University Hospital of La Coruña conducted a retrospective cohort analysis looking at trends in hospitalization of people with HIV/AIDS in northwestern Spain between 1993 -- before the advent of effective combination ART -- and 2013.

The analysis included 1937 people who together had 6917 hospital admissions. Three-quarters were men, the mean age was 36 years, and 37% had HCV coinfection. The median hospital stay was 8 days and 20% were readmitted within 30 days after discharge.

The researchers found that while overall in-hospital mortality did not change much among HIV-positive people hospitalized during 1993-2002 compared with 2003-2013 -- 6.8% vs 6.3%, respectively -- the reasons for hospitalization and causes of death shifted. A higher proportion of deaths were due to non-AIDS-defining conditions in the latter period.

Significant fewer patients were hospitalized due to infectious diseases (49.1% vs 35.3%) and psychiatric conditions (9.1% vs 5.2%), while more were admitted due to malignancies (3.6% vs 7.8%), cardiovascular disease (1.2% vs 3.7%), gastrointestinal conditions (9.2% vs 16.1%), and chronic respiratory disease (5.6% vs 10.9%).

HIV/HCV coinfected people had more hospitalizations (3 vs 2 on average) and a higher readmission rate (21.5% vs 19.1%) than those with HIV alone. Hospitalization rates declined substantially after the introduction of effective ART in 1996 (4.9% per year), but the decrease was less pronounced for coinfected patients (1.7% per year), leading the researchers to conclude that the impact of HCV coinfection is increasing in terms of hospitalizations, readmissions, and mortality.

Liver Fibrosis and Mortality

In another study, Paola Nasta of Spedali Civili in Brescia, Italy, and colleagues looked at the association between liver fibrosis and mortality among HIV/HCV coinfected patients on ART.

This analysis included 3338 coinfected participants in the Italian MASTER cohort. Fibrosis was estimated using the FIB-4 score, a biomarker index based on patient age, platelet count, and ALT and AST liver enzyme levels. People with hepatitis B triple infection or severe liver enzyme abnormalities at baseline were excluded.

A total of 291 participants (8.7%) died during the course of more than 45,000 patients-years of follow-up. Death rates rose with increasing fibrosis severity. About 40% of people who died had FIB-4 scores suggesting advanced fibrosis, compared with 16% of those who survived. People with high FIB-4 score were not only more likely to die from liver-related causes, as expected, but were also more likely to die due to any cause.

People with a FIB-4 score above 3.25 (indicating advanced fibrosis) had a 2-fold higher risk of all-cause death, while those with scores below 1.44 (indicating absent or mild fibrosis) reduced their risk of death by about half. Having clinical AIDS at baseline was also an independent risk factor for all-cause death, while HCV clearance was associated with reduced mortality.

Based on these findings, the researchers concluded that advanced fibrosis is independently associated with all-cause and liver-related mortality in HIV/HCV coinfected people, and that FIB-4 can help determine if liver disease is progressing and when hepatitis C treatment is needed.

Other Comorbidities

Turning at other types of comorbidities in people with HIV, Joel Gallant fromSouthwest CARE Center in Santa Fe,Nicole Meyer from Truven Health Analytics, and colleagues assessed trends in comorbidities using longitudinal medical records including Medicare, Medicaid, and commercial databases. They looked at outcomes among 18,944 patients in 2003 and 20,355 in 2013. About two-thirds were men and the median age was in the mid-40s.

They observed rising rates of several comorbidities and events from 2003 to 2013, including hypertension (15.7% vs 32.2%), diabetes (8.3% vs 12.7%), elevated blood lipids (7.7% vs 24.3%), kidney impairment (4.4% vs 7.0%), and cardiovascular disease (2.9% vs 4.3%).

Gallant suggested that in addition to the increasing age of the population, long-term effects of antiretroviral drug exposure may also be contributing to increased comorbidities.

Researchers from the Upstate NY Veterans’ Healthcare Administration and the University of New Mexico identified another way HIV treatment and comorbidity are related: drug-drug interactions between antiretroviral agents and medications for other conditions.

The researchers looked at medical records for 1329 veterans on standard ART regimens at these centers between 2000 and 2013. Patients had a median of 5 comorbidities and approximately 20% were taking 6 or more non-HIV medications.

They found that 9.6% were taking medications that were contraindicated due to potential drug interactions. This was more common with HIV protease inhibitors (16.1%) -- which have a greater propensity for interactions due to the way they're processed in the liver -- than with NNRTIs (5.6%) or integrase inhibitors (8.0%). Patients using the pharmacoenhancing or boosting agents ritonavir and cobicistat had more interactions. People who used contraindicated combinations had a higher likelihood of hospitalization than those who did not (25.0% vs 15.2%), as did those with multiple comorbidities.

Taken together, these study findings indicate that comorbidities are a growing concern as HIV-positive reach older ages, and that understanding and managing these conditions is important for improving the quality of life and survival of people living with HIV.

10/1/15

References

V Berthaud. Survival Analysis of Patients Co-Infected with HIV and Hepatitis C in a Medically Underserved Minority Community of the Deep South: A Retrospective 10-Year Cross-Sectional Study. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, September 17-21, 2015. Abstract H-1216, 2015.

HM Míguez, Á Mena de Cea, I Rodríguez Osorio, et al. Trends in Hospitalizations, Readmissions and In-Hospital Mortality in HIV Infected Patients Between 1993-2013. Impact of Hepatitis C Coinfection. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, September 17-21, 2015.

P Nasta, M Giralda, A Spinetti, et al. Assessing Mortality in Patients with Hepatitis C virus and HIV, Using Indirect Markers of Fibrosis (MASTER Cohort). 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, September 17-21, 2015. Abstract H-1217.

N Meyer, JE Gallant, P Hsue, et al. Comorbidities of Patients with Human Immunodeficiency Virus (HIV) in the USA - a Longitudinal Analysis of Prevalent HIV Patients Over 11 Years. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, September 17-21, 2015.

B Jakeman, M Nasiri, L Ruth, et al. Relationship Between Type of ART, Drug-Drug Interactions, and Hospitalizations. 55th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). San Diego, September 17-21, 2015. Abstract H-780.