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Hepatitis C cure does not slow kidney decline in people with Hep C and HIV.

Being cured of hepatitis C virus (HCV) infection through anti-HCV drug therapy did not slow falling kidney function in people infected with both HCV and HIV. (1) Among people whose HCV got cured, those who recently injected cocaine had a faster drop in kidney function than those who did not use drugs like cocaine or opioids.

As people with HIV live longer, they often acquire the age-related non-HIV illnesses seen in everyone who lives into their 50s, 60s, and beyond. As the first study in this issue found, 2 or more non-HIV age-related illnesses often affect the same person. (2) And the rate of these combined illnesses is growing in people with HIV, (2) who often have more risk factors for these conditions than people without HIV.

HIV and HCV infection often occur in the same person because they share the same infection routes--sharing drug-injecting equipment and having sex. Chronic kidney disease also often affects people with HIV. Several factors may contribute to high rates of chronic kidney disease in people with HIV, and one of those factors is HCV infection. (3-5) Kidneys play many important roles in maintaining health, including removing waste products and drugs, helping control blood pressure, producing vitamin D, and controlling production of red blood cells.

Over the past few years, new anti-HCV drugs greatly improved treatment of HCV infection. Various combinations of these drugs now cure more than 90% of people with HCV, including those who also have HIV infection. Curing HCV infection lowers the risk of death with liver disease because HCV mainly affects the liver (Figure 1). But little is known about whether curing HCV infection improves kidney function in people with HIV. Researchers working in Canada conducted this study to learn more about how curing HCV infection affects kidney function in people with HIV.

How the study worked. Study participants came from the Canadian Co-Infection Cohort (CCC),an ongoing analysis of people with HIV and HCV seen at 18 clinics across Canada. (6) People in the CCC complete a questionnaire every 6 months. Also twice a year, health professionals collect key health data on CCC members. This analysis included people who entered the CCC between January 2003 and December 2016.

Researchers selected people with chronic HCV infection who were cured by anti-HCV drug therapy. They defined cure as undetectable HCV in blood with a standard HCV test at least 12 weeks after a person finished anti-HCV therapy. For each person cured of HCV infection, the researchers picked 2 people with chronic HCV infection who were not cured. When matching cure and noncure study participants, the investigators used a technique that attempts to create similar groups of participants even though the cure participants got treated and the noncure participants could have been treated but were not. (7)

The research team determined kidney function by measuring estimated glomerular filtration rate (eGFR), * a standard way to assess kidney function. The main aim of the study was to compare yearly change in eGFR in cure participants and noncure participants. The method used to make this comparison accounted for the potential impact of several factors that can affect eGFR. In this way the researchers could be more confident that cure alone--apart from other factors--did or did not explain any cure-versus-noncure difference in eGFR over time.

Finally, the researchers identified participants who used injected or noninjected drugs. Then they used an accepted statistical method to assess the impact of cocaine, crack, or opioid use on yearly change in eGFR. Again this method simultaneously considered several factors that may affect eGFR to determine whether drug use alone explained changes in eGFR.

What the study found. The study included 384 participants cured of HCV infection with anti-HCV drugs and 768 participants not treated and not cured. As planned, the cure and noncure groups matched closely in most ways, including median (midpoint) age (51 years in both groups), proportion of women (21% cured and 22% not cured), median CD4 count (530 cells/[mm.sup.3] in both groups), proportion with a detectable HIV viral load (10% cured and 9% not cured), and median length of HCV infection (21 years in both groups).

Median initial eGFR (indicating kidney function) was the same in the cure and noncure groups, 91 mL/ min. Normal eGFR ranges from 90 to 120 mL/min. Through 1.5 years of observation, the yearly drop in kidney function was similar in the cure group and the noncure group (-1.32 and -1.19 mL/min per year). Even after the researchers made statistical adjustments for the small differences between the two groups, yearly decline in kidney function did not differ much between groups.

Among the 384 people cured of HCV infection, small proportions reported recent use of injected cocaine (11%), injected opioids (12%), noninjection crack/ cocaine (16%), and noninjection opioids (15%). Compared with cure participants who used none of these drugs, people who injected cocaine had a faster yearly drop in kidney function (-2.16 versus -0.67 mL/min per year). When the researchers projected these drops in kidney function over 5 years in cured participants, they determined that eGFR (kidney function) would be 76 mL/min in injection cocaine users versus 86 mL/min in people who used no street drugs.

What the findings mean for you. Highly effective anti-HCV drugs now cure HCV infection in more than 90% of treated people, including people with HIV. As a result, successfully treated people with HCV are avoiding liver cirrhosis (scarring) and liver cancer and thus living longer, healthier lives. People infected with both HCV and HIV infection are also enjoying these benefits. (8)

But while curing HCV protects the liver and guards against liver-related death, this study found that curing HCV does not quickly protect the kidneys from declining function in people with HCV and HIV (Figure 1). (1) Comparing treated people cured of HCV infection with people not treated and not cured showed similar rates of falling kidney function over the 1.5-year study period. Therefore successful HCV treatment may not lower the rate of new kidney disease in people with HCV and HIV.

This finding is important for two main reasons: (1) People with HCV and people with HIV run an increased risk of kidney disease. When a person has both HCV and HIV infection, risk of kidney complications may be even higher. (2) Because curing HCV does not slow declining kidney function in people with HIV, these people must be aware of kidney disease risk factors and take steps to prevent or control kidney disease.

The study produced another important finding: Kidney function fell faster in people cured of HCV who injected cocaine than in people who did not use cocaine, crack, or opioids. This finding underlines the importance of avoiding improper drug use, which can damage the kidneys and other vital organs and systems.

The Centers for Disease Control and Prevention (CDC) (9) and the National Kidney Foundation (10) list common risk factors for chronic kidney disease (Table 1). Several of these factors can be prevented or controlled. Others (like age and race) can't be controlled, but they're important to know so you can figure out your overall kidney disease risk. The CDC stresses that preventing or managing kidney disease risk factors is the best way to prevent or delay chronic kidney disease (Table 2).

REFERENCES

(1.) Rossi C, Saeed S, Cox J, et al; Canadian Co-Infection Cohort Investigators. Hepatitis C virus cure does not impact kidney function decline in HIV co-infected patients. AIDS. 2018;32:751-759.

(2.) Wong C, Gange SJ, Moore RD, et al. Multimorbidity among persons living with human immunodeficiency virus in the United States. Clin Infect Dis. 2018;66:1230-1238.

(3.) Peters L, Grint D, Lundgren JD, et al. Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients. AIDS. 2012;26:1917-1926.

(4.) Jotwani V, Li Y, Grunfeld C, Choi AI, Shlipak MG. Risk factors for ESRD in HIV-infected individuals: traditional and HIV-related factors. Am J Kidney Dis. 2012;59:628-635.

(5.) Rossi C, Raboud J, Walmsley S, et al; Canadian Observational Cohort (CANOC) Collaboration. Hepatitis C co- infection is associated with an increased risk of incident chronic kidney disease in HIV-infected patients initiating combination antiretroviral therapy. BMC Infect Dis. 2017;17:246

(6.) Klein MB, Rollet KC, Saeed S, et al. HIV and hepatitis C virus coinfection in Canada: challenges and opportunities for reducing preventable morbidity and mortality. HIV Med. 2013;14:10-20.

(7.) Statistics how to. What is a propensity score? http://www.statisticshowto.com/propensity-score-matching/

(8.) Klein MB, Rockstroh JK, Wittkop L. Effect of coinfection with hepatitis C virus on survival of individuals with HIV-1 infection. Curr Opin HIV AIDS. 2016;11:521-526.

(9.) Centers for Disease Control and Prevention (CDC). Chronic kidney disease. https://www.cdc.gov/dotw/ckd/

(10.) National Kidney Foundation. About chronic kidney disease. https://www.kidney.org/atoz/content/about-chronic- kidney-disease

* Words in boldface are explained in the Technical Word List at the end of this issue.

Caption: Figure 1. Curing HCV infection with anti-HCV drugs spares the liver (top) from further damage by HCV and so promotes better health and longer life. But in this study of 1152 people with HIV and HCV, curing HCV infection did not slow declining function of the kidneys (below). (Illustrations from Servier PowerPoint Image Bank, http:// smart.servier.com/).
Table 1. Controllable and noncontrollable risk factors for
chronic kidney disease

Controllable risk factors              Noncontrollable risk
                                           factors

* Obesity                              * Family history of kidney
                                        disease or failure
* Diabetes                             * Older age
                                       * Being African American,
* High blood pressure (hypertension)   Hispanic, American Indian,
* Heart disease                        or Pacific Islander

Sources: Centers for Disease Control and Prevention (CDC) (9) and
the National Kidney Foundation. (10)

Table 2. Steps to prevent of delay chronic kidney disease
from the CDC

The best way to prevent or delay chronic kidney
disease is to prevent, treat, and manage its risk
factors, such as diabetes and high blood pressure:

** Monitor your A1C, * blood pressure, and
cholesterol levels to keep your kidneys healthy.

** Manage your blood sugar, blood pressure, and
cholesterol by:

--Eating more fruits and vegetables.

--Staying physically active.

--Taking your medications as directed.

--Getting regular checkups.

** If you have diabetes, have an A1C test at least
twice a year. An A1C test measures the average
level of blood sugar over the past 3 months.

** Talk to your provider about medicines and other
ways to manage your A1C, blood pressure, and
cholesterol.

* A1C, also called HbA1C, is a simple blood test that
measures average blood sugar over the past 3 months.

Source: Centers for Disease Control and Prevention (CDC). (9)
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Title Annotation:ARTICLE 12
Publication:HIV Treatment: ALERTS!
Date:Dec 1, 2018
Words:1768
Previous Article:Drug use with sex tied to condom-free sex, HCV, and STIs in gay men with HIV.
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