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HIV-positive people with HCV have worse response to first antiretroviral combination.

HIV-positive people who also had hepatitis C virus (HCV) infection had a worse response to their first an-tiretrovlral

* combination than HIV-positive people without HCV, according to results of a 3041-person study.' The group infected with both HCV and HIV had a worse viral load response to antiretrovirals, a worse CD4 count response, and a doubled risk of AIDS or death. The researchers who conducted the study believe their findings support an earlier start to antiretroviral therapy in people also infected with HCV.

Almost one third of HIV-positive people in the United States also have HCV infection. These two viruses often infect the same people because they are both carried in blood and thus can pass between people who share drug-injecting equipment or who have sex together. HCV infects the liver and can cause serious liver damage and death if left untreated (Figure 1). But drug therapy can cure HCV infection, and anti-HCV drugs that became available in the past few years have made cures more common.

People who study HIV and HCV agree that HIV can worsen HCV infection."

But researchers still disagree on how HCV affects the course of HIV infection. Studies on how HCV affects HIV infection have reached conflicting conclusions, possibly because many of these studies were small, involved differing groups of people with HIV and HCV, and assessed different antiretroviral combinations, many of which are no longer used today.

To get an up-to-date look at how HCV affects people with HIV infection, AIDS Clinical Trials Group researchers combined the results of four studies of antiretroviral therapy. They compared the impact of antiretroviral treatment in people infected only with HIV and in those infected with both HIV and HCV. * How the study worked. The AIDS Clinical Trials Group (ACTG) studies HIV infection and its complications, often comparing leading antiretroviral combinations. For this analysis of how HCV affects response to antiretroviral therapy, an ACTG team combined findings from four clinical trials.6-'2 All of these trials studied key antiretrovirals, most of which are still widely used today. All trials accepted people with HCV infection and tested people for HCV when they entered the trial.

Trial participants returned regularly to the study clin-ic--usually every 12 weeks--for measurement of HIV viral load, CD4 count, and other medical data typically collected in trials of this kind. Every 24 weeks, study participants reported whether they took all their antiretroviral doses in the previous 7 days.

This new analysis focused on three racial/ethnic groups: black non-Hispanics, white non-Hispanics, and Hispanics. By comparing HIV-plus-HCV-positive people with HIV-only trial participants, the researchers aimed to learn how HCV affected four results:

1. Virologic failure, defined as two consecutive viral loads of (1) at least 1000 copies at or after study week 16 and before week 24, or (2) at least 200 copies at or after week 24

2. Change in C1)4 count and CD4 percent

3. Time to a new AIDS illness or death, or time to death alone

4. Time to first serious (grade 3 or 4) signs or symptoms or laboratory abnormalities

The researchers used accepted statistical methods to determine how HCV affected response to antiretrovirals measured by these four results. By simultaneously considering several factors that can affect these results, this type of analysis can pinpoint individual factors that affect results regardless of whatever other risk factors a person has.

* What the study found. This analysis involved 3041 people, including 1197 whites (39%), 1117 blacks (37%), and 727 Hispanics (24%). Most study participants (81%) were men. Of these 3041 people with HIV, 279 (9%) also had HCV infection. Compared with HIV-only people, those with HIV and HCV were older (median 44 versus 37), more likely to be black (47% versus 36%), and more likely to inject drugs currently or in the past (52% versus 5%). Depending on the measure used, 10% to 13% of HIV/HCV-infected people had signals of severe liver scarring called fibrosis (Figure 1).

Compared with people infected only with HIV, those infected with HIV plus HCV had a significantly shorter time to treatment failure after starting antiretroviral therapy. The estimated time when 20% of people in each group had virologic failure (defined at number 1 in the preceding section) was 112 weeks in people infected only with HIV, compared with only 48 weeks in people with HIV and HCV. Statistical analysis that weighed the impact of many treatment failure risk factors determined that people with HIV and HCV had a 43% higher risk of failure than people with only HIV (Figure 2). The worse viral load response in people with HIV plus HCV did not differ according to which antiretroviral combination people took.

Antiretroviral treatment outcomes in people with HCV infection

Virologic failure       1.43
AIDS or alone           2.11
Death alone             5.14
Serious safety concern  1.51

Figure 2. Compared with people in-fected only with HIV, those
infectrd with HCV plus HIV had higher rates of vi-rologic failure
(detectable viral load), AIDSor death, death alone, orserious
safety concerns  in a3041-person study. (For providers: 95%
cinfidence intervals around thesepoint estimates were 1.07-1.91
for AIDS or death, 2.48-10.67for death alone, and 1.26-1.81 for
death alone, and 1.26-1.81 for safety safety concerns).

Table made from bar graph.

People with HIV and HCV gained fewer CD4 cells after starting antiretrovirals in these four trials than did people infected only with HIV. After 48 weeks, CD4 counts were an average 32.8 cells lower in the HIV-plus-HCV group than in the HIV-only group. At that point the average CD4 gain in people with HIV and HCV was 27.8 cells smaller than the average gain of people infected only with HIV. The lower CD4-cell gain in the HIV-plus-HCV group persisted through 144 weeks of antiretroviral therapy. And the worse CD4-cell response in people with HIV plus HCV held true when the researchers limited the analysis to people in whom antiretrovirals were not failing to control viral load. Finally, the lower CD4 gains in people with HIV plus HCV did not differ according to which antiretroviral combination people took.

During the study period, 11% of people with HIV plus HCV had a new AIDS disease or died, compared with 5% of people with HIV alone. Statistical analysis that considered several factors that may affect chances of death or development of an AIDS illness determined that people with HIV plus HCV had a doubled risk of AIDS or death compared with the HIV-only group (Figure 2). The same kind of analysis figured that people with HIV plus HCV had a 5 times higher risk of death alone (Figure 2). Among people who died, death could be attributed to accidents, suicides, or substance abuse in 41.2% of the HIV-plus-HCV group versus 20.69 of the HIV-only group.

A higher proportion of people with HIV plus HCV than with HIV alone had a serious (grade 3 or 4) safety concern (65% versus 53%). Most of this difference could be explained by a higher rate of liver enzyme elevation, a signal of poor liver function, in the HIV-plus-HCV group (14% versus 3%). Statistical analysis considering multiple factors that may affect serious safety concerns determined that people with HIV and HCV had a 51% higher risk of such concerns than people with HIV alone (Figure 2).

After 24 weeks of antiretroviral therapy, people infected with both HIV and HCV reported 100% antiretroviral pill-taking more often than people infected only with HIV. At that point the HIV-plus-HCV group had a 73% higher chance of perfect pill-taking. After 48, 72, and 96 weeks of antiretroviral therapy, rates of perfect pill-taking were similar in people with HIV plus HCV and in those with HIV alone.

* What the results mean for you. This large and well-planned analysis of HIV-positive people with and without HCV infection in four antiretroviral treatment trials made several important findings. Compared with people infected only with HIV, those infected with HIV plus HCV before starting their first antiretroviral combination had:

  A faster time to antiretroviral treatment failure measured
  by viralload response A lower increase in CD4 count and CD4

  A higherrisk of a new AIDS illness or death A higher risk
  of death alone

The researchers who conducted this study suggest these results support starting antiretroviral therapy earlier in HIV-positive people who also have HCV infection. Earlier treatment might help people with HIV plus HCV reach and maintain an undetectable viral load, gain more CD4 cells, and avoid new AIDS illnesses and death. Antiretroviral experts working with the US Department of Health and Human Services recommend early antiretroviral therapy for people also infected with HCV or hepatitis B virus, including people who have high CD4 counts or cirrhosis (liver scarring)."

The worse antiretroviral treatment outcomes in people with HCV also suggest that HIV clinicians should check viral loads, CD4 counts, and possible safety concerns very closely in such people to catch the earliest hints of trouble.

Another important finding of this study is that people with HIV plus HCV took their antiretrovirals on time more than people infected only with HIV through the first 24 weeks of treatment. After that, the HIV-plus-HCV group and the HIV-only group did not differ in how faithfully they took their antiretrovirals through 96 weeks of observation. The researchers who conducted this study observe that people who had injected drugs before entering the original four trials may have been evaluated very closely by trial physicians to exclude people with bad pill-taking habits. As a result, HCV-positive former drug injectors who entered these trials may have been a select group with particularly good pill-taking habits.

But even if that's true, the good pill-taking by HIV-plus-HCV people in this study demonstrates that such people--including people who have injected drugs--can take their antiretroviral doses on time. Taking your antiretrovirals exactly as your HIV provider directs is critical to achieving the best possible response to antiretroviral therapy, whether you have HCV or not.

Finally, the ACTG team that ran this study points out that treatment for HCV infection in changing rapidly right now. New, stronger, easier-to-take anti-HCV drugs are becoming available, and they are improving results of anti-HCV therapy. Improved responses to anti-HCV drugs could have a big impact on how HCV infection affects the response to antiretroviral therapy in people with HIV.

*Words in bold are defined in the Technical Word List at the end of this issue of HIV Treatment Alerts.


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Publication:HIV Treatment: ALERTS!
Date:Mar 1, 2014
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