HIV makes HCV infection worse. Compared with people infected only with HCV, those burdened by both viruses get cirrhosis faster1,2 and die sooner.3,4 Taking combination antiretroviral therapy (cART) eased HIV's baneful impact on HCV progression in a 3567-person meta-analysis, but not completely.1
Does HCV infection make HIV infection worse? Studies addressing this question yield different -- and sometimes conflicting -- answers. No one should be surprised. These studies used different methods to analyze different populations, different endpoints, and different periods (before and after the arrival of cART). And some of the cART-era studies involve more toxic and inconvenient antiretrovirals rarely used today. According to an AIDS Clinical Trials Group (ACTG) team that recently explored these issues,5 the controversy breaks down this way:
This article dissects these and other studies to answer three questions:
Answers to these questions have already informed guidelines on caring for people with potential and confirmed HCV/HIV coinfection. Tables 1 and 2 outline current guidelines. A 1-page handout in this issue of RITA! offers HCV/HIV patients 10 pointers on preventing transmission of these viruses and avoiding treatment complications.
|Table 1. Screening and Prevention Guidelines for HCV and HIV Coinfection|
People positive for HCV antibody should have HCV RNA measured to determine whether HCV infection is active (HIVMA/IDSA).31
HCV RNA should be measured in HCV antibody-negative people with a history of injection drug use or unexplained increased serum transaminases because HCV antibodies do not develop in approximately 6% of HCV/HIV-coinfected people (HIVMA/IDSA).31
Infants born to HCV- or HBV-infected women should be screened for HCV and HBV. Infants can be tested for HCV RNA after age 2 months and for HCV antibody after 18 months of age (HIVMA/IDSA).31
To assess kidney function, HCV/HIV-coinfected people should be screened for proteinuria when they begin care and annually thereafter (HIVMA/IDSA).31
All HCV/HIV-coinfected people should be tested for hepatitis A virus (HAV) and hepatitis B virus (HBV) and vaccinated if not immune (HRSA).32
HCV/HIV-coinfected people vaccinated against HBV in the past should have their anti-HBV titer checked to make sure they remain protected (HRSA).32
People with HCV infection should be counseled to avoid alcohol and medications toxic to the liver, including fluconazole, isoniazid, and large doses of acetaminophen (HRSA).32
People with HCV infection should be counseled to reduce risk of HCV transmission through unprotected sex, perinatal exposure, or sharing drug-injecting equipment, razors, tattoo equipment, or sex toys (HRSA).32
|Table 2. HIV and HCV Care Guidelines for People With Coinfection|
Combination antiretroviral therapy (cART) should be considered for coinfected patients regardless of CD4 count because cART may slow liver disease progression by preserving or restoring immune function and reducing HIV-related immune activation (DHHS Adult).30
Liver function should be monitored closely in coinfected people on cART (HRSA).32
Consideration of potential drug-drug interactions and overlapping toxicities should guide antiretroviral selection in coinfected people receiving treatment for HCV infection (DHHS Adult).30
Because of pill burden, drug-drug interactions, and overlapping toxicities when treating coinfected people, some clinicians may choose to defer cART until antiretroviral-naive people with a CD4 count at or above 500 cells/mm3 complete anti-HCV therapy* (DHHS Adult).30
For people with a CD4 count below 200 cells/mm3, it may be preferable to start cART first and begin HCV therapy after the CD4 count rises (DHHS Adult).30
Interferon alfa and pegylated interferon are not recommended during pregnancy, and ribavirin is contraindicated during pregnancy (DHHS Perinatal).33
Men and women taking ribavirin should use contraception consistently during ribavirin therapy and for 6 months after completing ribavirin therapy (HRSA).32
Treatment of HCV infection in HIV-positive people is evolving rapidly as direct-acting antivirals (DAAs) become available and their interactions with antiretrovirals are defined. For the latest treatment advice, see the table "Unique Patient Populations: HIV/HCV Coinfection" in Recommendations for Testing, Managing, and Treating Hepatitis C, from the Infectious Diseases Society of America. Also see the article on DAAs in this issue of Research Initiative, Treatment Action! and the interview with Douglas Dieterich.
People with HCV infection who inject drugs should be strongly counseled to enter a treatment program to end their dependence (HRSA).32
* Recent and ongoing approval of stronger direct-acting antivirals (DAAs) for HCV infection with 8- to 24-week courses could strengthen the rationale for treating HCV infection before starting cART.34
The impression that HCV does not affect survival in people with HIV dates to the pre-cART era, when HIV-positive people died of AIDS long before they could die of heart, kidney, or liver disease. Two emblematic studies involve medium-size U.S. HIV cohorts -- one largely male and one entirely female.35,36
Researchers compared survival in 115 HIV-positive veterans with HCV and 235 without HCV in the HIV Atlanta Veterans Affairs Medical Cohort Study (Table 3).35 These people were in care at some point from January 1992 to May 1997, and all but 5 were men. Most participants had taken antiretrovirals, but only 20% had taken a protease inhibitor, so this was a largely cART-naive cohort. Multivariate analysis identified no links between antiretroviral treatment history and HCV antibody positivity.
|Table 3. Impact of HCV Infection on Survival in Atlanta VA Cohort Before cART and With cART|
|Observation Period||January 1992 Through May 1997||January 1997 Through May 2001|
|HCV plus HIV|
(n = 115)
(n = 235)
|HCV plus HIV|
(n = 306)
(n = 664)
|Had AIDS||81 (70%)||164 (70%)||213 (70%)||433 (65%)|
|Took cART||19 (16%)*||50 (21%)*||199 (65%)†||509 (77%)†|
|Died||24 (21%)||46 (20%)||67 (22%)‡||72 (11%)‡|
|Time from HIV Dx to death||No difference by Cox proportional hazards model||aHR HCV+ vs HCV-: 2.47|
(95% CI 1.26 to 4.82, P = 0.0085)
|Time from AIDS Dx to death||No difference by Cox proportional hazards model||aHR HCV+ vs HCV-: 1.84|
(95% CI 1.09 to 3.10, P = 0.022)
aHR, adjusted hazard ratio; Dx, diagnosis.
* Reported as protease inhibitor use.
† P = 0.001.
‡ P < 0.0001.
The same proportion of people in the coinfected group and the HIV-only group -- 70% -- had AIDS.35 Twenty-four people with coinfection (21%) and 46 with HIV alone (20%) died during the study period (Table 3). Cox proportional hazards models discerned no difference between the coinfected group and the monoinfected group in time from HIV diagnosis to death or time from AIDS diagnosis to death. In this group, largely in care before the benefits of cART took hold, HCV coinfection did not shorten survival.
A Women and Infants Transmission Study (WITS) analysis involved 652 women -- 190 (29%) with HCV and none with an AIDS diagnosis -- who enrolled in the cohort when pregnant from 1989 through 1995, before cART arrived.36 Only 124 women (19%) tried a cART combination during follow-up (with no difference between coinfected and monoinfected women). Forty-three women (7%) died, 26 of them (4%) without a documented AIDS diagnosis. Cox proportional hazards analysis determined that coinfected women did not have faster progression to an initial class C AIDS diagnosis or death (relative hazard 0.75, 95% confidence interval [CI] 0.37 to 1.53).
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