Page 154 - HIV/AIDS Guidelines

infection should undergo repeat testing annually. HCV-seropositive patients should be tested for HCV
RNA using a qualitative or quantitative assay to confirm the presence of active infection. 17
• Patients with HIV/HCV coinfection should be counseled to avoid consuming alcohol and to use
appropriate precautions to prevent transmission of HIV and/or HCV to others. HIV/HCV-coinfected
patients who are susceptible to hepatitis A virus (HAV) or hepatitis B virus (HBV) infection should be
vaccinated against these viruses.
• All patients with HIV/HCV coinfection should be evaluated for HCV therapy. HCV treatment is
recommended according to standard guidelines. 18, 19 Strong preference should be given to commence
HCV treatment in patients with higher CD4 counts. For patients with lower CD4 counts (e.g., <200
cells/mm ), it may be preferable to initiate ART and delay HCV therapy until CD4 counts increase as a
3
result of HIV treatment. 17, 20-22

Antiretroviral Therapy in HIV/Hepatitis C Virus Coinfection

• When to start antiretroviral therapy: The rate of liver disease (liver fibrosis) progression is accelerated in
3
HIV/HCV-coinfected patients, particularly in individuals with low CD4 counts (≤350 cells/mm ). Data
largely from retrospective cohort studies are inconsistent regarding the effect of ART on the natural
history of HCV disease. 6, 23, 24 However, ART may slow the progression of liver disease by preserving or
restoring immune function and reducing HIV-related immune activation and inflammation. 25-27 Thus, for
most coinfected patients, including those with high CD4 counts and those with cirrhosis, the benefits of
ART outweigh concerns regarding DILI. Therefore, ART should be initiated for most HIV/HCV-
coinfected patients, regardless of CD4 count (BII). However, in HIV treatment-naive patients with CD4
3
counts >500 cells/mm , some clinicians may choose to defer ART until completion of HCV treatment.
• What antiretroviral to start and what antiretroviral not to use: Initial ARV combination regimens for most
HIV treatment-naive patients with HCV are the same as those for patients without HCV infection.
Special considerations for ARV selection in HIV/HCV-coinfected patients include:

• When both HIV and HCV treatments are indicated, the choice of ARV regimen should be guided by
the HCV treatment regimen selected with careful consideration of potential drug-drug interactions
and overlapping toxicities (as discussed below).
• Cirrhotic patients should be carefully assessed for signs of liver decompensation according to the
Child-Turcotte-Pugh classification system because hepatically metabolized ARV drugs may require
dose modification or avoidance in patients with Child-Pugh class B and C disease. (See Appendix B,
Table 7.)
• Hepatotoxicity: DILI following initiation of ART is more common in HIV/HCV-coinfected patients than
in those with HIV monoinfection. The greatest risk of DILI may be observed in coinfected individuals
28
with advanced liver disease (e.g., cirrhosis or end-stage liver disease). Eradication of HCV infection
with treatment may decrease the likelihood of ARV-associated DILI. 29
• Given the substantial heterogeneity in patient populations and drug regimens, comparison of DILI
incidence rates for individual ARV agents across clinical trials is difficult. In such studies, the highest
incidence rates of significant elevations in liver enzyme levels (>5 times the upper limit of the
laboratory reference range) have been observed during therapy with ARV drugs that are no longer
commonly used in clinical practice, including stavudine (d4T) (with or without didanosine [ddI]),
nevirapine (NVP), or full-dose ritonavir (RTV) (600 mg twice daily). Additionally, certain ARV
30
agents should be avoided if possible because they have been associated with higher incidence of
serious liver-associated adverse effects, such as fatty liver disease with nucleoside reverse
transcriptase inhibitors (NRTIs) such as d4T, ddI, or zidovudine (ZDV); noncirrhotic portal
31
hypertension associated with ddI; and hepatotoxicity associated with RTV-boosted tipranavir. 33
32

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents J-6

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