Page 155 - HIV/AIDS Guidelines

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels should be monitored at
1 month after initiation of ART and then every 3 to 6 months. Mild to moderate fluctuations in ALT
and/or AST are typical in individuals with chronic HCV infection. In the absence of signs and/or
symptoms of liver disease these fluctuations do not require interruption of ART. Significant ALT
and/or AST elevation should prompt careful evaluation for signs and symptoms of liver insufficiency
and for alternative causes of liver injury (e.g., acute HAV or HBV infection, hepatobiliary disease, or
alcoholic hepatitis); short-term interruption of the ART regimen or of the specific drug suspected to
be responsible for the DILI may be required. 34

Treating Both HIV and Hepatitis C Virus Infection
Concurrent treatment of HIV and HCV is feasible but may be complicated by high pill burden, drug
interactions, and overlapping drug toxicities. In this context, the decision to treat chronic HCV should also
include consideration of the medical need for such treatment on the basis of an assessment of HCV disease
stage. Some clinicians may choose to defer HCV therapy in HIV/HCV-coinfected patients with no or
minimal liver fibrosis. If treatment with PegIFN/RBV alone or in combination with one of the HCV NS3/4A
PIs (boceprevir or telaprevir) is initiated, the ART regimen may need to be modified to reduce the potential
for drug interactions and/or toxicities that may develop during the period of concurrent HIV and HCV
treatment.

Considerations for using certain nucleoside reverse transcriptase inhibitors and
hepatitis C virus treatments:

• ddI should not be given with RBV because of the potential for drug-drug interactions leading to life-
threatening ddI-associated mitochondrial toxicity including hepatomegaly/steatosis, pancreatitis, and
lactic acidosis (AII). 35
• Combined use of ZDV and RBV is associated with increased rates of anemia, making RBV dose
36
reduction necessary. Therefore, this combination should be avoided when possible. Because the risk of
anemia may further increase when boceprevir or telaprevir is combined with PegIFN/RBV, ZDV should
not be given with this combination (AIII).
• Abacavir (ABC) has been associated with decreased response to PegIFN/RBV in some, but not all,
retrospective studies; current evidence is insufficient to recommend avoiding this combination. 37-39

Considerations for the use of HCV NS3/4A protease inhibitors (boceprevir or
telaprevir) and antiretroviral therapy:
• Boceprevir is approved for the treatment of HCV genotype 1 infection in patients without HIV infection.
After 4 weeks of PegIFN/RBV therapy, boceprevir is added to the regimen for 24, 32, or 44 additional
weeks of HCV therapy. Data on the use of an HCV regimen containing boceprevir together with ART in
HIV/HCV-coinfected individuals are limited. In 1 small study of coinfected patients, higher HCV
response was observed with boceprevir plus PegIFN/RBV (64 patients) than with PegIFN/RBV alone
(34 patients). In this study, patients received ART that included HIV-1 ritonavir-boosted atazanavir
(ATV/r), darunavir (DRV/r), or lopinavir (LPV/r) or raltegravir (RAL) plus dual NRTIs. 40
Boceprevir is primarily metabolized by aldo-keto reductase, but because the drug is also a substrate and
inhibitor of CYP3A4/5 and p-gp enzymes, it may interact with ARVs metabolized by these pathways.
Based on drug interaction studies in healthy volunteers, boceprevir can be coadministered with RAL. 41
However, coadministration of boceprevir with ATV/r, DRV/r, LPV/r, or efavirenz (EFV) is not
recommended because of bidirectional drug interactions (see Table 15a and 15b). 42, 43 Importantly, the
pharmacokinetic (PK) interactions of HIV PIs with boceprevir were not identified before the approval of
boceprevir and before participant enrollment in the HIV/HCV-coinfection trial; consequently, some

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