Page 89 - HIV/AIDS Guidelines

What Not to Use (Last updated March 27, 2012; last reviewed March 27, 2012)

Some antiretroviral (ARV) regimens or components are not generally recommended because of suboptimal
antiviral potency, unacceptable toxicities, or pharmacologic concerns. These are summarized below.

Antiretroviral Regimens Not Recommended
Monotherapy with nucleoside reverse transcriptase inhibitor (NRTI). Single-NRTI therapy does not
demonstrate potent and sustained antiviral activity and should not be used (AII). For prevention of mother-
to-child transmission (PMTCT), zidovudine (ZDV) monotherapy is not recommended but might be
considered in certain unusual circumstances in women with HIV RNA <1,000 copies/mL, although the use
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of a potent combination regimen is preferred. (See Perinatal Guidelines, available at http://aidsinfo.nih.gov.)
Single-drug treatment regimens with a ritonavir (RTV)-boosted protease inhibitor (PI), either lopinavir
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(LPV), atazanavir (ATV), or darunavir (DRV) 4-5 are under investigation with mixed results, and cannot be
recommended outside of a clinical trial at this time.
Dual-NRTI regimens. These regimens are not recommended because they have not demonstrated potent
and sustained antiviral activity compared with triple-drug combination regimens (AI). 6
Triple-NRTI regimens. In general, triple-NRTI regimens other than abacavir/lamivudine/zidovudine
(ABC/3TC/ZDV) (BI) and possibly lamivudine/zidovudine + tenofovir (3TC/ZDV + TDF) (BII) should not
be used because of suboptimal virologic activity 7-9 or lack of data (AI).

Antiretroviral Components Not Recommended
Atazanavir (ATV) + indinavir (IDV). Both of these PIs can cause Grade 3 to 4 hyperbilirubinemia and
jaundice. Additive adverse effects may be possible when these agents are used concomitantly. Therefore,
these two PIs are not recommended for combined use (AIII).
Didanosine (ddI) + stavudine (d4T). The combined use of ddI and d4T as a dual-NRTI backbone can result
in a high incidence of toxicities, particularly peripheral neuropathy, pancreatitis, and lactic acidosis. 10-13 This
combination has been implicated in the deaths of several HIV-infected pregnant women secondary to severe
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lactic acidosis with or without hepatic steatosis and pancreatitis. Therefore, the combined use of ddI and
d4T is not recommended (AII).

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Didanosine (ddI) + tenofovir (TDF). Use of ddI + TDF may increase ddI concentrations and serious ddI-
associated toxicities including pancreatitis and lactic acidosis. 16-17 These toxicities may be lessened by ddI
dose reduction. The use of this combination has also been associated with immunologic nonresponse or CD4
cell decline despite viral suppression, 18-19 high rates of early virologic failure, 20-21 and rapid selection of
resistance mutations. 20-22 Because of these adverse outcomes, this dual-NRTI combination is not generally
recommended (AII). Clinicians caring for patients who are clinically stable on regimens containing ddI +
TDF should consider altering the NRTIs to avoid this combination.

Two-non-nucleoside reverse transcriptase inhibitor (2-NNRTI) combinations. In the 2NN trial, ARV-
naive participants were randomized to receive once- or twice-daily nevirapine (NVP) versus efavirenz (EFV)
versus EFV plus NVP, all combined with d4T and 3TC. A higher frequency of clinical adverse events that
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led to treatment discontinuation was reported in participants randomized to the two-NNRTI arm. Both EFV
and NVP may induce metabolism of etravirine (ETR), which leads to reduction in ETR drug exposure. 24
Based on these findings, the Panel does not recommend using two NNRTIs in combination in any
regimen (AI).

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

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