Infectious Diseases II

In general, if one of the antiretroviral therapies has to be discontinued, all of the therapies should

be discontinued to decrease the promotion of resistance caused by the suboptimal suppression of

viral replication. Rationale: Nonnucleoside reverse transcriptase inhibitors (NNRTIs) have long

half-lives (as long as 3 weeks); therefore, if NNRTIs are discontinued at the same time as other

antiretrovirals with shorter half-lives, there will be a period of functional NNRTI monotherapy.

May consider continuing antiretrovirals with shorter half-lives, if possible, for 1–2 weeks to

minimize selection of NNRTI resistance.

Possible ICU drug interactions – See Table 12.

HAART-associated adverse drug reactions

Newer generations of HAART regimens are generally well tolerated; however, many patients still

receive older HAART therapy.

Many of the HAART-associated adverse effects have no specific treatment; therefore, early

recognition and prompt discontinuation of the offending agent is crucial.

Lactic acidosis

Two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) (e.g., lamivudine and

tenofovir) remain the backbone of many HAART regimens.

ii.

NRTIs are associated with a variety of mitochondrial toxicities.

iii.

Older NRTIs, such as zidovudine, stavudine, and didanosine, have been associated with lactic

acidosis.

iv.

Symptoms: Fatigue, malaise, nausea, vomiting, abdominal pain, hepatomegaly

Management: Supportive therapy and discontinuing the potential offending agent

Symptoms: Fever, rash, gastrointestinal (GI) symptoms

ii.

Reaction associated with the presence of the HLA-B*5701 allele, which has an 8% prevalence

among whites in North America. Genetic screening for this allele is recommended.

iii.

Management: Supportive care and discontinuing agent, with rechallenge contraindicated

because of the possibility of life-threatening hemodynamic compromise

Other HAART-associated significant adverse effects:

Nevirapine hypersensitivity: Rash (may progress to Stevens-Johnson syndrome), fever,

hepatotoxicity

ii.

Raltegravir-associated rhabdomyolysis

iii.

Tipranavir-associated hepatotoxicity and intracranial hemorrhage

iv.

Protease inhibitor–associated pancreatitis