HIV drug-drug interactions

It is beyond the scope of this article to describe all possible drug-drug interactions in persons taking HIV antiretroviral medications, but this section will identify the most frequent interactions between HAART drugs and medications frequently prescribed for patients.

Antifungals and antibiotics. Medications to treat opportunistic infections are prone to interactions with some NNRTIs and PIs. The “azole” antifungals can increase concentration of other medications. The use of voriconazole (Vfend) with ritonavir (Norvir) 400 mg or efavirenz (Sustiva) is contraindicated because it results in a decreased blood concentration of voriconazole. Fluconazole (Diflucan) is a better choice.4

The use of such macrolide antibiotics as erythromycin and clarithromycin (Biaxin) appear to increase the risk for fatal cardiac arrhythmia when co-administered with antiretroviral drugs using the CYP450 pathway. The use of macrolide antibiotics can inhibit this system, resulting in prolonged QT interval, which can lead to cardiac arrhythmias.5 Azithromycin (Zithromax, Zmax) is a better choice because it does not have a detrimental effect on this pathway.


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Interactions between antiretrovirals and rifamycins (used to treat TB) are a growing concern, especially in resource-limited countries where TB remains a major cause of AIDS-related death. Although rifampin (Rifadin, Rimactane) is part of the standard first-line regimens for TB prophylaxis and treatment, it is a known inducer of CYP3A4 and can reduce the levels of PIs and NNRTIs to subtherapeutic levels.6 Rifampin should not be used with any PI. Rifabutin (Mycabutin) is a more moderate enzyme inducer than is rifampin. Concurrent use of NRTIs and rifamycins is not contraindicated and does not require dose adjustments Dose adjustments needed when HIV antiretrovirals and TB medication are co-administered are listed in Table 2.

Acid-lowering drugs.This classification of drugs must be looked at carefully before being prescribed to patients on HAART. These medications, which reduce the acidity of gastric secretions, can interfere with the absorption of certain PIs. Atazanavir (Reyataz) requires an acid environment for absorption; co-administering such drugs as proton pump inhibitors can alter the pH of stomach acidity for 24 hours or longer and will prevent atazanavir from being absorbed.4 OTC antacid medications exert their acid-neutralizing effects for short intervals and can be taken within one to two hours of HAART.

Cholesterol-lowering drugs. Research has shown that just being HIV-positive increases a person’s risk for elevated cholesterol and lipid levels.7 In addition, PIs are linked to increased cardiovascular risk factors, thus requiring the addition of a lipid-lowering medication. The statins are one class of commonly prescribed drugs used for this purpose; their concentrations can be increased to dangerous levels when used with PIs.8

Table 3 serves as an excellent guide for practitioners who find it necessary to prescribe cholesterol-lowering medications to their patients who are taking antiretrovirals.

Medications for psychiatric conditions. Many HIV-infected individuals complain of anxiety and depression. Agents used to treat these conditions have many interactions with HAART that the clinician must be understand before prescribing.

Benzodiazepines. Such benzodiazepines as midazolam (Versed), triazolam (Halcion), alprazolam (Xanax), and diazepam (Valium) can reach high levels of toxicity when used concomitantly with HIV antiretrovirals. Lorazepam (Ativan) and temazepam (Restoril) are safer alternatives.9

Anticonvulsants. The antiseizure medications phenytoin (Dilantin), carbamazepine (Tegretol) and phenobarbital (Solfoton) are CYP450 inducers that can render some PIs and NNRTIs ineffective. PIs may decrease levels of phenytoin. To avoid possible drug interactions, consider valproic acid (Depakote), lamotrigine (Lamictal), or levetiracetam (Keppra).10

Antidepressants. When taken with PIs—especially ritonavir—doses of medications in the SSRI classification might result in increased serum levels of antidepressants. This is a result of ritonavir being an inhibitor of 2D6 and CYP 3A4 pathways—the same pathway used for metabolism of most SSRIs.4

The Columbia University Medical Center publication Psychiatric Medications and HIV Antiretrovirals: A Guide to Interactions for Clinicians is an excellent source of information when prescribing an antidepressant for a patient on HAART therapy.11

Oral contraceptives. HIV-positive women taking efavirenz, nevirapine (Viramune), nelfinavir (Viracept), ritonavir, and lopinavir while using oral birth control that contains ethinyl estradiol or other forms of estrogen should be cautioned that these drugs may reduce hormone levels low enough to cause pregnancy.12

HIV-positive women taking the aforementioned antiretrovirals should be advised to use an additional method of birth control. Suggested contraceptives include combination estrogen/progesterone pills, progesterone-containing pills, or a barrier method (i.e., condoms).