HIV and other illnesses

GUIDELINES: SOME DOS AND DONTS FOR POSITIVE PATIENTS ON MEDS

Patients very often receive therapy for a host of other conditions.

Most of the time people with HIV tend to have other conditions too, chronic or acute. Or some just take over-thecounter medications, even herbal or traditional medicines.

I find literature not so available for patients to know what the risks are. Most of the literature that is out there is meant for clinicians.

Let us start by saying it is very important that as an HIV positive patient on antiretrovirals, when you visit your clinician you must give a thorough medication history that includes prescription medications, including those prescribed by other providers, over-the-counter medications, recreational drugs and herbal/alternative therapies.

This will allow the clinician to accurately predict drugs that may lead to significant interactions. The clinician will also then be able to identify dietary restrictions with ARV drugs.

Current treatment guidelines recommend the use of a combination of at least three ARV drugs for the treatment of HIV-infected patients.

In addition to medications to treat HIV infection, patients often receive therapy for other conditions and prevention of opportunistic infections.

Because of the number of drugs that the HIV-infected patient receives, clinicians must often rely on clinical judgment and are forced to predict drug interactions without supporting data.

Drug interactions are classified as pharmacokinetic or pharmacodynamics.

Pharmacokinetic means the interaction leads to a change in the absorption, distribution, metabolism or excretion of the drug. This can lead to increased available dosages of the drug leading to toxicity or decrease leading to poor effect of the drug, or just changed activity of the drug.

Pharmacodynamic means the interaction leads to additive, synergistic or antagonistic effects. This can cause increased or decreased effect of the drug.

Find out which class of ARVs you are taking from your doctor as this has an effect on how they act when they come in contact with other drugs. Commonest are NNRTIs and PIs.

Common drug interactions 1. Anticonvulsants/Antiepileptics

It is very important that the doctor monitors your anticonvulsant levels if you are taking concurrent ARV and anticonvulsant therapy.

The doctor should avoid prescribing carbamazepine, phenobarbital and phenytoin for patients if you are taking NNRTIs or PIs. Other newer epilepsy drugs can be considered.

Because of the capacity of phenytoin, phenobarbital, and carbamazepine to induce metabolic enzymes, these drugs should be avoided in patients receiving NNRTIs or PIs.

They have the potential to significantly reduce HIV serum con-

centrations leading to increased risk of convulsions.

2. Antifungal Drugs

The management of HIV infection includes antifungal drugs that are used for the treatment of oral candidiasis (thrush) or for maintenance therapy of cryptococcal meningitis.

The commonest drug used is fluconazole. Data evaluating interactions with fluconazole and concurrent PI therapy have demonstrated drug interactions of minimal clinical significance.

Ketoconazole has been shown to increase saquinavir, amprenavir, and indinavir levels and this can lead to toxicity.

Conversely, ritonavir and lopinavir/ritonavir (commonly known as Alluvia) can increase ketoconazole levels threefold when used concurrently; therefore requiring reduction of its dose when used to treat fungal infections.

Voriconazole has also been used to treat fungal infections in HIV-infected patients.

Efavirenz (Stocrin), commonly part of the often used three-inone therapy, decreases voriconazole concentration and efavirenz becomes increased.

Therefore, if efavirenz and voriconazole are co-administered, dose adjustment is required. Caution should be used when combining voriconazole with other NNRTIs.

3. TB Treatment

You should not use rifampin with any PI. The alternative is rifabutin with proper dose adjustment.

Drug interactions are well documented between the TB drugs (rifampin, rifabutin, and clarithromycin) and ARVs.

The greatest concern is with rifamycin-based regimens because of the risk of significant reductions in PI concentrations.

In general, rifampin should be avoided during concurrent therapy with PIs, due to marked reductions in PI levels.

Alterations in clarithromycin levels have been reported during concurrent therapy with PIs. Caution should be exercised and the doses adjusted accordingly.

4. Erectile Dysfunction Agents

Sildenafil, vardenafil, and tadalafil are all extensively metabolised by the same enzymes that metabolise PIs.

When sildenafil was given concurrently with indinavir, saquinavir, or ritonavir, the concentration for sildenafil was increased by a factor of twofold to tenfold.

The concentrations of vardenafil and tadalafil were increased when given with ritonavir. Based on these data, the following is generally recommended when erectile dysfunction agents are combined with PIs:

Sildenafil – use reduced initial dose of 25 mg q48h and monitor for adverse effects

Tadalafil – use initial dose of 5 mg, and do not exceed a single dose of 10 mg in 72 hours

Vardenafil – use initial dose of 2.5 mg, and do not exceed a single 2.5-mg dose in 72 hours

5. Herbal Therapy

In the setting of PI- or NNRTI-based ARVs, supplemental garlic and St John’s Wort are contraindicated.

All herbal products should be used with caution until further data are available regarding their effects with concurrent HAART.

Herbal therapy use has become more frequent in both the general population and the HIV-infected population. Because most providers cannot accurately predict whether you use herbal therapy, it is important to volunteer the information and discuss ARV/ herbal therapy drug interactions with the doctor.

Even if you use traditional medicine, especially those that you ingest because it is common practice in the South African context.

Drug interactions are known to occur when PIs are used concurrently with St John’s Wort or garlic supplementation.

Concurrent use of St John’s Wort and unboosted indinavir resulted in a 57% reduction in indinavir concentration. Data also demonstrated that concurrent saquinavir soft-gel capsule and garlic supplementation reduced saquinavir plasma concentrations by 51%.In the setting of PI- or NNRTI-based HAART, supplemental garlic and St John’s Wort are contraindicated.

6. Anti-cholesterol medication

Clinicians should not prescribe simvastatin or lovastatin for patients taking PIs.

Hypercholesterolaemia occurs in approximately 70% of patients taking PIs, often requiring the use of cholesterol treatment.

Studies have been conducted evaluating the potential interaction between PIs and the anticholesterol agents commonly known as “statins” (pravastatin, atorvastatin, lovastatin, rosuvastatin, and simvastatin).

When these drugs were studied with concurrent ritonavir/ saquinavir, the concentration of simvastatin increased by a factor of 32 and atorvastatin by a factor of 4.5, whereas the concentration for pravastatin was reduced by a factor of 0.5. Significant drug interactions have also been reported with lopinavir/ritonavir when given concurrently with simvastatin or atorvastatin.

After co-administration, the concentration increased by 5.9fold for atorvastatin, whereas the pravastatin levels increased 0.3fold.

Similar results have also been reported with co-administration of nelfinavir with atorvastatin or simvastatin. Discuss with your doctor to find out which is the safest statin to use for you and the dose, and do not forget the importance of diet and physical activity in managing the cholesterol.

The large increases in concentration associated with concurrent ritonavir/saquinavir and simvastatin administration demonstrates that simvastatin should not be used during PI therapy.

One case report describes a patient who received concurrent simvastatin with nelfinavir therapy that resulted in death from acute rhabdomyolysis. Similar cases have also been reported with concurrent statin and lopinavir/ritonavir use.

7. Oral Contraceptives

Caution should be used when taking oral contraceptives if you are receiving ARVs because of the variations in effect on oestrogen levels.

In fact it is said that women who are taking efavirenz, nevirapine, lopinavir/ ritonavir, nelfinavir, ritonavir, tipranavir/ritonavir, darunavir/ritonavir, or saquinavir must use alternate or additional forms of birth control.

A study found that the concentration of oestrogen levels were reduced in patients concurrently taking ritonavir. Similar results have been reported with nelfinavir, darunavir/ritonavir, and lopinavir/ritonavir.

In contrast, data for indinavir and unboosted atazanavir demonstrated an increase in the concentration for both oestrogen and progesterone.

Therefore, when co-administered with unboosted atazanavir, oral contraceptives should contain no more than 30 mcg oestrogen.

However, when co-administered with atazanavir/ritonavir, oral contraceptives should contain at least 35 mcg oestrogen.

8. Psychotropic Therapies

Tricyclic antidepressants should be used with caution or avoided in patients using PIs.

If you are on any mental illness medication, please speak to your doctor as the concentrations of some of the drugs can be significantly increased by concurrent use with ARVs.

9. Sedative/Hypnotics

Patients on PIs should not take midazolam or triazolam. Lorazepam or oxazepam may be considered.

Ritonavir has been shown to significantly impair the oral clearance of alprazolam and triazolam. This potential for increased benzodiazepine levels would lead to potentiation of the sedation and respiratory depression associated