View the Table: Treatments Considered for COVID-19

The FDA has approved Biktarvy (Gilead), a once-daily, fixed-dose combination of bictegravir, a new integrase strand transfer inhibitor (INSTI), and the nucleoside reverse transcriptase inhibitors (NRTIs) emtricitabine and tenofovir alafenamide (TAF), for treatment of HIV-1 infection in adults. The new combination is indicated for use in patients who are antiretroviral-naive or who have been virologically suppressed on a stable antiretroviral regimen for ≥3 months with no history of treatment failure and no known substitutions associated with resistance to any component of the combination.

The FDA has approved Mavyret (Abbvie) and Vosevi (Gilead), two new fixed-dose combinations of direct-acting antiviral (DAA) drugs, for treatment of chronic hepatitis C virus (HCV) infection caused by any of the six major HCV genotypes in patients without cirrhosis or with compensated cirrhosis. Both are approved for use in treatment-experienced patients. Mavyret is also approved for treatment-naive patients.

The FDA has approved elvitegravir (Vitekta – Gilead), an integrase strand transfer inhibitor (INSTI), for use with a protease inhibitor (PI) plus ritonavir and other antiretroviral drugs for treatment of HIV-1 infection in treatment-experienced adults. Elvitegravir is also available in a fixed-dose combination (Stribild) with the pharmacokinetic enhancer cobicistat and the nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) emtricitabine and tenofovir disoproxil fumarate (DF). A similar combination (Genvoya) that includes tenofovir alafenamide instead of tenofovir DF was recently approved by the FDA and will be reviewed in a future issue.

Cobicistat, a pharmacokinetic enhancer that boosts levels of some HIV drugs but has no antiretroviral activity of its own, is now available alone as Tybost (Gilead) and in fixed-dose combinations with the protease inhibitors atazanavir (Evotaz — BMS) and darunavir (Prezcobix — Janssen) for treatment of HIV-1 infection. Both atazanavir and darunavir have traditionally been used in combination with the CYP3A inhibitor ritonavir (Norvir) to boost their serum concentrations, but neither is available in a fixed-dose combination with ritonavir.

The FDA has approved Viekira Pak (Abbvie), a fixed-dose combination of two new direct-acting antiviral agents (ombitasvir, paritaprevir) with the pharmacologic enhancer ritonavir in one tablet, co-packaged with a third new direct-acting antiviral agent (dasabuvir) in a second tablet, for oral treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Genotype 1 is responsible for 70-80% of HCV infections in the US.

The FDA has approved Triumeq (Viiv Healthcare), a fixed-dose combination of the integrase strand transfer inhibitor (INSTI) dolutegravir and the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine, for once-daily treatment of HIV-1 infection. Dolutegravir (Tivicay) was approved as a single agent in 2013.

Antiretroviral therapy is recommended for all HIV-infected patients, both to reduce the risk of disease progression and to prevent transmission of the virus to others. Various guidelines for treatment of HIV infection are available.

The FDA has approved dolutegravir (doll-you-TEG-rah-veer; Tivicay – Viiv Healthcare), an integrase strand transfer inhibitor (INSTI), for treatment of HIV-1 infection in adults and in children ≥12 years old who weigh at least 40 kg. It is the third INSTI to be approved by the FDA; raltegravir and elvitegravir were approved earlier.

Tuberculosis (TB) is still a common cause of death worldwide, and the prevalence of drug-resistant TB poses challenges to its treatment and control. Guidelines with detailed management recommendations are available from the American Thoracic Society, Centers for Disease Control and Prevention (CDC) and Infectious Diseases Society of America (IDSA).

Guidelines for use of antiretroviral agents continue to shift toward earlier and more continuous treatment, both to treat the patient and to prevent transmission of the disease to others. Resistance testing is now recommended when antiretroviral drugs are started. Increases in HIV RNA levels ("viral load") while on therapy may indicate development of drug resistance, requiring further testing and a change in the treatment regimen. Antiretroviral drugs interact with each other and with many other drugs; complete information on these interactions is available at www.aidsinfo.nih.gov.

Even though the incidence continues to decline in the United States, tuberculosis (TB) is still a common cause of death worldwide, and the prevalence of drug-resistant TB poses severe challenges to its treatment and control. Guidelines with detailed management recommendations are available from the Centers for Disease Control and Prevention (CDC), American Thoracic Society and Infectious Diseases Society of America (IDSA).

New guidelines for use of antiretroviral agents have been published, with a shift towards earlier and more continuous treatment. HIV infection is treated with combinations of antiretroviral drugs depending on the patientÆs HIV RNA levels ("viral load") and CD4 cell count. Increases in viral load while on therapy may indicate development of drug resistance, requiring further testing and a change in treatment regimen. Resistance testing is now recommended when a patient is first seen, regardless of when therapy will be started.

A recent letter to the editor of the Annals of Internal Medicine documented a single case of myopathy apparently due to an interaction between simvastatin (Zocor, and others) and green tea. Since it became available generically, simvastatin has surpassed atorvastatin (Lipitor) as the best selling statin. As such, it is probably the most common cause of statin-induced myopathy, which is often a result of drug interactions.

Etravirine (Intelence - Tibotec), a new non-nucleoside reverse transcriptase inhibitor (NNRTI), has received fast-track FDA approval for use in combination therapy in treatment-experienced adults who have HIV-1 infection resistant to an NNRTI and other antiretroviral agents.

The approval of new drugs and continuing concerns about drug toxicity and resistance have prompted new antiretroviral treatment guidelines. Resistance testing is not recommended before starting antiretroviral therapy. HIV infection is treated with combinations of antiretroviral drugs while monitoring the patient's HIV RNA levels ("viral load") and CD4 cell count. Increases in viral load while on therapy may indicate development of drug resistance requiring further testing and a change in treatment regimen.

Tipranavir (Aptivus - Boehringer Ingelheim), a new protease inhibitor, has received accelerated approval from the FDA. It must be given with ritonavir (Norvir). The combination is indicated for use with other antiretrovirals to treat HIV infection in highly treatment-experienced adults who have ongoing viral replication or in those with HIV strains known to be resistant to multiple protease inhibitors.

Serious adverse interactions between drugs continue to be reported. Many of these are due to inhibition or induction of cytochrome P450 (CYP) enzymes, particularly CYP3A4. CYP3A is thought to be involved in the metabolism of more than 50 percent of currently prescribed drugs.2 CYP3A4, which is more abundantly expressed than CYP3A5, accounts for most CYP3A activity in vivo.

Tuberculosis (TB) is still a problem in the United States, even though the incidence continues to decline in most of the country (MMWR Morbid Mortal Wkly Rep 2004; 53:209). Treatment of TB can be divided into treatment of latent infection diagnosed by a positive PPD and treatment of active clinical TB. Guidelines with detailed management recommendations are available from the US Centers for Disease Control and Prevention (CDC) (MMWR Morbid Mortal Wkly Rep 2003; 52RR-11:1).

New drug approvals as well as continuing concerns about drug toxicity and the development of resistance have prompted new antiretroviral treatment guidelines (Panel on Clinical Practices for Treatment of HIV Infection, November 10, 2003, www.aidsinfo.nih.gov).

Atazanavir (Reyataz - Bristol-Myers Squibb), a new protease inhibitor (PI), and emtricitabine (Emtriva - Gilead), a nucleoside analogue reverse transcriptase inhibitor (NRTI) chemically similar to lamivudine, have been approved by the FDA for treatment of HIV-1 infection. Both are taken once daily, unlike most anti-HIV drugs.