Opinion: HIV Management Is Ready for A Long-Term View

January 13, 2021
Anthony Mills, MD

Sponsored by ViiV Healthcare

Let’s face it, delivering the news to a patient that they’re HIV positive is still incredibly hard. The stigma and misinformation around HIV are overwhelming and their life is forever changed. But, thanks to treatment advances, I can tell my patients with conviction that advancing in their career, growing old with their loved ones, having children–these things all remain possible.

We’ve come a long way since the first antiretroviral drug (ARV) was approved. Since then, many different powerful classes of drugs have been approved, and we evolved from taking many drugs, multiple times a day, to taking one pill a day for many patients. The evolution prompted researchers to challenge the belief that HIV needed to be managed by three or more medicines. They were onto something, and the hypothesis for two-drug regimens was then validated by numerous peer-reviewed and pivotal studies in both treatment-naïve and virologically suppressed patients.

DOVATO (dolutegravir [DTG] 50 mg, and lamivudine [3TC] 300 mg) was the first complete, two-drug regimen approved by the U.S. Food and Drug Administration for adults starting and switching ARV regimens with no known resistance to its two components. DOVATO is indicated for treatment-naïve and virologically suppressed adults with HIV-1. See full indication below.

IMPORTANT SAFETY INFORMATION:

BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1 EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen. Please see full Important Safety Information below.

In addition, DOVATO is strongly recommended as an initial regimen for most people living with HIV and as a regimen for most virologically suppressed adults by the DHHS Antiretroviral Treatment Guidelines, marking the first time a complete, two-drug regimen has been recommended by the DHHS in the treatment-naïve setting. The AI* rating DOVATO received is the highest rating, meaning it is backed by the highest level of evidence. There are three exceptions in these guidelines, reflective of the exclusion criteria in the pivotal GEMINI 1 & 2 trials which supported the approval of DOVATO. Specifically, DOVATO is not recommended for use in individuals with HBV co-infection, those who will start antiretroviral therapy before results of HIV genotypic resistance testing for RT or HBV testing are available, or those who have HIV RNA >500,000 copies/mL.

So why does this matter? Many living with HIV will be on treatment for decades. To deliver on my commitment that everything is possible, I focus on long-term treatment goals like reducing the number of ARVs taken per day. These considerations often point me toward a two-drug regimen, like DOVATO.

The most incredible realization is that HIV treatment research is now centered around the patient. Whether that’s examining regimens or removing medicines, we’re helping to navigate the HIV treatment journey. Recently, I prescribed DOVATO for a young man who was just about to start college. It was important for me to anticipate both short-term and long-term side effects and toxicities as he moves into the future.

INDICATION

DOVATO is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of DOVATO.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.

Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.

Contraindications

  • Do not use DOVATO in patients with previous hypersensitivity reaction to dolutegravir or lamivudine

  • Do not use DOVATO in patients receiving dofetilide

Warnings and precautions

Hypersensitivity Reactions:

  • Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury

  • Discontinue DOVATO immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

  • Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors

  • Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of DOVATO. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn

  • Monitoring for hepatotoxicity is recommended

Embryo Fetal Toxicity:

  • Alternative treatments to DOVATO should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects

  • Perform pregnancy testing before use of DOVATO and counsel that consistent use of effective contraception is recommended while using DOVATO in individuals of childbearing potential

Lactic Acidosis and Severe Hepatomegaly with Steatosis:

Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue DOVATO if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO and other drugs may occur (see Contraindications and Drug interactions).

Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of DOVATO.

Adverse reactions

The most common adverse reactions (incidence ≥2%, all grades) with DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).

Drug interactions

  • Consult full Prescribing Information for DOVATO for more information on potentially significant drug interactions
  • DOVATO is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
  • Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir
  • Administer DOVATO 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, DOVATO and supplements containing calcium or iron can be taken with food

Use in specific populations

  • Pregnancy: There are insufficient human data on the use of DOVATO during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. If planning a pregnancy or if pregnancy is confirmed while taking DOVATO during the first trimester, assess the risks and benefits of continuing DOVATO versus switching to another antiretroviral regimen. For individuals actively trying to become pregnant, initiation of DOVATO is not recommended unless there is no suitable alternative
  • Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
  • Females and Males of Reproductive Potential: Perform pregnancy testing before initiation of DOVATO. Advise individuals of childbearing potential to consistently use effective contraception while taking DOVATO
  • Renal Impairment: DOVATO is not recommended for patients with creatinine clearance <50 mL/min
  • Hepatic Impairment: DOVATO is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)

Please see full Prescribing Information, including Boxed Warning, for DOVATO.

* “A” standing for strongly recommended by an expert panel and “I” for having undergone one or more randomized trials with positive clinical outcomes and/or validated laboratory end points.

For US HCPs only.
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DLLOGM200008 December 2020
Produced in USA.