Last reviewed: March 2019
Last updated: March  2019
09 Nov 2018

US guidelines now recommend doravirine for the treatment of HIV

Updated guidelines published by the US Department of Health and Human Services now recommend doravirine-based antiretroviral regimens as an initial option for the treatment of HIV infection in some groups of patients.

According to the guideline, doravirine-based treatment is now recommended as an initial regimen in certain clinical situations (e.g., patients who cannot tolerate integrase strand transfer inhibitors [INSTIs] and wish to use an NNRTI with a lower risk of adverse effects). However, it is not yet recommended as an initial regimen in most people due to a lack of data comparing doravirine to INSTI-based regimens, the current treatment of choice.

Doravirine, a new non-nucleoside reverse transcriptase inhibitor (NNRTI), was approved by the US Food and Drug Administration in August 2018 in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults with no prior antiretroviral treatment history. The drug is available as a single-ingredient formulation or in a co-formulation with lamivudine and tenofovir disoproxil. It has also been recommended for approval in Europe, with a final decision pending.

Approval was based on two clinical trials which showed that doravirine/tenofovir/lamivudine was non-inferior to efavirenz- and darunavir/ritonavir-based regimens. Doravirine is generally better tolerated, with a more favourable lipid profile, a lower incidence of rash, and fewer central nervous system adverse effects compared to efavirenz. The updated DHHS guideline also incorporates recommendations for the use of dolutegravir in women of childbearing potential and pregnancy.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • fevers and night sweats
  • weight loss
  • skin rashes and post-inflammatory scars
  • oral ulcers, angular cheilitis, oral thrush, or oral hairy leukoplakia
  • diarrhoea
  • wasting syndrome
  • changes in mental status or neuropsychiatric function
  • recent hospital admissions
  • tuberculosis (TB)
  • medical comorbidities
  • sexual activity
  • generalised lymphadenopathy
  • Kaposi's sarcoma
  • genital STDs
  • chronic vaginal candidiasis
  • shingles
  • headaches
  • periodontal disease
  • retinal lesions on fundoscopy
  • shortness of breath on exertion, cyanosis on exertion, dry cough, silent chest on auscultation

Other diagnostic factors

  • current and prior use of other substances
  • peripheral neuropathy
  • recurrent herpes simplex
  • hepatomegaly or splenomegaly
  • meningeal signs (bacterial or viral meningitis)

Risk factors

  • needle sharing with intravenous drug use
  • unprotected receptive anal intercourse
  • unprotected receptive penile-vaginal sexual intercourse
  • percutaneous needle stick injury
  • high maternal viral load (mother to child transmission)
  • use of progestin-only injectable contraceptives
  • herpes simplex virus type 2 (HSV-2) infection

Diagnostic investigations

1st investigations to order

  • serum HIV enzyme-linked immunosorbent assay (ELISA)
  • serum HIV rapid test
  • HIV non-invasive tests
  • serum Western blot
  • serum p24 antigen
  • serum HIV DNA polymerase chain reaction (PCR)
  • CD4 count
  • serum viral load (HIV RNA)
  • drug resistance testing
  • pregnancy test
  • serum hepatitis B serology
  • serum hepatitis C serology
  • serum venereal disease research laboratory test
  • Treponema pallidum haemagglutination test
  • rapid plasma reagin
  • tuberculin skin test
  • FBC with differential
  • serum electrolytes
  • serum creatinine
  • urinalysis
Full details

Investigations to consider

  • chest x-ray
  • liver function tests (LFTs)
  • lipid profile
  • plasma glucose
  • hepatitis A serology (IgG)
  • toxoplasma serology (IgG)
  • gonorrhoea and chlamydia testing
  • human leukocyte antigen-B*5701 testing
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Assistant Professor of Medicine

Infectious Diseases

Northwestern Memorial Hospital

Chicago

IL

Disclosures

CJA has been a member of an advisory board on HIV, aging and telomeres for Viiv, and has done consultant work as a member of DSMBs for ABIVAX, Atea, and Biotron. He has also received a grant for Investigator Sponsored Research from Gilead.

Dr Chad J Achenbach would like to gratefully acknowledge Dr Richard Rothman, Dr Michael Ehmann, Dr Linda-Gail Bekker, Dr Catherine Orrell, and Dr Lisa Capaldini, the previous contributors to this topic. ME, LGB, and CO declare that they have no competing interests. RR attended a symposium/conference hosted by a funding agency, Gilead HIV FOCUS program, from which he receives research funds. RR pays staff for an implementation/research program grant from Gilead HIV FOCUS for development of HIV testing programs in Emergency Departments. LC is on the speakers' bureau for the following pharmaceutical companies: GlaxoSmithKline, BMS, Merck, Gilead, Roche, Pfizer, Solvay, Lilly, Serrano, and Tibotec.

Peer reviewers VIEW ALL

Clinical Assistant Professor

University of British Columbia

Vancouver

Canada

Disclosures

MH is a member of an advisory board and/or speakers' bureau for Gilead Sciences Canada Inc, Merck Canada Inc, and ViiV Healthcare.

Assistant Professor of Medicine

Harvard Medical School

Director of Research

Global Health Delivery Project

Harvard School of Public Health

Boston

MA

Disclosures

WR declares that he has no competing interests.

Infectious Disease Physician

Oxford University Clinical Research Unit

Hospital for Tropical Diseases

Ho Chi Minh City

Vietnam

Disclosures

JD declares that he has no competing interests.

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