14. Initiation of Antiretrovirals in Acute OI

Overview

Patients diagnosed with AIDS-defining opportunistic or significant bacterial infections should initiate ART as soon as possible, with several notable exceptions which are discussed in this section. Initiation of ART should involve discussion of risks and benefits with the patient and consultation with an ID specialist.

Management

  • Early ART initiation is important for treating infections with ineffective specific therapy: PML, cryptosporidium, microsporidiosis, Kaposi sarcoma
  • Please see the Ward 86 Treatment Guidelines for recommendations on when to start ART in patients who are hospitalized with OIs (http://hivinsite.ucsf.edu/InSite?doc=md-ward86-art-oi&page=md-ward86-index). In general, ART should be started as soon as possible in hospitalized patient with a few exceptions:
    • Cryptococcal meningitis: optimal timing controversial, recommend waiting 2-5 weeks after start of antifungal treatment
    • Ocular OIs, especially CMV retinitis: recommend waiting 14 days after starting antimicrobial OI therapy prior to initiation of ART
    • CNS OIs (other than TB or cryptococcal meningitis): if imaging evidence of edema or mass effect, recommend waiting 2 weeks after starting OI antimicrobial therapy prior to initiation of ART. May also consider waiting 2 weeks for patients with CNS OI and neurologic deficit
    • Intubated/hypotensive patients: consider waiting 5-7 days prior to initiation of ART
    • Newly diagnosed TB:
      • CD4 count < 50: ART should be initiated within 2 weeks of mycobacterial treatment
      • CD4 count ³ 50: ART should be initiated within 8 weeks of mycobacterial treatment
      • TB meningitis: ART should be delayed for 8 weeks of mycobacterial treatment regardless of CD4 count, an expert should be consulted, and requires close monitoring for adverse events
    • Newly diagnosed disseminated MAC: recommend starting ART after two weeks of mycobacterial therapy
  • Concerns and considerations of starting ART in setting of active OI
    • Decreased absorption of drugs due to acute illness (with subtherapeutic levels leading to increased resistance)
    • Toxicities of treatment difficult to distinguish from disease manifestations
    • Increased drug-drug interactions
    • Decreased adherence to treatment regimens due to pill burden and side effects
    • Occurrence of IRIS and difficulty distinguishing from other clinical conditions

Key Points

  • Patients diagnosed with AIDS-defining opportunistic or significant bacterial infections should initiate ART as soon as possible, with several notable exceptions

Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on June 1, 2020).

Jacobson MA Diagnosis and Management of Disseminated Mycobacterium avium Complex Infection. HIVInSite 2018.

Gandhi M Initiating Antiretroviral Therapy in Hospitalized HIV-Infected Patients. HIVInSite 2019.

Chamie G Treatment of Tuberculosis and Latent Mycobacterium tuberculosis Infection in HIV-Patients. HIVInSite 2018.

Zolopa AR, Andersen J, Komarrow L, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial.  PLoS One 4(5):e5575.

Grant PM, Komarrow L, Andersen J, et al. Risk factor analyses for immune reconstitution inflammatory syndrome in a randomized study of early vs. deferred ART during an opportunistic infection.  PLoS One 2010 5(7): e11416.

Abdool Marik SS, Naidoo K, Grobler, A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy.  N Engl J Med 2010 362(8):697-706.

Payam Nahid, Susan E. Dorman, Narges Alipanah, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis, Clinical Infectious Diseases, Volume 63, Issue 7, 1 October 2016, Pages e147–e195, https://doi.org/10.1093/cid/ciw376