Disseminated Mycobacterium avium complex
Ethionamide, thiacetazone (not available in the US), and cycloserine have been combined with first-line agents as salvage regimens and may have activity. However, their role in this setting is not well defined, and are associated with substantial toxicities.[261]Wang F, Langley R, Gulten G, et al. Mechanism of thioamide drug action against tuberculosis and leprosy. J Exp Med. 2007 Jan 22;204(1):73-8.
http://jem.rupress.org/cgi/content/full/204/1/73
http://www.ncbi.nlm.nih.gov/pubmed/17227913?tool=bestpractice.com
Although under investigation, due to insufficient data no recommendation can be made for the use of immunomodulators as adjunctive therapy.[1]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 2025 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
Cryptococcal meningitis
There are few data regarding the use of newer triazoles, such as voriconazole and posaconazole, as either primary or follow-up therapy for individuals with cryptococcosis. Voriconazole should be used cautiously with protease inhibitors and efavirenz.[1]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 2025 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
[262]Spanakis EK, Aperis G, Mylonakis E. New agents for the treatment of fungal infections: clinical efficacy and gaps in coverage. Clin Infect Dis. 2006 Oct 15;43(8):1060-8.
http://cid.oxfordjournals.org/content/43/8/1060.full
http://www.ncbi.nlm.nih.gov/pubmed/16983621?tool=bestpractice.com
In HIV-associated cryptococcal meningitis, the addition of a short course of interferon gamma to standard treatment significantly increased the rate of clearance of cryptococcus from the cerebrospinal fluid without an increase in adverse events, yet further definitive clinical studies are needed.[263]Jarvis JN, Meintjes G, Rebe K, et al. Adjunctive interferon-γ immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial. AIDS. 2012 Jun 1;26(9):1105-13.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640254
http://www.ncbi.nlm.nih.gov/pubmed/22421244?tool=bestpractice.com
Cytomegalovirus (CMV)
Letermovir is a CMV viral terminase complex inhibitor that has been approved by the Food and Drug Administration for CMV prophylaxis in high-risk recipients of hematopoietic stem cell transplants. Its role in the treatment of CMV retinitis is unclear and it can significantly interact with several antiretroviral agents.[264]Turner N, Strand A, Grewal DS, et al. Use of letermovir as salvage therapy for drug-resistant cytomegalovirus retinitis. Antimicrob Agents Chemother. 2019 Mar;63(3):e02337-18.
https://journals.asm.org/doi/10.1128/aac.02337-18
http://www.ncbi.nlm.nih.gov/pubmed/30642941?tool=bestpractice.com
Maribavir is a CMV viral kinase UL97 inhibitor that has been studied in transplant recipients but data on its use for CMV disease in individuals with HIV are lacking.
Tuberculosis (TB)
A regimen of 1 month of daily isoniazid plus rifapentine has been evaluated in a randomized, open-label, phase 3 trial and found to be noninferior to 9 months of isoniazid alone for preventing TB in people with HIV who were living in areas of high TB prevalence or who had evidence of LTBI.[265]Swindells S, Ramchandani R, Gupta A, et al. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011.
https://www.doi.org/10.1056/NEJMoa1806808
http://www.ncbi.nlm.nih.gov/pubmed/30865794?tool=bestpractice.com
US guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV include the 1-month regimen as an alternative option for treatment of LTBI in people with HIV.[1]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 2025 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
However, it is not currently recommended in the National Tuberculosis Controllers Association and Centers for Disease Control and Prevention guidelines.[72]National Tuberculosis Coalition of America. Testing and treatment of latent tuberculosis infection in the United States: a clinical guide for health care providers and public health programs. Feb 2025 [internet publication].
https://tbcontrollers.org/resources/tb-infection/clinical-recommendations
Disseminated histoplasmosis
Isavuconazonium (a prodrug of isavuconazole), an extended-spectrum triazole antifungal, has been shown to have in vitro activity against Histoplasma capsulatum, although there are insufficient clinical data available and has been used in too few individuals with histoplasmosis to be routinely recommended in the treatment of histoplasmosis.[1]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 2025 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/whats-new
[266]Seyedmousavi S, Verweij PE, Mouton JW. Isavuconazole, a broad-spectrum triazole for the treatment of systemic fungal diseases. Expert Rev Anti Infect Ther. 2015 Jan;13(1):9-27.
http://www.ncbi.nlm.nih.gov/pubmed/25488140?tool=bestpractice.com