Updated HIV Guidelines

The very useful, well-written, and widely-used Department of Health and Human Services (DHHS) Guidelines for the use of antiretroviral agents in HIV-infected persons were updated about 3 weeks ago.¹ While there were not many unexpected or “earth-shattering” changes, it is worth noting a few of the important changes and updates in the document.

• The recently-approved new formulation of tenofovir (tenofovir alafenamide or TAF), when co-formulated with emtricitabine (FTC) as “Descovy,” has been added to all of the recommended and alternative regimens that previously used the older formulation of tenofovir plus FTC (“Truvada”). The alafenamide formulation of tenofovir results in higher intra-cellular levels of tenofovir (where the drug is active) and considerably lower serum levels, such that the incidence of kidney injury and bone mineral density loss is substantially reduced.
• Note that Descovy does not require dose adjustment as long as the estimated glomerular filtration rate is greater than 30 mL/min. Below this level, it should not be used.
• Note that the older formulation (Truvada) has been associated with more favorable lipid effects than either Descovy or an abacavir-containing co-formulated product.
• Note that a urinalysis is recommended every 6 months for those individuals on either Descovy or Truvada.
• Descovy also is a recommended component of antiretroviral regimens in individuals who are co-infected with hepatitis B (HBV) and HIV. If neither Descovy nor Truvada can be used in HBV/HIV co-infected persons, than either lamivudine (3TC) or FTC should be used in combination with entecavir.
• Resistance testing is recommended in all persons at baseline, as it has been for quite some time. However:
• If transmitted drug resistance in the integrase strand transfer class is a concern, as it may be now that both raltegravir and elvitegravir have been available for years, a separate resistance test for mutations in that class should be ordered.
• In certain circumstances, such as acute (or early) HIV infection or pregnancy, the guidelines now indicate that initiation of antiretroviral therapy should not be delayed until the resistance test results are known. If necessary, the regimen can be changed if drug limiting mutations are detected.
• A “next-generation” resistance assay that analyzes HIV-1 proviral DNA from individuals with an “undetectable” HIV RNA level now is commercially available. However, the clinical utility of that assay has not been determined.
• Especially in those circumstances in which therapy must be started before resistance testing results are available, or for those individuals for whom adherence has been, or is likely to be, suboptimal, the Guidelines now note that either a boosted darunavir-based regimen, or a dolutegravir-based regimen, are particularly good options. Transmitted resistance to the protease inhibitor class remains infrequent, and darunavir has a high genetic barrier to the development of resistance; dolutegravir resistance is uncommon in those failing therapy with a dolutegravir-based regimen, and transmitted resistance to dolutegravir has not been reported.
• The drug interaction section and tables have been updated to include information about potential interactions between antiretrovirals and the recently-approved HCV drugs daclatasvir and the coformulated comination of elbasvir plus grazoprevir.
• The “regimen switching” section has been expanded to emphasize well-studied options and safety, especially for those with undetectable levels of HIV RNA.
• The “tuberculosis” section has been greatly expanded and updated. Specifically:
• It now is recommended that antiretroviral therapy be initiated within 8 weeks of starting TB therapy in persons with active TB, regardless of CD4 count. When the CD4+ cell count is less than 50 cells/uL, antiretroviral therapy should be initiated within 2 weeks.
• For the management of latent TB infection (LTBI), there now are 3 treatment options:
• INH monotherapy daily or twice weekly for 9 months.
• INH plus rifapentine, each once weekly, for 12 weeks; however, this regimen should be used only in those HIV-infected persons on either an efavirenz- or a raltegravir-based regimen.
• Rifampin or rifambutin monotherapy daily for 4 months.
• Early initiation of antiretroviral therapy (ie, when the CD4+ cell count is more than 500 cells/uL) substantially reduced the risk of acquiring TB in TB-endemic areas.

Disclosures:

• Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Accessed 03 August 2016.