Updated recommendations from the International Antiviral Society-USA panel on antiretroviral (ARV) drug therapy for HIV infection integrate treatment and prevention for the first time.

“This reflects the emergence of data over the past decade from 10 efficacy trials regarding the use of antiretrovirals for preexposure prophylaxis (PrEP), which was found to be highly effective in protecting diverse populations at risk of HIV, including men who have sex with men, younger heterosexuals, and injecting drug users,” note the authors of an editorial published with the new guidelines today in JAMA.

The guidelines state that newer data support the “widely accepted” recommendation to initiate ARV therapy in all people with HIV infection with detectable viremia regardless of CD4 cell count.

They say optimal initial regimens for most patients are two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). “The integrase inhibitors have risen to the top and stand by themselves really as obvious components of treatment,” Dr. Volberding told Reuters Health.

“The reason InSTIs have moved into a key position as first-line therapy is because these drugs have been shown to be highly effective, with the highest and most rapid rates of virologic suppression compared with protease inhibitors and nonnucleoside reverse transcriptase inhibitors, which previously had been mainstays of the antiretroviral ‘cocktail,'” write editorialists Dr. Kenneth Mayer and Dr. Douglas Krakower, of Fenway Health in Boston, Massachusetts. “Moreover, InSTIs are extremely well tolerated and several are coformulated with nucleoside analogs, allowing for potent, well-tolerated treatment to be delivered as a single pill taken once a day.”

Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs, the guidelines say.

 The guidelines provide recommendations for special populations such as pregnant women and in the settings of opportunistic infections and concomitant conditions such as hepatitis B or C coinfection.

They recommend laboratory assessments before treatment, and monitoring during treatment to assess response, adverse effects, and adherence. The guidelines provide advice on how and when to switch ARV regimens and say reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities.

The guidelines encourage PrEP with daily tenofovir disoproxil fumarate/emtricitabine to prevent HIV infection in individuals at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure.


Recommendations for When to Start Antiretroviral Therapy

♦   Antiretroviral therapy (ART) is recommended for all viremic patients with established HIV infection, regardless of CD4 cell count (evidence rating AIa).
♦   Initiation of ART is recommended as soon as possible in the setting of acute HIV infection (evidence rating BIII).
♦   Planned discontinuation of early ART after a specific duration of treatment is not recommended outside a research setting (evidence rating AIa).
♦   Initiation of ART is recommended for individuals who have persistent undetectable viral load without ART but have declining CD4 cell counts (evidence rating BIII).

Recommendations for Initial ART Regimens

  • Recommended initial regimens (listed in alphabetic order by InSTI component):

    • Dolutegravir/abacavir/lamivudine (evidence rating AIa)

    • Dolutegravir plus TAF/emtricitabine (evidence rating AIa)

    • Elvitegravir/cobicistat/TAF/emtricitabine (evidence rating AIa)

    • Raltegravir plus TAF/emtricitabine (evidence rating AIII)

  • HLA-B*5701 testing should be performed prior to abacavir use (evidence rating AIa); those who test positive should not be given abacavir (evidence rating AIa).

  • Tenofovir disoproxil fumarate is not recommended for individuals with or at risk of kidney or bone disease (osteopenia or osteoporosis) (evidence rating BIII).

  • Recommended initial regimens for individuals in whom an InSTI is not an option (listed in alphabetic order by InSTI component):

  • Darunavir (boosted) plus TAF (or TDF)/emtricitabine or abacavir/lamivudine (evidence rating AIa)

    • Efavirenz/TDF/emtricitabine (evidence rating AIa)

    • Rilpivirine/TAF (or TDF)/emtricitabine (evidence rating AIa)

  • Initial 2-drug regimens are recommended only in rare situations in which a patient cannot take abacavir, TAF, or TDF (evidence rating BIa).

  • HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to their infant (evidence rating AIa).

  • For HIV-infected patients with hepatitis B virus coinfection should initiate ART that contains TDF or TAF (evidence rating AIa), lamivudine or emtricitabine, and a third component (evidence rating AIa).

  • Entecavir may be used to treat hepatitis B virus infection (evidence rating AIII). If HIV RNA is not suppressed, entecavir should be avoided because it can select for drug-resistant HIV (evidence rating AIII).

  • HIV-infected patients with hepatitis C virus coinfection should start an ART regimen with drugs that do not have significant drug interactions with hepatitis C virus therapies (evidence rating AIIa).

  • Tenofovir disoproxil fumarate is not recommended for patients with osteopenia or osteoporosis (evidence rating BIII).

  • Monitoring for development of kidney disease with estimated glomerular filtration rate, urinalysis, and testing for glycosuria and albuminuria or proteinuria is recommended when ART is initiated or changed and every 6 months (along with HIV RNA) once HIV RNA is stable (evidence rating BIII).

  • Tenofovir disoproxil fumarate should be avoided or dose adjusted in patients with a creatinine clearance rate below 60 mL/min (evidence rating AIa).

  • Tenofovir alafenamide is not recommended in patients with a creatinine clearance rate below 30 mL/min (evidence rating AIa).

  • Tenofovir disoproxil fumarate or TAF should be discontinued if a patient’s renal function worsens, particularly if there is evidence of proximal tubular dysfunction (evidence rating AIIa).

  • HIV-infected patients with end-stage renal disease should be evaluated for kidney transplantation with expectation of high rates of patient and graft survival (evidence rating AIIa).

View full recommendations.