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Initiating Antiretroviral Therapy

When to Initiate ART

The guidelines for when to initiate antiretroviral treatment reflect a balance between: wanting to suppress HIV as much and as soon as possible to preserve immune function versus the long-term toxicity of current medications, as well as the challenge of long-term adherence. The "golden moment" to start ART is thus dependent on the properties of currently licensed medications. It is therefore crucial that providers check the most current ART guidelines before initiating therapy. Although there are clinical indications to begin treatment, it is also vital to assess the adolescent's treatment readiness as described below.

Let's begin with clinical guidelines for starting treatment.

Indications for Initiating Antiretroviral Therapy for the Chronically HIV-Infected Patient
Clinical Condition and/or CD4 CountRecommendation
  • History of AIDS-defining illness
  • CD4 count <200 cells/mm3
  • CD4 count 200-350 cells/mm3
  • Pregnant women*
  • Persons with HIV-associated nephropathy
  • Persons coinfected with hepatitis B virus (HBV), when HBV treatment is indicated (Treatment with fully suppressive antiviral drugs active against both HIV and HBV is recommended.)
Antiretroviral therapy should be initiated.
Patients with CD4 count >350 cells/mm3 who do not meet any of the specific conditions listed above.The optimal time to initiate therapy in asymptomatic patients with CD4 count >350 cells/mm3 is not well defined. Patient scenarios and comorbidities should be taken into consideration.
Adapted from U.S. Department of Health and Human Services. Table 5a. Indications for Initiating Antiretroviral Therapy for the Chronically HIV-1 Infected Patient. In: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. November 3, 2008.

Selecting ART Regimens

Initiation of ART is a critical decision that always should be made jointly between a collaborative physician and an informed patient. Generally, the decision should be made only after unhurried discussions (ideally, over the course of several patient visits), which can give the patient an understanding of the potential risks and benefits of alternative therapeutic approaches and can facilitate the patient's commitment to the ART regimen that is chosen.

The following recommendations are based on current DHHS Guidelines.

Recommended Components of Initial Antiretroviral Treatment
Therapy should consist of either:
  • 1 NNRTI + 2 NRTIs, or
  • 1 PI (preferably boosted with ritonavir) + 2 NRTIs
Column A: NNRTI or PI Options
+Column B: Dual-NRTI Options
Preferred Components NNRTI
  • efavirenza
or PI
  • atazanavir + ritonavir (QD)
  • darunavir + ritonavir (QD)
  • fosamprenavir + ritonavir (BID)
  • lopinavir/ ritonavir (BID or QD)b
Preferred Dual NRTI
  • tenofovir + emtricitabine (QD)
Alternative ComponentsNNRTI
  • nevirapine (QD or BID)c
or PI
  • atazanavir (QD)d
  • fosamprenavir (BID)
  • fosamprenavir + ritonavir (QD)
  • saquinavir + ritonavir (BID)
Alternative Dual NRTI
  • abacavir + lamivudine (QD or BID)e
  • didanosine + (emtricitabine or lamivudine) (QD)f
  • zidovudine + lamivudine (BID)

Key to abbreviations: PI = protease inhibitor; NNRTI = nonnucleoside reverse transcriptase inhibitor; NRTI = nucleoside/nucleotide analogue; BID = twice daily; QD = once daily.

a. Efavirenz should not be used during the 1st trimester of pregnancy or in sexually active women with childbearing potential who are not using effective contraception.
b. Do not use QD lopinavir/ritonavir in pregnant women.
c. Nevirapine should not be initiated in women with CD4+ T cell count >250 cells/µL or in men with CD4+ T cell count >400 cells/µL because of increased risk of hepatotoxicity. Do not use in patients with moderate or severe hepatic impairment.
d. Atazanavir must be boosted with ritonavir if used in combination with tenofovir. Do not use in patients on high-dose proton pump inhibitors; caution in patients on PPIs (any dose), H2 blockers, or antacids.
e. Test for HLA-B*5701 before treating with abacavir; do not use in patients who test positive. Caution in patients with HIV RNA >100,000 copies/mL: higher rate of virologic failure compared with tenofovir + emtricitabine.
f. Do not use with unboosted atazanavir.

Adapted from U.S. Department of Health and Human Services. Table 6. Antiretroviral Therapy for Treatment-Naive Patients. In: Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. November 3, 2008.

Once-Daily Dosing

Because challenges to adherence can compromise the long-term success of treatment, and because even modest inconveniences can become significant in the context of lifelong therapy, the focus of ART is shifting toward the use of simpler regimens. In addition to improving convenience and facilitating adherence, once-daily dosing permits the administration of ART as directly observed therapy (DOT), in which a provider observes the ingestion of medication. DOT has been shown to be successful in improving HIV treatment, especially among hard-to-reach populations, but is labor intensive. Providers may consider DOT during a 3-6 month period to improve patient education and medication self-administration.6

There are 11 medications currently approved for once-daily dosing:

  • Abacavir
  • Didanosine
  • Lamivudine
  • Emtricitabine
  • Tenofovir
  • Efavirenz
  • Atazanavir
  • Ritonavir-boosted atazanavir
  • Ritonavir-boosted darunavir
  • Ritonavir-boosted fosamprenavir
  • Ritonavir-boosted lopinavir
Antiretroviral Medications Not Recommended in Initial Treatment
ReasonMedication
High rate of early virologic failure
  • didanosine + tenofovir
Inferior antiviral activity
  • 3-NRTI regimens
  • atazanavir + didanosine + emtricitabine
  • delavirdine
  • nelfinavir
  • saquinavir as sole PI (unboosted)
  • tipranavir + ritonavir
High incidence of toxicities
  • stavudine + lamivudine
  • indinavir + ritonavir
  • ritonavir used as sole PI
High pill burden / dosing inconvenience
  • indinavir (unboosted)
  • nelfinavir + saquinavir
Lack of data in initial treatment
  • abacavir + tenofovir
  • abacavir + didanosine
  • darunavir (unboosted)
  • enfuvirtide
  • etravirine
  • maraviroc
  • raltegravir
No benefit over standard regimens
  • 3-class regimens
  • 3 NRTIs + NNRTI
From Coffey S. Initiation of Therapy. AETC National Resource Center. Presentation developed to accompany the DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. November 3, 2008.

References

  1. Machtinger EL, Bangsberg DR. Adherence to HIV Antiretroviral Therapy. In: Peiperl L, Coffey S, Volberding PA, eds. HIV InSite Knowledge Base [textbook online]; San Francisco: UCSF Center for HIV Information; May 2005.