NORTHWEST AIDS EDUCATION AND TRAINING CENTER

Updated HIV Treatment Guidelines 2014 Brian R. Wood, MD Assistant Professor of Medicine, University of Washington Medical Director, NW AETC ECHO

Last Updated: May, 2014

Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

US Health and Human Services (HHS) May 1, 2014 Antiretroviral Therapy Guidelines

HHS Antiretroviral Therapy Guidelines: May 1, 2014 Recommended Regimens Regardless of Baseline HIV RNA or CD4 Count

Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

Class Therapy Pill Burden

NNRTI-Based Efavirenz-Tenofovir-Emtricitabine

PI-Based Atazanavir + Ritonavir + Tenofovir-Emtricitabine

Darunavir + Ritonavir + Tenofovir-Emtricitabine

INSTI-Based

Raltegravir + Tenofovir-Emtricitabine

^Elvitegravir-Cobicistat-Tenofovir-Emtricitabine

Dolutegravir + *Abacavir-Lamivudine

Dolutegravir + Tenofovir-Emtricitabine

^Elvitegravir-Cobicistat-Tenofovir-Emtricitabine: only for patients with pre-ART CrCl ≥ 70 ml/min *Abacavir recommended only if HLA-B5701 negative

HHS Antiretroviral Therapy Guidelines: May 1, 2014 Recommended Regimens if Baseline HIV RNA <100,000 copies/mL

Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

^Rilpivirine-Tenofovir-Emtricitabine recommended only if CD4 count >200 cells/mm3

*Abacavir recommended only if HLA-B5701 negative

Class Therapy Pill Burden

NNRTI-Based Efavirenz + *Abacavir-Lamivudine

^Rilpivirine-Tenofovir-Emtricitabine

PI-Based Atazanavir + Ritonavir + *Abacavir-Lamivudine

.

Dolutegravir Phase 3 Studies in Treatment-Naïve Subjects

Study ARV History Comparison Results

1 SPRING-2 ARV-Naïve Dolutegravir QD versus Raltegravir

•  Non-inferior (88% versus 85%)

2 SINGLE ARV-Naïve Dolutegravir QD versus Efavirenz

•  Dolutegravir superior (88% versus 81%)

3 FLAMINGO ARV-Naïve Dolutegravir QD versus Darunavir+ritonavir

•  Dolutegravir superior (90% versus 83%)

1 Raffi F, et al. Lancet 2013;381:735-43. 2 Walmsley S. N Engl J Med. 2013:369:1807-18. 3 Clotet B, et al. Lancet. 2014 March 31 [Epub ahead of print]

Source: Wainberg MA, et al. BMC Medicine. 2013;11:249-

Source: Wainberg MA, et al. BMC Medicine. 2013;11:249-

“Virological failure with resistance mutations in treatment-naïve patients treated with dolutegravir has not been reported.”

Considerations When Selecting an ART Regimen for Initial Therapy

•  Genotype resistance assay result •  Pre-treatment viral load •  Likely adherence; regimen’s barrier to resistance •  Potential adverse effects •  Potential drug interactions •  Comorbidities (HBV, HCV, renal disease, psych illness, etc) •  Pregnancy or pregnancy potential •  Convenience (pill burden, pill size, food requirement) •  Cost/access

Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

Clinical Scenario Viral Load Monitoring CD4 Count Monitoring

Before Initiating ART

At entry into care (AIII) If ART initiation is deferred, repeat before initiating ART (AIII) In patients not initiating ART, repeat testing is optional (CIII)

At entry into care (AI) If ART is deferred, every 3 to 6 months (AIII)

After initiating ART

Preferably within 2 to 4 weeks (and no later than 8 weeks) (AIII); thereafter, every 4 to 8 weeks until viral load suppressed (BIII)

3 months after initiation of ART (AIII)

During first 2 years of ART Every 3 to 4 months (AIII) Every 3 to 6 months (BII)

After 2 years of ART (VL consistently suppressed, CD4 consistently 300-500 cells/mm3 )

Every 6 months for patients with consistent viral suppression for ≥2 years (AIII)

Every 12 months (BII)

After 2 years of ART (VL consistently suppressed, CD4 consistently >500 cells/mm3)

Every 6 months for patients with consistent viral suppression for ≥2 years (AIII)

Optional (CIII)

HHS Antiretroviral Therapy Guidelines: May 1, 2014 Recommended Monitoring of CD4 Count and HIV RNA

Source: 2014 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

Source: 2014 HHS Perinatal Treatment Guidelines. AIDS Info (www.aidsinfo.nih.gov)

US Health and Human Services (HHS) March 28, 2014 Perinatal Treatment Guidelines

Preferred Alternative Insufficient Data Avoid

Tenofovir-Emtricitabine

Darunavir + ritonavir

Dolutegravir Abacavir-Lamivudine-Zidovudine

^Abacavir-Lamivudine

Saquinavir + ritonavir

Rilpivirine Stavudine, Didanosine

Zidovudine-lamivudine

Raltegravir Maraviroc Indinavir + ritonavir

Atazanavir + ritonavir

ŦNevirapine Elvitegravir Nelfinavir

Lopinavir + ritonavir

Fosamprenavir + ritonavir

Etravirine

§Efavirenz Enfuvirtide

Tipranavir

HHS Recommended ARV’s for Treatment-Naïve Pregnant Women: 2014

^Abacavir recommended only if HLA-B5701 negative §Efavirenz should be started after 8 weeks gestation ŦAvoid nevirapine if CD4 count >250 cells/mL in women

Source: 2014 HHS Perinatal Treatment Guidelines. AIDS Info (www.aidsinfo.nih.gov)

Other Key Points from Perinatal Guidelines

•  Updated sections on ARV-oral contraceptive interactions and conception options for discordant couples

•  CD4 count monitoring can be every 6 months if stable on ART with consistently suppressed RNA level

•  C-section & IV AZT recommended if maternal HIV RNA >1,000 copies

Source: 2014 HHS Perinatal Treatment Guidelines. AIDS Info (www.aidsinfo.nih.gov)

Other Key Points from Perinatal Guidelines

•  If maternal HIV RNA suppressed on ART, 6 weeks AZT recommended for infant (can consider 4 weeks)

•  If maternal HIV RNA not suppressed, 6 weeks AZT and 3 doses NVP recommended for infant

•  Discussion of case of functional cure for infant and ongoing studies

Source: 2014 HHS Perinatal Treatment Guidelines. AIDS Info (www.aidsinfo.nih.gov)