Page 578 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPTEr 39 HIV and Acquired Immunodeficiency Syndrome 555

after diagnosis to reduce morbidity and mortality and to prevent
Testing for Viral Tropism and Abacavir Hypersensitivity transmission of HIV (see also HIV prevention). Randomized
Additional assays should be performed before the initiation of controlled trials have demonstrated that ART should be initiated
specific ARV medications. A viral tropism assay should be in all patients with HIV infection, regardless of disease stage.
performed before initiation of a CCR5 antagonist. HLA-B*57:01 The urgency to initiate ART is greatest for patients with lower
testing is indicated before initiation of abacavir, as this HLA CD4 counts, in whom the absolute risk of opportunistic infections,
phenotype is associated with abacavir hypersensitivity in 5–8% non-AIDS morbidity, and death is highest. However, the START
of patients early in the course of treatment. (Strategic Timing of Anti-Retroviral Therapy) and the French
National Agency for Research on AIDS and viral hepatitis (ANRS)
TREATMENT 12136 “Temprano” trials provide the evidence that morbidity
and mortality is reduced in individuals with CD4 counts >500
Antiretroviral Therapy: Attacking HIV’s Lifecycle cells/mm at the start of ART, resulting in strong recommenda-
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Combinations of ARV medications are used to maximally inhibit tions, from both the US HIV treatment panel and the World
HIV replication and to reduce HIV-associated morbidity and Health Organization (WHO), to initiate ART in all patients
mortality. Combination ART refers specifically to a combination regardless of CD4 cell count. In the START trial—a large,
of at least three ARV medications inhibiting the HIV lifecycle multinational, randomized controlled clinical trial with 4685
(see Fig. 39.3; Fig. 39.7). Current US guidelines recommend participants—ART-naive adults with CD4 counts >500 cells/
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initiation of ART-naïve persons with a combination of two mm were randomized to initiate ART soon after randomization
nucleoside reverse transcriptase inhibitors (NRTIs) plus an or to wait to initiate ART until their CD4 counts declined to
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integrase strand transfer inhibitor, a nonnucleoside reverse <350 cells/mm , or until they developed a clinical indication for
transcriptase inhibitor (NNRTI), or a protease inhibitor (PI) therapy. Serious AIDS or non-AIDS events endpoint was reported
with a pharmacokinetic enhancer (cobicistat or ritonavir). In in 42 (1.8%) early ART participants and in 96 (4.1%) deferred
ART-experienced patients, modification of ARV regimens and ART participants (hazard ratio [HR] 0.43, favoring early ART
use of other classes of ARVs is guided, in part, by consideration [95% confidence interval (CI), 0.30–0.62; p < 0.001]). The
of a number of factors, including viral resistance patterns, majority (59%) of clinical events in the delayed ART arm occurred
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potential side effects, available medication formulations, pill in participants whose CD4 counts were still >500 cells/mm ,
burden, frequency of dosing, tolerability, short-term and long- evidence for a benefit of immediate ART even before CD4 count
term adverse event profiles, desire for pregnancy, and desire to declines below this threshold. The TEMPRANO ANRS 12136
preserve subsequent treatment options. 24,25 study—a study of more than 2000 participants in Cote d’Ivoire,
who were randomized to immediate or deferred ART—showed
When to Start Therapy the benefit of immediate treatment over deferred treatment in
There are significant data to support treating all HIV-infected reducing a combination of all-cause deaths, AIDS diseases,
individuals with ART and starting treatment as soon as possible non-AIDS malignancies, and non-AIDS invasive bacterial diseases,

RTI PI Fusion inhibitor
Abacavir (ABC) Atazanavir (ATV) Enfuvirtide
Didanosine (ddI) Darunavir (DRV) (ENF, T-20)
Emtricitabine (FTC) Fosamprenavir
Lamivudine (3TC) (FPV)
Stavudine (d4T) Indinavir (IDV) CCR5 Antagonist
Tenofovir DF (TDF) Lopinavir (LPV) Maraviroc (MVC)
Tenofovir alafenamide (TAF) Nelfinavir (NFV)
Zidovudine (AZT, ZDV Saquinavir (SQV) Pharmacokinetic (PK) booster
Tipranavir (TPV) Ritonavir (RTV)
Cobicistat (COBI)
NNRTI
Delavirdine (DLV) Integrase inhibitor (INSTI)
Efavirenz (EFV) Dolutegravir (DTG)
Etravirine (ETR) Elvitegravir (EVG)
Nevirapine (NVP) Raltegravir (RAL)
Rilpivirine (RPV)
One-pill regimen DTG/ABC/3TC; only if HLA-B*57:01 negative
EFV/TDF/FTC
EVG/COBI/TDF/FTC
EVG/COBI/TAF/FTC
RPV/TDF/FTC (if HIV RNA <100,000 copies/mL and CD4 >200
cells/µL)

RPV/TAF/FTC (if HIV RNA <100,000 copies/mL and CD4 >200
cells/µL)
fIG 39.7 Antiretroviral (ARV) medications approved by the U.S. Food and Drug Administration
(FDA).