HIV and AIDS
Table 1: Initial Combination Regimen for Antiretroviral Naïve Patient Antiretroviral Guidelines for Adults and EACS Guidelines
Adolescents-NIH 2009
Recommended NNRTI regimen
EFV or
Ritonavir boosted PI ATV/r DRV/r
TDF/FTC 2009
NNRTI EFV
NVP* or
Ritonavir boosted PI ATV/r DRV/r
Alternative regimen EFV
ABC/3TC or
ZDV/3TC NVP ZDV/3TC
SQV/r or
FPV/r RAL
ZDV/3TC or
ddI/3TC or FTC
TDF/FTC or
ABC/3TC**,***
French Recommendations 2010
NNRTI EFV
TDF/FTC
Ritonavir boosted PI TDF/FTC ATV/r DRV/r LPV/r
Ritonavir boosted PI ABC/3TC**,*** ATV/r LPV/r NVP or
TDF/FTC
SQV/r or
RAL EFV or
DRV/r or
ATV/r or
FPV/r LPV/r or
SQV/r
ABC/3TC or
ZDV/3TC ABC/3TC or
ZDV/3TC or
TDF/FTC
*Use with extreme caution in women with CD4 >250/µl and men with CD4 >400/µl. **Contraindicated if HLAB5701 positive.
***Should be used with caution in patients with a high cardiovascular risk and/or patients with a viral load higher than 100,000 copies/ml. 3TC = lamivudine; ABC = abacavir; ATV = atazanavir; ddI = didanosine; DRV = darunavir; EACS = European AIDS Clinical Society; EFV = efavirenz; FPV = fosamprenavir; FTC = emtricitabine; LPV = lopinavir; NIH = National Institutes of Health; NRTI = nucleos(t)ide reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PI = protease inhibitor; r = low dose ritonavir; RAL = raltegravir; SQV = saquinavir; TDF = tenofovir; ZDV = zidovudine.
never, per se, considered as criteria of treatment choice, yet it might change in the coming years. Secondly, we must be ready to more frequently tailor the regimen according to the individual characteristics of the patients. Viral eradication cannot be achieved at the present time and ARV must be readily modified given the lifetime duration of therapy.
All expert groups currently recommend a combination of two nucleoside reverse transcriptase inhibitor (NRTI) backbone with a third agent being either a non-nucleoside reverse inhibitor transcriptase (NNRTI) or a ritonavir boosted protease inhibitor (PI). Only the US recommendations have recently added raltegravir, the first approved anti-integrase inhibitor as a third agent in treatment naïve patients (see Table 1).1,2,3
Choice of Nucleoside Reverse Transcriptase Inhibitor Combinations
While stavudine/didanosine with lamivudine were the backbones of ARV triple therapy for many years, data showing short- and long-term toxicities, including sub-optimal viral suppression, has led to substantial decrease in their support.
All experts currently recommend tenofovir or abacavir plus lamivudine or emtricitabine as first-line NRTI combinations. Both lamivudine and emtricitabine have excellent tolerability, but may select for the M184V resistance mutation, known to confer high-level resistance to both
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Presently, the prescription of either tenofovir or abacavir guides the decision of concomitant, fixed-dose treatment with FTC or 3TC, respectively.
drugs (low genetic barrier). Both have activity against hepatitis B virus (HBV) replication, yet the rate of emerging resistant strains is high when no other anti HBV active drugs are concomitantly given (50 % after two years). The clinical relevance in pharmacokinetic differences between lamivudine (3TC) and emtricitabine (FTC), of which the later drug has a longer intracellular half-life, has not been convincingly established. The M184V mutation may impact HIV fitness by reducing replication, which advocates the use of 3TC or FTC even for mutant virus, however, clinical relevance has yet to be established.4
FPV/r PI/r or
EFV ZDV/3TC ABC/3TC**,***
Tenofovir/Emtricitabine – Coformulated Combination of tenofovir/lamivudine or emtricitabine, as part of an efavirenz-based regimen in treatment-naïve patients, demonstrated potent virological suppression5
and was superior to
zidovudine (AZT)/lamivudine in virological efficacy at up to 144 weeks and with a lower frequency of lipodystrophy and anaemia.6
In a
number of randomised clinical trials, tenofovir with emtricitabine or lamivudine has been studied in combination with several different boosted PIs and demonstrated good virological control.7–10
Tenofovir/emtricitabine was compared with abacavir/lamivudine in the ACTG 5202 study11
and the HEAT trial.12 The ACTG trial was a four arm trial evaluating these NRTI combinations with either efavirenz or EUROPEAN INFECTIOUS DISEASE
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