Adding on drugs and drug classes

Other than nucleoside reverse transcriptase inhibitor (NRTI)-only regimens, combinations containing more than three drugs have not been widely studied in treatment-naive patients. Such patients typically do not have extensive drug resistance and usually can achieve good outcomes with less intensive treatment.

Combinations containing three drug classes (NRTIs, non-nucleoside reverse transcriptase inhibitor [NNRTIs] and protease inhibitors) have also been less well studied than other strategies. The concern with this approach is that it may lead to the development of resistance to three different drug classes, which could make constructing a subsequent regimen very difficult.

An ACTG 5095 analysis compared AZT/3TC/efavirenz against AZT/3TC/abacavir/efavirenz in treatment-naive patients. After three years of follow-up, similar proportions of people experienced treatment failure (26 vs 25%) and achieved viral suppression below 50 cells/mm3 (85% vs 88%) in the two arms, showing that the additional drug offered no extra benefit in this case.1

The ACTG 384 study showed that adding an extra NNRTI, nelfinavir, to the AZT/3TC/efavirenz regimen provided no additional benefit.2

Similarly, in the INITIO study, people randomly assigned to start therapy using AZT/3TC/nelfinavir/efavirenz did no better in terms of viral suppression or immune recovery than those taking AZT/3TC/nelfinavir or AZT/3TC/efavirenz after three years of follow-up. There also were no differences with regard to side-effects or progression to AIDS or death.3

In the 2NN study, using both efavirenz plus nevirapine, with d4T/3TC provided no advantage over efavirenz or nevirapine alone plus the backbone, but caused greater toxicity.4

Current UK and US treatment guidelines do not recommend regimens containing more than three drugs or more than two drugs classes for people who are new to treatment.

References

  1. Gulick RM et al. Intensification of a triple-nucleoside regimen with tenofovir or efavirenz in HIV-1-infected patients with virological suppression. AIDS 21: 813  823, 2007
  2. Shafer RW et al. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 349: 2304-2315, 2003
  3. Cooper D et al. Virological and immunological outcomes at 3 years following initiation of ART with regimens containing a NNRTI or PI or both: the INITIO Trial. Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 165LB, 2005
  4. van Leth F et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 363: 1253-1263, 2004
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.