How does type of treatment affect resistance?

As the number of available antiretrovirals and drug classes grow, so does the complexity of calculating drug resistance. Encouraging news came from a Canadian study that looked at resistance in over 2300 patients who initiated antiretroviral treatment between 1996 and 2004 and were followed for an average of 56 months.

They found that the probability of emergent drug resistance was decreasing. This trend was mainly attributed to the use of ritonavir-boosted protease inhibitor regimens. The likelihood of developing resistance was the same between those initiating therapy with either an NNRTI-based or a protease inhibitor-based regimen; however, there was a 2.4-fold lower odds ratio for developing HIV drug resistance in those who started with a boosted protease inhibitor regimen. This finding held true at every level of adherence.

Increased probability of resistance was also associated with higher baseline viral load, a history of injecting drug use, incomplete adherence, use of an NNRTI-based regimen, and therapy initiated in the period from 1996 to 1998.

In a meta-analysis of data from nearly 8000 patients, researchers found significantly fewer drug resistance mutations, including NRTI-associated mutations, in people who had experienced treatment failure while taking first-line HIV treatment based on boosted PIs than in people taking NNRTI-based therapy.

Genotypic NNRTI resistance was much more common than PI resistance. The NRTI-associated M184V and (in non-AZT-containing regimens) K65R mutation were more common in cases of NNRTI failure than of PI failure. Data were drawn from a meta-analysis of participants in 20 clinical trials for whom first-line treatment failure was seen after 48 weeks or less.1

Within any drug class, suboptimal adherence levels, defined as adherence between 80 and 94%, were associated with the highest risk of resistance. However, different drug classes had their own adherence-resistance patterns. Because boosted protease inhibitors have a longer half-life, they are more forgiving of missed or mistimed dosing than are NNRTI drugs.

Gender, diagnosis of AIDS, and CD4 cell count were not significantly associated with an increased risk of developing drug resistance.

With the use of genotypic and phenotypic testing to select first and subsequent regimens, the option to sequence drugs within some of the drug classes, reduced dosing times, and a lower overall pill burden, it may be possible to continue a temporal trend of reduced drug resistance. However, that will only be a possibility in settings where all the above are obtainable.

The potential effects of pre-exposure prophylaxis (PrEP) on drug resistance levels are currently a matter of debate. PrEP is the use of antiretroviral treatment by HIV-negative individuals as a preventive measure against HIV infection. Tenofovir and emtricitabine (FTC), singly or in dual combination (Truvada), are the only drugs currently being studied as PrEP.

While not all experts agree, some investigators warn that the wide adoption of PrEP could lead to a high frequency of transmitted drug resistance. The University of Pittsburgh's John Mellors has noted that tenofovir/FTC PrEP could have high failure rates where tenofovir and FTC resistance mutations are prevalent in individuals receiving antiretroviral therapy.2 In fact, many widely used drugs worldwide frequently fail with the M184V mutation, which confers complete resistance to FTC; the tenofovir-associated K65R mutation is also seen in 5 to 10% of cases of failure. Furthermore, individuals who did become HIV-positive while on PrEP would be on suboptimal therapy, with a high chance of developing further resistance.

However, the results of the first large placebo-controlled trial of PrEP, in men who have sex with men, produced no evidence of resistance in the small number of men who did become infected despite taking the active drugs.3


  1. Gupta R et al. Emergence of drug resistance in HIV type 1-infected patients after receipt of first-line highly active antiretroviral therapy: a systematic review of clinical trials. Clin Infect Dis 47:712-722, 2008
  2. Mellors J. Antiretrovirals for treatment and prevention – two trains on a collision course? Microbicides 2010 Conference, Pittsburgh. Symposium presentation 225, 2010
  3. Grant RM et al Preexposure chemoprophylaxis for HIV prevention in men. New Engl Jour Med, advance online publication, 23 November, 2010
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

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.