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Lifelong suppression
May 29, 2007

First, thank you for providing this wonderful resource.

I am HIV+ 7+ years, undetectable on ART therapy; WILD genotype; 99.99% medication adherance.

Previously, I was told by my physician that "lifelong suppression" is achievable. Recently, I was told by a Nurse Practitioner (I was a participant in the SMART clinical trial, this NP is my clinical trial liaison) that developing resistance is inevitible. These 2 seem to be at odds with one another.

Is "lifelong suppression" possible?

Is development of drug resistance inevitible?

I understand there are many variables including genotype, drug adherance, lifestyle, nutrition etc.

Thanks for your insights.

Response from Dr. Sherer

Thank you for these questions, they commonly recur on this website.

Both statements have considerable evidence in support of them, but neither statement is a proven fact, yet.

After 7 years with good virologic control, you are a good example of the hope that lifelong viral load suppression is possible. The longest standing clinical trial of HIV medication showed that 2/3 of study subjects on the same regimen had the same excellent virologic control after 7 years, so we know this can be achieved by many individuals. I would add that the chances of achieving this status are increased if 1) a fully potent ART regimen was used as the first-ever regimen, and 2) if the individual was, as you suggest, 99.9% adherent during those 7 years.

You are right to suggest some factors that might affect the chances of a good outcome for 7 years, or for a lifetime. Lifestyle is certainly one, e.g. people who use drugs or alcohol heavily are more prone to lapses in good adherence. Genotype is another, i.e. an individual who acquires an HIV strain that is already resistant to some ART medications may have a more difficult time achieving prolonged virologic suppression.

An earlier question today addressed whether drug resistance is 'inevitable'. The evidence that suggests that drug resistance might be inevitable is that HIV replication continues, even in individuals with complete virologic suppression in their plasma and with viral loads below detection, in sequestered sites such as the central nervous system and the gonads. Hence ongoing replication and new mutations continue to develop, even in people on ART with complete suppression. However, it appears that in many such individuals, their ART is able to control all viral strains, even small clones with some drug resistance. That has been the case for you for 7 years.

Hence I would answer your questions in this way:

'Lifelong suppression' appears possible, and there is good evidence that prolonged suppression of up to 7 years can occur in a majority of patients under optimmal conditions.

I like to offer the possibility of lifelong suppression to my patients, without certainty, based on these positive, durable outcomes, in order to motivate them and help them achieve the best and most durable outcome possible.

Development of drug resistance is not inevitable, based on the observation of individuals who have done so well for over 5 years, but the virus is a clever adversary that requires the vigilence of patients and doctors alike.

I urge you to take your questions and these responses to your doctor and discuss them with him or her.

mutations when 100% adherent
Viral Replication

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