Infection with multi-drug resistant virus is lifelong, Canadian expert argues

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Patients infected with HIV resistant to all three widely used classes of antiretrovirals will keep that resistance for life, and not revert back to wild type virus, the Seventh International Congress on Drug Therapy in HIV Infection was told in Glasgow today.

Dr. Mark Wainberg of McGill University AIDS Centre in Montreal, Canada added that the clinical consequences of infection with multi-drug resistant (MDR) virus were unpredictable, varying from repeated treatment failure to long-term non-progression.

Wainberg presented findings from a cohort of 31 patients who were diagnosed during primary HIV infection. Six patients from the 31 had three-class resistant virus, while ten had resistance to at least one class, enabling a comparative longitudinal study of their clinical progress.

Glossary

capacity

In discussions of consent for medical treatment, the ability of a person to make a decision for themselves and understand its implications. Young children, people who are unconscious and some people with mental health problems may lack capacity.

superinfection

When somebody already infected with HIV is exposed to a different strain of HIV and becomes infected with it in addition to their existing virus.

 

longitudinal study

A study in which information is collected on people over several weeks, months or years. People may be followed forward in time (a prospective study), or information may be collected on past events (a retrospective study).

long-term non-progressor

An HIV-infected person who remains free of AIDS symptoms (such as immune system decline or opportunistic diseases) for an unusually long period of time in the absence of treatment. These individuals typically have strong CD8+ T-cell responses, minimal lymph node damage and a relatively low viral load. About 10% of HIV-positive people seem to be long-term non-progressors. Most, but not all, are elite (or HIV) controllers. 

wild-type virus

The naturally occurring, non-mutated strain of a virus. When exposed to antiretroviral (ARV) drugs, wild-type HIV can develop mutations that make the virus resistant to specific HIV drugs. 

 

The six patients with MDR virus were followed for a period of two to seven years from infection. During this time the pattern of resistance mutations carried by their HIV scarcely changed. The only exception was that in two patients the M184V 3TC/FTC resistance mutation reverted to wild type.

In two cases it was possible to do comparative genotypes of the HIV carried by the source and recipient of an MDR virus. In one, the source patient's virus reverted back to a wild-type genotype within 12 weeks of initiating a break from HAART. In contrast his partner had exactly the same resistance mutations when he was genotyped again 47 weeks after infection, with the exception of losing the M184V mutation, which had disappeared by week 36.

“This person’s MDR virus was, in effect, his wild type,” commented Wainberg. He presented data from another patient who had kept exactly the same pattern of NNRTI and protease mutations for seven years.

One patient out of the 31 in the PHI cohort was not only infected with an MDR virus but later acquired a second MDR virus some 30-40 weeks after his first infection. The superinfection was detected because the patient’s viral load, which had been very low (in the region of 200-1,000 copies) suddenly increased tenfold to several thousand copies/ml. This compared with 10,000-70,000 copies/ml in the patients with wild-type virus.

Genotyping showed that a different pattern of resistance mutations had taken over; while the first virus had thymidine analogue mutations, the second one lacked these, while still having the M184V mutation and the V108I NNRTI mutation.

The clinical consequences of infection with MDR virus were unpredictable, Wainberg said.

The physician actually responsible for the care of the superinfected patient was in the audience, and in response to a question added that his patient had failed several regimens and was now on a treatment break with a CD4 count of under 200.

However in other cases patients maintained a low viral load without needing treatment. One of these patients was also in the audience and said he regarded himself as “essentially a long term non-progressor”.

This would be due to the relative replicative capacity of MDR viruses compared with wild type, Wainberg said. The viral fitness of the two viruses in the superinfected patient had been assayed. The first virus had 1-2 per cent of the replicative capacity of wild type, and the second 2-3 per cent.

Wainberg added that he personally thought superinfection, at least with resistant viruses, was a relatively rare event, being observed in only one patient from this closely-followed cohort.