Antiretroviral combinations do not eliminate HIV entirelyBMJ 1997; 315 doi: https://doi.org/10.1136/bmj.315.7121.1485i (Published 06 December 1997) Cite this as: BMJ 1997;315:1485
Researchers in the United States have confirmed that, although combinations of potent antiretroviral drugs are effective in arresting replication of HIV, they fail to eliminate the virus entirely.
The drug combinations-typically a mixture of reverse transcriptase and protease inhibitors-act synergistically to disable the reproductive capacity of the virus and have helped to prolong the life of patients with AIDS. With HIV infection suppressed, patients' immune systems can combat opportunistic infections. The new studies show that even patients whose viral titres are suppressed to serologically undetectable levels harbour copies of HIV in quiescent immune cells.
Three teams, working independently but using similar research methods, reached the same conclusion-that CD4 memory cells can harbour latent but viable HIV and that these cells, when activated, can be induced to produce competent and infective viral copies (Science 1997:278;1291-4, 1295-300; Proceedings of the National Academy of Sciences 1997:94;13193-7). The study populations ranged from 6 to 22 patients.
Blood was harvested from patients who had been taking antiretroviral “triple” treatment for 30 months and whose viral loads were serologically undetectable. When this blood was mixed with undetected blood in culture and a T cell stimulant added, CD4 memory cells harbouring latent HIV could activate the virus, which then entered HIV naive cells, propagating the infection.
Since the latent HIV is in a non-replicative state, it is not susceptible to antiretrovirals and cannot develop resistance to them. Dr David Ho of the Aaron Diamond Research Center in New York said: “This shows that the drugs are really quite good and are doing what they are supposed to do. It should be a motivation for patients to carry on and adhere closely to their regimen.”
However, although drug resistance in the study groups was negligible, such resistance may not be reflected in the general population: compliance may be a problem as the drugs must be taken regularly, according to a strict regimen, and many have unpleasant side effects. Moreover, the drugs are expensive-$15000 (£9400) a year.