American researchers are suggesting that commencing antiretroviral treatment soon after infection with HIV could eradicate the infection within eight years. Their study, which involved seven patients, is published in the June 15th edition of the Journal of Infectious Diseases. The investigators found that the reservoir of resting, HIV-infected CD4 cells fell by 50% every five months of HIV therapy and they estimated that the pool of cells latently infected with HIV would be eradicated in 7.7 years.
But the authors of an accompanying editorial are rather sceptical. They highlight the slower rate of viral decay seen in four of the patients in the study, and suggest that the persistence of just a few HIV-infected cells would potentially be enough to reignite infection with HIV should therapy be discontinued. The authors of the editorial also note that there is a slight chance that HIV could persist in cells other than CD4 cells, or in tissue.
Current HIV treatment strategies have been unable to eradicate HIV infection. This is mainly because of the persistence of reservoirs of HIV, particularly a pool of HIV-infected resting CD4 cells.
As eradication of HIV is not possible as long as these latent infected cells persist, investigators wished to determine the half-life of these reservoirs. Such information could, they hope, help develop HIV-eradication strategies involving the use of newer, more potent antiretroviral drugs such as integrase inhibitors.
Investigators therefore closely monitored seven patients who had initiated HIV therapy shortly after they contracted with infection.
The seven individuals commenced HIV therapy an average of seven months after they experienced an HIV seroconversion illness and had their infection diagnosed. All were prescribed antiretroviral therapy consisting of at least one protease inhibitor with two nucleoside reverse transcriptase inhibitors. The mean duration of HIV therapy was 40 months and all the patients achieved and maintained an undetectable plasma vital load.
Tests showed that the reservoir of latently infected cells decayed in all the patients and the investigators calculated that it fell by an average of 50% every 4.6 months. They therefore estimated the complete elimination of HIV-infected resting CD4 cells in an average of 7.7 years.
“The present study demonstrates that decay of the latent viral reservoir does occur in resting CD4 T-cells in patients in whom antiviral therapy was initiated during the early phase of HIV infection”, write the investigators.
They believe that their finding could have significant clinical implications, particularly “regarding the design of future therapeutic strategies aimed at eradicating HIV. Although ongoing HIV infection cannot be ruled out in individuals who began antiviral therapy early in HIV infection, it would be of considerable interest to pursue evidence for the possibility of eradicating HIV in such individuals whose duration of therapy has reached [eight years].”
They note that they will be able to examine this hypothesis in a sizeable population. Potent anti-HIV therapy became available in 1996 and there will soon be a significant number of patients who started treatment soon after infection and have maintained viral suppression for a protracted period.
They also plan to use Merck's new integrase inhibitor raltegravir (Isentress) and the Roche fusion inhibitor enfuvirtide (Fuzeon) in future patients, in order to increase the speed at which viral load declines during the initial phase of treatment, in the hope that this will reduce the pool of infected cells and thus shorten the period of treatment required for the pool to decay. The drugs will also be used in patients already under study.
The authors of an accompanying editorial are somewhat more cautious. They note “a close examination of the data suggests that, at least in 4 of the patients studied, a second, slower phase of viral decay appears to exist.” They add that the persistence of just “a few infected cells…may be enough to reignite infection.” Furthermore, “the possibility exists that HIV may rarely persist in cells other than resting CD4 T-cells or that circulating resting cells somewhat underrepresent infection in resting cells in the tissue.”
Studies showing the presence of HIV in cerebrospinal fluid and the central nervous system are also highlighted by the editorial’s authors, who also point to evidence of the persistence of HIV in lymphoid tissue in the gut.
Antiretroviral therapy can mean that HIV-infected individuals enjoy a normal prognosis. Therefore, the authors believe that the “bar for improving over current therapies is high.” HIV treatment is becoming more potent, but not at the cost of added inconvenience or toxicity, consequently “therapies that attempt to eradicate HIV must avoid undue risk and toxicity."