Minority can have CD4 rises and no illness for more than 3 years after treatment failure

Edwin J. Bernard
Published: 11 December 2003

People with a stable low detectable viral load who continue with existing treatment continue to have rising CD4 cell counts and no clinical progression for up to three and a half years, according to a retrospective study from a Chicago clinic, published in the December 15th issue of JAIDS.

The current definition of treatment failure - two viral load tests above 50 copies/ml - continues to be challenged by clinicians and researchers who are finding that a minority of their patients maintain viral load between 50 and 20,000 copies/ml, continue to experience CD4 rises and remain free of clinical progression, for at last two years.

Earlier this year, at the Second International AIDS Society Conference on HIV Treatment and Pathogenesis in Paris, Raffanti and colleagues presented a paper that showed individuals who kept their viral load below 20,000 copies/ml have a comparable risk of disease progression to individuals with a viral load below 400 copies/ml over a median of 2.4 years.

The jury is still out as to why this should occur, but theories include decreased immune activation and reduced replication capacity. This report from Chicago asks more questions than it answers, but provides more evidence that so-called discordant CD4 rises in individuals with detectable viraemia are not rare.

The Chicago group identified 25 people (out of 600 attending their clinic) who had had a stable viral load between 200 and 10,000 copies/ml (low level viraemia) for at least six months. Fourteen of them were on HAART and 11 were on dual NRTI therapy, the latter having begun before the PI era and remaining on what is now currently seen as suboptimal therapy. The researchers compared them with 10 people on HAART with stable undetectable (less than 200 copies/ml) viral load and people on HAART with a viral load above 10,000 copies/ml (high level viraemia).

They found that the median change in CD4 cells per year of therapy was a gain of 55 cells in those who had undetectable viral load; a gain of 32 cells in those who were on HAART with low level viraemia; a loss of 11 in those on dual NRTIs with had low level viraemia; and a loss of -1.8 in those with high level viraemia (who began with a mean of only 15 cells, compared with 203-293 in the other groups). The only statistically significant differences were found when comparing those who had undetectable viral load and those with high viraemia (p<0.01) and when comparing those with low level and high level viraemia (p<0.01).

The authors also found that Candida antigen and CMV-specific CD4 T-cell immune responses were present in most of the people receiving any kind of antiretroviral therapy, although the magnitude of response was inversely correlated with viral load, with the strongest responses seen in those with undetectable viral load.

Although some drug resistance was found in most of the people in the study, most of the people on HAART with low level viraemia retained susceptibility to at least one drug in two other classes of antiretrovirals, which suggests that maintaining low level viraemia might not limit future options for salvage regimens.

Currently it is impossible to predict how long low level viraemia will be sustained at that level, or when or whether a blip will turn into low or high level viraemia, since the factors that allow this phenomenon to occur have not yet been identified. Prospective studies are already taking place that should begin to tease out factors responsible, which could include: baseline viral load, initial viral load drop on HAART, drug resistance and viral fitness, immune activation, coinfection, and genetic and/or behavioural factors.

References

Tenorio AR et al. HIV-1 infected antiretroviral-treated patients with prolonged partial viral suppression: clinical, virologic, and immunologic course. JAIDS 34 (5): 491-496, 2003.

Raffanti SR et al. Moderate viraemia and HIV disease progression. Second International AIDS Society Conference on HIV Treatment and Pathogenesis, Paris, abstract LB35, 2003.

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