In a spirited response to presentations at today’s ongoing International AIDS Conference in Barcelona, Dr Julio Montaner, a Vancouver-based HIV physician of some seniority, urged delegates to do more to “tease out the data” on the timing of HAART initiation. Following a series of reports from observational cohorts over the last few years, the status quo is thus – there is little evidence of benefit associated with beginning HAART at CD4 counts above 200, at least over the short-term.
These cohort studies, in the context of concern over HAART’s long-term tolerability and the absence of more robust randomised, controlled trial data, have strongly influenced the more cautious approach to antiretroviral initiation which now prevails in well-resourced health care settings.
Having led the field to review this question previously, Professor Andrew Phillips of London’s Royal Free University College Medical School, today introduced another provocative analysis which should usefully inform discussions between people with HIV and their physicians on how long therapy can be delayed.
Phillips reviewed data from the CASCADE cohort, including participants who had not been diagnosed with AIDS and were either treatment naïve or had received monotherapy (treatment with one drug alone). Noting the conventional reliance on data from the US MACS cohort when predicting risk of disease progression, Phillips argued that the MACS’ three year probability forecasts of the risk of AIDS in the absence of treatment do not constitute an ideal timescale: “Clinicians are generally more interested in the risk over the period of time before the person is next assessed (three to six months)”.
The analysis included 3,226 people with viral load and CD4 data before beginning treatment, or during the AZT monotherapy era (defined as pre-1995). This gave 5,126 person-years of follow-up, during which time 219 people developed AIDS. The following table shows the risk of developing AIDS within six months according to baseline CD4 and viral load (RNA) level:
| CD4 | below 200 | 200-349 | above 350 |
| RNA below 10,000 | 4.9% | 0.5% | 0.2% |
| RNA 10,000 to 30,000 | 12.7% | 1.6% | 0.5% |
| RNA 30,000 to 100,000 | 17.7% | 3.2% | 0.9% |
| RNA above 100,000 | 22.4% | 4.7% | 2.2% |
When those who were exposed to monotherapy were excluded from the analysis, the results were similar. Phillips also presented six month risk profiles based on age (not shown here) which indicated, as expected, that risk grew in older patients.
Drawing a parallel between the MACS data and the current CASCADE analysis, Phillips highlighted that according to MACS, the three year risk of AIDS for a person with viral load above 55,000 copies and CD4 above 350 is 39.6%. However, using data from CASCADE, the six month risk for someone with a CD4 count above 350 and viral load above 100,000 is 2.2%. “Many might consider this risk acceptable and defer therapy at least until the next patient visit in three to six months when a further CD4 count and viral load are available” says Phillips.
While this breathing space may only be temporary, it may provide a useful opportunity to ensure that initiation of HAART is well-planned and supported, allowing time to consider available treatment options fully and evaluate likely needs regarding adherence support.
Phillips AN et al. Short-term risk of AIDS according to the current CD4 count and viral load in antiretroviral naïve individuals or those treated in the monotherapy era. Fourteenth International AIDS Conference, Barcelona, 7-12 July, abstract TuPeC4709, 2002.