AIDS events with a viral cause decline most steeply after starting HAART

The incidence of all new AIDS-defining events decreases significantly in the first three years after the initiation of HAART, according to an international study published in the February 28^th edition of The Archives of Internal Medicine. Investigators also found that the incidence of AIDS-defining events with a viral cause declined most rapidly.

There are few data to demonstrate the changed incidence of AIDS-defining events in treatment naïve individuals during the early years of HAART. There is therefore uncertainty if the pattern of decline for AIDS-defining events is similar for all groups of conditions.

Accordingly a team of international investigators analysed data from 13 cohorts from Europe and North America which included adult, treatment-naïve HIV-positive individuals who started HAART with a median duration of follow-up of at least one year.

The investigators wished to describe changes in the overall incidence of AIDS-defining events in the three years following the commencement of HAART, and in particular see if the pattern of decline was similar for events with bacterial, viral, fungal, protozoal and other causes. In addition, the investigators also wished to establish if changes in the incidence of new AIDS-defining events could be fully explained by changes in CD4 cell counts and viral load.

Data from a total of 12,574 individuals were included in the investigators analysis. At the time of HAART initiation, individuals had a median CD4 cell count of 250 cells/mm³ and a median viral load of 63,000 copies/ml. The overwhelming majority of patients commenced therapy with a regimen containing a protease inhibitor (85%), with 11% of patients starting an NNRTI-based regimen, 2% a triple-NRTI regimen and 1% a combination containing both an NNRTI and a protease inhibitor.

Patients in the study contributed just under 23,000 per years of follow-up for analysis, during which time 928 new AIDS-defining events occurred and 325 patients died. In total 25% of new AIDS illnesses had a viral cause, 25% had a bacterial cause, 21% had a fungal origin, 8% were caused by a protozoa, and 21% had another cause.

The incidence of new AIDS-defining events fell from 129 per 1000 patient years in the first three months of HAART to 13 per 1000 patient years in the third year of HAART (p

Events with viral causes declined most steeply (87% per year) and the lowest rate of decline was seen for events with a fungal cause (54% per year). This had an impact on the relative frequency with which events occurred. In the first three months after starting HAART, 33% of new AIDS-events had a viral origin and 25% had a bacterial cause. Over time, the proportion of illnesses with a viral origin dropped and those with a fungal or other/unknown origin increased. Therefore, by the third year of analysis, AIDS events caused by a fungus were the most common (37%), and AIDS-defining illnesses caused by a virus accounted for only 6% of all events.

After six months of HAART, median CD4 cell count had increased to 343 cells/mm³, although 27% of patients still had a CD4 cell count below 200 cells/mm³ at this point. At the same point, 72% of patients had a viral load below 500 copies/ml. Even after the investigators adjusted for changes in CD4 cell count and viral load, the decline in the incidence of bacterial and viral illnesses remained significant during both the first six months and the second six months after starting HAART. However, changes in the incidence of illness with a fungal, protozoal or other origin ceased to be significant after adjustment.

“We have demonstrated that the incidence of all AIDS-defining events decreased substantially during the first three years after HAART initiation. Although events of a viral etiology experienced the most rapid decline in incidence, this trend was seen for all events, regardless of etiology”, write the investigators.

The investigators are unclear as to the reasons why different rates of decline were seen for AIDS-events with different etiological causes. However, they suggest that the more pronounced decline in events with an underlying viral cause could be because relatively small increases in CD4 cell count may be sufficient to protect against AIDS-defining illnesses with a viral origin.

Although an improvement in CD4 cell count and a reduction in viral load can largely explain the reduction in AIDS-events, the investigators note that the incidence of bacterial and viral AIDS-events in the second six month follow-up period were significantly lower than could be expected looking at improvements in CD4 cell counts and falls in viral load. Several possibilities for this are suggested by the investigators including closer monitoring of individuals during the first few months of HAART, or an effect of HAART on bacteria and viruses not mediate through an improved immune system.

The investigators conclude: “We demonstrated a significant reduction in the incidence of opportunistic events, regardless of etiology. The pattern of decline was most pronounced for events of viral etiology and was maintained during the three-year follow-up. For events of viral, bacterial, and fungal etiology, this decline was greater than expected on the basis of changes in CD4 cell count and HIV RNA level, suggesting a benefit of HAART beyond surrogate markers.”