Well over half of a cohort of patients who were given antiretrovirals in 1996 when they had what was then apparently terminal AIDS are alive, the Eleventh European AIDS Conference heard last week, 70% of those have undetectable HIV, and over half a CD4 cell count above 500 cells/mm3.
A second study documented changing causes of hospitalisation and, unusually, was able to quantify what percentage of hospital admissions was due to ARV side-effects.
Anne Libois of Saint-Pierre University Hospital in Brussels was presenting ten-year follow-up data on patients recruited for the PICASSO cohort. This was a group of patients originally recruited for a comparative trial of the protease inhibitors indinavir (Crixivan) and ritonavir (Norvir) – both in their old, full-dose, unboosted forms.
Three hundred and ninety-five patients were originally included in the study and so far there have been 2,504 patient years of follow-up. This was a very sick group of people. The maximum CD4 cell count in the cohort was 100 cells/mm3, and the median CD4 count in the group was 26. Three-quarters of them had clinical AIDS-defining illnesses. They had a median viral load of 160,000 copies/ml and 97% had experience of treatment with nucleoside analogue (NRTI) drugs.
Three quarters of them were white and nearly all the others African, and 72% were male. In terms of infection route, 40% were gay men, heterosexual sex accounted for 46% of exposures and injecting drug use 7%.
Ten years later (data collected up to the end of 2005), what was the picture? Of the 253 patients for whom a full data set was available, one third (82) had died. One in six were lost to follow-up. That meant that just over half (51%) were definitely known to be alive, and 61% if those lost to follow-up were excluded, so the true figure lies somewhere in between. Mortality dropped precipitously after the first year on ARVs and then stayed pretty much the same or only declined slightly per year for the following decade: there were 13 deaths in 1996 but never more than five in any subsequent year.
Just over half (52%) of all deaths were AIDS-related, 33% non-AIDS-related and 15% of unknown cause, but AIDS became less important than other causes after the first year: whereas in 1996 three-quarters of deaths were AIDS-related, in following years 43% were non-AIDS-related, 40% due to AIDS and 17% of unknown cause. Of non-AIDS causes of death, 40% were due to infectious disease, half of it bacterial pneumonia, while one in six deaths were due to cancer.
Details of what drug regimens patients are now taking are still being analysed but Libois said that 70% were now on protease inhibitor-based regimens, 18% on an NNRTI-based one, and 12% at the end of 2005 were taking the fusion inhibitor T-20 (enfuvirtide, Fuzeon).
The median CD4 cell count in the 201 patients still in follow-up with full data sets was 364 cells/mm3. Seventy per cent had a viral load under 50. Fifty-five per cent of this group had CD4 counts over 500 cells/mm3, and of those 80% had a viral load under 50 copies/ml; 25% had a count between 200 and 350 cells/mm3 and of those, 61% had undetectable viral load; 18% (39 patients) had a count under 200 cells/mm3 and of those, 46% (17) were undetectable, so about 10% of patients still alive were, at the end of 2005, still lacking effective treatment options.
A second study looked at the St Pierre Hospital’s entire patient group from 1998 to 2005, thus excluding the PICASSO patients, and only including patients referred in the HAART era. It found that just 6.2% of patients (188 deaths) had died, compared to a third of the PICASSO patients. Altogether 3,048 patients were referred to the HIV clinic between 1998 and 2005. There was no influence of gender or age, though other demographic characteristics were not collected.
Just under half (49%) of deaths of known cause were due to AIDS, 29% due to non-AIDS defining cancers, heart disease or infectious disease, and 21% to other causes. Nine per cent were due to liver disease and eight per cent to cardiovascular disease.
The study also documented hospitalisations due to any cause. There were 2,864 hospital admissions during the study, or almost one per patient. Of these, 28.5% (855) were due to AIDS-related conditions. Of the rest 630 (21%) were due to a non-AIDS-related infectious disease, six per cent due to gastro-intestinal symptoms (cause unspecified), 4.6% due to non-AIDS-defining cancers, and 3.6% due to cardiovascular disease. One hundred and seventeen admissions (3.9%) were for psychiatric illness, and 23.1% due to other causes like injuries, scheduled operations and so on.
Between 5% and 9% of all patients found themselves admitted for an AIDS-defining illness between 1998 and 2001, and then this proportion went down to a steady 3-4% a year; conversely, less than 1% of patients were admitted for a non-AIDS reason in 1998 and 1999, and this then increased to 2-4% a year after 2000. Liver-related admissions and deaths increased during the course of the study.
That left 148 admissions where the cause of admission was the HIV drugs themselves, of which 127 (4.2%) were due to an acute side effect of ARVs (the others were for things like a period of observation during a regimen change, as when patients started T-20).
So it’s possible to say that 4.4%, or one in every 22.5 hospital admissions, were due to HAART side effects, though the investigators say that these were “rarely direct causes of death”. However hospitalisations due to HAART side-effects decreased over the study period.
Libois A et al. Ten year follow-up of patients starting protease inhibitor (PI) with CD4 below 110/μl: the PICASSO Cohort. Eleventh European AIDS Conference, Madrid, abstract PS1/1, 2007.
De Wit S et al. Causes of death and hospitalisation in the Brussels Saint-Pierre Cohort 1998-2005. Eleventh European AIDS Conference, Madrid, abstract P18.4/02, 2007.