CATIE TreatmentUpdate 93, 1998 November - Volume 10 Issue 9
Long-term use of combination therapy with protease inhibitors
has brought benefit to many treated people. Increased CD4+ cell
counts and decreased viral levels probably result in greater
protection against the life-threatening complications that are
the hallmark of AIDS. Not all people, however, experience the
same results, even when treatment is identical. In a study of
162 subjects given indinavir in combination with 2 nucleoside
analogues (nukes), doctors in Paris found that about 21% had an
unusual response to therapy. Half of that group developed
increased CD4+ counts without a significant fall in viral load.
The other half had a significant decrease in viral load without
a significant increase in their CD4+ count. Life-threatening
infections were more likely to occur in subjects whose CD4+
cell counts did not rise despite a significant drop in viral
Researchers in Paris enrolled 162 subjects (27 women, 135 men)
with an average CD4+ count of 69 cells and a viral load of
56,000 copies. All subjects had received treatment with various
nukes (AZT, 3TC, ddC, ddI and d4T) before entering this study.
None had used protease inhibitors before. About 43% of subjects
had developed symptoms of AIDS before receiving PI therapy. All
subjects received indinavir 800 mg three times daily combined
with two nukes (AZT, d4T and 3TC).
Fifty-seven percent of subjects had an increase of at least 50
CD4+ cells and a decrease in their viral load levels by at
least 1 log. Indeed, on average, by the 12th month of the study
some subjects gained as many as 180 CD4+ cells. More
importantly, researchers found some unusual patterns in
response to therapy in a large proportion of subjects, such as:
11% (17 subjects) had increased CD4+ counts without a
significant decrease in viral load;
11% had decreased viral loads without a significant increase in
their CD4+ cell count;
5% (8 subjects) failed to show any significant change in either
CD4+ counts or viral load;
12% (20 subjects) initially had their viral load decline only
to see it rise well before the end of the study.
An increased risk of infections?
Interestingly, a trend toward an increased number of
life-threatening infections was seen among the 17 subjects who
did not have increased CD4+ counts despite "a significant
decrease in viral load" as compared to subjects who had
increased CD4+ counts with or without a fall in viral load.
Researchers analysed many factors, such as pre-study values for
viral load, CD4+ counts, age, gender, stage of HIV infection,
type and length of prior nuke therapy, but could find no
significant differences between people that responded to
therapy and those who did not.
Their results, which suggest that rising CD4+ counts have a
protective effect, are supported by results from studies of
PHAs with CMV retinitis who have stopped taking their anti-CMV
medications because of improved cell counts due to PI therapy.
In fact, several studies have found that an increased cell
count seems to keep the retinitis in check. The French study
described above raises questions about relying solely on viral
load measurements in assessing the benefit of PI therapy.
1. Piketty C, Castie P, Belec L, et al. Discrepant responses to
triple combination antiretroviral therapy in advanced HIV
disease. AIDS 1998;12:745-750.
2. Vrabec TR, Baldassano VF and Whitcup SM. Discontinuation of
maintenance therapy in patients with quiescent cytomegalovirus
retinitis and elevated CD4+ counts. Ophthalmology
3. Komanduri KV, Viswanahan MN, Wiedder ED, et al. Restoration
of cytomegalovirus-specific CD4+ T-lymphocyte responses after
ganciclovir and highly active antiretroviral therapy in
individuals infected with HIV-1. Nature Medicine