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CATIE
(CATIE) Indinavir - study highlights importance of CD4+ counts over viral load
Hosein, SR
November 10, 1998
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 load.

Study details 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).

Results 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.

REFERENCES: 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 1998;105:1259-1264.

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 1998;4(8):953-956.

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