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Trizivir in Treatment-Naives: can it still be considered as a first line treatment option?
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Reported by Jules Levin
Myrto Astriti and colleagues (Hôpital Pitié-Salpétrière Hospital, Paris, France, Center of Infectious Diseases Control of Greece) presented an oral talk at the 9th EACS in Warsaw (Oct 2003) on the use of Trizivir as a first line treatment option. Trizivir (TZV) was reported to have less viral potency in ARV naive patients in ACTG 5095 when compared to efavrienz (Sustiva). The purpose of the study was to examine the efficacy of TZV in ARV naive patients and to define the reasons of virological failure. They reported on the experience of the Dpts of Infectious Diseases of Pitié-Salpétrière Hospital, Paris, and CHRU Hotel Dieu Hospital, Nantes, France.
This was a retrospective study non-comparative study conducted at 2 sites. evaluating first line treatment with TZV. Plasma viral load evaluation at week 48 was the primary study objective. Intent-to-treat (missing=failure) and as observed (AO) analyses were performed. The secondary study objectives were tolerance, reasons for discontinuations, CD4 changes, genotype changes for viral failures.
Summary. 120 patients with advanced HIV (CD4=223, VL=100,000 copies/ml; 28% had AIDS) were studied, retrospectively by looking at their records. After week 48 on Trizivir, 70% had <200 copies/ml (ITT). Patients with <100,000 copies/ml were more likely to achieve <200 copies/ml (73% vs 59%). Over 48 weeks, 17 patients were lost to follow-up, 27 discontinued Trizivir either for intolerance (n=24) or viral failure (7.5%); leaving 73 patients on Trizivir at week 48. Authors reported that the main reason for TZV discontinuation was adverse events--18% of discontinuations were due to adverse events: 9% hypersensitivity; 5% hemotologic (anemia); 4% GI. Authors further concluded that failures are mostly due to intolerance or non-compliance in this population of naïve patients with advanced HIV and prior undiagnosed HIV infection; hypersensitivity reactions were more frequent in patients with concomitant treatments for OI and may be over attributed to TZV. almost all hemotologic and GI tract toxicities were grade I/II
Patient Characteristics
Patients had relatively advanced HIV. The average viral load was 4.96 log (about 100,000 copies/ml. Average CD4 count was 223. 28% had AIDS. 55% had TB. 15% PCP. 12% toxoplasmosis. 12% KS. 34% were taking concmitant treatment for OU or other infection.
A total of 120 patients were included (62% male); 37 yrs old; 56% Caucasian, 40% African, 4% Asian. 8.8% were HCV/HIV coinfected, 6.3% HBV/HIV coinfected.
Patient Disposition
Over 48 weeks:
--17 pts were lost to follow-up (14%)
--27 pts discontinued TZV either for: intolerance (n=24) (18%) or virological failure (n=4) (7.5%)
--leaving 73 patients on TZV at week 48 (60%).
VIRAL LOAD and CD4 Response
At week 48, the % of pts with viral load <200 copies/ml by ITT was 70% (70/120) and by AT 85 % (62/73); median changes in VL and CD4 were -2.40 log10 cp/ml and +130 cells/mm3. The average CD4 count was 355 at week 48 compared to 223 at baseline.
--73% with baseline viral load <100,000 copies/ml had <200 copies/ml at week 48.
--59% with baseline viral load >100,000 c/ml had <200 copies/ml at week 48.
The authors said that patients with <100,000 c/ml VL at baseline responded more quickly and were more likely to have <200 c/ml at week 48.
On Treatment Analysis: 93% with VL <100,000 c/ml had <200 c/ml at wk 48; 75% with >100,000 c/ml had <200 c/ml at wk 48.
Viral Failures
There were 9/120 (7.5%) viral failures: after week 12, 2 consecutive VL>200 c/ml on Trizivir).
--5/9 primary failures: never achieved <200 c/ml within first 3 months
--4/9 had viral rebounds between 6-12 months (had at least one previous VL <200 c/ml
--5/9 admitted non-compliance
--average VL was 4.36 log (23,000 c/ml)
--3/9 have switched to another treatment before wk 48
Resistance
All 9 patients experiencing a viral failure had WT virus at baseline. Resistance testing at the time of viral failue (8/9):
--3 patients had WT virus
--3 patients had M184V
--2 patientshad M184V, D67N, K70R
Viral Outcomes
In total 17/120 (14%) of patients had at least one VL >200 c/ml after week 12:
--there were 2 blips (one VL <1,000 c/ml between two VLs <200 c/ml)
--6 slow responders (VL <1000 c/ml at wk 12 followed by VL <200 c/ml)
Patient Outcome After TZV Discontinuation
N=29
66% (19/29) of patients have <200 copies/ml
--11/29 pts stayed on triple nukes (38%) and 8/11 have <200 c/ml
--10/29 on PI regimen (34%) & 6/10 have <200 c/ml
--5/29 on NNRTI regimen (17%) & 3/5 have <200 c/ml
--2/2 on double NRTI regimen due to pregnancy (7%) & 2/2 have <200 c/ml
--1/29 not on any ART (3.5%) & they have detectable HIV RNA
Trizivir Discontinuations Due To Adverse Events
22/120 (18%)
hypersenstivity (n=11), 9%
--7/11 were taking a concomitant treatment for OI (TB, toxo)
--at least 4/11 were judged “unlikely” or “not probably” HSR
Hemotological toxicity (n=6), 5%
--4/6 anemias, grade III
--2/6 neutropenias, 1 grade III
GI tract intolerance (n=5), 4%
--nausea, diarrhea, abdominal pain, grade I/II
Relationship Between Hypersensitivity Reactions and Concomitant Medications
The authors concluded that taking a concomitant OI treatment at time of Trizivir initiation doubles the risk of TZV discontinuation for hypersensitivity.
Concomitant Treatment
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Yes |
No |
| HSR |
| Yes |
7 (70%) |
3 (30%) |
| No |
34 (31%) |
76 (69%) |
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Author Conclusions
--Trizivir had a low rate of virological failure in ARV naive patients: 70% <200 (ITT).
--Patients with <100,000 copies/ml were more likely to achieve <200 copies/ml
--Failures are mostly due to intolerance or non-compliance in this population of naïve patients with advanced HIV and prior undiagnosed HIV infection
--the main reason for TZV discontinuation was adverse events (18%)
--hypersensitivity reactions were more frequent in patients with concomitant treatments for OI and may be over attributed to TZV
--almost all hemotologic and GI tract toxicities were grade I/II
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