Abstract
Background. Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily. Methods. This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0-log10 copies/mL decrease in HIV-1 RNA level by week 8, (2) an HIV-1 RNA rebound of ≥1.0 log10 copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions. Results. We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log10 copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV-1 RNA data from ≥8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P < .001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels <50 copies/mL. Conclusion. The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used.
| Original language | English |
|---|---|
| Pages (from-to) | 1921-1930 |
| Number of pages | 10 |
| Journal | Journal of Infectious Diseases |
| Volume | 192 |
| Issue number | 11 |
| DOIs | |
| State | Published - Dec 1 2005 |
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ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
- Immunology
Cite this
Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects. / Gallant, Joel E.; Rodriguez, Allan E; Weinberg, Winkler G.; Young, Benjamin; Berger, Daniel S.; Lim, Michael L.; Liao, Qiming; Ross, Lisa; Johnson, Judy; Shaefer, Mark S.
In: Journal of Infectious Diseases, Vol. 192, No. 11, 01.12.2005, p. 1921-1930.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects
AU - Gallant, Joel E.
AU - Rodriguez, Allan E
AU - Weinberg, Winkler G.
AU - Young, Benjamin
AU - Berger, Daniel S.
AU - Lim, Michael L.
AU - Liao, Qiming
AU - Ross, Lisa
AU - Johnson, Judy
AU - Shaefer, Mark S.
PY - 2005/12/1
Y1 - 2005/12/1
N2 - Background. Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily. Methods. This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0-log10 copies/mL decrease in HIV-1 RNA level by week 8, (2) an HIV-1 RNA rebound of ≥1.0 log10 copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions. Results. We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log10 copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV-1 RNA data from ≥8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P < .001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels <50 copies/mL. Conclusion. The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used.
AB - Background. Antiretroviral combinations that reduce the number of pills and dosing frequency have the potential to simplify therapy. We compared 2 regimens dosed as 2 pills once daily. Methods. This was a randomized, open-label, multicenter study of tenofovir disoproxil fumarate versus efavirenz, both administered once daily with the abacavir/lamivudine fixed-dose combination in treatment-naive human immunodeficiency virus type 1 (HIV-1)-infected subjects. After reports of early nonresponse, an unplanned interim analysis was performed. Virologic nonresponse was defined as (1) a <2.0-log10 copies/mL decrease in HIV-1 RNA level by week 8, (2) an HIV-1 RNA rebound of ≥1.0 log10 copies/mL above the nadir, or (3) for subjects with 2 consecutive HIV-1 RNA measurements <50 copies/mL, a subsequent increase to >400 copies/mL on 2 consecutive occasions. Results. We randomized 340 subjects. Median baseline HIV-1 RNA level and CD4+ cell count were 4.7 log10 copies/mL and 251 cells/mm3, respectively; 194 subjects with HIV-1 RNA data from ≥8 weeks were included in the interim analysis. Virologic nonresponse occurred in 50 (49%) of 102 subjects in the tenofovir disoproxil fumarate arm, compared with 5 (5%) of 92 of subjects in the efavirenz arm (P < .001). Within 12 weeks, viral genotypes for nonresponders in the tenofovir disoproxil fumarate arm showed M184V or I/M/V mixtures in 40 (98%) of 41 subjects and K65R and M184V or mixtures in 22 (54%) of 41 subjects. The protocol was immediately amended to modify the tenofovir disoproxil fumarate arm. The efavirenz arm continued unchanged; after 48 weeks, 120 (71%) of 169 subjects achieved HIV-1 RNA levels <50 copies/mL. Conclusion. The tenofovir disoproxil fumarate/abacavir/lamivudine regimen resulted in an unexpected and unacceptably high rate of nonresponse and incidence of K65R and M184V/I. This 3-drug regimen should not be used.
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U2 - 10.1086/498069
DO - 10.1086/498069
M3 - Article
VL - 192
SP - 1921
EP - 1930
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 11
ER -