Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

Review


Preproduction summary of clinical studies in which a correlation has been made between baseline genotype, treatment, and subsequent virologic response.
  1. Further edits, updates, and a complete explanation for all abbreviations is pending.
  2. Feedback is welcome, especially if you are an author of one of the studies.
Note: Many important studies of salvage therapy are not listed because correlations with genotypic data were not part of the study.
Table of contents
  1. Correlations Between HIV-1 Protease Inhibitor (PI) Resistance Mutations and Response to a New PI-Containing Regimen
  2. Correlations Between HIV-1 NRTI Resistance Mutations and Response to an NRTI-Containing Treatment Regimen
  3. Correlations Between HIV-1 NNRTI Resistance Mutations and Response to an NNRTI-Containing Treatment Regimen
  4. Genotypic Predictors of Response to Simplified Maintenance Therapies
  5. Effect of Baseline Mutations in Previously Untreated Persons on Response to Initial HAART Therapy
  6. References


1. Correlations Between HIV-1 Protease Inhibitor (PI) Resistance Mutations and Response to a New PI-Containing Regimen

Reference Previous PI Follow-up PI No. Patients Weeks Effect of Baseline Mutations on Response
to the Follow-up Therapy
Harrigan(29) >= 1 PI SQV/RTV 67 24
  • In the papers by Harrigan and Zolopa, the number of mutations at codons 46, 48, 54, 82, 84, and 90 correlated with a lack of response to SQV/RTV.
  • In the paper by Zolopa, RNA decrease of >=0.5 occurred in patients with <= 3 of these mutations. D30N did not affect response to SQV/RTV.
  • In the paper by Tebas, 17/24 patients had RNA levels <500 at W24.
  • In the paper by Deeks, only 4/18 patients had a sustained decrease in 0.5 log RNA decrease at W24.
  • In the abstract by Marcelin, 0, 1, and >=2 mutations at codons 24, 62, 82, 84, and 90 were associated with a median RNA decrease of 2.2, 1.2, and 0.3 logs, respectively.
Deeks(18) IDV or RTV SQV/RTV 18 24
Tebas(69) NFV SQV/RTV 24 24
Zolopa(78) >=1 PI SQV/RTV 54 26
Marcelin(47) >=1 PI SQV/RTV 72 NA
Para (57) SQV IDV 89 8
  • In the paper by Para, mutations at codons 10, 20, 48, 82, 84, 90 predicted a poor response to IDV salvage therapy
  • In the paper by Saah, L90M predicted a higher risk of virologic failure than D30N
  • In the paper by Shulman, 10/14 vs 3/14 subjects with >=3 mutations at the following positions responded to RTV boosting: 10, 20, 30, 32, 33, 36, 46, 47, 48, 50, 54, 71, 73, 77, 82, 84, 88, 90.
  • In the paper by Campo, virologic response correlated better with adherence than the pattern of mutations or level of phenotypic drug resistance.
Saah (63) NFV IDV 29 48
Shulman (65) IDV ± PIs other than RTV IDV/RTV 31 48
Campo (10) >=1 PI IDV/RTV 28 24
Lawrence (44) SQV NFV 16 24
  • In the paper by Lawrence, L90M predicted virologic failure.
  • In the paper by Walmsley, 41% and 22% had RNA declines >=0.5 logs at 24 and 48 weeks respectively. Mutations at codons 48, 82, 84, and 90 correlated with a poor virologic response.
  • In the paper by Cosado, 35% and 56% of patients had RNA <50 after 6 and 12 months. L90M (0% vs 43%) but not V82A (38% vs 36%) decreased the rate of response.
Walmsley (71) >=1 PI NFV 63 24-48
Cosado (11) IDV ± RTV NFV/SQV 31 26-52
Klein (40) >=1 PI APV 51 12
  • In the abstract by Klein, I84V and L90M predicted virologic failure; D30N did not.
  • In the paper by Falloon, 9 heavily treated patients with mutations at codons 82, 90 and 46 +/- 54 had no virologic response to salvage with an APV-containing regimen.
  • In the abstract by Descamps, <4 of the following mutations was associated with an HIV-1 RNA decrease of >= 1.0 log at W12: L10I, V32I, M46I/L, I47V, I54V, G73S, V82A/T/F/S, I84V, L90M
  • In the paper by Duval, 13/14 receiving APV/RTV vs 2/8 receiving APV had HIV-1 RNA <200 W24. Most patients had >= 1 mutation at position 46, 54, 82, or 90
  • In the paper by Marcelin, 70% of 49 patients had plasma HIV-1 RNA <400. Lack of response was associated with >5 of the following mutations: L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S, I84V.
  • In the paper by Lastere, univariate analyses showed that mutations at positions 19, 20,36, 73, 82, and 90, as well as well as insertions in the p6 PTAPP region were associated with poorer virological response.
Falloon (23) >=1 PI APV 10 24
Descamps (21) NARVAL >=1 PI APV 46 12
Duval (22) >=1 PI APV vs APV/RTV 22 24
Marcelin (48) Genophar >=1 PI APV/RTV 49 12
Lastere (43)NARVAL >=1 PI APV 84 12
Clevenbergh (13) PharmAdapt >=1 PI APV/RTV 61 16
  • Of the 252 patients in the PharmAdapt study, 40 in the control arm and 21 in the TDM arm received a regimen containing APV/RTV. Baseline genotyping of 39 patients was described.
  • The number of mutations associated with resistance according to the French ANRS algorithm of 2002 (L10I, V32I, M46I/L, I47V, I50V, I54L/M/V, G73S, V82A/F/I/T/S, I84V, L90M) was correlated with RNA changes. The median RNA decrease was 1.4 logs in 25 patients with <=3 mutations and 0.3 logs in 14 patients with >=4 mutations. In univariate analyses, mutations at positions 33 and 90 but not 82 and 84 were significantly associated with a poor virological response.
Kempf (39) M98-957 >=1 PI LPV/RTV 50 72
  • In the paper by Kempf, mutations at 11 positions were associated with drug resistance (10, 20, 24, 46, 53, 54, 63, 71, 82, 84, 90).
  • All patients were NNRTI-na.bŽïve and were also treated with EFV.
  • 21/23 with 0-5 of the above mutations, 15/21 with 6-7 mutations, and 2/6 with 8-10 mutations had RNA <400 at W72.
  • In the paper by Masquelier, 34% of persons had RNA <400. Lack of response was associated with the baseline mutations M46I, I54V, and V82A and with >=5 of the mutations described by Kempf et al.
  • In the paper by Bongiovanni, 22/134 (16%) patients had 6 of the above mutations of whom 5 had undetectable virus at W12. 71/112 with <5 mutations had undetectable virus at W12.
Masquelier (50) >=2 PI LPV/RTV 68 12
Bongiovanni (5) >=1 PI LPV/RTV 134 12
Loutfy (45) >= PI LPV/RTV 456 4-12
  • In univariate analyses, the mutations most predictive of virologic failure were M46I, Q58E, V82A/F/T, and L90M. The most predictive 3-mutation combination was L10F/I/R/V, M46I, and V82A/T/F.
  • Previous NNRTI use, previous AIDS diagnosis, and baseline RNA were also significantly associated with virologic failure.
Delaugerre (19) PI-naive (21);>1 PI (48) LPV/RTV 69 24-72
  • In this observational study of children, L10I/F, M46I, I54V/L, A71V/I, V82A/F/S/T, and L90M were associated with virologic failure.
Yerly (75) Swiss Cohort Study >=1 PI ATV/RTV 37 12
  • In this observational study, there was a median 2.1 log decrease by week 12.
  • At baseline, patients had a median of 6 mutations at positions reported by Colonno to be associated with ATV resistance (10, 20, 24, 33, 36, 46, 54, 63, 71, 73, 82, 84, 90).
  • Concomitant treatments were listed as RTI+TDF (50%), RTI+SQV (8%), RTI+T20 (10%)
  • In nonparametric univariate analyses, mutations at positions 10, 16, 20, 33, 35, 36, 43, 46, 54, 82, 84, 85, 89, and 90 were associated with reduced virologic response. The number of these mutations correlated better with virologic response than the number of the original Colonno mutations.


2. Correlations Between HIV-1 NRTI Resistance Mutations and Response to an NRTI-Containing Treatment Regimen

Reference Previous Rx Follow-up Rx No. Patients Weeks Effect of Baseline Mutations on Response
to the Follow-up Therapy
Japour (34) AZT AZT or ddI 188 52
  • 215Y/F was associated with increased risk of disease progression but this did not reach statistical significance in a model that also included CD4, syncytium inducing phenotype, AIDS diagnosis, and treatment assignment. M41L and T215Y/F were associated with an increased risk of disease progression regardless of treatment assignment.
Yerly (74) AZT ddI 121 12
  • T215Y/F was associated with a poorer CD4 count response to ddI monotherapy.
Shulman (66) AZT d4T 31 8
  • K70R alone did not prevent a subsequent virologic response to d4T.
  • All other TAMS did interfere with a subsequent response.
Holodniy (31) AZT AZT/ddI 4 30
  • T215Y was associated with lack of virologic response.
Izopet (33) AZT + ddC d4T/ddI 20 24
  • The 13 patients containing TAMs (11/13 had 215Y ± 41L ± 210W) had significantly less RNA suppression (-0.5 and -0.1 logs) at W12 and W24 compared with the 7 lacking TAMs (-1.6 and -2.0 logs).
Montaner (54) AZT d4T/3TC 48 4
  • In a multivariate model, T215Y/F was associated with an odds ratio = 23 of failing to achieve a virologic response.
Calvez (9) AZT ± ddI or ddC d4T/3TC 26 24
  • T215Y/F together with two additional TAMs was associated with a poor virologic response.
Kuritzkes (41) AZT AZT/3TC/RTV 40 48
  • In the studies by Kuritzkes and Gulick, the presence of TAMs did not appear to limit the effectiveness of AZT + 3TC + RTV and AZT + 3TC + IDV
  • In the study by Descamps and Joly, >=2 TAMs were present in 123/155 patients. Virologic failure (RNA > 5000) occurred in 7/24 classified as AZT-susceptible and in 26/131 classified as AZT-resistant by the ANRS algorithm. The proportion of patients with RNA >50 at W24 did not differ between the AZT- and d4T-containing arms
Gulick (27) AZT AZT/3TC/IDV 33 156
Descamps, Joly (20, 35) AZT ± (ddI,ddC) AZT/3TC/IDV or d4T/3TC/IDV 155 24
Lanier (42) NRTI,NNRTI,PI Addition of ABC 166 12-24
  • The Lanier study was a retrospective combined analysis of 5 studies of ABC intensification. >=3 TAMs + M184V or >=4 TAMs was associated with a poor virologic response
  • In the paper by Katlama, M184V did not preclude an antiviral response in that 73% of patients with M184V had a >=1.0 log RNA decrease.
  • In the paper by Brun-Vezinet, of 175 patients treated with ABC, virologic response was -0.2 logs, -0.7 logs, and -1.6 logs in persons containing 5-6, 4, or <4 mutations at the following positions: 41, 67, 210, 215, 74, and 184.
Katlama (37) CNA3002 NRTI,NNRTI,PI Addition of ABC 92 16
Brun-Vezinet (7) NNRTI,NNRTI,PI ABC as part of a new HAART regimen 175 12
Cabrera (8) NRTI + PI and/or NNRTI (but ABC-naive) Median 4 NRTI (2-5), 1 NNRTI (0-3), 3 PIs (0-5) ABC as part of a new HAART regimen 100 24
  • 29 patients added ABC and these patients had a median RNA decrease of 0.2. But a large proportion received additional active drugs and the Kaplan-Meier estimate of the median 24W RNA decrease was 0.86 logs.
  • 37% had RNA <=500. Lower baseline RNA and more active drugs (according to Rega algorithm) were highly predictive of response.
  • The ANRS algorithm was the most predictive of a response to therapy. The number of the following mutations showed a weak association with RNA decrease (M41L, D67N, K70R, L210W, T215FY, K219QE, K65R, L74V, Y115F, M184V, E44D, V118I). The impact of specific mutations on response was difficult to discern and not described as the degree of genotypic ABC resistance was believed to influence the choice of other drugs in the regimen.
Miller (52) Gilead Sciences 902 and 907 NRTI, NNRTI, PI Addition of TDF 222 24-48
  • Among those persons receiving 300 mg TDF, there was a mean 0.6 log RNA decrease at week 24 by ITT.
  • The presence of 41L, 210W, and 215Y, were inversely associated with virologic benefit. Mutations at positions 67, 70, and 219 did not affect response.
  • M41L and L210W were the best predictors of reduced response, because in the absence of these mutations, persons with T215Y/F had a 0.7 log RNA response. Persons with all three mutations had a 0.2 log RNA response.
  • M184V was associated with a modest but significant improved response. For example among persons with TAMs, RNA decrease was 0.52 log copies with M184V compared with 0.45 log copies without M184V.
  • K65R was present at baseline in only 6 persons and was associated with virological nonresponse
  • Additional mutations present in the final multivariate model included mutations at positions 39, 43, 74, and 208.
Barrios (4) NRTI, NNRTI, PI TDF as part of a new HAART regimen 153 24
  • The presence of 41L, 210W, and 215Y were inversely associated with virologic benefit. 184V did not affect response.
Masquelier (51) NRTI, NNRTI, PI TDF as part of a new HAART regimen 161 12
  • The strongest association with decrease in HIV-1 RNA was with a set of 7 mutations: M41L, E44D, D67N, T69D/N/S, L74V, L210W, and T215Y/F.
  • A score of <3 was associated with a median RNA reduction of -1.3 log-copies; a score of 3-5 was associated with a median reduction of 0.8 log copies; a score of >=6 was associated with a median increase of 0.1 log copies.
  • K65R and T69ins were not included in the score because although these mutations are associated with phenotypic resistance, there were insufficient patients with these mutations.
Albrecht (2) AZT + (ddI or ddC) Addition or substitution of 3TC 195 8-48
  • Addition or substitution of 3TC was associated with a 0.5 log RNA reduction at week 8 but most of virologic benefit was lost by week 48 suggesting that 3TC has activity in the presence of TAMs but that using 3TC in maximally suppressive regimens is preferred
Frank (24) ACTG 307 45% naive; 55% had received 1-2 NRTI including 3TC (31%) ddI 200 mg bid vs hydroxyurea x 12W followed by ddI 200 mg bid + hydroxyurea (1000 vs 1500 mg qd) x 12W 134 24
  • Hydroxyurea + ddI was associated with a greater RNA decrease than ddI alone at week 8 (~1.8 vs 0.8 logs). The combination was associated with a sustained response ~1.2-1.6 logs at week 24.
  • At week 8, there was a greater reduction in RNA in the treatment naive group (1.7 vs 1.2 logs) but there was little difference in response between those with M184V (1.2 logs in 18 3TC-experienced patients with M184V vs 1.4 logs in 61 3TC-naive patients).
Molina (53) NRTI, NNRTI, PI Addition of ddI 110 4
  • Patients with 0-1 TAMs had 0.8-1.0 log RNA decrease (n=40); those with 2 TAMs had 0.7 log RNA decrease (n-10); those with 3 TAMs had 0.5 log RNA decrease (n=25); those with 4 TAMs had 0.2 log RNA decrease (n=21).
  • Median log RNA decrease in the presence of 184V (n=92) was 0.6
  • Median log RNA decrease in the presence of L74V (n=9) was 0.1
Rusconi (61) NRTI, PI ± NNRTI Change from 3TC to ddI 16 8
  • In 6 of 8 patients with M184V + multiple TAMs, change from 3TC to ddI resulted in HIV-1 RNA decline lowered by >= 0.5 logs.
Albrecht, Winters (1, 72) ACTG 364 NRTI NRTI change and addition of NFV, EFV, or NFV/EFV 195 16-48
  • In patients without isolates containing M184V, addition of 3TC was associated with an improved virologic response
  • In patients with isolates containing M184V, substitution of ddI for 3TC was associated with an improved virologic response
Clevenbergh (14) NRTI ± NNRTI, PI; Q151M + linked mutations (10) or T69 insertion (2) Treatment with boosted PI ± NRTI± NNRTI 12 48
  • Virologic response (RNA <20) observed only among 5 persons with no nonpolymorphic PI resistance mutations and among 2 persons with L90M alone.
Gallego (25) NRTI (22), NNRTI (20), PI (22); Q151M + linked mutations (12) or T69ins (10) Individualized treatments 22 24
  • 12 (55%) showed >= 1 log response to salvage; 7 had sustained RNA <50
  • The use of a boosted PI and a lower number of PI-resistance mutations were the two factors that predicted virologic response.



3. Correlations Between HIV-1 NNRTI Resistance Mutations and Response to an NNRTI-Containing Treatment Regimen

Reference Previous Rx Follow-up Rx No. Patients Weeks Effect of Baseline Mutations on Response
to the Follow-up Therapy
Shulman (67) NRTI, PI ± NNRTI EFV + NRTI ± PI 33 12-24
  • 14/33 patients were NNRTI experienced.
  • NNRTI-resistance mutations were observed at baseline in 8 of the 14 NNRTI-experienced patients: K103N ± 1 or more other NNRTI mutation (5 patients), Y181C and or G190A ± 1 or more other NNRTI mutation. Four additional NNRTI-treated persons had 1 or more NNRTI mutation when last on NNRTI therapy.
  • The 21 patients who never had an NNRTI-resistance mutation had a median 2.3 log RNA reduction by week 24. Those with Y181C alone or G190A had a median 1.3 log reduction at week 4 with return of RNA towards baseline by week 24. Those with K103N or more than one NNRTI resistance had <0.5 log virologic response at week 4 with rapid return of RNA to baseline.
Antinori (3) NVP-HAART (19); PI-HAART (60) EFV-HAART 79 12
  • Among the 19 NVP-HAART failures, 12 had 1 NNRTI-resistance mutation not considered to be associated with high-level EFV resistance (Y181C-6, G190A-3, V106A-2, V108I-1) and 7 had no NNRTI-resistance mutations.
  • Only 2 of 12 (16%) with an NNRTI-resistance mutation had RNA <500 at 3 months compared with 35/67 (52%) without an NNRTI-resistance mutation. The median RNA decrease was 0.63 logs with a single NNRTI-resistance mutation vs 1.3 logs without an NNRTI-resistance mutation.
Harrigan (28) Untreated 2-NRTIs + NNRTI (usually NVP) 262 52
  • 64 (24%), 17 (6%), and 15 (5%) had >4-fold decreased susceptibility (Virco Sntivirogram) to DLV, NVP, and EFV at baseline.
  • Two patients had V108I, one had Y188H, and one had K101E and G190A.
  • During 25 M of follow-up there was no difference in the risk of virologic failure between those with <4-fold or >4-fold decreased NNRTI susceptibility.
Jourdain (36) Single Dose (SD) NVP D4T/3TC/NVP 269 24
  • Among women receiving SD-NVP, 32% had NNRTI mutations detectable by sequencing 10 days postpartum.
  • After 24W, RNA was <50 in 49% of those who received SD-NVP compared with 68% of the control patients that did not receive SD-NVP.
  • Response (RNA <50) was 38% in those with NNRTI mutations and 52% in those without NNRTI mutations at day 10.



4. Genotypic Predictors of Response to Simplified Maintenance Therapies

Reference Previous Rx Follow-up Rx No. Patients Weeks Effect of Baseline Mutations on Response
to the Follow-up Therapy
Havlir (30) ACTG 343 AZT ± (ddI, ddC, d4T) AZT/3TC/IDV followed by AZT/3TC 107 >=24
  • T215Y was strongly associated with virologic failure during the AZT/3TC maintenance phase
Clumeck (15) 2-NRTI + PI (90% previously untreated). RNA < 50 x 6 months. 2-NRTI + ABC vs continued 2-NRTI+PI 221 48
  • 4/105 patients receiving abacavir and 2/106 receiving continued PI therapy experienced virologic failure (RNA > 400 copies/ml on two occasions)
Opravil (56) Swiss HIV Cohort Study 2-NRTI + PI with RNA <400 x 6M. Previous NRTI but no AZT/3TC failure or proviral 215 mutation. AZT/3TC/ABC (84) vs 2-NRTI+PI (79) 163 84
  • By ITT, virologic failure (RNA > 400 x 2) occurred in 13 (15%) of AZT/3TC/ABC group vs 5 (6.0%) of continued therapy group.
  • Prior ZDV monotherapy or dual NRTI therapy with archived PBMC DNA mutations were significant predictors of virologic failure in the AZT/3TC/ABC group.
  • In persons without prior ZDV mono- or dual NRTI therapy, the risk of virologic failure with AZT/3TC/ABC was significantly lower at weeks 48 and 96 than among those with prior ZDV (6% vs 24% and 11% vs 33% respectively).
Maggiolo F (46) 2-NRTI + PI (IDV,NFV,SQV); No previous NNRTI or ABC; RNA <50 x 6M 2-NRTI+ABC (69); 2-NRTI+EFV (70); continued 2-NRTI+PI (70) 209 104
  • Treatment failure (RNA > 500 x2) rates were lower in the ABC and EFV groups (35% and 29%, respectively) compared with the continued PI group. (61%).
  • 21 of 69 receiving ABC, 18 of 70 receiving EFV, and 19 of 70 receiving continued PIs had NRTIs prior to PI-containing HAART. Among these patients, the rates of treatment failure were 19% for ABC, 10% for EFV, and 58% for continued PI.
  • Virologic failure occurred in 10%, 3%, and 6%, respectively of the ABC, EFV, and PI groups. Therefore most failures were caused by intolerability.
Chiesa (12) Initial PI-containing HAART regimen x > 6M with RNA <80 x 6M. 2-NRTI+ABC (38); 2-NRTI+EFV (85); 2-NRTI+NVP (54) 177 ~48
  • In this observational study, there were no significant differences in virologic or immunologic failure between the 3 arms. Virologic failure occurred in 4/71 on EFV, 6/47 on NVP, and 3/33 on ABC.
Martinez (49) 2-NRTI + PI. RNA < 200 x 6 Months 2-NRTI+NVP vs 2-NRTI+EFV vs 2-NRTI+ABC 460 48
  • 13% receiving abacavir, 10% receiving nevirapine, and 6% receiving efavirenz developed the primary endpoint of death, AIDS, or CD4 < 200. 23 of 29 virologic failures had received suboptimal NRTIs before starting maintenance.
Katlama (38) 2-NRTI + PI or 2-NRTI + NNRTI or 3-NRTI x 6 months with RNA < 50. AZT/3TC/ABC vs continued therapy 209 48
  • The proportion of patients with treatment failure (RNA > 400 on two occasions) was 22% in each arm.
  • Five subjects in the AZT/3TC/ABC arm vs 1 subject in the control arm had virologic failure
Saberg (64) PI-based HAART preceded by NRTIs for a mean of 24M in 14 pts; RNA < 50 x > 11M ABC + 2-3 NRTIs usually including AZT/3TC. 29 120
  • In this observational study, virologic failure (RNA > 50 x 2) occurred after a mean of 2M in 6 (21%) pts. 22 (76%) pts, observed for a mean of 28M, have had persistent virologic success. 1 pt. had ABC hypersensitivity reaction.
  • All 6 had been on NRTIs (15M-76M) prior to PI HAART. 6 had T215Y, 4 had M41L, 4 had V118I, and 3 had M184V. 7 pre-NRTI treated pts that were treated successfully with ABC maintenance had fewer TAMs and did not have M184V or V118I.
Hoogewerf (32) RNA < 50 on stable HAART: 2NRTI+PI (4), 2NRTI+NNRTI (1), 3 NRTI (AZT/3TC/ABC-2, D4T/3TC/ABC-1) TDF/3TC/ABC 8 ~16
  • 5 of the 8 patients developed virologic failure within a median of 16 weeks. Of note, the 3 who did not experience virologic failure included the 3 patients who were on a different triple NRTI at the time of the change.
Wirden (73) 2-NRTI + PI (9); 3-NRTI + PI (2); 2-NRTI + NNRTI (19); 3-NRTI (11); RNA < 200; Change of 1 NRTI (ZDV-8, d4T-17, ddI-13, ABC-3) to TDF; 41 24
  • After a follow-up of > 6M, virologic failure ( > 200 x 2) occurred in 7/41 (17%) persons, all of whom switched to a 3-NRTI regimen: ZDV/3TC/ddI => TDF/3TC/ddI (2 pts); d4T/3TC/ddI => TDF/3TC/ddI (3 pts), ZDV/3TC/ABC => ZDV/3TC/TDF (2 pts).
  • No failures occurred in the 30 patients substituting TDF who were also receiving a PI or an NNRTI.
  • The authors claim that prior suboptimal NRTI therapy was infrequent and that 6 of the 7 failures were with M184V and/or K65R; whereas only 1 failure had multiple TAMs.
Negredo (55) Dual NRTI + PI or NNRTI BID with RNA < 50 x 6 Months TDF/ddI/NVP qd (n=85) vs continued BID HAART (n=84) 169 48
  • TDF/ddI/NVP maintained virologic suppression but was associated with a mean decrease CD4 count of 95 cells/ul. (Note: Full ddI dose of 400 mg/day was used).
Gil (26) 2 NRTI + PI (IDV, NFV, or SQV); RNA < 200 x 3M. 79 were rx-na.AŽïve prior to HAART; 31 had prior NRTIs Change from PI to NVP 110 156
  • 68 persons were followed 3 years. RNA remained undetectable in all but 8 persons.
  • There was a mean CD4 increase of 90 cells/ul.
  • 16 patients discontinued NVP due to toxicity, 14 were lost to follow-up, and 8 discontinued therapy for other reasons.
de la Rosa (16) Phillips JID 2002, Raffi F CID 2000 PI-based HAART with (n=81) or without (n=19); suboptimal NRTI rx; RNA < 50 x 6M NVP (~75%) or EFV (~21%)+2-NRTIs, 3-NRTIs (4 patients). 100 ~90
  • 26 patients who began NNRTI-based HAART are not included in this summary
  • Adherence < 95% and suboptimal therapy were associated with virologic rebound defined as RNA > 50 x 2).
  • PBMC sequencing was done on 45 patients before the change in therapy including 33 with and 12 without suboptimal rx. TAMs were significantly more common in those with suboptimal rx (~55% vs 10%).



5. Effect of Baseline Mutations in Previously Untreated Persons on Response to Initial HAART Therapy

Reference Previous Rx Follow-up Rx No. Patients Weeks Effect of Baseline Mutations on Response
to the Follow-up Therapy
Violin (70) ICONA Study Group None 2NRTI+SQV (5); 2NRTI+IDV (5); 2NRTI+RTV (1); 2NRTI+EFV (1); 3NRTI (1); 13 52
  • 6 (47%) of 13 chronically infected persons with a T215 revertant (C,D,E,S,N,A,V) experienced virologic failure compared with 30% of 392 without a T215 revertant (p=0.05). Use of SQV (invirase formulation) was also associated with risk of failure.
Perno (58) ICONA Study Group None 3TC-containing HAART regimen 9 >=24
  • In 9 untreated persons, 118I was not associated with an increased risk of virologic failure in persons receiving a 3TC-containing HAART regimen
Perno (59) (60)ICONA Study Group None 2NRTI+IDV (149); 2NRTI+SQV(67); 2NRTI+NFV(11); 2NRTI+RTV(24); 248 24
  • Virologic failure defined as RNA >400 at week 24 occurred in 62 (25%) persons.
  • NRTI resistance mutations (usually 1) were found in 6.0%.
  • PI resistance mutations (nearly all polymorphic mutations at positions 10, 20, 36, 71, and 77) were found in 55%.
  • Mutations at positions 10, 36, and 71 were weakly associated with an increased risk of virologic failure, particularly the combination of mutations at positions 10 and 36.
  • The 2004 paper suggested that the presence of mutations at positions 10 and 36 at baseline is associated with a higher risk of developing L90M at virologic failure.
Saag (62), Borroto-Esoda (6) None FTC+ddI+EFV vs d4T+ddI+EFV 546 48
  • 90 (16%) entered the study with either an NRTI or NNRTI-resistance mutation
  • The presence of pre-therapy NNRTI-resistance mutations was significantly predictive of virologic failure for both 3-drug combinations. Among 14 patients with virus containing K103N at baseline, 3/7 receiving FTC/ddI/EFV and 5/7 receiving d4T/ddI/EFV developed virologic failure.
  • The presence of NRTI-resistance mutations was significantly predictive of virologic failure only for the d4T/ddI/EFV regimen
Jourdain(36) Single Dose (SD) NVP D4T/3TC/NVP 269 24
  • Among women receiving SD-NVP, 32% had NNRTI mutations detectable by sequencing 10 days postpartum.
  • After 24W, RNA was < 50 in 49% of those who received SD-NVP compared with 68% of the control patients that did not receive SD-NVP.
  • Response (RNA<50) was 38% in those with NNRTI mutations and 52% in those without NNRTI mutations at day 10.



References

  1. Albrecht, M. A., R. J. Bosch, S. M. Hammer, S. H. Liou, H. Kessler, M. F. Para, J. Eron, H. Valdez, M. Dehlinger, and D. A. Katzenstein. 2001. Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. N. Engl. J. Med. 345:398-407.
  2. Albrecht, M. A., M. D. Hughes, S. H. Liou, D. A. Katzenstein, R. Murphy, H. H. Balfour, M. F. Para, H. Valdez, and S. M. Hammer. 2000. Effect of lamivudine in HIV-infected persons with prior exposure to zidovudine/didanosine or zidovudine/zalcitabine. AIDS Res. Hum. Retrovirus. 16:1337-44.
  3. Antinori, A., M. Zaccarelli, A. Cingolani, F. Forbici, M. G. Rizzo, M. P. Trotta, S. Di Giambenedetto, P. Narciso, A. Ammassari, E. Girardi, A. De Luca, and C. F. Perno. 2002. Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure. AIDS Res. Hum. Retrovirus. 18:835-8.
  4. Barrios, A., C. de Mendoza, L. Martin-Carbonero, E. Ribera, P. Domingo, M. J. Galindo, J. Galvez, V. Estrada, D. Dalmau, V. Asensi, and V. Soriano. 2003. Role of baseline human immunodeficiency virus genotype as a predictor of viral response to tenofovir in heavily pretreated patients. J. Clin. Microbiol. 41:4421-3.
  5. Bongiovanni, M., T. Bini, F. Adorni, P. Meraviglia, A. Capetti, F. Tordato, P. Cicconi, E. Chiesa, L. Cordier, A. Cargnel, S. Landonio, S. Rusconi, and A. d'Arminio Monforte. 2003. Virological success of lopinavir/ritonavir salvage regimen is affected by an increasing number of lopinavir/ritonavir-related mutations. Antivir. Ther. 8:209-14.
  6. Borroto-Esoda, K., J. Harris, J. Waters, J. Hinkle, A. Shaw, J. Quinn, and F. Rousseau. 2004. Baseline genotype as a predictor of virological failure in patients receiving emtricitabline once daily or stavudine twice daily in combination with didanosine and efavirenz [abstract 672]. 11th Conference on Retroviruses and Opportunisticin Infections, San Francisco.
  7. Brun-Vezinet, F., D. Descamps, A. Ruffault, B. Masquelier, V. Calvez, G. Peytavin, F. Telles, L. Morand-Joubert, J. L. Meynard, M. Vray, and D. Costagliola. 2003. Clinically relevant interpretation of genotype for resistance to abacavir. AIDS 17:1795-1802.
  8. Cabrera, C., A. Cozzi Lepri, A. Phillips, C. Loveday, O. Kirk, M. Ait-Khaled, P. Reiss, J. Kjaer, B. Ledergerber, and L. Ruiz. 2004. Baseline resistance and virological outcome in patients with virological failure who start a regimen containing abacavir: EuroSida study. Antivir. Ther. 9:787-800.
  9. Calvez, V., D. Costagliola, D. Descamps, A. Yvon, G. Collin, A. Cecile, C. Delaugerre, F. Damond, A. G. Marcelin, S. Matheron, A. Simon, M. A. Valantin, C. Katlama, and F. Brun-Vezinet. 2002. Impact of stavudine phenotype and thymidine analogues mutations on viral response to stavudine plus lamivudine in ALTIS 2 ANRS trial. Antivir. Ther. 7:211-8.
  10. Campo, R. E., J. N. Moreno, G. Suarez, N. Miller, M. A. Kolber, D. J. Holder, M. Shivaprakash, D. M. DeAngelis, J. L. Wright, W. A. Schleif, E. A. Emini, and J. H. Condra. 2003. Efficacy of indinavir-ritonavir-based regimens in HIV-1-infected patients with prior protease inhibitor failures. AIDS 17:1933-9.
  11. Casado, J. L., F. Dronda, K. Hertogs, R. Sabido, A. Antela, P. Marti-Belda, P. Dehertogh, and S. Moreno. 2001. Efficacy, tolerance, and pharmacokinetics of the combination of stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or indinavir failure. AIDS Res. Hum. Retrovirus. 17:93-8.
  12. Chiesa, E., T. Bini, F. Adorni, A. Capetti, G. Rizzardini, I. Faggion, C. Mussini, S. Sollima, S. Melzi, M. Bongiovanni, F. Tordato, P. Cicconi, B. Castelnuovo, S. Rusconi, and A. d'Arminio Monforte. 2003. Simplification of protease inhibitor-containing regimens with efavirenz, nevirapine or abacavir: safety and efficacy outcomes. Antivir. Ther. 8:27-35.
  13. Clevenbergh, P., R. Boulme, M. Kirstetter, and P. Dellamonica. 2004. Efficacy, safety and predictive factors of virological success of a boosted amprenavir-based salvage regimen in heavily antiretroviral-experienced HIV-1-infected patients. HIV Med 5:284-8.
  14. Clevenbergh, P., M. Kirstetter, J. Y. Liotier, M. Dupon, P. Philibert, C. Jacomet, E. Cua, N. Montagne, J. C. Schmit, and P. Dellamonica. 2002. Long-term virological outcome in patients infected with multi-nucleoside analogue-resistant HIV-1. Antivir. Ther. 7:305-8.
  15. Clumeck, N., F. Goebel, W. Rozenbaum, J. Gerstoft, S. Staszewski, J. Montaner, M. Johnson, B. Gazzard, C. Stone, R. Athisegaran, and S. Moore. 2001. Simplification with abacavir-based triple nucleoside therapy versus continued protease inhibitor-based highly active antiretroviral therapy in HIV-1-infected patients with undetectable plasma HIV-1 RNA. AIDS 15:1517-26.
  16. de la Rosa, R., E. Ruiz-Mateos, A. Rubio, M. A. Abad, A. Vallejo, L. Rivero, M. Genebat, A. Sanchez-Quijano, E. Lissen, and M. Leal. 2004. Long-term virological outcome and resistance mutations at virological rebound in HIV-infected adults on protease inhibitor-sparing highly active antiretroviral therapy. J Antimicrob Chemother 53:95-101.
  17. De Meyer, S., M. Peeters, C. Jordens, P. McKenna, R. van der Geest, R. Pauwels, and M. de Bethune. 2003. TMC114, a potent next-generation protease inhibitor: characterization of antiviral activity in multiple protease inhibitor-experienced patients participating in a Phase IIa study. Antivir. Ther. 8:S18.
  18. Deeks, S. G., R. M. Grant, G. W. Beatty, C. Horton, J. Detmer, and S. Eastman. 1998. Activity of a ritonavir plus saquinavir-containing regimen in patients with virologic evidence of indinavir or ritonavir failure. AIDS 12:F97-102.
  19. Delaugerre, C., J. P. Teglas, J. M. Treluyer, P. Vaz, V. Jullien, F. Veber, C. Rouzioux, M. L. Chaix, and S. Blanche. 2004. Predictive Factors of Virologic Success in HIV-1-Infected Children Treated With Lopinavir/Ritonavir. J. Acquir. Immune Defic. Syndr. 37:1269-1275.
  20. Descamps, D., P. Flandre, V. Joly, V. Meiffredy, G. Peytavin, J. Izopet, C. Tamalet, A. F. Zeng, M. Harel, S. Lastere, J. P. Aboulker, P. Yeni, and F. Brun-Vezinet. 2002. Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine or stavudine, each in combination with lamivudine and indinavir. J. Acquir. Immune Defic. Syndr. 31:464-71.
  21. Descamps, D., B. Masquelier, J. P. Mamet, C. Calvez, A. Ruffault, F. Telles, A. Goetschel, P. M. Girard, F. Brun-Vezinet, and D. Costagliola. 2001. A genotypic sensitivity score for amprenavir based genotype at baseline and virological response. Antivir. Ther. 6:103.
  22. Duval, X., C. Lamotte, E. Race, D. Descamps, F. Damond, F. Clavel, C. Leport, G. Peytavin, and J. L. Vilde. 2002. Amprenavir inhibitory quotient and virological response in human immunodeficiency virus-infected patients on an amprenavir-containing salvage regimen without or with ritonavir. Antimicrob. Agents. Chemother. 46:570-4.
  23. Falloon, J., S. Piscitelli, S. Vogel, B. Sadler, H. Mitsuya, M. F. Kavlick, K. Yoshimura, M. Rogers, S. LaFon, D. J. Manion, H. C. Lane, and H. Masur. 2000. Combination therapy with amprenavir, abacavir, and efavirenz in human immunodeficiency virus (HIV)-infected patients failing a protease- inhibitor regimen: pharmacokinetic drug interactions and antiviral activity. Clin. Infect.Dis. 30:313-8.
  24. Frank, I., R. Bosch, S. Fiscus, F. Valentine, C. Flexner, Y. Segal, P. Ruan, R. Gulick, K. Wood, S. Estep, L. Fox, T. Nevin, M. Stevens, and J. J. Eron Jr. 2004. Activity, safety, and immunological effects of hydroxyurea added to didanosine in antiretroviral-naive and experienced HIV type 1-infected subjects: a randomized placebo-controlled trial, ACTG 307. AIDS Res. Hum. Retrovirus. 20:916-926.
  25. Gallego, O., C. d Mendoza, P. Labarga, C. Altisent, J. Gonzalez, I. Garcia-Alcalde, L. Valer, E. Valencia, and V. Soriano. 2003. Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes. HIV Clin Trials 4:372-81.
  26. Gil, P., M. de Gorgolas, V. Estrada, A. Arranz, P. Rivas, C. Yera, R. Garcia, J. J. Granizo, and M. Fernandez-Guerrero. 2004. Long-Term Efficacy and Safety of Protease Inhibitor Switching to Nevirapine in HIV-Infected Patients with Undetectable Virus Load. Clin. Infect.Dis. 39:1024-9.
  27. Gulick, R. M., J. W. Mellors, D. Havlir, J. J. Eron, A. Meibohm, J. H. Condra, F. T. Valentine, D. McMahon, C. Gonzalez, L. Jonas, E. A. Emini, J. A. Chodakewitz, R. Isaacs, and D. D. Richman. 2000. 3-year suppression of HIV viremia with indinavir, zidovudine, and lamivudine. Ann. Intern. Med. 133:35-9.
  28. Harrigan, P. R., K. Hertogs, W. Verbiest, B. Larder, B. Yip, Z. L. Brumme, C. Alexander, J. Tilley, M. V. O'Shaughnessy, and J. Montaner. 2003. Modest decreases in NNRTI susceptibility do not influence virologic outcome in patients receiving initial NNRTI-containing triple therapy. Antivir. Ther. 8:395-402.
  29. Harrigan, P. R., K. Hertogs, W. Verbiest, R. Pauwels, B. Larder, S. Kemp, S. Bloor, B. Yip, R. Hogg, C. Alexander, and J. S. Montaner. 1999. Baseline HIV drug resistance profile predicts response to ritonavir-saquinavir protease inhibitor therapy in a community setting. AIDS 13:1863-71.
  30. Havlir, D. V., I. C. Marschner, M. S. Hirsch, A. C. Collier, P. Tebas, R. L. Bassett, J. P. Ioannidis, M. K. Holohan, R. Leavitt, G. Boone, and D. D. Richman. 1998. Maintenance antiretroviral therapies in HIV infected patients with undetectable plasma HIV RNA after triple-drug therapy. AIDS Clinical Trials Group Study 343 Team. N. Engl. J. Med. 339:1261-1268.
  31. Holodniy, M., D. Katzenstein, L. Mole, M. Winters, and T. Merigan. 1996. Human immunodeficiency virus reverse transcriptase codon 215 mutations diminish virologic response to didanosine-zidovudine therapy in subjects with non-syncytium-inducing phenotype. J. Infect. Dis. 174:854-857.
  32. Hoogewerf, M., R. M. Regez, W. E. Schouten, H. M. Weigel, P. H. Frissen, and K. Brinkman. 2003. Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression. Lancet 362:1979-80.
  33. Izopet, J., A. Bicart-See, C. Pasquier, K. Sandres, E. Bonnet, B. Marchou, J. Puel, and P. Massip. 1999. Mutations conferring resistance to zidovudine diminish the antiviral effect of stavudine plus didanosine. J. Med. Virol. 59:507-11.
  34. Japour, A. J., S. Welles, R. T. D'Aquila, V. A. Johnson, D. D. Richman, R. W. Coombs, P. S. Reichelderfer, J. O. Kahn, C. S. Crumpacker, and D. R. Kuritzkes. 1995. Prevalence and clinical significance of zidovudine resistance mutations in human immunodeficiency virus isolated from patients after long-term zidovudine treatment. AIDS Clinical Trials Group 116B/117 Study Team and the Virology Committee Resistance Working Group. J. Infect. Dis. 171:1172-1179.
  35. Joly, V., P. Flandre, V. Meiffredy, F. Brun-Vezinet, J. A. Gastaut, C. Goujard, G. Remy, D. Descamps, A. Ruffault, A. Certain, J. P. Aboulker, and P. Yeni For The Novavir Study Group. 2002. Efficacy of zidovudine compared to stavudine, both in combination with lamivudine and indinavir, in human immunodeficiency virus-infected nucleoside-experienced patients with no prior exposure to lamivudine, stavudine, or protease inhibitors (novavir trial). Antimicrob. Agents. Chemother. 46:1906-13.
  36. Jourdain, G., N. Ngo-Giang-Huong, S. Le Coeur, C. Bowonwatanuwong, P. Kantipong, P. Leechanachai, S. Ariyadej, P. Leenasirimakul, S. Hammer, and M. Lallemant. 2004. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N. Engl. J. Med. 351:229-40.
  37. Katlama, C., B. Clotet, A. Plettenberg, J. Jost, K. Arasteh, E. Bernasconi, V. Jeantils, A. Cutrell, C. Stone, M. Ait-Khaled, and S. Purdon. 2000. The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. CNA3002 European Study Team. AIDS 14:781-9.
  38. Katlama, C., S. Fenske, B. Gazzard, A. Lazzarin, N. Clumeck, J. Mallolas, A. Lafeuillade, J. P. Mamet, and L. Beauvais. 2003. TRIZAL study: switching from successful HAART to Trizivir (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence results. HIV Med 4:79-86.
  39. Kempf, D. J., J. D. Isaacson, M. S. King, S. C. Brun, J. Sylte, B. Richards, B. Bernstein, R. Rode, and E. Sun. 2002. Analysis of the virological response with respect to baseline viral phenotype and genotype in protease inhibitor-experienced HIV-1-infected patients receiving lopinavir/ritonavir therapy. Antivir. Ther. 7:165-74.
  40. Klein, A., M. Maguire, D. Paterson, P. Nacci, N. Mustafa, J. Yeo, W. Snowden, and J. P. Kleim. 2000. Virological response to amprenavir combination therapy in PI-experienced paediatric patients: association with distinct baseline HIV-1 protease variants - study PROAB3004. Antivir. Ther. 5 Supplement 2:4.
  41. Kuritzkes, D. R., A. Sevin, B. Young, M. Bakhtiari, H. Wu, M. St Clair, E. Connick, A. Landay, J. Spritzler, H. Kessler, and M. M. Lederman. 2000. Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine-lamivudine-ritonavir: genotypic analysis of human immunodeficiency virus type 1 isolates from AIDS clinical trials group protocol 315.ACTG Protocol 315 Team. J. Infect. Dis. 181:491-7.
  42. Lanier, E., M. Ait-Khaled, J. Scott, C. Stone, T. Melby, G. Sturge, M. St Clair, H. Steel, S. Hetherington, G. Pearce, B. Spreen, and S. Lafon. 2004. Antiviral efficacy of abacavir in antiretroviral-therapy experienced adults harbouring HIV-1 with specific patterns of resistance to nucleoside reverse transcriptase inhibitors. Antivir. Ther. 9:37-45.
  43. Lastere, S., C. Dalban, G. Collin, D. Descamps, P. M. Girard, F. Clavel, D. Costagliola, and F. Brun-Vezinet. 2004. Impact of insertions in the HIV-1 p6 PTAPP region on the virological response to amprenavir. Antivir. Ther. 9:221-7.
  44. Lawrence, J., J. Schapiro, M. Winters, J. Montoya, A. Zolopa, R. Pesano, B. Efron, D. Winslow, and T. C. Merigan. 1999. Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor- experienced persons. J. Infect. Dis. 179:1356-1364.
  45. Loutfy, M. R., J. M. Raboud, S. L. Walmsley, R. Saskin, J. S. Montaner, R. S. Hogg, C. A. Thompson, and P. R. Harrigan. 2004. Predictive value of HIV-1 protease genotype and virtual phenotype on the virological response to lopinavir/ritonavir-containing salvage regimens. Antivir. Ther. 9:595-602.
  46. Maggiolo, F., A. Callegaro, C. Arici, G. Quinzan, G. Gregis, D. Ripamonti, A. Tebaldi, A. Goglio, and F. Suter. 2003. Salvage therapy with abacavir in HIV-1-infected patients with previously documented M184V mutation: a possibility of NRTI recycling. Antivir. Ther. 8:121-6.
  47. Marcelin, A., C. Dalban, G. Peytavin, C. Delaugerre, R. Agher, C. Katlama, D. Costagliola, and V. Calvez. 2003. Clinically relevant interpretation of genotype for resistance to ritonavir (100 mg twice daily) plus saquinavir (800 mg twice daily) in HIV-1-infected protease inhibitor-experienced patients. Antivir. Ther. Volume 8:S117.
  48. Marcelin, A. G., C. Lamotte, C. Delaugerre, N. Ktorza, H. Ait Mohand, R. Cacace, M. Bonmarchand, M. Wirden, A. Simon, P. Bossi, F. Bricaire, D. Costagliola, C. Katlama, G. Peytavin, and V. Calvez. 2003. Genotypic inhibitory quotient as predictor of virological response to ritonavir-amprenavir in human immunodeficiency virus type 1 protease inhibitor-experienced patients. Antimicrob. Agents. Chemother. 47:594-600.
  49. Martinez, E., J. A. Arnaiz, D. Podzamczer, D. Dalmau, E. Ribera, P. Domingo, H. Knobel, M. Riera, E. Pedrol, L. Force, J. M. Llibre, F. Segura, C. Richart, C. Cortes, M. Javaloyas, M. Aranda, A. Cruceta, E. de Lazzari, and J. M. Gatell. 2003. Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection. N. Engl. J. Med. 349:1036-46.
  50. Masquelier, B., D. Breilh, D. Neau, S. Lawson-Ayayi, V. Lavignolle, J. M. Ragnaud, M. Dupon, P. Morlat, F. Dabis, and H. Fleury. 2002. Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients. Antimicrob. Agents. Chemother. 46:2926-32.
  51. Masquelier, B., C. Tamalet, B. Montes, D. Descamps, G. Peytavin, L. Bocket, M. Wirden, J. Izopet, V. Schneider, V. Ferre, A. Ruffault, P. Palmer, A. Trylesinski, M. Miller, F. Brun-Vezinet, and D. Costagliola. 2004. Genotypic determinants of the virological response to tenofovir disoproxil fumarate in nucleoside reverse transcriptase inhibitor-experienced patients. Antivir. Ther. 9:315-23.
  52. Miller, M. D., N. Margot, B. Lu, L. Zhong, S. S. Chen, A. Cheng, and M. Wulfsohn. 2004. Genotypic and phenotypic predictors of the magnitude of response to tenofovir disoproxil fumarate treatment in antiretroviral-experienced patients. J. Infect. Dis. 189:837-46.
  53. Molina, J. M., A. G. Marcelin, J. Pavie, C. Merle, M. Troccaz, G. Leleu, and V. Calvez. 2003. Didanosine (ddI) in treatment experienced HIV-infected patients: results from a randomized double-blind study (AI454-176 Jaguar) [Abstract H-447]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL.
  54. Montaner, J. S., T. Mo, J. M. Raboud, S. Rae, C. S. Alexander, C. Zala, D. Rouleau, and P. R. Harrigan. 2000. Human immunodeficiency virus-infected persons with mutations conferring resistance to zidovudine show reduced virologic responses to hydroxyurea and stavudine-lamivudine. J. Infect. Dis. 181:729-32.
  55. Negredo, E., J. Molto, D. Burger, P. Viciana, E. Ribera, R. Paredes, M. Juan, L. Ruiz, J. Puig, A. Pruvost, J. Grassi, E. Masmitja, and B. Clotet. 2004. Unexpected CD4 cell count decline in patients receiving didanosine and tenofovir-based regimens despite undetectable viral load. AIDS 18:459-63.
  56. Opravil, M., B. Hirschel, A. Lazzarin, H. Furrer, J. P. Chave, S. Yerly, L. R. Bisset, M. Fischer, P. Vernazza, E. Bernasconi, M. Battegay, B. Ledergerber, H. Gunthard, C. Howe, R. Weber, and L. Perrin. 2002. A randomized trial of simplified maintenance therapy with abacavir, Lamivudine, and Zidovudine in human immunodeficiency virus infection. J. Infect. Dis. 185:1251-60.
  57. Para, M. F., D. V. Glidden, R. Coombs, A. Collier, J. Condra, C. Craig, R. Bassett, R. Leavitt, S. Snyder, V. J. McAuliffe, and C. Boucher. 2000. Baseline human immunodeficiency virus type I phenotype, genotype, and RNA response after switching from long-term hard-capsule saquinavir to indinavir or soft-gel-capsule saquinavir in AIDS clinical trials group protocol 333. J. Infect. Dis. 182:733-43.
  58. Perno, C. F., A. Cozzi-Lepri, C. Balotta, F. Forbici, M. Violin, A. Bertoli, G. Facchi, P. Pezzotti, G. Angarano, C. Arici, P. Narciso, A. Orani, E. Raise, A. Scalzini, A. Poggio, G. Ippolito, M. Moroni, and A. D. Monforte. 2001. Impact of mutations conferring reduced susceptibility to lamivudine on the response to antiretroviral therapy. Antivir. Ther. 6:195-8.
  59. Perno, C. F., A. Cozzi-Lepri, C. Balotta, F. Forbici, M. Violin, A. Bertoli, G. Facchi, P. Pezzotti, G. Cadeo, G. Tositti, S. Pasquinucci, S. Pauluzzi, A. Scalzini, B. Salassa, A. Vincenti, A. N. Phillips, F. Dianzani, A. Appice, G. Angarano, L. Monno, G. Ippolito, M. Moroni, and A. Monforte. 2001. Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy. J. Infect. Dis. 184:983-91.
  60. Perno, C. F., A. Cozzi-Lepri, F. Forbici, A. Bertoli, M. Violin, M. Stella Mura, G. Cadeo, A. Orani, A. Chirianni, C. De Stefano, C. Balotta, and A. d'Arminio Monforte. 2004. Minor mutations in HIV protease at baseline and appearance of primary mutation 90M in patients for whom their first protease-inhibitor antiretroviral regimens failed. J. Infect. Dis. 189:1983-7.
  61. Rusconi, S., S. La Seta Catamancio, P. Citterio, E. Bulgheroni, S. Kurtagic, M. Galazzi, F. Croce, M. Moroni, and M. Galli. 2001. Virological response in multidrug-experienced HIV-1-infected subjects failing highly active combination regimens after shifting from lamivudine to didanosine. Antivir. Ther. 6:41-6.
  62. Saag, M. S., P. Cahn, F. Raffi, M. Wolff, D. Pearce, J. M. Molina, W. Powderly, A. L. Shaw, E. Mondou, J. Hinkle, K. Borroto-Esoda, J. B. Quinn, D. W. Barry, and F. Rousseau. 2004. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial. JAMA 292:180-9.
  63. Saah, A. J., D. W. Haas, M. J. DiNubile, J. Chen, D. J. Holder, R. R. Rhodes, M. Shivaprakash, K. K. Bakshi, R. M. Danovich, D. J. Graham, and J. H. Condra. 2003. Treatment with indinavir, efavirenz, and adefovir after failure of nelfinavir therapy. J. Infect. Dis. 187:1157-62.
  64. Saberg, P., K. Koppel, G. Bratt, E. L. Fredriksson, B. Hejdeman, G. Sitbon, and E. Sandstrom. 2004. The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection. Scand J Infect Dis 36:40-5.
  65. Shulman, N., A. Zolopa, D. Havlir, A. Hsu, C. Renz, S. Boller, P. Jiang, R. Rode, J. Gallant, E. Race, D. J. Kempf, and E. Sun. 2002. Virtual inhibitory quotient predicts response to ritonavir boosting of indinavir-based therapy in human immunodeficiency virus-infected patients with ongoing viremia. Antimicrob. Agents. Chemother. 46:3907-16.
  66. Shulman, N. S., R. A. Machekano, R. W. Shafer, M. A. Winters, A. R. Zolopa, S. H. Liou, M. Hughes, and D. A. Katzenstein. 2001. Genotypic correlates of a virologic response to stavudine after zidovudine monotherapy. J. Acquir. Immune Defic. Syndr. 27:377-80.
  67. Shulman, N. S., A. R. Zolopa, D. J. Passaro, U. Murlidharan, D. M. Israelski, C. L. Brosgart, M. D. Miller, S. Van Doren, R. W. Shafer, and D. A. Katzenstein. 2000. Efavirenz- and adefovir dipivoxil-based salvage therapy in highly treatment-experienced patients: clinical and genotypic predictors of virologic response. J. Acquir. Immune Defic. Syndr. 23:221-6.
  68. Squires, K., S. McCallister, A. Lazzarin, P. Kumar, E. DeJesus, J. Nadler, J. Gallant, S. Walmsley, P. Yeni, V. Kohlbrenner, D. Hall, S. Spinosa, C. Dohnanyi, and D. Mayers. 2003. Tipranavir/ritonavir (TPV/r) demonstrates a robust resistance profile in multiple protease-inhibitor-experienced patietns: Correlation of baseline genotype and antiviral activity in BI 1182.52 (abstract 812). International AIDS Conference, Paris.
  69. Tebas, P., A. K. Patick, E. M. Kane, M. K. Klebert, J. H. Simpson, A. Erice, W. G. Powderly, and K. Henry. 1999. Virologic responses to a ritonavir--saquinavir-containing regimen in patients who had previously failed nelfinavir. AIDS 13:F23-F28.
  70. Violin, M., A. Cozzi-Lepri, R. Velleca, A. Vincenti, S. D'Elia, F. Chiodo, F. Ghinelli, A. Bertoli, A. d'Arminio Monforte, C. F. Perno, M. Moroni, and C. Balotta. 2004. Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy. AIDS 18:227-35.
  71. Walmsley, S. L., M. I. Becker, M. Zhang, A. Humar, and P. R. Harrigan. 2001. Predictors of virological response in HIV-infected patients to salvage antiretroviral therapy that includes nelfinavir. Antivir. Ther. 6:47-54.
  72. Winters, M. A., R. J. Bosch, M. A. Albrecht, and D. A. Katzenstein. 2003. Clinical impact of the M184V mutation on switching to didanosine or maintaining lamivudine treatment in nucleoside reverse-transcriptase inhibitor-experienced patients. J. Infect. Dis. 188:537-40.
  73. Wirden, M., A. G. Marcelin, R. Tubiana, M. A. Valantin, J. Ghosn, C. Duvivier, S. Dominguez, L. Paris, R. Agher, G. Peytavin, C. Katlama, and V. Calvez. 2004. Virologic Outcome After Switching From a Nucleoside Reverse Transcriptase Inhibitor to Tenofovir in Patients With Undetectable HIV-1 RNA Plasma Level. J. Acquir. Immune Defic. Syndr. 36:876-878.
  74. Yerly, S., N. Denereaz, B. Mermillod, B. Hirschel, and L. Perrin. 1996. Predictive value of codon 215 reverse transcriptase mutation on the efficacy of didanosine in HIV-infected, zidovudine-experienced patients. Antivir. Ther. 1:167-71.
  75. Yerly, S., S. Vora, H. GŽünthard, P. Vernazza, H. Furrer, A. Zinkernagel, B. Hirschel, L. Perrin, and t. S. H. C. S. (SHCS). 2004. Virological response following switch to atazanavir/ritonavir in relation to baseline genotypic resistance pattern Antivir. Ther. Volume 9:S165.
  76. Zaccarelli, M., C. F. Perno, F. Forbici, F. Soldani, S. Bonfigli, C. Gori, M. P. Trotta, M. C. Bellocchi, G. Liuzzi, R. D'Arrigo, P. De Longis, E. Boumis, R. Bellagamba, V. Tozzi, P. Narciso, and A. Antinori. 2004. Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. Clin. Infect.Dis. 38:433-7.
  77. Zolopa, A., H. Rice, J. Nadler, J. Schaenman, T. Hawkins, C. Cohen, R. Rode, and D. Kempf. 2003. Genotypic predictors of response to lopinavir/ritonavir (LPV/r) in clinical practice (abstract 823). 2nd International AIDS Soceity Conference, Paris, France.
  78. Zolopa, A. R., R. W. Shafer, A. Warford, J. G. Montoya, P. Hsu, D. Katzenstein, T. C. Merigan, and B. Efron. 1999. HIV-1 genotypic resistance patterns predict response to saquinavir- ritonavir therapy in patients in whom previous protease inhibitor therapy had failed. Ann. Intern. Med. 131:813-821.

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