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The effect of HIV-1 resistance mutations after first-line virological failure on the possibility to sequence antiretroviral drugs in second-line regimens.
Antivir Ther. 2006; 11(7):923-9.AT

Abstract

BACKGROUND

One of the more vigorous debates in the field of highly active antiretroviral therapy (HAART) is how to start it and what the optimal drug sequence is.

METHODS

A retrospective cohort analysis was performed. The aim was to evaluate which variables could influence the virological response to second-line genotypic-based HAART in patients with virological documented first-line HAART failure. A positive response was defined as a confirmed HIV RNA level < 50 copies/ml.

RESULTS

Two hundred and eight patients were included. Demographic characteristics, risk factors for HIV acquisition, and drugs included in the initial treatment did not significantly influence the considered outcome. According to a multiple logistic model, the presence of thymidine analogue mutations (TAMs) had a negative association with the virological outcome (P = 0.006), whereas the use of a boosted protease inhibitor (PI) in second-line HAART was positively associated with the endpoint (P = 0.001). Patients receiving a genotypic-based second-line HAART containing a boosted PI achieved a viral load < 50 copies/ml in a 74.2% of cases compared with 52.2% of those whose therapy did not contain a boosted PI. This difference was statistically significant (P = 0.002) with an odds ratio (OR) of 2.63 and a 95% confidence interval (CI) ranging from 1.46 to 4.76. This last variable positively influenced the outcome even when the analysis was restricted to patients harbouring a virus presenting TAMs. In this case, second-line HAART was successful in 66.7% of cases with an OR of 3.25 and a 95% CI ranging from 1.28 to 8.25 (P = 0.014).

CONCLUSIONS

the wider range of available therapeutic options has made resistance and drug-sequencing considerations a crucial point in selecting first-line HAART. Our data indicate that, by limiting the risk of selecting or accumulating TAMs, it could be possible to save further therapeutic options. In second-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of the use of NRTI backbones, which retain only a partial effectiveness.

Authors+Show Affiliations

Divisione di Malattie Infettive, Ospedali Riuniti, Bergamo, Italy. franco31556@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

17302255

Citation

Maggiolo, Franco, et al. "The Effect of HIV-1 Resistance Mutations After First-line Virological Failure On the Possibility to Sequence Antiretroviral Drugs in Second-line Regimens." Antiviral Therapy, vol. 11, no. 7, 2006, pp. 923-9.
Maggiolo F, Ripamonti D, Torti C, et al. The effect of HIV-1 resistance mutations after first-line virological failure on the possibility to sequence antiretroviral drugs in second-line regimens. Antivir Ther. 2006;11(7):923-9.
Maggiolo, F., Ripamonti, D., Torti, C., Arici, C., Antinori, A., Quiros-Roldan, E., Minoli, L., Sighinolfi, L., Nasta, P., & Suter, F. (2006). The effect of HIV-1 resistance mutations after first-line virological failure on the possibility to sequence antiretroviral drugs in second-line regimens. Antiviral Therapy, 11(7), 923-9.
Maggiolo F, et al. The Effect of HIV-1 Resistance Mutations After First-line Virological Failure On the Possibility to Sequence Antiretroviral Drugs in Second-line Regimens. Antivir Ther. 2006;11(7):923-9. PubMed PMID: 17302255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of HIV-1 resistance mutations after first-line virological failure on the possibility to sequence antiretroviral drugs in second-line regimens. AU - Maggiolo,Franco, AU - Ripamonti,Diego, AU - Torti,Carlo, AU - Arici,Claudio, AU - Antinori,Andrea, AU - Quiros-Roldan,Eugenia, AU - Minoli,Lorenzo, AU - Sighinolfi,Laura, AU - Nasta,Paola, AU - Suter,Fredy, AU - ,, PY - 2007/2/17/pubmed PY - 2007/3/16/medline PY - 2007/2/17/entrez SP - 923 EP - 9 JF - Antiviral therapy JO - Antivir Ther VL - 11 IS - 7 N2 - BACKGROUND: One of the more vigorous debates in the field of highly active antiretroviral therapy (HAART) is how to start it and what the optimal drug sequence is. METHODS: A retrospective cohort analysis was performed. The aim was to evaluate which variables could influence the virological response to second-line genotypic-based HAART in patients with virological documented first-line HAART failure. A positive response was defined as a confirmed HIV RNA level < 50 copies/ml. RESULTS: Two hundred and eight patients were included. Demographic characteristics, risk factors for HIV acquisition, and drugs included in the initial treatment did not significantly influence the considered outcome. According to a multiple logistic model, the presence of thymidine analogue mutations (TAMs) had a negative association with the virological outcome (P = 0.006), whereas the use of a boosted protease inhibitor (PI) in second-line HAART was positively associated with the endpoint (P = 0.001). Patients receiving a genotypic-based second-line HAART containing a boosted PI achieved a viral load < 50 copies/ml in a 74.2% of cases compared with 52.2% of those whose therapy did not contain a boosted PI. This difference was statistically significant (P = 0.002) with an odds ratio (OR) of 2.63 and a 95% confidence interval (CI) ranging from 1.46 to 4.76. This last variable positively influenced the outcome even when the analysis was restricted to patients harbouring a virus presenting TAMs. In this case, second-line HAART was successful in 66.7% of cases with an OR of 3.25 and a 95% CI ranging from 1.28 to 8.25 (P = 0.014). CONCLUSIONS: the wider range of available therapeutic options has made resistance and drug-sequencing considerations a crucial point in selecting first-line HAART. Our data indicate that, by limiting the risk of selecting or accumulating TAMs, it could be possible to save further therapeutic options. In second-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of the use of NRTI backbones, which retain only a partial effectiveness. SN - 1359-6535 UR - https://www.unboundmedicine.com/medline/citation/17302255/The_effect_of_HIV_1_resistance_mutations_after_first_line_virological_failure_on_the_possibility_to_sequence_antiretroviral_drugs_in_second_line_regimens_ L2 - http://www.diseaseinfosearch.org/result/9735 DB - PRIME DP - Unbound Medicine ER -