Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-1infected patients

Alessandro Soria, Klaudia Porten, Jean Calvin Fampou-Toundji, Laura Galli, Rose Mougnutou, Vincent Buard, Anfumbom Kfutwah, Aurelia Vessière, Dominique Roussert, Roger Teck, Alexandra Calmy, Laura Ciaffi, Andriano Lazzarin, Nicola Gianotti

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Abstract

Background: The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring. Methods: Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped. Results: Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count ≤50 cells/mm3 at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm3 (2.10 versus 0.56; P+ T-cell count ≤50 cells/mm3 predicted ≥1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [Cl] 2.20-32.14), ≥1 NNRTI mutation (AOR 4.25, 95% Cl 1.36-15.48), ≥1 thymidine analogue mutation (AOR 8.45, 95% Cl 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% Cl 1.49-32.29) and etravirine (AOR 4.72, 95% Cl 1.53-15.70). Conclusions: Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.

Original languageEnglish
Pages (from-to)339-347
Number of pages9
JournalAntiviral Therapy
Volume14
Issue number3
Publication statusPublished - 2009

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HIV-1
Viral Load
Reverse Transcriptase Inhibitors
Odds Ratio
CD4 Lymphocyte Count
Mutation
T-Lymphocytes
Nucleotides
efavirenz
etravirine
Therapeutics
Implosive Therapy
Stavudine
Didanosine
Nevirapine
Lamivudine
Zidovudine
Nucleosides
Drug Resistance
Thymidine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-1infected patients. / Soria, Alessandro; Porten, Klaudia; Fampou-Toundji, Jean Calvin; Galli, Laura; Mougnutou, Rose; Buard, Vincent; Kfutwah, Anfumbom; Vessière, Aurelia; Roussert, Dominique; Teck, Roger; Calmy, Alexandra; Ciaffi, Laura; Lazzarin, Andriano; Gianotti, Nicola.

In: Antiviral Therapy, Vol. 14, No. 3, 2009, p. 339-347.

Research output: Contribution to journalArticle

Soria, A, Porten, K, Fampou-Toundji, JC, Galli, L, Mougnutou, R, Buard, V, Kfutwah, A, Vessière, A, Roussert, D, Teck, R, Calmy, A, Ciaffi, L, Lazzarin, A & Gianotti, N 2009, 'Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-1infected patients', Antiviral Therapy, vol. 14, no. 3, pp. 339-347.
Soria, Alessandro ; Porten, Klaudia ; Fampou-Toundji, Jean Calvin ; Galli, Laura ; Mougnutou, Rose ; Buard, Vincent ; Kfutwah, Anfumbom ; Vessière, Aurelia ; Roussert, Dominique ; Teck, Roger ; Calmy, Alexandra ; Ciaffi, Laura ; Lazzarin, Andriano ; Gianotti, Nicola. / Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-1infected patients. In: Antiviral Therapy. 2009 ; Vol. 14, No. 3. pp. 339-347.
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abstract = "Background: The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring. Methods: Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped. Results: Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count ≤50 cells/mm3 at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm3 (2.10 versus 0.56; P+ T-cell count ≤50 cells/mm3 predicted ≥1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95{\%} confidence interval [Cl] 2.20-32.14), ≥1 NNRTI mutation (AOR 4.25, 95{\%} Cl 1.36-15.48), ≥1 thymidine analogue mutation (AOR 8.45, 95{\%} Cl 2.16-40.16) and resistance to didanosine (AOR 6.36, 95{\%} Cl 1.49-32.29) and etravirine (AOR 4.72, 95{\%} Cl 1.53-15.70). Conclusions: Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.",
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T1 - Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-1infected patients

AU - Soria, Alessandro

AU - Porten, Klaudia

AU - Fampou-Toundji, Jean Calvin

AU - Galli, Laura

AU - Mougnutou, Rose

AU - Buard, Vincent

AU - Kfutwah, Anfumbom

AU - Vessière, Aurelia

AU - Roussert, Dominique

AU - Teck, Roger

AU - Calmy, Alexandra

AU - Ciaffi, Laura

AU - Lazzarin, Andriano

AU - Gianotti, Nicola

PY - 2009

Y1 - 2009

N2 - Background: The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring. Methods: Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped. Results: Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count ≤50 cells/mm3 at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm3 (2.10 versus 0.56; P+ T-cell count ≤50 cells/mm3 predicted ≥1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [Cl] 2.20-32.14), ≥1 NNRTI mutation (AOR 4.25, 95% Cl 1.36-15.48), ≥1 thymidine analogue mutation (AOR 8.45, 95% Cl 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% Cl 1.49-32.29) and etravirine (AOR 4.72, 95% Cl 1.53-15.70). Conclusions: Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.

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