Background: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC).Methods and results: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/mu l. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02-0.63, p = 0.012 and OR 0.28, 95% CI 0.06-1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL.Conclusions: While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC.

De Luca, A., Sidumo, Z.j., Zanelli, G., Magid, N.a., Luhanga, R., Brambilla, D., et al. (2017). Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: Implications for the activity of next-line regimens from a longitudinal study in Mozambique. BMC INFECTIOUS DISEASES, 17(1) [10.1186/s12879-017-2709-x].

Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: Implications for the activity of next-line regimens from a longitudinal study in Mozambique

Liotta G.;Mancinelli S.;Palombi L.;
2017

Abstract

Background: We describe the accumulation of HIV-1 drug resistance and its effect on the activity of next-line components in patients with virological failure (HIV-1 RNA >1000 copies/mL) after 1 year (t1) of first-line antiretroviral therapy (ART) not switching to second-line drugs for one additional year (t2) in low-middle income countries (LMIC).Methods and results: We selected 48 patients from the DREAM cohort (Maputo, Mozambique); their median pre-ART CD4+ cell count was 165 cells/mu l. At t1 patients were receiving ART since a median of 12.2 months (mainly zidovudine/lamivudine/nevirapine), their median HIV RNA was 3.8 log10 copies/mL, 43 (89.6%) presented at least one resistance-associated mutation (RAM), most frequently for lamivudine/emtricitabine, nevirapine and efavirenz. Resistance to tenofovir, was 10% at 1 year and higher than 20% at 2 years, while projection at 3 years was >30%. At t2, 42 (89.4%) had a predicted low-level or higher resistance to at least 1 s-line drug. At t1, the frequency of RAM in patients with a lower adherence to pharmacy appointments (<95%) was significantly lower (12/20, 60% for NRTI and 14/20, 70% for NNRTI) than in those with a better adherence (26/28, 92.8% for NRTI and 25/28, 89.3% for NNRTI) (OR 0.12, 95% CI 0.02-0.63, p = 0.012 and OR 0.28, 95% CI 0.06-1.29, p = 0.103, respectively). Overall thymidine analogue mutations (TAMs) accumulation rate was 0.32/year, 0.50/year in the subgroup with HIV RNA >10,000 copies/mL; NNRTI RAM accumulation rate was 0.15/year, 0.40/year in the subgroup with HIV RNA >10,000 copies/mL.Conclusions: While the activity of NNRTIs is compromised early during failure, tenofovir and zidovudine activity are reduced more frequently after 1 year of documented virological failure of thymidine analogue-based first-line ART, with RAMs accumulating faster in patients with higher viral loads. The present observation may help informing decisions on when to switch to a second line ART in patients on virological failure in LMIC.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/42 - Igiene Generale e Applicata
Settore MED/17 - Malattie Infettive
English
Con Impact Factor ISI
Antiretroviral drug resistance; HIV-1; HIV-1 RNA; Second-line ART; Virological failure; Adult; Antiretroviral Therapy, Highly Active; Benzoxazines; CD4 Lymphocyte Count; Drug Resistance, Viral; Female; HIV Infections; HIV-1; Humans; Lamivudine; Longitudinal Studies; Male; Mozambique; Mutation; Nevirapine; Reverse Transcriptase Inhibitors; Tenofovir; Treatment Failure; Viral Load; Zidovudine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584020/
De Luca, A., Sidumo, Z.j., Zanelli, G., Magid, N.a., Luhanga, R., Brambilla, D., et al. (2017). Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure: Implications for the activity of next-line regimens from a longitudinal study in Mozambique. BMC INFECTIOUS DISEASES, 17(1) [10.1186/s12879-017-2709-x].
De Luca, A; Sidumo, Zj; Zanelli, G; Magid, Na; Luhanga, R; Brambilla, D; Liotta, G; Mancinelli, S; Marazzi, Mc; Palombi, L; Ceffa, S
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
2017 Accumulation of HIV-1 drug resistance in patients on a standard thymidine analogue-based first line antiretroviral therapy after virological failure.pdf

accesso aperto

Licenza: Non specificato
Dimensione 478.14 kB
Formato Adobe PDF
478.14 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/195420
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 11
social impact