From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adultsReport as inadecuate

From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults - Download this document for free, or read online. Document in PDF available to download.

BMC Research Notes

, 9:515

Health services research


BackgroundHIV care programs in resource-limited settings have hitherto concentrated on antiretroviral therapy ART access, but HIV drug resistance is emerging. In a cross-sectional study of HIV-positive adults on ART for ≥6 months enrolled into a prospective cohort in Uganda, plasma HIV RNA was measured and genotyped if ≥1000 copies-ml. Identified Drug resistance mutations DRMs were interpreted using the Stanford database, 2009 WHO list of DRMs and the IAS 2014 update on DRMs, and examined and tabulated by ART drug classes.

FindingsBetween July 2013 and August 2014, 953 individuals were enrolled, 119 12.5% had HIV-RNA ≥1000 copies-ml and 110 were successfully genotyped; 74 67.3% were on first-line and 36 32.7% on second-line ART regimens. The predominant HIV-1 subtypes were D 34.5%, A 33.6% and Recombinant forms 21.8%. The commonest clinically significant major resistance mutations associated with the highest levels of reduced susceptibility or virological response to the relevant Nucleoside Reverse Transcriptase Inhibitor NRTI were; the Non-thymidine analogue mutations Non-TAMS M184V—20.7% and K65R—8.0%; and the TAMs M41L and K70R both 8.0%. The major Non-NRTI NNRTI mutations were K103N—19.0%, G190A—7.0% and Y181C—6.0%. A relatively nonpolymorphic accessory mutation A98G—12.0% was also common. Seven of the 36 patients on second line ART had major Protease Inhibitor PI associated DRMS including; V82A—7.0%, I54V, M46I and L33I all 5.0%. Also common were the accessory PI mutations L10I—27%, L10V—12.0% and L10F—5.0% that either reduce PI susceptibility or increase the replication of viruses containing PI-resistance mutations. Of the 7 patients with major PI DRMs, five had high level resistance to ritonavir boosted Lopinavir and Atazanavir, with Darunavir as the only susceptible PI tested.

ConclusionsIn resource-limited settings, HIV care programs that have previously concentrated on ART access, should now consider availing access to routine HIV viral load monitoring, targeted HIV drug resistance testing and availability of third-line ART regimens.

KeywordsAntiretroviral therapy Drug resistance Mutations Third-line regimen AbbreviationsHIVhuman immunodeficiency virus

ARTantiretroviral therapy

RNAribonucleic acid

DRMdrug resistance mutation

WHOWorld Health Organisation

IASInternational AIDS Society

NRTInucleoside reverse transcriptase inhibitors

NNRTInon nucleoside reverse transcriptase inhibitors

PIprotease inhibitors

AIDSacquired immune deficiency syndrome


CoLTARTComplications of Long-Term Antiretroviral Therapy

DARTdevelopment of antiretroviral therapy in Africa

RIPrecombinant identification program

TDRtransmitted drug resistance

IASInternational AIDS Society

CPRcalibrated population resistance tool

Download fulltext PDF

Author: Ivan Namakoola - Ivan Kasamba - Billy N. Mayanja - Patrick Kazooba - Joseph Lutaakome - Fred Lyagoba - Anne A. Kapaata -


Related documents