Accumulation of protease mutations among patients failing second-line antiretroviral therapy and response to salvage therapy in Nigeria.
BACKGROUND
To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1(st)- and 2(nd)-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3(rd)-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.


RESULTS
From 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0-5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0-6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0-1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.


CONCLUSIONS
This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access.
Brigham and Women's Hospital, Boston, Massachusetts, United States of America ; Harvard School of Public Health, Boston, Massachusetts, United States of America.
Holly E
HE
Rawizza
Beth
B
Chaplin
Seema T
ST
Meloni
Kristin M
KM
Darin
Oluremi
O
Olaitan
Kimberly K
KK
Scarsi
Chika K
CK
Onwuamah
Rosemary A
RA
Audu
Philippe R
PR
Chebu
Godwin E
GE
Imade
Prosper
P
Okonkwo
Phyllis J
PJ
Kanki
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008297:Male; D009154:Mutation; D009549:Nigeria; D010447:Peptide Hydrolases / Q000235:genetics*; D016879:Salvage Therapy / Q000379:methods*
D019380:Anti-HIV Agents; D010447:Peptide Hydrolases