Genotypic HIV-1 Drug Resistance Among Patients Failing Tenofovir-Based First-Line HAART in South India

Abstract

According to 2013 WHO guidelines, tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. A total of 167 HIV-1-infected patients attaining immunological failure after TDF-based first-line HAART were included in this study, RT region of HIV-1 pol gene was sequenced for them, IAS-USA 2014 list and Stanford HIV drug resistance database were used for mutation interpretation. REGA V3.0 was used for HIV subtyping. The predominant NRTI and NNRTI mutations observed were M184IV (59.9%), K65R (28.1%), and thymidine analogue mutations (TAMs, 29.3%) and K103NS (54.5%), V106AM (39.5%), and Y181CIV (19.8%), respectively. Mutational association shows, K65R was negatively associated with TAMs (OR 0.31, p .008), M184V (OR 0.14, p .57), and K70E (OR 0.29, p .02). Genotypically predicted level of drug resistance based on mutation pattern shows 88% can be opted for azidothymidine (AZT) and still 65% can be opted for TDF. Considering the nature of K65R mutation in increasing susceptibility to AZT and its low prevalence, we conclude that in most patients failing TDF-based first-line therapy, AZT can be considered for second-line therapy followed by TDF itself.

HIV Drug Resistance in Adults Receiving Early vs. Delayed Antiretroviral Therapy: HPTN 052

“…Higher rates of resistance have been reported in other studies in which ART was initiated at lower CD4 cell counts (50–95%). 8–12,17 The risk of resistance increases if individuals continue to receive an ART regimen after virologic failure. 26–29 The lower frequency of resistance observed in HPTN 052 compared to previous studies may reflect frequent viral load monitoring, which may have limited exposure to ART in participants who were not virally suppressed.…”

“…HIV drug resistance is frequently observed at the time of ART failure. 8–12 Several factors have been associated with drug resistance at failure, including the presence of resistance prior to treatment, prior exposure to antiretroviral (ARV) drugs, higher baseline viral load, lower baseline CD4 cell count (<50 cells/mm 3 ), low adherence to ART, younger age in women, and having no education/schooling. 13–15 Some studies suggest that individuals who initiate ART at higher CD4 cell counts (>350 cells/mm 3 ) may be less likely to have drug resistance at failure.…”

HIV-1 drug resistance testing is essential for heavily-treated patients switching from first- to second-line regimens in resource-limited settings: evidence from routine clinical practice in Cameroon

“…substitution of several NRTIs) [2, 5, 6]. Thus, implementing local strategies to ensure a successful switch to SLC is warranted [10].…”

“…With the complete phased-out of stavudine (D4T) from current first-line ART in RLS, tenofovir (TDF)-containing regimens are now widely used while patients with contraindication to TDF are generally being prescribed zidovudine (AZT)-containing regimens as an alternative [9, 10].…”

“…After VF on a standard first-line ART in RLS, an optimal selection of SLC is challenging due to limited access to HIVDR testing [2, 5, 6]. In such situations, 3TC could be recycled as part of the NRTI-backbone in SLC because it selects for the M184 V mutation, which decreases viral replication and increases susceptibility to AZT and TDF for potential use in SLC with PI/r [10, 11]. In this frame, the WHO guidelines also recommend the use of AZT + 3TC as NRTI backbone for SLC for those patients failing on TDF-containing first-line regimen; likewise, TDF + 3TC is recommended as NRTI backbone in SLC for patients failing on AZT-containing first-line regimen [9, 11].…”