The ability of antiretroviral (ARV) drugs to penetrate and suppress viral replication in tissue reservoir sites is critical for HIV remission. We evaluated ARV levels and their impact on HIV transcription in lymph nodes (LN).
This was a sub-study involving participants of the RV254/SEARCH010 Acute HIV Infection Cohort in Bangkok, Thailand. Group 1 (n=6) initiated and continued ARVs with 2 NRTI, dolutegravir (DTG) and maraviroc (MVC). Group 2 (n=12) initiated ARVs on 2 NRTI plus efavirenz and were switched to 2 NRTI plus DTG. HIV RNA+ and DNA+ cells were measured by RNAscope®. Cell-associated HIV RNA and total HIV DNA were measured by PCR. ARV levels were measured by liquid chromatography, tandem mass spectrometry.
Participants, median age 27 yrs, were all MSM. At LN biopsy all had plasma HIV-RNA <20 copies/mL. Group 2 had longer durations of ARV (median 135wks, p<0.001) and DTG use (median 63wks, p=0.002) compared to group 1 (median 44wks, Table). Fiebig stage, HIV viral load, CD4 and CD8 T cell counts at baseline and at LN biopsy were not different between groups. Median PBMC levels (fmol/10^6 cells) were: TFV-DP, 32; 3TC-TP, 8390; CBV-TP, 45. LN cellular levels (Table) of TFV-DP, 3TC-TP, DTG and MVC were measured in all participants; CBV-TP was quantifiable in 4/14 (29%) vs 100% of PBMC samples. Median ratios of LN cellular to in-vitro inhibitory levels (IC50-or-90) were: TFV-DP, 1.8; 3TC-TP, 4.1; CBV-TP, 0.5 (in n=4 with quantifiable levels); DTG, 0.8; MVC, 38.8. Ongoing viral expression was detected by RNAscope® in all participants. There were trends for lower RNA+ (median of 71350 vs 99750 cells/g, p=0.111) and DNA+ cells (median 169137.5 vs 303389 cells/g, p=0.512) in group 1 vs 2. PBMC levels of cell-associated HIV RNA and total HIV DNA were not different between groups.
PBMC levels of TFV-DP, 3TC-TP and CBV-TP were consistent with literature values, as were LN levels of TFV-DP and 3TC-TP. This is the first report of LN penetration of CBV-TP and MVC. CBV-TP LN levels were commonly not quantifiable and 