HIV-1 persistent viremia is frequently followed by episodes of low-level viremia

Abstract

After the start of antiretroviral therapy (ART), plasma HIV-RNA levels should fall below the limit of detection (LOD) within 24 weeks. Hence, the prolonged decline of HIV-RNA after ART initiation is defined as persistent viremia (PV). In this retrospective study, we analyzed factors associated with PV. Next-generation sequencing of viral RNA/DNA was performed to study viral evolution and the emergence of drug-resistance mutations in HIV-infected patients with PV (n = 20). In addition, HIV-DNA species, immunological parameters, and clinical data of the patients were analyzed. We found that the possible causes for PV were divers, and both virologic and host parameters of this particular cohort were heterogeneous. We identified viruses with therapy-associated DRMs in six patients (30%); two of these were detected as minority variants. Five patients had sub-optimal drug levels (25%) and the baseline plasma viral loads were relatively high. Strikingly, we observed that >40% of the PV patients finally reaching HIV levels below the LOD later on showed up with episodes of low-level viremia (LLV). However, the amount of PBMC derived HIV-DNA species was not correlated with the likelihood of LLV after PV. According to our data, we conclude that drug-resistant viruses, sub-optimal drug level, and high baseline viral loads might be probable reasons for the prolonged RNA decline only in a sub-set of patients. In the absence of emerging DRMs and/or compliance issues, the clinical implications of PV remain unclear; however, PV appears to be a risk factor for episodes of LLV.

Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation

“…Our study was not well suited to evaluate this effect, as rifampin was co-administered with NVP in only three participants. Suboptimal antiretroviral concentrations at times of LLV have been reported from other studies [ 48 – 50 ], suggesting that poor-adherence or drug–drug interactions could be a cause of LLV. However, given the generally therapeutic levels in our study, this was not likely a cause of LLV.…”

Concurrent administration of IFNα14 and cART in TKO-BLT mice enhances suppression of HIV-1 viremia but does not eliminate the latent reservoir

“…By using an input volume of 100 µl plasma the detection limit was 300 copies/ml. Total HIV-1 DNA was quantified performing a pre-PCR followed by a probe-based real-time PCR approach as described previously 19,20 . Briefly, genomic DNA was isolated from splenic CD4 + cells using QIAamp DNA Mini Kit (Qiagen).…”

“…TaqMan probes for CD3 and HIV-1-DNA quantification were dually labelled with YAK-BHQ-1 and 6-FAM-BHQ-1, respectively. Standard curves were generated with plasmid DNA templates harboring the corresponding amplicon regions or genomic DNA of HIV-1 LTR-harbouring cells for the quantification of integrated provirus 20 . Determinations of HIV infection levels in plasma for group assignments were done by p24 ELISA (Advanced Bioscience Laboratories, Rockville MD).…”

The CCL2 Chemokine Promotes Early Seeding of the Latent HIV Reservoir

“…Depending on the available sample volume, the detection limit was 375 cp/mL during follow-up or 150 cp/mL at the time of euthanasia. For the quantification of HIV DNA, genomic DNA of splenocytes was isolated using QIAamp DNA blood mini kit (Qiagen) and subjected to a probebased real-time PCR approach, as previously described 71,72 . Briefly, HIV-specific and control (hCD3) DNA sequences were pre-amplified (12 cycles) in a TProfessional TRIO Thermocycler…”