HIV-1 residual risk and pre-treatment drug resistance among blood donors: A sentinel surveillance from Gabon

Abstract

Background: Surveillance of HIV-1 pre-treatment drug resistance (PDR) is essential for ensuring the success of first-line antiretroviral therapy (ART). Beside population-based surveys, sentinel surveillance of PDR and circulating HIV-1 clades in specific populations such as blood donors could efficiently inform decision-making on ART program. We therefore sought to ascertain HIV-1 residual infection, the threshold of PDR and viral diversity among recently-diagnosed blood donors in Gabon.

Methods: A sentinel surveillance was conducted among 381 consenting blood donors at the National Blood Transfusion Center (NBTC) in Gabon from August 3,2020 to August, 31, 2021. In order to determine the residual risk of HIV transmission, viral load and HIV-1 Sanger-sequencing were performed at the Chantal BIYA International Reference Center (CIRCB)-Cameroon on HIV samples previously tested seronegative with ELISA in Gabon. Phylogeny was performed using MEGA X, PDR threshold>10% was considered high and data were analysed using p≤0.05 for statistical significance.

Results: Five HIV-negative blood donors had a detectable viral load indicating a high residual risk of HIV transmission. Among the samples successfully sequenced, four participants had major drug resistance mutations (DRMs), giving a threshold of PDR of 25% (4/16). By drug class, major DRMs targeting NNRTI (K103N, E138G), NRTIs (L210W) and PI/r (M46L). The most representative viral clades were CRF02_AG and subtype A1. The genetic diversity of HIV-1 had no significant effect on the residual risk in blood transfusion (CRF02_AG, P = 0.3 and Recombinants, P = 0.5).

Conclusion: This sentinel surveillance indicates a high residual risk of HIV-1 transfusion in Gabon, thereby underscoring the need for optimal screening strategy for blood safety. Moreover, HIV-1 transmission goes with high-risk of PDR, suggesting suboptimal efficacy of ART. Nonetheless, the genetic diversity has limited (if any effect) on the residual risk of infection and PDR in blood donors.

Fig 1. Characterization of molecular strains of HIV-1 in donors.

A1, F2, G: HIV-1 group M subtypes. CRF45_cpx and CRF02_AG: Recombinant forms of HIV-1 group M.

Fig 2. Phylogenetic tree of HIV-I strains.

On the phylogenetic tree, strains Al, F2, G, CRF02_AG and CRF45_cpx were identified with colored symbols in red, green, yellow, blue and black respectively. Reference strains downloaded from the Los Alamos database. Out of six clusters identified, three clusters had drug resistant strains. These six clusters constituted of the sequences identified in Gabon, Equatorial Guinea, Italy, Democratic Republic of Congo and the United States. The percentage of replicated trees in which related strains are clustered in the bootstrap test (500 replicates) is shown next to the branches.