Skip to main content
Figure 8 | Retrovirology

Figure 8

From: Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection

Figure 8

Importance of both CD8+ cell-mediated immune responses and continuous tenofovir treatment in RT-SHIV infected animal 30577. As indicated in Figure 3, animal 30577 was inoculated with RT-SHIV (time zero). Panel A and B represent viral RNA levels in plasma, and cell counts in peripheral blood (as measured by flow cytometry), respectively. Tenofovir treatment was started at 20 weeks of infection (vertical dotted line), resulting in an initial rapid 47-fold reduction of viremia (with estimated half-life of productively infected cells of 1.3 days). Despite an initial rebound associated with emergence of K70E followed by K65R viral mutants (table 1; Fig. 6), viremia became undetectable at 55 weeks of infection. At 264 weeks of infection, CD8+ cells were depleted using administration of 3 doses of cM-T807, while tenofovir treatment was continued (at a maintenance regimen of 2.5 mg/kg once daily). After a ~6 log increase in viremia (consisting of K65R virus), virus levels decreased rapidly (with estimated half-life of productively infected cells of 0.9 days) as soon as CD8+ cells started to return. At 289 weeks of infection, tenofovir treatment was interrupted for 9 weeks, and when viremia increased, restarted at the same regimen. The increased viremia during both experimental manipulations demonstrate that both CD8+ cells and continued tenofovir therapy were required for optimal suppression of viremia.

Back to article page