Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection

Abstract

ObjectivesThe magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI).DesignTwo populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450) trials.MethodsTime for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences in pVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression. Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimated through a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop.ResultsOf 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48–51) weeks after stopping ART. Four weeks after stopping treatment, although the proportion with pVL≥400 copies/ml was similar (78% PHI versus 79% CHI), levels were 0.45 (95% CI 0.26–0.64) log10 copies/ml lower for PHI versus CHI, and remained lower up to 48 weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir >500 cells/mm3 was comparable to that experienced by PHI participants.ConclusionsStopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increased transmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.

The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption

“…One previously published study with more limited participants also compared HIV rebound kinetics between those treated during acute vs. chronic HIV infection and support our findings that those treated during acute infection were more likely to have delayed viral rebound [33]. A second study also found that post-ATI viral loads were lower in those treated during acute infection [34]. Possible explanations for these findings include a more restricted HIV reservoir [35][36][37] and immune preservation in participants who initiate ART during early infection.…”

HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice

“…This form of therapy combines at least three drugs, each of which can target a unique step in the viral life cycle including reverse transcription, integration, proteolytic processing, and viral entry (3). However, treatment must be continued indefinitely because ART interruption leads to rapid viremic rebound (4,5), and attempts at treatment intensification by additional drugs have not improved viremic control (6,7). Moreover, therapy is associated with a number of side effects and emergence of resistance, highlighting the need to explore new therapeutic modalities against HIV-1 (3).…”

Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus

“…However, the development of an effective vaccine or an alternative therapy remains the ideal solution since cART has several disadvantages. Adverse effects [1] , high costs of therapy, emergence of resistant viruses [2,3] and in particular, the fact that life-long continuous treatment is required [4][5][6] are just a few examples. Years of research pursuing an HIV-1 vaccine have shown how challenging this task continues to be, with even the most promising trials showing only marginal efficacy [7,8] .…”