Late presentation for HIV impairs immunological but not virological response to antiretroviral treatment

Abstract

Objectives: The aim of this study was to examine the impact of late presentation (CD4 þ cell count <350 cells/ml or an AIDS-defining event) on effectiveness and safety of initial antiretroviral therapy (ART) and to evaluate whether treatment response depends on first-line ART regimen in late presenters.Design: ART-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting triple ART between 2010 and 2018.Methods: We used multivariable models to assess differences in viral suppression (viral load <50 copies/ml), immunological response (change in CD4 þ cell count, CD4% (>29%) and CD4/CD8 normalization (>0.4 and >1) multiple T-cell marker recovery (MTMR): CD4 þ cell count more than 500 cells/ml and CD4% >29% and CD4/CD8 >1), and treatment discontinuation due to adverse events (TDAE) at 48 weeks from ART initiation.Results: Out of 8002 participants, 48.7% were late presenters. Of them, 45.8% initiated ART with a NNRTI-(mostly TDF/FTC/EFV), 33.9% with a protease inhibitor (mostly TDF/FTCþboosted DRV) and 20.3% with an INI-based regimen (mostly ABC/ 3TC/DTG). At 48 weeks, late presenters had similar viral suppression, but worse immunological response, than non-late presenters with no difference on TDAE. Late presenters initiating with NNRTI-based regimens were more likely to achieve viral suppression than those starting with INI-based, due to the higher chance of achieving viral suppression observed with TDF/FTC/RPV compared to ABC/3TC/DTG. Initial treatment with NNRTI or protease inhibitor based showed similar immunological response than the INI-based regimens, which showed lower rates of TDAE than NNRTIand protease inhibitor based regimens. Conclusion:Despite safety and effectiveness of initial ART in terms of viral suppression, late presenters may not experience complete immunological response. In late

Advanced HIV Infection in Treatment-Naïve Individuals: Effectiveness and Persistence of Recommended 3-Drug Regimens

“…In 5 European HIV treatment centers in Germany, Spain, and England, no difference in the frequency of suppression at <50 copies/mL was detected between PWH with a CD4 cell count <200 cells/μL and/or an AIDS-defining condition on an INSTI (86%) and those on a PI (81%) after 48 weeks of treatment [ 28 ]. Similarly, in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) between 2010 and 2018, no difference in viral suppression to <50 copies/mL was observed between PWH with CD4 cell counts <350 cells/μL on an INSTI or a PI (adjusted odds ratio [OR], 1.03; 95% CI, 0.75–1.43), although a higher likelihood of viral suppression was observed with NNRTIs compared with INSTIs (adjusted OR, 1.36; 95% CI, 1.00–1.85) [ 29 ].…”

“…Only 1 trial was restricted to participants with CD4 cell counts <200 cells/μL (DRV/r vs RAL, in combination with abacavir/lamivudine [ABC/3TC]) [ 25 ], and in 2 trials, at least a third of participants had CD4 cell counts <200 cells/μL (dolutegravir [DTG] vs efavirenz, in combination with tenofovir disoproxil fumarate [TDF] + 3TC; DRV/r vs lopinavir/r, in combination with emtricitabine [FTC]/TDF) [ 26 , 27 ]. Moreover, recent observational studies conducted in Europe have been focused on class associations rather than specific regimens [ 28 , 29 ]. This study aimed to compare regimen discontinuation, virologic effectiveness, and immunologic response with common first-line 3-drug regimens (3DRs) in ART-naïve PWH initiating ART with CD4 cell counts <200 cells/μL in a real-world setting in the United States.…”

Late cART Initiation Consistently Driven by Late HIV Presentation: A Multicenter Retrospective Cohort Study in Taiwan from 2009 to 2019

“…In the present study, both etiologies of LI of cART were associated with a high all-cause mortality rate, and this effect was not related to the antiretroviral agent class at initiation. The association between LI of cART and all-cause mortality may be attributed to poor immune recovery after cART in patients with advanced HIV [ 1 , 60 , 61 ], resulting in a higher rate of AIDS-defining illnesses [ 1 ] or clinical progression (AIDS events and death) [ 62 ].…”

Epidemiology, comorbidities at diagnosis and outcomes associated with HIV late diagnosis from 2010 to 2019 in a Belgian reference centre: A retrospective study

“…PIs were potentially preferred for their high genetic barrier and despite their possible adverse impact on lipid profile and on renal function in patients often presenting dyslipidaemia and renal impairment. Although INIs have a more favourable side effect profile and seem to be well tolerated by LD in previous retrospective studies, they induce a steep virological suppression that could be associated with an increased risk of inflammatory reconstitution immune syndrome, notably in very immunocompromised LD [7,10,41,42]. Studies comparing these two classes, such as the LAPTOP study of the NEAT ID network, will provide comparative data regarding efficacy and tolerability in this specific population.…”

“…Late diagnosis (LD), with a CD4 count ≤350/mm 3 or an AIDS-defining event, has medical, societal, and economic consequences. Late diagnosis has been associated with increased risk of clinical progression to AIDS or death, particularly within the first 2 years after diagnosis, blunted CD4 cell count increases, increased risk of immune reconstitution inflammatory syndrome, and hospitalization, resulting in a significant burden of morbidity and mortality and in higher medical costs [2][3][4][5][6][7][8][9][10].…”