Immune reconstruction effectiveness of combination antiretroviral therapy for HIV-1 CRF01_AE cluster 1 and 2 infected individuals

Abstract

There are great disparities of the results in immune reconstruction (IR) of the HIV-1 infected patients during combined antiretroviral therapy (cART), due to both host polymorphisms and viral genetic subtypes. Identifying these factors and elucidating their impact on the IR could help to improve the efficacy. To study the factors influencing the IR, we conducted a 15-year retrospective cohort study of HIV-1 infected individuals under cART. The trend of CD4 + count changes was evaluated by the generalized estimating equations. Cox proportional model and propensity score matching were used to identify variables that affect the possibility of achieving IR. The tropism characteristics of virus were compared using the coreceptor binding model. In addition to baseline CD4 + counts and age implications, CRF01_AE cluster 1 was associated with a poorer probability of achieving IR than infection with cluster 2 (aHR, 1.39; 95%CI, 1.02-1.90) and other subtypes (aHR, 1.83; 95%CI, 1.31-2.56). The mean time from cART initiation to achieve IR was much longer in patients infected by CRF01_AE cluster 1 than other subtypes/sub-clusters ( P < 0.001). In-depth analysis indicated that a higher proportion of CXCR4 viruses were found in CRF01_AE clusters 1 and 2 ( P < 0.05), and showed tendency to favour CXCR4 binding to V3 signatures. This study indicated the immune restoration impairment found in patients were associated with HIV-1 CRF01_AE cluster 1, which was attributed to the high proportion of CXCR4-tropic viruses. To improve the effectiveness of cART, more efforts should be made in the early identification of HIV-1 subtype/sub-cluster and monitoring of virus phenotypes.

Transmission network and phylogenetic analysis reveal older male-centered transmission of CRF01_AE and CRF07_BC in Guangxi, China

“…Especially in Guangxi, CRF01_AE predominated in the sexual transmission of HIV [ 41 ]. Moreover, due to the high proportion of X4 tropism [ 42 , 43 ], CRF01_AE tended to be associated with rapid disease progression and advanced immunodeficiency [ 44 ]. Even with combination ART, poor immune recovery was more frequent with CRF01_AE [ 45 ].…”

The Molecular Epidemiological and Immunological Characteristics of HIV-1 CRF01_AE/B Recombinants in Nanjing, China

“…CRF01_AE/B recombinants manifested similar negative effects on disease progression and immune reconstitution as CRF01_AE, more severe than CRF07_BC. Notably, the CRF_01AE subtype has been reported to be more pathogenic than other subtypes in the studies of Asian population, such as lower level of baseline CD4 + T-cell count, greater CD4 + T-cell count loss, shorter median survival, and poorer immune reconstruction ability, compared with other subtypes (Nelson et al, 2007;Rangsin et al, 2007;Ng et al, 2011;Li X. et al, 2014;Li et al, 2022). The pathogenic impact of CRF01_AE on HIV-1 disease progression might be explained by the larger proportion of CXCR4-tropic viruses and higher frequency of R5 to X4/DM switch (Li X. et al, 2014;Cui et al, 2019;Ge et al, 2021).…”

“…In the part of the assessment of the efficacy of immune reconstruction, we included patients who received first-line cART for at least 2 years and maintained persistent virological suppression (undetectable viral load) during the treatment. The immune reconstruction was defined as two successive CD4 + T-cell counts of more than 500 cells/µl after cART initiation, while poor immune reconstruction was defined as CD4 + T-cell count <500 cells/µl at all follow-up visits (Kelley et al, 2009;Li et al, 2022). In our study, we enrolled the newly diagnosed HIV-1-infected patients during 2015-2019; thus, there were two different criteria for these patients of whether receiving cART in China.…”

“…It has been widely recognized that HIV-1 subtypes may affect disease progression and immune recovery of patients (Taylor et al, 2008;Keller et al, 2009;Amornkul et al, 2013;Li et al, 2022). Several studies have revealed that patients infected with CRF01_AE showed an increased rate of CD4 + T-cell count decline (Ng et al, 2011;Cui et al, 2019), whereas CRF07_BC was associated with relatively slow HIV disease progression (Ye et al, 2022).…”

“…Several studies have revealed that patients infected with CRF01_AE showed an increased rate of CD4 + T-cell count decline (Ng et al, 2011;Cui et al, 2019), whereas CRF07_BC was associated with relatively slow HIV disease progression (Ye et al, 2022). The impaired immune recovery after the combined antiretroviral therapy (cART) has also been reported in patients infected with CRF01_AE cluster 1 (Li et al, 2022). As the newly emerging strains, the impact of CRF01_AE/B recombinants on disease progression and immune reconstruction efficacy has not been clarified yet.…”