HIV-1 CRF01_AE subtype and HIV-1 DNA level among patients with chronic HIV-1 infection: a correlation study

Abstract

Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay. Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log 10 copies/10 6 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log 10 copies/10 6 PBMCs) at week 96 were evaluated using a logistic regression model. Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log 10 copies/10 6 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log 10 copies/10 6 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4 + T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log 10 copies/10 6 PBMCs. Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log 10 copies/10 6 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART.

HIV-1 subtype diversity and immuno-virological outcomes among adolescents failing antiretroviral therapy in Cameroon: A cohort study

“…The higher infectivity observed in infection with this variant may be attributed to its enhanced replicative fitness over its pure subtype constituents and hence improved adaptation to its host. HIV-1 subtypes C, D, and the genetic variant CRF01_AE observed in our study have been associated with faster HIV-1 disease progression to AIDS [ 7 , 10 , 22 , 23 ] and advanced immunodeficiency. Evidence suggests that recombinant forms have a faster rate of disease progression when compared to pure lineages.…”

“…This makes it difficult to assess the effect of these less predominant viral clades. Studies carried out in China, where variant CRF01_AE is the most predominant clade, revealed that this variant is associated with fast progression to AIDS (with a shorter median time from the estimated date of seroconversion to AIDS) and advanced immunodeficiency (shorter median time from estimated date of seroconversion to CD4 cell count <100 cells/μl) as compared to non-CRF01_AE viral clades [ 22 , 23 ]. However, a study in Nigeria reported similar rates of CD4 cell count recovery across all subtypes [ 24 ], which is concordant with the results obtained in our evaluation.…”

Comparative Transcriptional Analysis Identified Characteristic Genes and Patterns in HIV-Infected Immunological Non-Responders

“…Secondly, we applied the PBMC samples to measure HIV reservoirs, considering the availability and convenience of acquiring samples. Despite the fact that HIV reservoirs would be mainly represented in lymphoid tissues and gut-associated lymphoid tissue (GALT) (71,72), our previous studies exhibited that the measurement of HIV reservoirs through peripheral blood also provided valuable information (73)(74)(75)(76). Finally, we did not further study the connection between IFN response and microbial translocation, which was reported as a significant cause of persistent immune activation among INRs (20,(77)(78)(79).…”

Whole blood as an alternative to peripheral blood mononuclear cell for detection of total HIV-1 DNA

“…The high genetic diversity of HIV-1 represented by different subtypes may lead to the inaccuracy of HIV-1 DNA quantification [ 18 ]. In the large number of HIV infected samples we tested previously [ 19 , 20 ], the method was used to detect HIV-1 DNA in patients independent of subtypes. The quantification range for HIV-1 DNA using this assay was 20 to 5 × 10 6 copies/10 6 WBCs in our study.…”