scholarly journals Early Initiation of Combination Antiretroviral Therapy in HIV-1-Infected Newborns Can Achieve Sustained Virologic Suppression With Low Frequency of CD4+ T Cells Carrying HIV in Peripheral Blood

2014 ◽  
Vol 59 (7) ◽  
pp. 1012-1019 ◽  
Author(s):  
A. Bitnun ◽  
L. Samson ◽  
T.-W. Chun ◽  
F. Kakkar ◽  
J. Brophy ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Low Frequency ◽  
Early Initiation ◽  
Virologic Suppression ◽  
Combination Antiretroviral Therapy ◽  
Hiv 1

scholarly journals Peripheral T Follicular Helper Cells Are the Major HIV Reservoir within Central Memory CD4 T Cells in Peripheral Blood from Chronically HIV-Infected Individuals on Combination Antiretroviral Therapy

2015 ◽  
Vol 90 (6) ◽  
pp. 2718-2728 ◽  
Author(s):  
Suresh Pallikkuth ◽  
Mark Sharkey ◽  
Dunja Z. Babic ◽  
Sachin Gupta ◽  
Geoffrey W. Stone ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Central Memory ◽  
T Cell Subsets ◽  
Combination Antiretroviral Therapy ◽  
Hiv Persistence ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Hiv 1

ABSTRACTIn this study, we examined the peripheral blood (PB) central memory (TCM) CD4+T cell subsets designated peripheral T follicular helper cells (pTfh cells) and non-pTfh cells to assess HIV permissiveness and persistence. Purified pTfh and non-pTfh cells from healthy HIV-negative donors were tested for HIV permissiveness using green fluorescent protein (GFP)-expressing HIV-1NL4-3/Ba-L, followed by viral reactivation using beads coated with anti-CD3/anti-CD28 monoclonal antibodies. The role of pTfh cells in HIV persistence was analyzed in 12 chronically HIV-1 infected patients before and 48 weeks after initiation of raltegravir-containing combination antiretroviral therapy (cART). Total cellular HIV-1 DNA and episomes containing two copies of the viral long terminal repeat (2LTR circles) were analyzed in using droplet digital PCR in the purified pTfh and non-pTfh cells. Activation-inducible HIV p24 expression was determined by flow cytometry. Results indicate that pTfh cells, in particular PD1+pTfh cells, showed greater permissiveness for HIV infection than non-pTfh cells. At week 48 on cART, HIV DNA levels were unchanged from pre-cART levels, although a significant decrease in 2LTR circles was observed in both cell subsets. Inducible HIV p24 expression was higher in pTfh cells than in non-pTfh cells, with the highest frequencies in the PD1+CXCR3−pTfh cell subset. Frequencies of HLADR+CD38+activated CD4 T cells correlated with 2LTR circles in pTfh and non-pTfh cells at both time points and with p24+cells at entry. In conclusion, among CD4 TCMcells in PB of aviremic patients on cART, pTfh cells, in particular the PD1+CXCR3−subset, constitute a major HIV reservoir that is sustained by ongoing residual immune activation. The inducible HIV p24 assay is useful for monitoring HIV reservoirs in defined CD4 T cell subsets.IMPORTANCEIdentification of the type and nature of the cellular compartments of circulating HIV reservoirs is important for targeting of HIV cure strategies. In lymph nodes (LN), a subset of CD4 T cells called T follicular helper (Tfh) cells are preferentially infected by HIV. Central memory (TCM) CD4 T cells are the major cellular reservoir for HIV in peripheral blood and contain a subset of CD4 TCMcells expressing chemokine receptor CXCR5 similar in function to LN Tfh cells termed peripheral Tfh (pTfh) cells. We found that the circulating pTfh cells are highly susceptible to HIV infection and that in HIV-infected patients, HIV persists in these cells following plasma virus suppression with potent cART. These pTfh cells, which constitute a subset of TCMCD4 T cells, can be readily monitored in peripheral blood to assess HIV persistence.

scholarly journals CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection

2021 ◽  
Vol 22 (2) ◽  
pp. 912
Author(s):  
Nabila Seddiki ◽  
John Zaunders ◽  
Chan Phetsouphanh ◽  
Vedran Brezar ◽  
Yin Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Significant Proportion ◽  
Long Term Memory ◽  
Ki 67 ◽  
Memory Cd4 T Cells ◽  
Hiv 1

HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4+ T cells in peripheral blood, which highly express the α-chain of the IL-7 receptor (CD127), but not CD38 or Ki-67, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease very early in HIV-1 infection. Indeed, CD73+ memory CD4+ T cells comprised a median of 7.5% (interquartile range: 4.5–10.4%) of CD4+ T cells in peripheral blood from healthy adults, but were decreased in primary HIV-1 infection to a median of 3.7% (IQR: 2.6–6.4%; p = 0.002); and in chronic HIV-1 infection to 1.9% (IQR: 1.1–3%; p < 0.0001), and were not restored by antiretroviral therapy. Moreover, we found that a significant proportion of CD73+ memory CD4+ T cells were skewed to a gut-homing phenotype, expressing integrins α4 and β7, CXCR3, CCR6, CD161 and CD26. Accordingly, 20% of CD4+ T cells present in gut biopsies were CD73+. In HIV+ subjects, purified CD73+ resting memory CD4+ T cells in PBMC were infected with HIV-1 DNA, determined by real-time PCR, to the same level as for purified CD73-negative CD4+ T cells, both in untreated and treated subjects. Therefore, the proliferative CD73+ subset of memory CD4+ T cells is disproportionately reduced in HIV-1 infection, but, unexpectedly, their IL-7 dependent long-term resting phenotype suggests that residual infected cells in this subset may contribute significantly to the very long-lived HIV proviral DNA reservoir in treated subjects.

scholarly journals Tenofovir-Based Highly Active Antiretroviral Therapy Is Associated with Superior CD4 T Cells Repopulation Compared to Zidovudine-Based HAART in HIV 1 Infected Adults

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Vitus Sambo Badii ◽  
Kwame Ohene Buabeng ◽  
Thomas Agyarko Poku ◽  
Arnold Donkor Forkuo ◽  
Bright Boafo Boamah ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Scientific Data ◽  
Highly Active ◽  
Median Period ◽  
Hiv 1 ◽  
Count Change ◽  
Zidovudine Regimen

Tenofovir-based highly active antiretroviral therapy (HAART) is one of the preferred first-line therapies in the management of HIV 1 infection. Ghana has since 2014 adopted this recommendation; however there is paucity of scientific data that reflects the safety and efficacy of the tenofovir-based therapy compared to zidovudine in the Ghanaian health system. This study sought to assess the comparative immune reconstitution potential between tenofovir and zidovudine-based HAART regimens, which includes lamivudine and efavirenz in combination therapy. It also aimed to investigate the adverse drug reactions/events (ADREs) associated with pharmacotherapy with these agents in a total of 106 HAART naïve HIV patients. The study included 80 patients in the tenofovir cohort while 26 patients were on the zidovudine regimen. The occurrence of HIV comorbidities profile was assessed at diagnosis and throughout the study period. The baseline CD4 T cells count of the participants was also assessed at diagnosis and repeated at a median period of five months (range 4–6 months), after commencing treatment with either tenofovir- or zidovudine-based HAART. After five months of the HAART, the tenofovir cohort recorded higher CD4 T cell count change from baseline compared to the zidovudine cohort (p<0.0001). The patients on the tenofovir-based HAART and female sex however appeared to be associated with more multiple ADREs.

scholarly journals Primary HIV-1 Infection Is Associated with Preferential Depletion of CD4+ T Lymphocytes from Effector Sites in the Gastrointestinal Tract

2004 ◽  
Vol 200 (6) ◽  
pp. 761-770 ◽  
Author(s):  
Saurabh Mehandru ◽  
Michael A. Poles ◽  
Klara Tenner-Racz ◽  
Amir Horowitz ◽  
Arlene Hurley ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Highly Active Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Cell Loss ◽  
Cd4 T Cell ◽  
Suppressive Therapy ◽  
Hiv 1 ◽  
Gi Mucosa

Given its population of CCR5-expressing, immunologically activated CD4+ T cells, the gastrointestinal (GI) mucosa is uniquely susceptible to human immunodeficiency virus (HIV)-1 infection. We undertook this study to assess whether a preferential depletion of mucosal CD4+ T cells would be observed in HIV-1–infected subjects during the primary infection period, to examine the anatomic subcompartment from which these cells are depleted, and to examine whether suppressive highly active antiretroviral therapy could result in complete immune reconstitution in the mucosal compartment. Our results demonstrate that a significant and preferential depletion of mucosal CD4+ T cells compared with peripheral blood CD4+ T cells is seen during primary HIV-1 infection. CD4+ T cell loss predominated in the effector subcompartment of the GI mucosa, in distinction to the inductive compartment, where HIV-1 RNA was present. Cross-sectional analysis of a cohort of primary HIV-1 infection subjects showed that although chronic suppression of HIV-1 permits near-complete immune recovery of the peripheral blood CD4+ T cell population, a significantly greater CD4+ T cell loss remains in the GI mucosa, despite up to 5 yr of fully suppressive therapy. Given the importance of the mucosal compartment in HIV-1 pathogenesis, further study to elucidate the significance of the changes observed here is critical.

scholarly journals Th1/17 Polarization of CD4 T Cells Supports HIV-1 Persistence during Antiretroviral Therapy

2015 ◽  
Vol 89 (22) ◽  
pp. 11284-11293 ◽  
Author(s):  
Hong Sun ◽  
Dhohyung Kim ◽  
Xiaodong Li ◽  
Maja Kiselinova ◽  
Zhengyu Ouyang ◽  
...  
Keyword(s):  
T Cells ◽  
Antiretroviral Therapy ◽  
Cd4 T Cells ◽  
Ex Vivo ◽  
Memory Cell ◽  
Viral Reservoir ◽  
Target Cells ◽  
Infected Cells ◽  
Hiv 1

ABSTRACTThe ability to persist long term in latently infected CD4 T cells represents a characteristic feature of HIV-1 infection and the predominant barrier to efforts aiming at viral eradication and cure. Yet, increasing evidence suggests that only small subsets of CD4 T cells with specific developmental and maturational profiles are able to effectively support HIV-1 long-term persistence. Here, we analyzed how the functional polarization of CD4 T cells shapes and structures the reservoirs of HIV-1-infected cells. We found that CD4 T cells enriched for a Th1/17 polarization had elevated susceptibilities to HIV-1 infection inex vivoassays, harbored high levels of HIV-1 DNA in persons treated with antiretroviral therapy, and made a disproportionately increased contribution to the viral reservoir relative to their contribution to the CD4 T memory cell pool. Moreover, HIV-1 DNA levels in Th1/17 cells remained stable over many years of antiretroviral therapy, resulting in a progressively increasing contribution of these cells to the viral reservoir, and phylogenetic studies suggested preferential long-term persistence of identical viral sequences during prolonged antiretroviral treatment in this cell compartment. Together, these data suggest that Th1/17 CD4 T cells represent a preferred site for HIV-1 DNA long-term persistence in patients receiving antiretroviral therapy.IMPORTANCECurrent antiretroviral therapy is very effective in suppressing active HIV-1 replication but does not fully eliminate virally infected cells. The ability of HIV-1 to persist long term despite suppressive antiretroviral combination therapy represents a perplexing aspect of HIV-1 disease pathogenesis, since most HIV-1 target cells are activated, short-lived CD4 T cells. This study suggests that CD4 T helper cells with Th1/17 polarization have a preferential role as a long-term reservoir for HIV-1 infection during antiretroviral therapy, possibly because these cells may imitate some of the functional properties traditionally attributed to stem cells, such as the ability to persist for extremely long periods of time and to repopulate their own pool size through homeostatic self-renewal. These observations support the hypothesis that HIV-1 persistence is driven by small subsets of long-lasting stem cell-like CD4 T cells that may represent particularly promising targets for clinical strategies aiming at HIV-1 eradication and cure.

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