The ARTμS: a novel microfluidic CD4+ T-cell enumeration system for monitoring antiretroviral therapy in HIV patients

ABSTRACT The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells.

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Susceptibility to opportunistic infections in HIV-infected patients with increased CD4 T-cell counts on antiretroviral therapy may be predicted by markers of dysfunctional effector memory CD4 T cells and B cells

HIV Medicine ◽

10.1111/j.1468-1293.2007.00445.x ◽

2007 ◽

Vol 8 (3) ◽

pp. 148-155 ◽

Cited By ~ 20

Author(s):

MA French ◽

NM Keane ◽

EJ McKinnon ◽

S Phung ◽

P Price

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Antiretroviral Therapy ◽

Cd4 T Cells ◽

Opportunistic Infections ◽

Cd4 T Cell ◽

Effector Memory ◽

Cell Counts ◽

Memory Cd4 T Cells

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Effects of HCV co-infection on apoptosis of CD4+ T-cells in HIV-positive patients

Clinical Science ◽

10.1042/cs20080532 ◽

2009 ◽

Vol 116 (12) ◽

pp. 861-870 ◽

Cited By ~ 29

Author(s):

Christian Körner ◽

Benjamin Krämer ◽

Daniela Schulte ◽

Martin Coenen ◽

Stefan Mauss ◽

...

Keyword(s):

T Cells ◽

Hepatitis C ◽

T Cell ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Cell Apoptosis ◽

Cd4 T Cells ◽

Cd4 T Cell ◽

Hiv Positive ◽

T Cell Apoptosis

Apoptosis importantly contributes to loss of CD4+ T-cells in HIV infection, and modification of their apoptosis may explain why HIV/HCV (hepatitis C virus)-co-infected patients are more likely to die from liver-related causes, although the effects of HCV on HIV infection remain unclear. In the present study, we studied in a cross-sectional and serial analysis spontaneous ex vivo CD4+ T-cell apoptosis in HIV/HCV-co-infected and HIV-mono-infected patients before and after HAART (highly active antiretroviral therapy). Apoptosis of peripheral blood CD4+ T-cells was measured by both a PARP [poly(ADP-ribose) polymerase] and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay to detect cells with irreversible apoptosis. Although hepatitis C alone did not increase CD4+ T-cell apoptosis, HCV co-infection disproportionately increased elevated rates of apoptosis in CD4+ T-cells from untreated HIV-positive patients. Increased CD4+ T-cell apoptosis was closely correlated with HIV, but not HCV, viral loads. Under HAART, increased rates of CD4+ T-cell apoptosis rapidly decreased both in HIV-mono-infected and HIV/HCV-co-infected patients, without any significant difference in apoptosis rates between the two patient groups after 4 weeks of therapy. Nevertheless residual CD4+ T-cell apoptosis did not reach the normal levels seen in healthy controls and remained higher in HIV patients receiving protease inhibitors than in patients with other antiretroviral regimens. The results of the present study suggest that HCV co-infection sensitizes CD4+ T-cells towards apoptosis in untreated HIV-positive patients. However, this effect is rapidly lost under effective antiretroviral therapy.

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The effect of tuberculosis on immune reconstitution among HIV patients on highly active antiretroviral therapy in Adigrat general hospital, eastern Tigrai, Ethiopia; 2019: a retrospective follow up study

BMC Immunology ◽

10.1186/s12865-019-0327-7 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Hadush Negash ◽

Haftom Legese ◽

Mebrahtu Tefera ◽

Fitsum Mardu ◽

Kebede Tesfay ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cells ◽

Immune Reconstitution ◽

Cd4 T Cell ◽

Highly Active ◽

Cell Counts

Abstract Background Ethiopia initiated antiretroviral therapy early in 2005. Managing and detecting antiretroviral treatment response is important to monitor the effectiveness of medication and possible drug switching for low immune reconstitution. There is less recovery of CD4+ T cells among human immunodeficiency virus patients infected with tuberculosis. Hence, we aimed to assess the effect of tuberculosis and other determinant factors of immunological response among human immunodeficiency virus patients on highly active antiretroviral therapy. A retrospective follow up study was conducted from October to July 2019. A total of 393 participants were enrolled. An interviewer based questionnaire was used for data collection. Patient charts were used to extract clinical data and follow up results of the CD4+ T cell. Current CD4+ T cell counts of patients were performed. STATA 13 software was used to analyze the data. A p-value ≤0.05 was considered a statistically significant association. Results The mean age of study participants was 39.2 years (SD: + 12.2 years) with 8.32 mean years of follow up. The overall prevalence of immune reconstitution failure was 24.7% (97/393). Highest failure rate occurred within the first year of follow up time, 15.7 per 100 Person-year. Failure of CD4+ T cells reconstitution was higher among tuberculosis coinfected patients (48.8%) than mono-infected patients (13.7%). Living in an urban residence, baseline CD4+ T cell count ≤250 cells/mm3, poor treatment adherence and tuberculosis infection were significantly associated with the immunological failure. Conclusions There was a high rate of CD4+ T cells reconstitution failure among our study participants. Tuberculosis infection increased the rate of failure. Factors like low CD4+ T cell baseline count, poor adherence and urban residence were associated with the immunological failure. There should be strict monitoring of CD4+ T cell counts among individuals with tuberculosis coinfection.

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Kinetics of CD4+ T-cell recovery amongst HIV load suppressed patients on first-line antiretroviral therapy in Yaoundé, Cameroon

International Journal of Biological and Chemical Sciences ◽

10.4314/ijbcs.v15i3.3 ◽

2021 ◽

Vol 15 (3) ◽

pp. 881-888

Author(s):

Cedric Happi Mbakam ◽

Julius Mbekem Nwobegahay ◽

Cybelle Fodieu Mezajou ◽

Franklin Agueguia Azebaze ◽

Leopold Mbous Nguimbus ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Antiretroviral Therapy ◽

Cd4 T Cells ◽

Standard Form ◽

University Teaching ◽

Cd4 T Cell ◽

Cell Recovery ◽

First Line ◽

Kinetics Of

HIV infected patients on Antiretroviral Therapy (ART) are exposed to various immunological disorders. Immune reconstitution is one of the most challenging problem linked to morbidity and mortality in HIV patients. This study aimed at evaluating the kinetics of CD4+ T-cell recovery amongst HIV load suppressed patients on first-line ART in Yaoundé, Cameroon. This was a retrospective cohort study performed at the care and treatment units of the Yaoundé University Teaching Hospital and Essos Hospital Center, with viral suppressed patients initiated on ART between March and July 2015. Data were collected using a standard form and analyzed using R.3.6.2 software. A p<0.05 was considered statistically significant for a 95%CI. Of the 499 viral suppressed participants, 32% (n=160) were male and 68% (n=339) female; 33% and 40% had severe and moderate immunodepression at baseline, respectively; 9% and 28% remain respectively on the same immunological state. CD4+ T-cell count increased by 73%, 49% and 29% for patients that started treatment, with CD4+ <150 cells/ml, 150<CD4+<350 cells/ml and 350<CD4+<500 cells/ml, respectively and 14%, 34% and 40% reached a target of 500 cells/ml or more after 4 years of treatment. Elder patients and males were likely to have CD4+ T-cells less than 350 Cells/ml. Approximately 35% of patient started treatment with CD4+ T-cells <350 Cells/ml. CD4+ T-cells increased significantly during 4 years of treatment but, just 29% in average achieved CD4+ ≥ 500 cells/ml. CD4 T-cells recovery represent and important challenge in the immunological monitoring of long-term HIV infected patients on ART.

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Platelets function as an acute viral reservoir during HIV-1 infection by harboring virus and T-cell complex formation

Blood Advances ◽

10.1182/bloodadvances.2020002420 ◽

2020 ◽

Vol 4 (18) ◽

pp. 4512-4521

Author(s):

Sydney R. Simpson ◽

Meera V. Singh ◽

Stephen Dewhurst ◽

Giovanni Schifitto ◽

Sanjay B. Maggirwar

Keyword(s):

T Cells ◽

T Cell ◽

Antiretroviral Therapy ◽

Complex Formation ◽

Platelet Activation ◽

Cd4 T Cells ◽

Cell Complex ◽

Cd4 T Cell ◽

Cell Recovery

Abstract Platelets were recently found to harbor infectious HIV virions in infected individuals who are on antiretroviral treatment with poor CD4+ T-cell recovery. In this study, we screened platelets from recently infected individuals, before and after antiretroviral therapy, for the presence of virus and examined platelet activation, as well as CD4+ T-cell recovery. This was followed by in vitro studies assessing platelet–CD4+ T-cell complex formation as a contributing factor to viral transmission. HIV+ platelets were detected in 10 of 10 acutely infected individuals with no prior history of antiretroviral therapy. The percentage of HIV+ platelets dropped significantly after 3 months of antiretroviral therapy in all of the study participants. These individuals also demonstrated significant recovery of CD4+ T cells. Interestingly, the percentage of HIV+ platelets correlated positively with viral load but not with CD4+ T-cell count. Furthermore, we found that platelet activation with soluble CD40L or thrombin receptor activator peptide 6 (TRAP6) increased platelet-virus interactions in vitro. TRAP6-mediated interactions were reduced by platelet antagonists, aspirin, and R406. We demonstrated that platelets transmit the virus to CD4+ T cells, and this transinfection was abolished by inhibiting platelet–T-cell complex formation via exposure to an anti-CD62P antibody. Additionally, treatment with TRAP6 significantly increased the transinfection, which was also inhibited by aspirin and R206. These results reveal that platelets have the potential to promote HIV viral spread during the acute stage of infection, by harboring infectious virus transmitting infection to susceptible CD4+ T cells through complex formation.

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