Molecular dating and viral load growth rates suggested that the eclipse phase lasted about a week in HIV-1 infected adults in East Africa and Thailand

Background: Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. Objective: To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR). Methods: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VL<50 and 200 copies/mL in TE (margin 12%). Durability of response, and safety were also measured. Results: 242 patients were included (53 TN and 189 TE). Two TN patients on 2-DR had VL≥50 copies/mL and 1 had VL≥200 copies/mL at week 24. In TE patients on 2-DR, 90.2% achieved VL<200 copies/mL at week 24 (difference: 3.8%; 95% CI = −6.3% to 14%) and 91.8% at week 48 (difference: 0.06%; 95% CI = −9% to 10%), meeting noninferiority criteria. Among the 53 TN patients, only 1 VF was observed in 2-DR. In TN patients, the risk of treatment discontinuation was similar between groups (hazard ratio [HR] = 0.37; P = 0.15); similar rates were also found in TE patients (HR = 0.94; P = 0.85). TE patients on 2-DR showed a better safety profile compared with 3-DR patients ( P<0.001). Conclusion and Relevance: Our results did not show noninferiority in terms of virological effectiveness. Nevertheless, all effectiveness measures support the use of 2-DR in a real-life cohort of TN and TE. Additionally, durability and safety of 2-DR were confirmed to be similar to that of 3-DR.

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STING and cGAS gene expressions were downregulated among HIV-1-infected persons after antiretroviral therapy

Virology Journal ◽

10.1186/s12985-021-01548-6 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Lorena Leticia Peixoto de Lima ◽

Allysson Quintino Tenório de Oliveira ◽

Tuane Carolina Ferreira Moura ◽

Ednelza da Silva Graça Amoras ◽

Sandra Souza Lima ◽

...

Keyword(s):

Gene Expression ◽

Viral Load ◽

T Cell ◽

Antiretroviral Therapy ◽

Cell Count ◽

Enzyme Linked Immunosorbent Assay ◽

Type I ◽

Α Level ◽

The Impact ◽

Hiv 1

Abstract Background The HIV-1 epidemic is still considered a global public health problem, but great advances have been made in fighting it by antiretroviral therapy (ART). ART has a considerable impact on viral replication and host immunity. The production of type I interferon (IFN) is key to the innate immune response to viral infections. The STING and cGAS proteins have proven roles in the antiviral cascade. The present study aimed to evaluate the impact of ART on innate immunity, which was represented by STING and cGAS gene expression and plasma IFN-α level. Methods This cohort study evaluated a group of 33 individuals who were initially naïve to therapy and who were treated at a reference center and reassessed 12 months after starting ART. Gene expression levels and viral load were evaluated by real-time PCR, CD4+ and CD8+ T lymphocyte counts by flow cytometry, and IFN-α level by enzyme-linked immunosorbent assay. Results From before to after ART, the CD4+ T cell count and the CD4+/CD8+ ratio significantly increased (p < 0.0001), the CD8+ T cell count slightly decreased, and viral load decreased to undetectable levels in most of the group (84.85%). The expression of STING and cGAS significantly decreased (p = 0.0034 and p = 0.0001, respectively) after the use of ART, but IFN-α did not (p = 0.1558). Among the markers evaluated, the only markers that showed a correlation with each other were STING and CD4+ T at the time of the first collection. Conclusions ART provided immune recovery and viral suppression to the studied group and indirectly downregulated the STING and cGAS genes. In contrast, ART did not influence IFN-α. The expression of STING and cGAS was not correlated with the plasma level of IFN-α, which suggests that there is another pathway regulating this cytokine in addition to the STING–cGAS pathway.

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Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3

Intervirology ◽

10.1159/000514385 ◽

2021 ◽

pp. 1-5

Author(s):

Mohammad Reza Jabbari ◽

Hoorieh Soleimanjahi ◽

Somayeh Shatizadeh Malekshahi ◽

Mohammad Gholami ◽

Leila Sadeghi ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

Cell Count ◽

Previous History ◽

Cd4 Count ◽

Cd4 Cell Count ◽

Cell Counts ◽

Immunodeficiency Virus ◽

Cd4 Cell ◽

Hiv 1

Objectives: The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count <100 cells/mm3 and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. Methods: This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count <100 cells/mm3, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). Results: Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (p value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (p < 0.02). Conclusions: We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count <100 mm3/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.

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