scholarly journals Fitness Cost of Antiretroviral Drug Resistance Mutations on the pol Gene during Analytical Antiretroviral Treatment Interruption among Individuals Experiencing Virological Failure

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1425
Author(s):  
James R. Hunter ◽  
Domingos E. Matos dos Santos ◽  
Patricia Munerato ◽  
Luiz Mario Janini ◽  
Adauto Castelo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
T Cell ◽  
Reverse Transcriptase ◽  
Virological Failure ◽  
Resistance Mutation ◽  
Treatment Interruption ◽  
People Living With Hiv ◽  
Analytical Treatment ◽  
Cell Counts

HIV cure studies require patients to enter an analytical treatment interruption (ATI). Here, we describe previously unanalyzed data that sheds light on ATI dynamics in PLHIV (People Living with HIV). We present drug resistance mutation dynamics on the pol gene among individuals with antiretroviral virological failure who underwent ATI. The study involved a 12-week interruption in antiretroviral therapy (ART), monitoring of viral load, CD4+/CD8+ T cell counts, and sequencing of the pol gene from 38 individuals experiencing virological failure and harboring 3-class resistant HIV strains: nucleoside reverse transcriptase inhibitors (NRTI) non-nucleoside inhibitors (NNRTI), and protease inhibitors (PI). Protease and reverse transcriptase regions of the pol gene were sequenced at baseline before ATI and every four weeks thereafter from PBMCs and at baseline and after 12 weeks from plasma HIV RNA using population-based Sanger sequencing. Average viral load increased 0.559 log10 copies per milliliter. CD4+ T cell count decreased as soon as ART was withdrawn, an average loss of 99.0 cells/mL. Forty-three percent of the mutations associated with antiretroviral resistance in PBMCs disappeared and fifty-seven percent of the mutations in plasma reverted to wild type, which was less than the 100% reversion expected. In PBMC, the PI mutations reverted more slowly than reverse transcriptase mutations. The patients were projected to need an average of 33.7 weeks for PI to revert compared with 20.9 weeks for NRTI and 19.8 weeks for NNRTI. Mutations in the pol gene can cause virological failure and difficulty in re-establishing effective virological suppression.

scholarly journals Detectable viral load among HIV -1 positive pregnant women on ART (Option B +) in northern Tanzania: Baseline results from the HIVDR study

2021 ◽  
Vol 3 (1) ◽  
pp. 44-50
Author(s):  
Nicholaus Steven Mazuguni ◽  
Festo Mazuguni ◽  
Eva Prosper Muro
Keyword(s):  
Drug Resistance ◽  
Viral Load ◽  
Virological Failure ◽  
Virologic Failure ◽  
Resistance Mutation ◽  
Resistance Testing ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Hiv 1 ◽  
Level Resistance

Introduction: In Tanzania, the Ministry of Health, Community Development, Gender, Elderly and Children (MoHCDEC) has implemented the Option B+ as one of the strategies to facilitate achievement of elimination of mother to child transmission of HIV. To prevent emergence of drug resistance mutations early identification of option B+ failure is critical. The emergence of drug resistance mutation and subsequent treatment failure poses a major concern for HIV program in low- and middle-income resource settings where treatment options are limited. Methodology: We recruited treatment naïve, treatment experienced HIV-1 positive pregnant women and those who had prophylaxis in their previous pregnancy in Kilimanjaro, northern Tanzania August 2016 to February 2017. Whole blood (2ml) for biochemistry, viral load and drug resistance testing were taken at baseline. ARV drug resistance testing was done on women with VL ≥ 1000 copies/ml. We used descriptive statistic and logistic regression to determine the strength of association between virologic outcome (virologic failure) and independent predictors. Results: One hundred and forty eight (148) pregnant HIV-positive women were enrolled in the study with mean age of 29.82 years (SD=6.17) from August, 2016 to February, 2017. Virologic failure was demonstrated in 34 (23%) with viral load   ≥ 1,000 copies/ml. Genotyping results were available from 26 women, mutations associated with ARV resistance were detected in 23.1% (n = 6/26). Among the six women with ARV resistance mutation 4(66.7%) had high level resistance and 2(33.3%) had low level resistance. Among the 26 samples genotyped 15(58%) viruses were subtype A, while eight were subtype C (31%) and three subtypes D (11%). The most dominant drug resistance mutations against the reverse transcriptase inhibitors for the women with high level resistance were K103N, Y188L, D67N, K70R, M184V, T215F, K219EQ, and the low-level resistance was E138A. The older age was associated with virological failure compared to those who were < 20 year of age. Conclusion: Viral load testing should be done on women who were already on antiretroviral treatment on their first antenatal visit to ensure early detection of virological failure and enable clinicians to take an appropriate course of action on their management. Educational intervention on adherence should be targeted at an early stage to women with virological failure during pregnancy to reduce the emergence of HIV-1 drug resistance mutations.

scholarly journals Viral load as a risk factor of reverse transcriptase inhibitor drug resistance mutation in antiretroviral-treated people living with HIV/AIDS

2021 ◽  
Vol 40 (3) ◽  
pp. 243-253
Author(s):  
Hotma Martogi Lorensi Hutapea ◽  
Tri Nury Kridaningsih ◽  
Khoirul Huda Prasetyo ◽  
Milton Boaheng Antwi
Keyword(s):  
Drug Resistance ◽  
Logistic Regression ◽  
Viral Load ◽  
Reverse Transcriptase ◽  
Cd4 Count ◽  
People Living With Hiv ◽  
Multiple Logistic Regression ◽  
Living With Hiv ◽  
Hiv 1 ◽  
Hiv Aids

Background The human immunodeficiency virus type 1 (HIV-1) is a major contagion faced by the population of Indonesia. The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). The aim of this study was to determine the association between CD4 count, CD4 count changes, viral load, adherence to therapy, and therapy history in the presence of DRM in people living with HIV/AIDS (PLWHA). MethodsThis was a cross-sectional study involving 269 adults who underwent antiretroviral (ARV) therapy for at least 6 months. The frequencies of DRM and polymorphisms were measured by partial amplification of the reverse transcriptase (RT) gene using RT-nested PCR on samples with viral loads of >1000 copies/mL. Sequencing was performed using the Sanger method, and edited by BioEdit. The edited sequences were submitted to http://hivdb.stanford.edu for DRM determination. Respondents’ medical data, CD4 count, viral load, and DRM were analyzed by simple and multiple logistic regression. ResultsThe multiple logistic regression analysis showed a significant association of CD4 count (aOR=12.47; 95% CI: 1.45 -107.39; p=0.023) and viral load at the time of study (aOR=29.56; 95% CI: 3.47-251.52; p=0.002) with the presence of DRM in respondents. ARV substitution history was not associated with the presence of DRM. There were 17 respondents (6.3%) carrying HIV-1 DRM, with M184V/I (11 sequences) as the most frequent pattern of NRTI resistance, and K103 (9 sequences) as that of NNRTI resistance. ConclusionThis study demonstrated that viral load at the time of the study was the most influential determinant factor for the presence of DRM in PLWHA.

scholarly journals Virological and Immunological Status of the People Living with HIV/AIDS Undergoing ART Treatment in Nepal

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Chet Raj Ojha ◽  
Geeta Shakya ◽  
Shyam Prakash Dumre
Keyword(s):  
Viral Load ◽  
Virological Failure ◽  
Care Center ◽  
Tertiary Care ◽  
People Living With Hiv ◽  
Cell Counts ◽  
The People ◽  
Route Of Transmission ◽  
Living With Hiv ◽  
Hiv 1

Antiretroviral therapy (ART) has increased the life span of the people living with HIV (PLHIV), but their virological and immunological outcomes are not well documented in Nepal. The study was conducted at a tertiary care center including 826 HIV-1 seropositive individuals undergoing ART for at least six months. Plasma viral load (HIV-1 RNA) was detected by Real Time PCR and CD4+T-lymphocyte (CD4+) counts were estimated by flow cytometry. The mean CD4+count of patients was 501 (95% CI = 325–579) cells/cumm, but about 35% of patients had CD4+T cell counts below 350 cells/cumm. With increasing age, average CD4+count was found to be decreasing (p=0.005). Of the total cases, 82 (9.92%) were found to have virological failure (viral load: >1000 copies/ml). Tenofovir/Lamivudine/Efavirenz (TDF/3TC/EFV), the frequently used ART regimen in Nepal, showed virological failure in 11.34% and immunological failure in 37.17% of patients. Virological failure rate was higher among children < 15 years (14.5%) (p=0.03); however, no association was observed between ART outcomes and gender or route of transmission. The study suggests there are still some chances of virological and immunological failures despite the success of highly active ART (HAART).

scholarly journals Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Anita Mesic ◽  
Alexander Spina ◽  
Htay Thet Mar ◽  
Phone Thit ◽  
Tom Decroo ◽  
...  
Keyword(s):  
Viral Load ◽  
Virological Failure ◽  
Antiretroviral Treatment ◽  
People Living With Hiv ◽  
First Line ◽  
Hiv Viral Load ◽  
Loss To Follow Up ◽  
History Of ◽  
Living With Hiv

Abstract Background Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. Methods We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months’ standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox’s regression was performed to identify risk factors for virological failure. Results We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0–39.1) and a median observation time of 5.4 years (IQR 3.7–7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20–1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14–1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42–1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41–1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07–1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. Conclusions VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

scholarly journals Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human Immunodeficiency Virus Type 1 Infection

2016 ◽  
Vol 90 (22) ◽  
pp. 10423-10430 ◽  
Author(s):  
Heather A. Prentice ◽  
Hailin Lu ◽  
Matthew A. Price ◽  
Anatoli Kamali ◽  
Etienne Karita ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Load ◽  
T Cell ◽  
Human Leukocyte ◽  
Neutralizing Antibody ◽  
Sensitivity Analyses ◽  
Supporting Evidence ◽  
Cell Counts ◽  
Cellular And Humoral Immunity ◽  
Hiv 1

ABSTRACT In individuals with HIV-1 infection, depletion of CD4 + T cells is often accompanied by a malfunction of CD8 + T cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well documented, the same does not apply to CD8 counts. Here, we examined the CD8 counts in a cohort of 497 Africans with primary HIV-1 infection evaluated in monthly to quarterly follow-up visits for up to 3 years in the absence of antiretroviral therapy. Statistical models revealed that (i) CD8 counts were relatively steady in the 3- to 36-month period of infection and similar between men and women; (ii) neither geography nor heterogeneity in the HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort ( P > 0.25 in all tests); and (iii) factors independently associated with relatively high CD8 counts included demographics (age ≤ 40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 ( P = 0.013), B*15:10 ( P = 0.007), and B*58:02 ( P < 0.001). Multiple sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with the CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4/CD8 ratio. IMPORTANCE Longitudinal data from 497 HIV-1 seroconverters allowed us to systematically evaluate the dynamics and correlates of CD8 + T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03:01), persistently maintain relatively high CD8 counts following HIV-1 infection, a finding which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as the intrinsic balances of these types of immunity, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.

scholarly journals Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

2021 ◽  
Author(s):  
Kathryn E. Stephenson ◽  
Boris Julg ◽  
C. Sabrina Tan ◽  
Rebecca Zash ◽  
Stephen R. Walsh ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Adverse Events ◽  
Antiviral Activity ◽  
Controlled Trial ◽  
Phase 1 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Cell Counts ◽  
Hiv 1

AbstractHuman immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg–1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg–1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

Psychological Distress is Associated With Decreased Memory Helper T-cell and B-cell Counts in Pre-AIDS HIV Seropositive Men and Women but Only in Those With Low Viral Load

2003 ◽  
Vol 65 (4) ◽  
pp. 627-635 ◽  
Author(s):  
Sarosh J. Motivala ◽  
Barry E. Hurwitz ◽  
Maria M. Llabre ◽  
Nancy G. Klimas ◽  
Mary Ann Fletcher ◽  
...  
Keyword(s):  
Psychological Distress ◽  
Viral Load ◽  
T Cell ◽  
B Cell ◽  
Helper T Cell ◽  
Men And Women ◽  
Cell Counts ◽  
Hiv Seropositive

scholarly journals COVID-19 Vaccination in People Living with HIV (PLWH) in China: A Cross Sectional Study of Vaccine Hesitancy, Safety, and Immunogenicity

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1458
Author(s):  
Ying Liu ◽  
Junyan Han ◽  
Xin Li ◽  
Danying Chen ◽  
Xuesen Zhao ◽  
...  
Keyword(s):  
T Cell ◽  
Negative Impact ◽  
Immunological Response ◽  
Cd4 T Cell ◽  
Vaccine Hesitancy ◽  
People Living With Hiv ◽  
Cross Sectional ◽  
Cell Counts ◽  
Increased Risk ◽  
Living With Hiv

The administration of COVID-19 vaccines is the primary strategy used to prevent further infections by COVID-19, especially in people living with HIV (PLWH), who are at increased risk for severe symptoms and mortality. However, the vaccine hesitancy, safety, and immunogenicity of COVID-19 vaccines among PLWH have not been fully characterized. We estimated vaccine hesitancy and status of COVID-19 vaccination in Chinese PLWH, explored the safety and impact on antiviral therapy (ART) efficacy and compared the immunogenicity of an inactivated vaccine between PLWH and healthy controls (HC). In total, 27.5% (104/378) of PLWH hesitated to take the vaccine. The barriers included concerns about safety and efficacy, and physician counselling might help patients overcome this vaccine hesitancy. A COVID-19 vaccination did not cause severe side effects and had no negative impact on CD4+ T cell counts and HIV RNA viral load. Comparable spike receptor binding domain IgG titer were elicited in PLWH and HC after a second dose of the CoronaVac vaccine, but antibody responses were lower in poor immunological responders (CD4+ T cell counts < 350 cells/µL) compared with immunological responders (CD4+ T cell counts ≥ 350 cells/µL). These data showed that PLWH have comparable safety and immune response following inactivated COVID-19 vaccination compared with HC, but the poor immunological response in PLWH is associated with impaired humoral response.

scholarly journals EBV AND HHV-6 CIRCULATING SUBTYPES IN PEOPLE LIVING WITH HIV IN BURKINA FASO, IMPACT ON CD4 T CELL COUNT AND HIV VIRAL LOAD

2017 ◽  
Vol 9 (1) ◽  
pp. 2017049 ◽  
Author(s):  
Lassina TRAORE ◽  
Ouéogo NIKIEMA ◽  
Abdoul Karim OUATTARA ◽  
Tegwindé Rébéca COMPAORE ◽  
Serge Théophile SOUBEIGA ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Cell Count ◽  
Cd4 Count ◽  
Cd4 T Cell ◽  
People Living With Hiv ◽  
Study Population ◽  
Living With Hiv ◽  
Hiv 1 ◽  
Cd4 T Cell Count

Epstein Barr Virus (EBV) and Human Herpes Virus 6 (HHV-6) are responsible for severe diseases, particularly in immunocompromised persons. There are poor data on the infection with these opportunistic viruses in Burkina Faso.The purpose of this study is to characterize EBV and HHV-6 subtypes and to assess their impact on CD4 T cell count, HIV-1 viral load and antiretroviral treatment in people living with HIV-1.The study population consisted of 238 HIV-positive patients with information on CD4 count, HIV-1 viral load and HAART. Venous blood samples collected on EDTA tubes were used for EBV and HHV-6 Real Time PCR subtyping.An infection rate of 6.7% (16/238) and 7.1% (17/238) were found respectively for EBV and HHV-6 in the present study. Among EBV infections, similar prevalences were noted for both subtypes (3.9% [9/238] for EBV-1 vs 4.6% [11/238] for EBV-2) with 2.1% (5/238) of co-infection. HHV-6A infection represented 6.3% (15/238) of the study population against 5.0% (12/238) for HHV-6B. . EBV-2 infection was significantly higher in patients with CD4 count ≥ 500 compared to those with CD4 count less than 500 cells (1.65% vs 8.56%, p = 0,011). The prevalence of EBV and HHV-6 infections were almost similar in HAART-naive and HAART-experienced patients.The present study provides information on the prevalence of EBV and HHV-6 subtypes in people living with HIV-1 in Burkina Faso. The study also suggests that HAART treatment has no effect on infection with these opportunistic viruses in people living with HIV-1.

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