Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

Metzner, Karin J.; Binley, James Μ.; Gettie, Agegnehu; Marx, Preston A.; Nixon, Douglas F.; Connor, Ruth I.

doi:10.1186/1742-4690-3-97

Cited by 15 publications

(4 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of a rapid rebound in all three animals can theoretically be due to low replication fitness of the virus, to strong antiviral immune responses, or to a combination of both. Previous experiments demonstrated that SIV and RT-SHIV isolates having the K65R mutation in combination with compensatory mutations have high replication fitness and virulence, and generally do not revert back to wild-type sequence following tenofovir withdrawal [ 10 , 11 , 13 , 16 , 17 ]. Also in the current study, withdrawal of tenofovir treatment did not lead to a detectable reversion from K65R to wild-type virus.…”

Section: Discussionmentioning

confidence: 99%

Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal

et al. 2012

View full text Add to dashboard Cite

Background We reported previously that while prolonged tenofovir monotherapy of macaques infected with virulent simian immunodeficiency virus (SIV) resulted invariably in the emergence of viral mutants with reduced in vitro drug susceptibility and a K65R mutation in reverse transcriptase, some animals controlled virus replication for years. Transient CD8+ cell depletion or short-term tenofovir interruption within 1 to 5 years of treatment demonstrated that a combination of CD8+ cell-mediated immune responses and continued tenofovir therapy was required for sustained suppression of viremia. We report here follow-up data on 5 such animals that received tenofovir for 8 to 14 years. Results Although one animal had a gradual increase in viremia from 3 years onwards, the other 4 tenofovir-treated animals maintained undetectable viremia with occasional viral blips (≤ 300 RNA copies/ml plasma). When tenofovir was withdrawn after 8 to 10 years from three animals with undetectable viremia, the pattern of occasional episodes of low viremia (≤ 3600 RNA/ml plasma) continued throughout the 10-month follow-up period. These animals had low virus levels in lymphoid tissues, and evidence of multiple SIV-specific immune responses. Conclusion Under certain conditions (i.e., prolonged antiviral therapy initiated early after infection; viral mutants with reduced drug susceptibility) a virus-host balance characterized by strong immunologic control of virus replication can be achieved. Although further research is needed to translate these findings into clinical applications, these observations provide hope for a functional cure of HIV infection via immunotherapeutic strategies that boost antiviral immunity and reduce the need for continuous antiretroviral therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Although high levels of adherence have been reported in small-scale HIV programs in Sub-Saharan Africa [ 1 ], more challenges arise as these programs scale-up particularly in countries with a growing burden of HIV and tuberculosis (TB), and limited healthcare management facilities [ 2 ]. Rapid scale-up of antiretroviral therapy is accompanied by an increasing risk of ART failure resulting from HIV drug resistance and this is a major obstacle to successful ART in HIV-infected patients [ 3 ]. ART failure may result in progression to AIDS characterized by immunological and haematological complications and opportunistic infections [ 4 ] with increased risk of morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Immuno-haematologic and virologic responses and predictors of virologic failure in HIV-1 infected adults on first-line antiretroviral therapy in Cameroon

et al. 2014

View full text Add to dashboard Cite

BackgroundContemporary data on the immunologic, haematologic and virologic responses and predictors of virologic failure after initiation of free antiretroviral treatment in Cameroon are needed to evaluate the current treatment-monitoring algorithm and to complement efforts to scale-up and improve on the management of HIV infections.MethodsThis was a cross-sectional study conducted between October 2010 and June 2012. A total of 951 participants aged 18–74 years were recruited from selected approved HIV treatment centres of the Northwest and Southwest regions. This comprised 247 males and 704 females. Demographic, self-reported risk behaviours and socioeconomic data were obtained using a structured questionnaire. Full blood and CD4 + T-cell counts were done using standard automated techniques. Determination of viral load (VL) was done using Abbott RealTime HIV-1 m2000™ system. Data was analysed using SPSS version 17. The statistical significance level was P < 0.05.ResultsThe median duration of antiretroviral therapy (ART) was 24 months. The population mean CD4 + T-cell count was 255.3 cells/μL [95% CI, 236.8 – 273.9]. Overall, 45.9%, 43.8% and 10.2% of the participants had CD4 + T-cell counts of < 200 cells/μL, 200–499 cells/μL and > 500 cells/μL respectively. Anaemia was present in 26.2% of the participants with 62.3%, 25.7% and 12% described as mild, moderate and severe anaemia respectively. Virologic failure occurred in 23.2% of the participants with 12.3% having VL > 10,000 RNA copies/mL. Meanwhile 76.8% of patients attained adequate viral suppression with 40.8% having undetectable viral load. The age group 18–29 years (p = 0.024), co-infection with tuberculosis (p = 0.014), anaemia (p = 0.028) and distance from the treatment centre (p = 0.011) independently predicted virologic failure.ConclusionThe majority of the participants achieved adequate viral suppression after ≥ 6 months of ART. Despite these favourable immuno-haematologic and virologic outcomes, the National AIDS Control Program should step-up efforts to improve on antiretroviral drug distribution, as well as proper assessment and management of anaemia, foster early diagnosis and treatment of tuberculosis and enhance treatment adherence counselling especially in younger patients.

show abstract

“…(2020) 75 , Metzner et al . (2006) 76 , and Stanford University HIV Drug resistance Database v.9.0, for Tenofovir, Emtricitabine, and Raltegravir.…”

Section: Methodsmentioning

confidence: 99%

High-throughput single-cell sequencing for retroviral reservoir characterization

Droske

Shank

Cash

et al. 2022

Preprint

View full text Add to dashboard Cite

During the course of infection, human immunodeficiency virus (HIV) maintains a stably integrated reservoir of replication-competent proviruses within the host genome that are unaffected by antiretroviral therapy. Curative advancements rely heavily on targeting the reservoir, though determinants of its evolutionary origins remain ill-supported through current strategies and are often limited by sample variety. Here, we describe a single-cell deoxyribonucleic acid sequencing (scDNA-seq) method, optimized for sequencing of proviral and host DNA from a treatment-interrupted HIV animal model. We report its benefits for improving viral reservoir resolution to support critical evolutionary events otherwise considered unreliable using traditional viral envelope gene signal alone, as well as comparative advantages to existing near-full-length genome sequencing methods. Given the variety of proviral characteristics that may influence viral rebound, scDNA-seq holds immense value in its ability to streamline many of the present-day applications available in viral reservoir studies, such as integration status and putative replication competency.

show abstract

Tenofovir treatment augments anti-viral immunity against drug-resistant SIV challenge in chronically infected rhesus macaques

Cited by 15 publications

References 44 publications

Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal

Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal

Immuno-haematologic and virologic responses and predictors of virologic failure in HIV-1 infected adults on first-line antiretroviral therapy in Cameroon

High-throughput single-cell sequencing for retroviral reservoir characterization

Contact Info

Product

Resources

About