scholarly journals Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study (Preprint)

2018 ◽  
Author(s):  
Karin Nielsen-Saines ◽  
Kate Mitchell ◽  
Tara Kerin ◽  
Jasmine Fournier ◽  
Leslie Kozina ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Los Angeles ◽  
Hiv Infection ◽  
New Orleans ◽  
Early Treatment ◽  
Viral Reservoirs ◽  
Hiv Reservoirs ◽  
Hiv 1 ◽  
Established Infection

BACKGROUND Early treatment studies have shown that prompt treatment of HIV with combination antiretroviral therapy (cART) can limit the size of latent viral reservoirs, thereby providing clinical and public health benefits. Studies have demonstrated that adolescents have a greater capacity for immune reconstitution than adults. Nevertheless, adolescents who acquired HIV through sexual transmission have not been included in early treatment studies because of challenges in identification and adherence to cART. OBJECTIVE This study aimed to identify and promptly treat with cART youth aged 12 to 24 years in Los Angeles and New Orleans who have acute, recent, or established HIV infection, as determined by Fiebig stages 1 to 6 determined by viral RNA polymerase chain reaction, p24 antigen presence, and HIV-1 antigen Western blot. The protocol recommends treatment on the day of diagnosis when feasible. Surveillance and dedicated behavioral strategies are used to retain them in care and optimize adherence. Through serial follow-up, HIV biomarkers and response to antiretroviral therapy (ART) are assessed. The study aims to assess viral dynamics, decay and persistence of viral reservoirs over time, and correlate these data with the duration of viral suppression. METHODS A total of 72 youth (36 acutely infected and 36 treatment naïve controls) are enrolled across clinical sites using a current community-based strategy and direct referrals. Youth are prescribed ART according to the standard of care HIV-1 management guidelines and followed for a period of 2 years. Assessments are conducted at specific time points throughout these 2 years of follow-up for monitoring of adherence to ART, viral load, magnitude of HIV reservoirs, and presence of coinfections. RESULTS The study began enrolling youth in July 2017 across study sites in Los Angeles and New Orleans. As of September 30, 2018, a total of 37 youth were enrolled, 12 with recently acquired, 16 with established HIV infection as determined by Fiebig staging, and 9 pending determination of Fiebig status. Recruitment and enrollment are ongoing. CONCLUSIONS We hypothesize that the size of the HIV reservoir and immune activation markers will be different across groups treated with cART, that is, those with acute or recent HIV infection and those with established infection. Adolescents treated early who are virally suppressed will have diminished HIV reservoirs than those with established infection. These youth may be potential candidates for a possible HIV vaccine and additional HIV remission intervention trials. Our study will inform future studies of viral remission strategies. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/10807

scholarly journals A New Perspective on HIV Diagnostics: Reinterpretation in the Age of Early Treatment

2019 ◽  
Vol 57 (10) ◽  
Author(s):  
Sheila M. Keating
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Viral Replication ◽  
Early Treatment ◽  
Clinical Microbiology ◽  
Link Type ◽  
New Perspective ◽  
Hiv Diagnostics ◽  
The Impact

ABSTRACT Early treatment of HIV infection with antiretroviral therapy in recently identified HIV-infected individuals reduces viral replication and decreases the risk of transmission. The screening and supplemental, confirmatory assays used to identify infection are influenced by early treatment and may obscure a clear diagnosis of HIV infection. In this issue of the Journal of Clinical Microbiology, Manak et al. demonstrate the impact of antiretroviral therapy on the evolution of biomarkers that have traditionally been used for identifying HIV infection (M. M. Manak, L. L. Jagodzinski, A. Shutt, J. A. Malia, et al., J Clin Microbiol 57:e00757-19, 2019, https://doi.org/10.1128/JCM.00757-19).

scholarly journals Specific Inhibition of HIV Infection by the Action of Spironolactone in T Cells

2016 ◽  
Vol 90 (23) ◽  
pp. 10972-10980 ◽  
Author(s):  
Benoît Lacombe ◽  
Marina Morel ◽  
Florence Margottin-Goguet ◽  
Bertha Cecilia Ramirez
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Tat Protein ◽  
Aldosterone Antagonist ◽  
Hiv Transcription ◽  
Hiv Tat ◽  
Cellular Cofactor ◽  
Hiv 1

ABSTRACTTat protein, the HIV transactivator, regulates transcription of the HIV genome by the host transcription machinery. Efficient inhibitors of HIV transcription that target Tat or the cellular cofactor NF-κB are well known. However, inhibition of HIV Tat-dependent transcription by targeting the general transcription and DNA repair factor II human (TFIIH) has not been reported. Here, we show that spironolactone (SP), an aldosterone antagonist approved for clinical use, inhibits HIV-1 and HIV-2 infection of permissive T cells by blocking viral Tat-dependent transcription from the long terminal repeat (LTR). We found that treatment of Jurkat and primary CD4+T cells with SP induces degradation of the XPB cellular helicase, a component of the TFIIH complex, without affecting cellular mRNA levels, T cell viability, or T cell proliferation. We further demonstrate that the effect of SP on HIV infection is independent of its aldosterone antagonist function, since the structural analogue, eplerenone, does not induce XPB degradation and does not inhibit HIV infection. Rescue experiments showed that the SP-induced block of HIV infection relies, at least partially, on XPB degradation. In addition, we demonstrate that SP specifically inhibits Tat-dependent transcription, since basal transcription from the LTR is not affected. Our results demonstrate that SP is a specific inhibitor of HIV Tat-dependent transcription in T cells, which additionally suggests that XPB is a cofactor required for HIV infection. Targeting a cellular cofactor of HIV transcription constitutes an alternative strategy to inhibit HIV infection, together with the existing antiretroviral therapy.IMPORTANCETranscription from the HIV promoter is regulated by the combined activities of the host transcription machinery and the viral transactivator Tat protein. Here, we report that the drug spironolactone—an antagonist of aldosterone—blocks viral Tat-dependent transcription, thereby inhibiting both HIV-1 and HIV-2 infection of permissive T cells. This inhibition relies on the degradation of the cellular helicase XPB, a component of the TFIIH transcription factor complex. Consequently, XPB appears to be a novel HIV cofactor. Our discovery of the HIV-inhibitory activity of spironolactone opens the way for the development of novel anti-HIV strategies targeting a cellular cofactor without the limitations of antiretroviral therapy of drug resistance and high cost.

scholarly journals Decreased Seroreactivity in Individuals Initiating Antiretroviral Therapy during Acute HIV Infection

2019 ◽  
Vol 57 (10) ◽  
Author(s):  
Mark M. Manak ◽  
Linda L. Jagodzinski ◽  
Ashley Shutt ◽  
Jennifer A. Malia ◽  
Mike Leos ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Western Blot ◽  
Research Collaboration ◽  
Virologic Suppression ◽  
Infection Status ◽  
Acute Hiv Infection ◽  
Western Blot Assay ◽  
Acute Hiv ◽  
Hiv 1

ABSTRACTAntiretroviral therapy (ART) during acute HIV infection (AHI) interrupts viral dynamics and may delay the emergence of serological markers targeted by current HIV screening and confirmatory assays, thus creating challenges for correctly classifying HIV infection status. The performance of three HIV antigen/antibody combination (HIV Ag/Ab Combo) assays (the Bio-Rad GS, Abbott Architect, and Bio-Rad BioPlex 2200 assays) was evaluated with samples collected from RV254/South East Asia Research Collaboration in HIV 010 (RV254/SEARCH010) study (Bangkok, Thailand) participants at weeks 12 and 24 following the initiation of ART at Fiebig stage I (FI) (n = 23), FII (n = 39), or FIII/IV (n = 22). Supplemental, confirmatory testing was performed by the Geenius HIV 1/2 and HIV-1 Western blot assays (Bio-Rad). Samples from 30 untreated, HIV-1-infected individuals demonstrated robust HIV Ag/Ab Combo assay reactivity with well-developed HIV-1 Western blotting profiles by 24 weeks after infection. In contrast, 52.2% of samples from individuals initiating ART at FI, 7.7% of samples from individuals initiating ART at FII, and 4.5% of samples from individuals initiating ART at FIII/IV were nonreactive by the HIV Ag/Ab Combo assays, with 36.4 to 39.1% of samples having low signal-to-cutoff (S/CO) results by the Architect and BioPlex assays (S/CO < 10). Seroreversion from a reactive to a nonreactive status was observed in 10 individuals initiating ART at FII and 3 individuals initiating ART at FIII/IV. The Geenius and HIV-1 Western blot assay results were negative or indeterminate for 73.9% and 69.6% of individuals, respectively, treated at FI; 50.0% and 26.3% of individuals, respectively, treated at FII; and 54.5% and 40.9% of individuals, respectively, treated at FIII/IV. Virologic suppression of HIV-1 by ART during AHI impedes seroconversion to biomarkers of infection, limiting the utility of HIV Ag/Ab Combo and supplemental, confirmatory assays for infection status determination.

scholarly journals 1265. Monitoring of Human Immunodeficiency Virus (HIV)-Infection Using the Cepheid HIV-1 Qualitative Assay

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S455-S455
Author(s):  
Erin Keizur ◽  
Drew Wood-Palmer ◽  
Maryann Koussa ◽  
Manuel Ocasio ◽  
Mary Jane Rotheram-Borus ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Los Angeles ◽  
Hiv Infection ◽  
Whole Blood ◽  
Viral Rna ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Pcr Test

Abstract Background Human immunodeficiency virus (HIV)-1 RNA quantification is the primary method of monitoring response to antiretroviral therapy. In the U.S. viral RNA testing is recommended for all HIV-infected patients at entry into care, at initiation or modification of therapy, and on a regular basis thereafter. HIV-1 DNA testing may pose additional advantages. For example, proviral DNA may predict early loss of viral suppression. The Cepheid® (Sunnyvale, CA) HIV-1 Qualitative (HIV Qual) assay detects total nucleic acid for both RNA and DNA and provides a qualitative result (HIV detectable or undetectable). Methods We tested participants aged 14–24 years old from the Adolescent Trials Network (ATN) CARES study with known HIV infection in Los Angeles, California and New Orleans, Louisiana. We tested participants using the Cepheid® HIV Qual assay and the quantitative HIV-1 RNA, real-time PCR test using the COBAS P6800 system (Roche, Branchburg, NJ). We used 100 μL of whole blood for the HIV Qual assay and results were provided in 90 minutes. We sent the remainder of the whole blood from the same visit to a commercial laboratory for HIV-RNA PCR testing and results were reported as “detected,” “detected, <20 copies/mL plasma” or “not detected, <20 copies/mL plasma.” We compared HIV Qual and HIV RNA PCR test results from the same visit for each participant. Results Overall, 57 HIV Qual tests were performed with concurrent HIV RNA PCR tests. Of those, 9/15 tests were concordant with HIV viral RNA suppression while 39/42 tests were concordant with HIV viral RNA detection. In 6 cases, the HIV RNA was not detected at <20 copies/mL by the Roche PCR while the HIV Qual assay detected HIV DNA. Of those 6 cases, 3 had subsequent HIV RNA PCR testing. All 3 cases had detectable HIV RNA at their next testing date (214 copies/mL, detected <20 copies/mL, 2130 copies/mL). Conclusion The HIV Qual test is feasible for the monitoring of HIV-infection. Due to its detection of HIV DNA, it may predict future lack of HIV RNA suppression. Disclosures All authors: No reported disclosures.

scholarly journals Impact of HIV-1 Infection and Antiretroviral Therapy on Bone Homeostasis and Mineral Density in Vertically Infected Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
D. Donà ◽  
E. Mozzo ◽  
D. Luise ◽  
R. Lundin ◽  
A. Padoan ◽  
...  
Keyword(s):  
Physical Activity ◽  
Antiretroviral Therapy ◽  
Side Effects ◽  
Hiv Infection ◽  
Antiretroviral Drugs ◽  
University Hospital ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Anthropometric Data ◽  
Hiv 1

Daily assumption of antiretroviral drugs and HIV-related immune activation lead to important side effects, which are particularly evident in vertically infected patients. Bone homeostasis impairment and reduction of bone mineral density (BMD) is one of the most important side effects. Primary aim of this study is to assess the prevalence of bone homeostasis alterations in a group of vertically infected patients; secondary aim is to analyze the relationship between bone homeostasis alterations and anthropometric data, severity of HIV infection, and antiretroviral therapy. We studied 67 patients with vertically transmitted HIV-1 (aged 6-31 years), followed by the Pediatric Infectious Disease Unit of the University Hospital of Padua, Italy. We analyzed bone turnover markers (P1NP and CTx) and we performed lumbar spine and femoral dual energy X-ray absorption densitometry (DXA). Personal and anthropometric data and information on HIV-infection severity and antiretroviral therapy were collected for all patients. We found that BMD values recorded by DXA showed a significant correlation with age, race, BMI, physical activity, and antiretroviral therapy duration. P1NP was increased in 43% of patients, while CTX in 61% of them. P1NP alteration was related to age, race, BMI, physical activity, therapy duration, and ever use of protease inhibitors and nucleotide reverse transcriptase inhibitors. CTX alteration was found to be correlated only with age. In conclusion, our study confirms that a wide percentage of HIV vertically infected patients show reduced BMD and impaired bone homeostasis. Strict monitoring is needed in order to early identify and treat these conditions.

scholarly journals Stochastic investigation of HIV infection and the emergence of drug resistance

2021 ◽  
Vol 19 (2) ◽  
pp. 1174-1194
Author(s):  
Damilola Olabode ◽  
◽  
Libin Rong ◽  
Xueying Wang ◽  
Keyword(s):  
Drug Resistance ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Stochastic Models ◽  
Early Stage ◽  
Critical Role ◽  
Resistance Mutations ◽  
Multitype Branching Process ◽  
Increased Risk ◽  
Hiv 1

<abstract><p>Drug-resistant HIV-1 has caused a growing concern in clinic and public health. Although combination antiretroviral therapy can contribute massively to the suppression of viral loads in patients with HIV-1, it cannot lead to viral eradication. Continuing viral replication during sub-optimal therapy (due to poor adherence or other reasons) may lead to the accumulation of drug resistance mutations, resulting in an increased risk of disease progression. Many studies also suggest that events occurring during the early stage of HIV-1 infection (i.e., the first few hours to days following HIV exposure) may determine whether the infection can be successfully established. However, the numbers of infected cells and viruses during the early stage are extremely low and stochasticity may play a critical role in dictating the fate of infection. In this paper, we use stochastic models to investigate viral infection and the emergence of drug resistance of HIV-1. The stochastic model is formulated by a continuous-time Markov chain (CTMC), which is derived based on an ordinary differential equation model proposed by Kitayimbwa et al. that includes both forward and backward mutations. An analytic estimate of the probability of the clearance of HIV infection of the CTMC model near the infection-free equilibrium is obtained by a multitype branching process approximation. The analytical predictions are validated by numerical simulations. Unlike the deterministic dynamics where the basic reproduction number $ \mathcal{R}_0 $ serves as a sharp threshold parameter (i.e., the disease dies out if $ \mathcal{R}_0 &lt; 1 $ and persists if $ \mathcal{R}_0 &gt; 1 $), the stochastic models indicate that there is always a positive probability for HIV infection to be eradicated in patients. In the presence of antiretroviral therapy, our results show that the chance of clearance of the infection tends to increase although drug resistance is likely to emerge.</p></abstract>

scholarly journals Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring

2018 ◽  
Vol 69 (3) ◽  
pp. 523-529 ◽  
Author(s):  
Sharon A Riddler ◽  
Jennifer E Balkus ◽  
Urvi M Parikh ◽  
John W Mellors ◽  
Carolyne Akello ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Disease Progression ◽  
Virologic Failure ◽  
Vaginal Ring ◽  
Phase Iii ◽  
Virologic Suppression ◽  
Cell Counts ◽  
The Impact ◽  
Hiv 1

Abstract Background A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). Methods HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network–020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. Results Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). Conclusions The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. Clinical Trials Registration NCT016170096 and NCT00514098.

scholarly journals Oxidative Imbalance in HIV-1 Infected Patients Treated with Antiretroviral Therapy

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Antonella Mandas ◽  
Eugenio Luigi Iorio ◽  
Maria Gabriella Congiu ◽  
Cinzia Balestrieri ◽  
Antonello Mereu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Highly Active Antiretroviral Therapy ◽  
Total Antioxidant Status ◽  
Treated Group ◽  
Oxidative Status ◽  
Haart Adherence ◽  
Oxidative Balance ◽  
Hiv 1

It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART) is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated), and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence) have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence). Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants). Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document