Podcasts about nrtis

Dr. Sung Soo Kim, ID clinical pharmacist, presents a talk on the spectrum of HIV therapy and ART (Antiretroviral Therapy)-related adverse drug interactions. Dr. Kim begins by describing the mechanisms by which HIV therapy-related adverse drug interactions occur. Next, he discusses the various classes of antiretrovirals and their specific drug interactions, including integrate inhibitors, NNRTIs, NRTIS, and Protease Inhibitors. Dr. Kim closes by discussing the consequences of unmanaged drug-drug interactions in patients on ARTs as well as the available drug-drug interaction resources available to the clinician.

In this episode, Renslow Sherer, MD, discusses managing a first ART failure in the setting of COVID-19, including:Guideline recommendations for resistance testingGuideline recommendations for selecting a new ART regimenData on retained efficacy of NRTIs in second-line regimens in the EARNEST and NADIA studiesConsideration of drug‒drug interactions between ART and COVID-19 treatmentPresenter: Renslow Sherer, MDDirector International HIV Training Center Professor of Medicine Section of Infectious Diseases and Global Health Department of Medicine University of Chicago Chicago, Illinois To download the slides: https://bit.ly/3OcqxIE To view the full online program: https://bit.ly/3ZjSFhg

In this episode, Carolyn Chu, MD, MSc, FAAFP, AAHIVS, discusses using HIV-ASSIST to aid in the selection of an ART regimen for PWH coinfected with HBV and HCV. Listen as she covers:How HIV-ASSIST supports ART selection in primary careUpdates to viral hepatitis recommendations including:               CDC HBV screening and testing recommendations             AASLD simplified HCV treatment approach for PWHHIV-ASSIST for managing HIV/HBV coinfections, including ensuring that NRTIs that are effective for both HIV and HBV are included in an ART regimen and alerting the user when an additional HBV treatment is needed HIV-ASSIST for managing HIV/HCV coinfections, including showing how the HIV-ASSIST tool incorporates drug‒drug interaction considerations from the University of Liverpool HIV Drug Interaction CheckerCarolyn Chu, MD, MSc, FAAFP, AAHIVSChief Clinical OfficerNational Clinician Consultation CenterProfessorClinical Family Community MedicineUniversity of California, San FranciscoSan Francisco, CaliforniaLink to full program: bit.ly/3pwaH2Y    

In this episode, Princy N. Kumar, MD, FIDSA, MACP, discusses key considerations for selecting ART in treatment-naive persons with HIV. Her discussion includes:DHHS Treatment Guideline recommendationsChoosing among first-line recommended integrase inhibitorsRecommended regimens for rapid ART startSelect key studies in treatment-naïve adults:AMBER study of virologic response with DRV/COBI/FTC/TAF vs DRV/COBI + TFC/TDFDRIVE-AHEAD and DRIVE-FORWARD efficacy study results, including resistance analyses of DOR + 2 NRTIs vs EFV or (DRV + RTV) + 2 NRTIsSafety and efficacy results from GEMINI-1 and GEMINI comparing DTG + 3TC vs DTG + FTC/TDFThe current/possible role of boosted PIs and NNRTIsSelection considerations between TDF and TAFPresenter:Princy N. Kumar, MD, FIDSA, MACPProfessor of Medicine and MicrobiologyChief, Division of Infectious Diseases and Travel MedicineSenior Associate Dean of StudentsGeorgetown University School of MedicineWashington, DCContent based on an online CME program supported by an independent educational grant from ViiV Healthcare.Link to full program:https://bit.ly/3VIsDTgFollow along with the slides:https://bit.ly/3PYy1zn

In this episode, Annette Haberl, MD, and William R. Short, MD, MPH, AAHIVS, discuss when to consider an ART switch during pregnancy, including:Current DHHS, EACS, WHO, BHIVA, and German/Austrian guidelines for the use of ARVs in pregnancyWhat data and recommendations for the use of ARVs during pregnancy are currently missing from the guidelinesAvailable data on newer ARVs in the ARV pregnancy registryPharmacokinetic data for newer ARVs including BIC/FTC/TAF and LA CAB + RPV in pregnancyRecommendations for 2-drug ART regimens in pregnancyWhat to do when someone becomes pregnant on a newer ART regimen that is not yet recommended by the guidelinesAnnette Haberl, MDPhysicianHead of HIV and WomenHIVCENTER FrankfurtDepartment of Infectious DiseaseHospital of the Johann Wolfgang Goethe UniversityFrankfurt, GermanyWilliam R. Short, MD, MPH, AAHIVSAssociate Professor of MedicineDivision of Infectious DiseasesDepartment of MedicinePerelman School of Medicine at the University of PennsylvaniaPhiladelphia, PennsylvaniaLink to full program:https://bit.ly/3HPu4Lk

In this episode, Tristan J. Barber, MA, MD, FRCP, and Darcy Wooten, MD, discuss switching ART with virologic suppression, including:Switching with prior or unknown resistanceData on switching to BIC/FTC/TAF with a preexisting M184V/I mutation from a pooled analysis of 6 phase III studiesThe impact of baseline resistance on outcomes following a switch to BIC/FTC/TAF in Black PWH from the BRAAVE 2020 studyA post hoc analysis of the SALSA study of DTG/3TC outcomes at Week 48 by baseline resistanceData from the SOLAR 3D study on switching to DTG/3TC from a 3- or 4-drug ART regimen with a history of M184VA retrospective analysis of switching to DTG/3TC with archived M184V/I from the French Dat'AIDS CohortSwitching to long-acting ARTGuidance on candidates for LA CAB + RPVData on risk factors for virologic failure with LA CAB + RPVConsidering an ART switch after weight gainData on weight gain after ART initiation by ARV class and drugMean change in weight by sex at Week 96 in the ADVANCE studyDHHS guideline recommendations regarding weight gain with ARTTristan J. Barber, MA, MD, FRCPHonorary Associate ProfessorInstitute for Global HealthUniversity College LondonConsultant in HIV MedicineIan Charleson Day CentreRoyal Free HospitalLondon, United Kingdom  Darcy Wooten, MDAssociate Professor of MedicineDivision of Infectious Diseases and Global Public HealthDepartment of MedicineUniversity of California, San DiegoSan Diego, California

Last episode we looked at the NRTIs now we have the NNRTIs. What's the difference besides the extra N you ask. Listen up and learn how they work they get used quite a bit.

Episode 70: HIV Prevention. Prevention is key in controlling HIV-AIDS. Listen to ways to prevent HIV, mainly by using condoms, PrEP and PEP.Introduction: HIV and AIDSBy Robert Dunn, MS3.Introduction: The Human Immunodeficiency Virus (HIV) is a retrovirus that is primarily transmitted via sex, needles or from mother to fetus. Once infected, the virus increases in its copies and decreases the individual's CD4+ cell count, thus leading to an immunocompromised state known as Acquired Immune Deficiency Syndrome (AIDS). Once with AIDS, the patient is susceptible to opportunistic infections. Prevention from AIDS includes several options. Condoms for safe sex practices are the least invasive and most readily accessible option for all patients. Pre-exposure prophylaxis (PrEP) is also an option for men who have sex with men (MSM) and transgender women. If the patient is also exposed to HIV, post-exposure prophylaxis (PEP) may also be an option to prevent infection but must be administer ideally 1-2 hours after exposure but no later than 72 hours after. Today we will briefly discuss how to prevent HIV infection.This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home.___________________________HIV Series IV: HIV Prevention. By Robert Dunn, MS3.Participation by Huda Quanungo, MS3; Bahar Hamidi, MS3; and Hector Arreaza, MD.  HIV PreventionIntroductionThe Human Immunodeficiency Virus (HIV) is a retrovirus that is primarily transmitted via sex, needles or from mother to fetus. Once infected, the virus increases in its copies and decreases the individual's CD4+ cell count, thus leading to an immunocompromised state known as Acquired Immune Deficiency Syndrome (AIDS). Once with AIDS, the patient is susceptible to opportunistic infections. Prevention from AIDS includes several options. Condoms for safe sex practices are the least invasive and most readily accessible option for all patients. Pre-exposure prophylaxis (PrEP) is also an option for men who have sex with men (MSM) and transgender women. If the patient is also exposed to HIV, post-exposure prophylaxis (PEP) may also be an option to prevent infection, but it must be administered ideally 1-2 hours after exposure but no later than 72 hours after. We will concentrate in prevention during this episode.   What is HIV?The Human Immunodeficiency Virus (HIV) is a retrovirus. When the virus gains access to our body via cuts on the skin or mucosa:The virus injects its 10kb sized RNA genome into our cells. The RNA is transcribed to DNA via viral reverse transcriptase and is incorporated into our cellular DNA genome. This causes our cells to become a virus producer. Viral proteins translated in the cell are transported to the edge of the cell and can bud off into new viruses without lysing the cell.  Acute HIV symptoms. Some potential early symptoms of HIV can include fever, chills, rash, night sweats, muscle aches, sore throat, fatigue, lymphadenopathy, and mouth ulcers. The most common acute symptom is NO SYMPTOM. Many people do not feel sick with the acute infection of HIV. Some people can live years with HIV in “clinical latency” without knowing they are infected, but they can still be contagious during this time. As viral load (the amount of virus copies you have in your blood stream) increases, the CD4+ cells that contribute to our adaptive immunity continues to fall. That's why the best test during this period is not going to be HIV antibody but you should test for antigens. Specifically, the 4th Generation HIV test, which tests for both antibody and p24 antigens.Chronic symptoms. Once patients begin to present with opportunistic infections (i.e. Pneumocystis pneumonia – PCP), or have a CD4 count below 200, the patient is considered to have Acquired Immune Deficiency Syndrome (AIDS) and makes them susceptible to more serious infections. Without treatment, patients with AIDS typically survive about 3 years. Epidemiology of HIVHIV incidence: In 2019, there were 34,800 new HIV infections in the United States. This is an 8% decline from 2015. Amongst age groups: Age 25-34 had the highest rate of incidence (30.1 per 100,000)Age 35-44 had the second highest rate (16.5 per 100,000)Age 45-54 remained stableAge 13-24 had decreasing rates of incidence Amongst ethnic groups: Black/African-American groups has the highest rate of incidence (42.1 per 100,000)Hispanic/Latino had the second highest rate (21.7 per 100,000)Person of multiple races had the third highest (18.4 per 100,000) Amongst sex: Males had the highest rate of incidence (21 per 100,000)Females had the lowest rate of incidence (4.5 per 100,000) HIV Prevalence:In 2019, 1.2 million people (Ages 13 and older) in the US have HIV and 13% of them do not even know it. In 2020, there were an estimated 1.5 million people worldwide that acquired a new HIV infection. This is a 30% decline since 2020. An estimated 66% are receiving some HIV care and 57% were virally suppressed. Mortality: In 2019, there were 15,815 deaths among adults and adolescents diagnosed with HIV in the US. Preventative ScreeningThe USPSTF gives a Grade A recommendation for HIV screening for: Pregnant people and everyone between 15-65 years of age. All pregnant people at any point of their pregnancy, including those who present in labor or delivery and have an unknown status of HIV.The USPSTF only recommends a one-time screening and shows no benefit of repeat screening thereafter. Women may also be screened for subsequent pregnanciesAlso screen all Adolescents and adults ages 15-65.  An effective approach is routine opt-out HIV screening. This approach includes HIV screening as part of the standard preventive tests. This approach removes the stigma associated with HIV testing, it promotes earlier diagnosis and treatment, reduces risk of transmission, and it is cost-effective. The determination for repeated screening of individuals should take into account the following risk factors: -Men who have sex with men (MSM)-Individuals who live in areas with high prevalence of HIVIncluding attending to tuberculosis clinics, stay in a correctional facility, or homelessness-Injection drug use-Transactional/commercial sex work-1 or more new sexual partners -History of previous STIs Annual screening for HIV is reasonable, however, clinicians may want to screen patients every 3-6 months if they have an increased risk of HIV.  CondomsA simple and very effective method in HIV prevention is the use of condoms for safe sex practices. In 2009, the American College of Physicians (ACP) and the HIV medicine Association called for the wider availability of condoms and education to minimize HIV transmission. A meta-analysis of 12 HIV studies amongst heterosexual couples demonstrated the use of condoms in all penetrative sex acts reduced the risk of HIV transmission 7.4 times in comparison to those who never used condoms. Other studies show a 90-95% effectiveness in HIV prevention when “consistently” using condoms. A Cochrane review shoed that the use of a male latex condom in all acts of penetrative vaginal sex reduced HIV incidence by 80%. Overall, condoms are effective in HIV prevention.Pre-Exposure Prophylaxis (PrEP)Truvada and Descovy:Another option for prevention amongst HIV negative individuals is the use of Pre-Exposure Prophylaxis (PrEP). It is an anti-retroviral pill that is taken daily to maintain a steady-state level of the medication in the blood stream. The medication specifically a combination of 2 antiretroviral medications – Tenofovir and Emtricitabine. Both medications are nucleoside reverse transcriptase inhibitors (NRTIs) that work by blocking the viral reverse transcriptase from HIV and prevent the enzyme from copying the RNA genome into DNA. Therefore, it stops viral replications. There are 2 formulations of PrEP: Truvada and Descovy. Truvada's primary side effects are renal and bone toxicity with long-term use. Descovy's primary side effects are mild weight gain and dyslipidemia. Truvada is the most commonly prescribed PrEP because it has the most data since it has been around the longest. However, extra consideration should be taken for: Adolescents should weigh at least 35 kg before being prescribed PrEPDescovy may be preferred for adolescents by the prescribing physician as it is not associated with reduction in bone density, as Truvada is. Estimated GFR between 30 – 60Truvada is associated with acute and chronic kidney disease whereas Descovy is safe for patients with a GFR greater than 30Patients with osteoporosisTruvada is associated with bone toxicity, whereas Descovy is not. It is important to note that PrEP has only been studied in men or people who were assigned men at birth. So, its efficacy in vaginal sex and with vaginal fluids cannot be generalized at this time. Future of PrEP: In May 2020, the HIV Prevention Trials Network (HPTN) 083 randomized trial demonstrated the potential of an injectable PrEP. Carbotegravir, is an integrase inhibitor, which prevents the HIV integrase from incorporating the HIV genome into the cellular genome. This study demonstrated its efficacy as PrEP in comparison to Truvada with few new infections (13 versus 39, respectively). Carbotegravir would be given via injection once every 8 weeks. In September 2021, the pharmaceutical company Moderna will begin 2 human clinical trials for an HIV vaccine that use mRNA technology. Previous studies conducted with non-mRNA vaccines demonstrated that B cells can be stimulated to create antibodies against HIV. Since HIV becomes integrated in the cellular genome within 72 hours of transmission, a high level of antibodies must be produced and present in the body to offer an adequate level of immunity. Post-Exposure Prophylaxis (PEP)If an individual is exposed to blood or bodily fluids with high risk of HIV via percutaneous, mucus membrane or nonintact skin route, post-exposure prophylaxis (PEP) may be an option. PEP is indicated when the HIV status of the exposure source is unknown and are awaiting test results, or if the exposure source is HIV positive. Therapy should be started within 1 or 2 hours of exposure and it is not effective after 72 hours of initial exposure. The recommended duration of therapy is 4 weeks but no evidence has been shown for an optimal duration. Occupational exposure. There are 2 regimens for PEP: Truvada with Dolutegravir Truvada  with Raltegravir Both Doltegravir and Raltegravir are integrase inhibitors which block the integration of the viral genome into the cellular DNA. The regiments are chosen based on efficacy, side effects, patient convenience, and completion rates. Dolutegravir is chosen because it is given once daily. While Raltegravir is taken twice daily, most experience with PEP has been with Raltegravir. Other risk with Raltegravir are potential skeletal muscle toxicity and systemic-cutaneous reactions resembling Steven-Johnson syndrome. One final word about prevention of vertical transmission is making sure pregnant women are treated during pregnancy and if the baby is delivered from a patient whose viral load is “detectable”, the baby needs to be treated, but we'll let that topic for another time to discuss. Joke: What do you call the patient zero of HIV? First Aids.HIV incidence is decreasing thanks to many prevention measures taken globally, and we discussed screening, condoms, PrEP and PEP as part of this prevention efforts. Stay tuned for more relevant medical information in our next episode. ____ Now we conclude our episode number 70 “HIV Prevention.” Robert, Huda and Bahar explained some ways to prevent HIV, mainly by screening those at risk, using condoms, PrEP (pre-exposure prophylaxis) and PEP (post-exposure prophylaxis). Let's also remember that having a monogamous relationship and avoiding high risk sexual behaviors confer significant protection against HIV. Even without trying, every night you go to bed being a little wiser.Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Robert Dunn, Huda Quanungo, and Bahar Hamidi. Audio edition: Suraj Amrutia. See you next week!   References:About HIV. Center for Disease Control and Prevention, CDC.gov, June 1, 2021. https://www.cdc.gov/hiv/basics/whatishiv.html . Accessed September 21, 2021. Simon V, Ho DD, Abdool Karim Q. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet. 2006 Aug 5;368(9534):489-504. doi: 10.1016/S0140-6736(06)69157-5. PMID: 16890836; PMCID: PMC2913538. [https://pubmed.ncbi.nlm.nih.gov/16890836/]   US Statistics. HIV.gov, June 2, 2021. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics . Accessed September 21, 2021.  The global HIV/AIDS Epidemic. HIV.gov, June 25, 2021. https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics. Accessed September 21, 2021.  Human Immunodeficiency Virus (HIV) Infection: Screening. U.S. Preventative Services Task Force, June 11, 2019. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/human-immunodeficiency-virus-hiv-infection-screening. Accessed September 21, 2021.  Holmes KK, Levine R, Weaver M. Effectiveness of condoms in preventing sexually transmitted infections. Bull World Health Organ. 2004 Jun;82(6):454-61. PMID: 15356939; PMCID: PMC2622864. [https://pubmed.ncbi.nlm.nih.gov/15356939/] Weller S, Davis K. Condom effectiveness in reducing heterosexual HIV transmission. Cochrane Database Syst Rev. 2002;(1):CD003255. doi: 10.1002/14651858.CD003255. PMID: 11869658. [https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003255/full] Mayer, Kenneth H, MD, and Douglas Krakower, MD. Administration of pre-exposure prophylaxis against HIV infection. UpToDate, June 24, 2020. Accessed September 21, 2021. [https://www.uptodate.com/contents/administration-of-pre-exposure-prophylaxis-against-hiv-infection?search=8)%09Administration%20of%20pre-exposure%20prophylaxis%20against%20HIV%20infection&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1] Zachary, Kimon C, MD. Management of health care personnel exposed to HIV. UpToDate, June 07, 2019. Accessed September 21, 2021. [https://www.uptodate.com/contents/management-of-health-care-personnel-exposed-to-hiv?search=9)%09Management%20of%20health%20care%20personnel%20exposed%20to%20HIV&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1]

In this series of 3 episodes, Geeta Gupta, MD, discusses strategies for optimizing ART in heavily treatment–experienced patients with HIV, including management of virologic failure and switching ART in virologically suppressed patients with underlying resistance. The 3 episodes will include analyses from:BENCHMRK, which demonstrated that the number of active drugs predicts outcomes in treatment-experienced patientsTMB-301, a study that added the monoclonal antibody ibalizumab in pretreated patients with multidrug-resistant HIV and demonstrated significant decreases in HIV-1 RNABRIGHTE, which showed that the addition of fostemsavir in heavily treatment–experienced patients with HIV led to a significant decrease in HIV-1 RNAVIKING-3, a study that demonstrated the addition of DTG dosed BID in INI-resistant patients was effective in decreasing HIV-1 RNASWITCHMRK, a study that showed underlying resistance matters when deciding to switch regimens in a treatment-experienced, virologically suppressed patient, especially when switching to a regimen with a low barrier to resistanceDAWNING, a study that demonstrated that DTG, when added to 2 NRTIs, was superior to RTV-boosted LPV in patients with virologic failure on an NNRTI plus 2 NRTIsBRAAVE, which evaluated safety and efficacy of switching to BIC/FTC/TAF in Black patients virologically suppressed on 2 NRTIs plus a third agentIn addition, Dr. Gupta reviews current DHHS ART guideline recommendations related to managing virologic failure, including drug resistance testing and drug selection, as well as switching recommendations in patients with viral suppression and underlying drug resistance.Presenter:Geeta Gupta, MDProfessorDirector, AIDS Education and Training CenterUniversity of California, IrvineOrange, CaliforniaFollow along with the slides at:https://bit.ly/3zxKBfLContent based on an online CME program supported by an educational grant from ViiV Healthcare.Link to full program:https://bit.ly/3ux6FF8

In this series of 3 episodes, Geeta Gupta, MD, discusses strategies for optimizing ART in heavily treatment–experienced patients with HIV, including management of virologic failure and switching ART in virologically suppressed patients with underlying resistance. The 3 episodes will include analyses from:BENCHMRK, which demonstrated that the number of active drugs predicts outcomes in treatment-experienced patientsTMB-301, a study that added the monoclonal antibody ibalizumab in pretreated patients with multidrug-resistant HIV and demonstrated significant decreases in HIV-1 RNA  BRIGHTE, which showed that the addition of fostemsavir in heavily treatment–experienced patients with HIV led to a significant decrease in HIV-1 RNA  VIKING-3, a study that demonstrated the addition of DTG dosed BID in INI-resistant patients was effective in decreasing HIV-1 RNASWITCHMRK, a study that showed underlying resistance matters when deciding to switch regimens in a treatment-experienced, virologically suppressed patient, especially when switching to a regimen with a low barrier to resistanceDAWNING, a study that demonstrated that DTG, when added to 2 NRTIs, was superior to RTV-boosted LPV in patients with virologic failure on an NNRTI plus 2 NRTIsBRAAVE, which evaluated safety and efficacy of switching to BIC/FTC/TAF in Black patients virologically suppressed on 2 NRTIs plus a third agentIn addition, Dr. Gupta reviews current DHHS ART guideline recommendations related to managing virologic failure, including drug resistance testing and drug selection, as well as switching recommendations in patients with viral suppression and underlying drug resistance.Presenter:Geeta Gupta, MDProfessorDirector, AIDS Education and Training CenterUniversity of California, IrvineOrange, CaliforniaFollow along with the slides at:https://bit.ly/3zxKBfLContent based on an online CME program supported by an educational grant from ViiV Healthcare.Link to full program:https://bit.ly/3ux6FF8

In this series of 3 episodes, Geeta Gupta, MD, discusses strategies for optimizing ART in heavily treatment–experienced patients with HIV, including management of virologic failure and switching ART in virologically suppressed patients with underlying resistance. The 3 episodes will include analyses from:BENCHMRK, which demonstrated that the number of active drugs predicts outcomes in treatment-experienced patientsTMB-301, a study that added the monoclonal antibody ibalizumab in pretreated patients with multidrug-resistant HIV and demonstrated significant decreases in HIV-1 RNABRIGHTE, which showed that the addition of fostemsavir in heavily treatment–experienced patients with HIV led to a significant decrease in HIV-1 RNA  VIKING-3, a study that demonstrated the addition of DTG dosed BID in INI-resistant patients was effective in decreasing HIV-1 RNASWITCHMRK, a study that showed underlying resistance matters when deciding to switch regimens in a treatment-experienced, virologically suppressed patient, especially when switching to a regimen with a low barrier to resistanceDAWNING, a study that demonstrated that DTG, when added to 2 NRTIs, was superior to RTV-boosted LPV in patients with virologic failure on an NNRTI plus 2 NRTIsBRAAVE, which evaluated safety and efficacy of switching to BIC/FTC/TAF in Black patients virologically suppressed on 2 NRTIs plus a third agentIn addition, Dr. Gupta reviews current DHHS ART guideline recommendations related to managing virologic failure, including drug resistance testing and drug selection, as well as switching recommendations in patients with viral suppression and underlying drug resistance.Presenter:Geeta Gupta, MDProfessorDirector, AIDS Education and Training CenterUniversity of California, IrvineOrange, CaliforniaFollow along with the slides at:https://bit.ly/3zxKBfLContent based on an online CME program supported by an educational grant from ViiV Healthcare.Link to full program:https://bit.ly/3ux6FF8

In this episode, Joseph J. Eron, Jr., MD, and Darcy Wooten, MD, share insights on HIV antiretroviral therapy safety and tolerability including recent data on weight gain and metabolic implications with INSTIs and NRTIs as well as the latest updates and recommendations on dolutegravir and pregnancy.Joseph J. Eron, Jr., MDProfessor of Medicine and EpidemiologyUniversity of North Carolina School of MedicineDirector, AIDS Clinical Trials UnitUniversity of North CarolinaChapel Hill, North CarolinaDarcy Wooten, MDAssociate Professor of MedicineDivision of Infectious Diseases and Global Public HealthDepartment of MedicineUniversity of California, San DiegoSan Diego, CaliforniaContent based on a CME program supported by independent educational grants from Janssen Therapeutics, Division of Janssen Products, LP, and ViiV HealthcareLink to full program:https://bit.ly/3ydMtcL

Dr. Burkhead, infectious diseases fellow at the University of South Florida, covers HIV History, the development of HIV antiviral therapy, and current treatment strategies in this comprehensive update. Dr. Burkhead begins by reviewing the different classes of antiretrovirals. He then traces the chronological history of antiretroviral development, from the initial trials of AZT through the introduction of other NRTIs, Protease inhibitors, NNRTIs, and the Integrase inhibitors. Next, Dr. Burkhead discusses antiretroviral therapy in special situations, such as in those who are pregnant, have chronic kidney disease, or cardiac disease. Important antiretroviral mutations are also discussed. Lastly, Dr. Burkhead closes the talk by discussing future directions for antiretroviral therapy.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.18.160077v1?rss=1 Authors: Wairkar, Y. P., Tang, S.-J., Bush, K., Barber, K., Martinez, J. Abstract: The success of antiretroviral therapy (ART) has improved the survival of HIV-infected patients significantly. However, significant numbers of patients on ART whose HIV disease is well controlled show peripheral sensory neuropathy (PSN), suggesting that ART may cause PSN. Although the nucleoside reverse transcriptase inhibitors (NRTIs), one of the vital components of ART, are thought to contribute to PSN, the mechanisms underlying the PSN induced by NRTIs are unclear. In this study, we developed a Drosophila model of NRTI-induced PSN that recapitulates the salient features observed in patients undergoing ART: PSN and nociceptive hypersensitivity. Furthermore, our data demonstrate that pathways known to suppress PSN induced by chemotherapeutic drugs are ineffective in suppressing the PSN or nociception induced by NRTIs. Instead, we found that increased dynamics of a peripheral sensory neuron may underlie NRTI-induced PSN and nociception. Our model provides a solid platform in which to investigate further mechanisms of ART-induced PSN and nociceptive hypersensitivity. Copy rights belong to original authors. Visit the link for more info

The purpose of the study reported here was to compare the antiviral efficacy against feline immunodeficiency virus (FIV) and cytotoxicity in feline peripheral blood mononuclear (PBM) cells of 9 nucleoside reverse transcriptase inhibitors (NRTIs), three of which had not been evaluated against FIV in feline cells before. PBM cells were isolated from the blood of three specific pathogen-free (SPF) cats. The cytotoxic effects of the test compounds were determined by colorimetric quantification of a formazan product resulting from bioreduction of a tetrazolium reagent by viable PBM cells. Each compound was tested in 12 concentrations ranging from 0.001 to 500 M. Uninfected cells from one SPF cat were used in these assays. PBM cells (from all three SPF cats) were infected with the molecular clone FIV pPPR and the antiviral efficacy of the test compounds was assessed using a FIV p24 antigen capture enzyme-linked immunosorbent assay. Each compound was tested in 5 concentrations ranging from 0.1 to 10 M. Cytotoxic effects in feline PBM cells were observed only at concentrations over 10 M for all 9 NRTIs. Comparison of the cytotoxic effect at the highest concentration investigated (500 M) revealed that didanosine and amdoxovir were significantly less toxic than abacavir. As no cytotoxicity was noted up to a concentration of 10 M, this was set as the highest concentration for the second part of this study investigating the anti-FIV efficacy of the test compounds. All drugs induced a dose-dependent reduction of FIV replication. When compared at the highest concentration investigated, there was no significant difference in the antiviral efficacy among the test compounds. The EC50 could not be determined as none of the test compounds achieved 50% viral inhibition. The evaluated NRTIs had low cytotoxicity against feline PBM cells and appear to be safe options for further in vivo evaluation for the treatment of FIV-infected cats. There was no evidence suggesting that the newly evaluated compounds would be superior to the existing NRTIs for reducing the FIV burden of infected cats.

This podcast provides further insights on mitochondrial pathology resulting from long-term treatment of patients infected with human immunodeficiency virus using cocktails of nucleoside analog reverse transcriptase inhibitors (NRTIs).  The respondent is Dr. Brendan Payne, a clinician at the Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK with an interest in diagnosis and treatment of infectious disease--and specifically human immunodeficiency virus (HIV); Dr. Payne is the senior author of a recent review article, "HIV Treatment and Associated Mitochondrial Pathology: Review of 25 Years of In Vitro, Animal, and Human Studies."  Dr. Payne's research suggests that the cumulative exposure to NRTIs is more important than the peak levels, indicating that the usual design of animal experiments (short terms with high doses, histopathology as a major endpoint) to model human responses may understate or even miss the consequences to patients who may be expected to remain on cocktails of these agents for life.  Dr. Payne describes the utility of various test modalities as potential means for detecting mitochondrial damage when such an outcome is suspected.   Click here to read the full article.  

Objective: To describe the pharmacokinetics of tenofovir and emtricitabine in the third trimester of pregnant HIV-infected women and at postpartum. Design: A nonrandomized, open-label, multicentre phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. Methods: HIV-infected pregnant women treated with the nucleotide/nucleoside analogue reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF 300 mg; equivalent to 245 mg tenofovir disoproxil) and/or emtricitabine (FTC 200 mg) were included in the study. Twenty-four-hour pharmacokinetic curves were recorded in the third trimester (preferably week 33) and postpartum (preferably week 4-6). Collection of a cord blood sample and maternal sample at delivery was optional. Pharmacokinetic parameters were calculated using WinNonlin software version 5.3. Statistical analysis was conducted using SPSS version 16.0. Results: Thirty-four women were included in the analysis. Geometric mean ratios of third trimester vs. postpartum 90% confidence interval (CI)] were 0.77 (0.71-0.83) for TDF area under the curve (AUC(0-24 h)); 0.81 (0.68-0.96) for TDF C-max and 0.79 (0.70-0.90) for TDF C-24 h and 0.75 (0.68-0.82) for FTC AUC(0-24 h); and 0.87 (0.77-0.99) for FTC C-max and 0.77 (0.52-1.12) for FTC C-24 h. The viral load close to delivery was less than 200 copies/ml in all but one patient, the average gestational age at delivery was 38 weeks. All children were tested HIV-negative and no congenital abnormalities were reported. Conclusion: Although pharmacokinetic exposure of the NRTIs TDF and FTC during pregnancy is approximately 25% lower, this was not associated with virological failure in this study and did not result in mother-to-child transmission. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:739-748

HIV-1 reverse transcriptase (RT) polymerase domain is known as target of nonnucleoside (NNRTIs) and nucleoside (NRTIs) reverse transcriptase inhibitors. However, resistance mutations in the polymerase domain lead repeatedly to therapeutic failure. The Connection (CN) and RNAse H domains of HIV-1 RT have recently gained more interest. They also might serve as independent new drug targets. Recently, in several in vitro studies several mutations in the CN and RNAse H domains were suggested to interfer with Polymerase resistance mutations (TAMs or finger domain mutations). In our in vivo approach, a clear differentiation between different HIV-1 subtypes was performed. Sequences of 57 HIV-1 subtype B infected patients were analysed. Their mutation status in the Connection and RNAse H domains was compared to a subtype-specific reference sequence. The sequences were studied for mutations. A potential correlation to Polymerase domain resistance mutation was analysed. Highly conserved amino acids and a number of natural polymorphisms were found for most of the studied positions. Subtype specific amino acid patterns were found. However, for positions 333, 359, 371, 390 and 558 a significant correlation to Polymerase domain resistance mutations was found. In conclusion, five positions were detected that might be involved in resistance mechanisms. The creation of a subtype specific reference sequence was necessary in order to distinguish between drug related mutations, subtype specific conservation or natural polymorphism. Extended sequence analysis to these regions are not recommended due to the small number of mutations found. Subtype speficication is highly recommended in order to gain resilient data.