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Premium member Presentation Transcript Revised HIV treatment guidelines: Revised HIV treatment guidelines Rushikesh MaheshwariWho is the culprit???: Who is the culprit???Human immunodeficiency virus(HIV): Human immunodeficiency virus(HIV) HIV is the etiologic agent of AIDS belongs to family retroviridae & subfamily lentiviruses . There are two types of hiv viruses HIV-1,HIV-2.Pay attention as!!!: Pay attention as!!! As we all know, there is no complete cure yet available for HIV infection. Quality of life markedly improves with the therapy. Survival benefits are well known with therapyWhat if patient is HIV positive???: What if patient is HIV positive???PowerPoint Presentation: Was written informed consent taken?? Patient is yet detected positive on hiv ELISA screening test… needs confirmation….!!! Do WBT Positive : Label ‘ confirm hiv positive ’ Intermediate result: patient may be in window period , can be repeated in 2 weekly intervals. Negative: ELISA was false positive Repeat testing is indicated after 3 months if strong suspicion.Initial Evaluation of the patient with HIV infection: Initial Evaluation of the patient with HIV infection History & physical examination. Routine chemistry & hematology. AST, ALT, direct & indirect bilirubin . Lipid profile & fasting glucose. CD4 T lymphocyte count. Two plasma HIV RNA levels. HIV resistance testing . HLA-B5701 screening. RPR or VDRL test. Anti- toxoplsma antibody titer. PPD skin test.Contd…: Contd… Mini-mental state examination Serologies for hep A, hep B,& hep C Immunisation with pneumococcal polysaccharide,influenza as indicated Immunisation with hep A & hep B if seronegative Counseling regarding natural history & transmissionWhy to treat hiv? : Why to treat hiv ?Principles of therapy of HIV infection: Principles of therapy of HIV infection Ongoing HIV replication leads to immune system damage and progression to AIDS Plasma HIV RNA levels indicate the magnitude of HIV replication and the rate of CD4 + T cell destruction .CD4+ cell counts indicate the current level of competence of the immune systemContd…: Contd … Rates of disease progression differ among individuals, & treatment decisions should be individualized based on plasma HIV RNA levels & CD4+ T cell counts Maximal suppression of viral replication is a goal of therapy; the greater the suppression the less likely the appearance of drug resistance.Contd…: Contd… The most effective therapeutic strategies involve the simultaneous initiation of combinations of effective anti-HIV drugs with which the patient has not been previously treated & that are not cross resistant with antiretroviral agents that the patient has already received The antiretroviral drugs used in combination regimens should be used according to optimum schedules & dosagesContd…: Contd … The number of available drugs are limited. Any decision on antiretroviral therapy have a long term impact on future options for the patient. Women should receive optimal antiretroviral therapy regardless of pregnancy statusContd…: Contd… The same principles apply to children & adults. The treatment of HIV-infected children involves unique pharmacologic, virologic, & immunologic considerations Compliance is an important part of ensuring maximal effect from a given regimen. The simpler the regimen, the easier it is for the patient to be compliant.PowerPoint Presentation: What is expected from us ???GOALS OF TREATMENT: GOALS OF TREATMENT Improve quality of life Reduce HIV-related morbidity and mortality Restore and/or preserve immunologic function Maximally and durably suppress HIV viral load Prevent HIV transmissionWhat to do, to achieve these goals… what we should not miss???: What to do, to achieve these goals… what we should not miss???Tools to achieve treatment goals: Tools to achieve treatment goals Selection of ARV regimen Maximizing adherence Pretreatment resistance testingPowerPoint Presentation: So what is recommended??? Reference Ernesto J. Lamadrid MD, AAHIVS Faculty , Florida/ Caribbean AIDS Education & training center Annual HIV conference, may 13-14 2011 oriando,FLRecommendations for Initiating ART : Recommendations for Initiating ART Clinical Category or CD4 Count History of AIDS-defining illness CD4 count <350 cells/µL CD4 count 350-500 cells/µL Pregnant women HIV-associated nephropathy (HIVAN) Hepatitis B (HBV) coinfection, when HBV treatment is indicate Recommendation- initiate ARTContd…: Contd… Clinical Category or CD4 Count CD4 count >500 cells/µL, asymptomatic, without conditions listed above Recommendation - 50% of the Panel favors starting ART; 50% views ART as optionalConsider More Rapid Initiation of ART: Consider More Rapid Initiation of ART Acute opportunistic infection Lower CD4 count (eg, <200 cells/µL) Rapid decline in CD4 Higher viral loadWhen to start ????: When to start ???? Early or Late ????Potential Benefits of Early Therapy (CD4 count >500 cells/µL): Potential Benefits of Early Therapy (CD4 count >500 cells/µL) Data shows survival benefit if ART initiated at CD4 count >500 cells/µL. Earlier ART may prevent HIV-related end organ damage; deferred ART may not reliably repair damage acquired earlier Increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation End organ damage occurs at all stages of infection.Contd… : Contd… Potential decrease in risk of many complications, including: HIV-associated nephropathy Liver disease progression from hepatitis B or hepatitis C Cardiovascular disease Malignancies (AIDS defining and non-AIDS defining) Neurocognitive decline Blunted immunological response owing to ART initiation at older age Persistent T-cell activation and inflammationContd…: Contd… Prevention of sexual and bloodborne transmission of HIV Prevention of mother-to-child transmission of HIVPotential Limitations of Early Therapy (CD4 count >500 cells/µL): Potential Limitations of Early Therapy (CD4 count >500 cells/µL) ARV-related toxicities Drug resistance Nonadherence to ART CostConsider Deferral of ART: Consider Deferral of ART Clinical or personal factors may support deferral of ART If CD4 count is low, deferral should be considered only in unusual situations, and with close follow-up When there is drug resistance proven, and low adherance If comorbidities complicate or prohibit ART “Elite controllers” and long-term nonprogressorsCurrent ARV Medications: Current ARV Medications NRTI Abacavir (ABC) 300 mg bid Didanosine (ddI) >60kg 200mg bid & <60kg 125mg bid Emtricitabine (FTC) 200mg qd Lamivudine (3TC) 150mg bid Stavudine (d4T) >60kg 40mg bid & <60kg 30mg bid Tenofovir (TDF) 300mg qd Zidovudine (AZT, ZDV) 200mg 8hrlyContd…: Contd… NNRTI Delavirdine (DLV) 400mg tid Efavirenz (EFV) 600mg qhs Etravirine (ETR) 200mg bid Nevirapine (NVP) 400mg qdContd…: Contd… PI Atazanavir (ATV) 400mg qd Darunavir (DRV) 600mg bid Fosamprenavir (FPV) 1400mg bid Indinavir (IDV) 800mg 8hrly Lopinavir (LPV) 400mg bid Nelfinavir (NFV) 750mg tid Ritonavir (RTV) 600mg bid Saquinavir (SQV) 1000mg bid Tipranavir (TPV) 500mg bidContd…: Contd… Integrase Inhibitor (II) Raltegravir (RAL) 400mg bid Fusion Inhibitor Enfuvirtide (ENF, T-20) Entry inhibitors Enfuviritide 90mg sc bid Maraviroc (only for adults infected with ccr5 tropic hiv1) 150-600mg bidFactors in Choosing an Initial Regimen: Factors in Choosing an Initial Regimen Regimen efficacy Comorbid conditions Tuberculosis, liver disease, depression, cardiovascular disease, chemical dependency, pregnancy Presence of transmitted resistance mutations Adherence potential Pill burden, dosing frequency, food and fluid considerations Potential adverse effects or drug-drug interactions Potential for development of drug resistance on failureAdditional Factors to Consider: Additional Factors to Consider Patient’s age Patient’s readiness Likelihood of treatment adherence Potential impact of antiretrovirals on patient’s quality of life Additional comorbidities that could impact success of therapy including depression Concurrent drugs not compatible with antiretroviral agents Long-term nonprogressors or elite controllersInitial ART Regimens: Initial ART Regimens Preferred regimens Randomized controlled trials show optimal efficacy and durability Favorable tolerability and toxicity profiles Alternative regimens Effective but have potential disadvantages May be the preferred regimen in individual patients Acceptable regimens Less virologic efficacy, lack of efficacy data, or greater toxicities May be acceptable but more definitive data are neededInitial Treatment: Preferred: Initial Treatment: Preferred NNRTI based EFV/TDF/FTC PI based ATV/r + TDF/FTC DRV/r (daily) + TDF/FTC II based RAL + TDF/FTC Pregnant women LPV/r (BID) + ZDV/3T CInitial Treatment: Alternatives: Initial Treatment: Alternatives NNRTI based EFV + [(ABC/3TC) or (ZDV/3TC)] NVP + ZDV/3TC PI based ATV/r + [(ABC/3TC) or (ZDV/3TC)] FPV/r (daily or BID) + [(ABC/3TC) or (ZDV/3TC) or (TDF/FTC)] LPV/r (daily or BID) + [(ABC/3TC) or (ZDV/3TC) or (TDF/FTC)]Initial Treatment: Acceptable: Initial Treatment: Acceptable NNRTI based EFV + ddI + (3TC or FTC) PI based ATV + [(ABC/3TC) or (ZDV/3TC) ] CCR5 Antagonist based MVC + ZDV/3TCInitial Treatment: May Be Acceptable but More Definitive Data Needed: Initial Treatment: May Be Acceptable but More Definitive Data Needed PI based DRV/r + (ABC/3TC) 1,2 or (ZDV/3TC) 2 II based RAL + (ABC/3TC) 1,2 or (ZDV/3TC) 2 CCR5 Antagonist based MVC 3 + TDF/FTC 2 or ABC/3TC 1,2Initial Treatment: Use with Caution : Initial Treatment: Use with Caution NNRTI based NVP + ABC/3TC NVP + TDF/FTC PI based FPV + (ABC/3TC) or (ZDV/3TC) or TDF/FTC SQV/r + TDF/FTC SQV/r + ABC/3TC or ZDV/3TCCommonly used Combinations of formulations of antiretroviral drugs: Commonly used Combinations of formulations of antiretroviral drugs Name Combination Combivir Zidovudine+ lamivudine Epzicom Zidovudine+ abacavir Trizivir Zidovudine+ lamivudine+ abacavir Truvada Tenofovir+ emtricitabine Atripla Tenofovir+ emtricitabine+ efavirenz Triomune Stavudine+ lamivudine+ nevirapine Ref- Harrisons text book of medicine 18 th edition.ARVs Not Recommended in Initial Treatment: ARVs Not Recommended in Initial Treatment High rate of early virologic failure ddI + TDF Inferior virologic efficacy ABC + 3TC + ZDV as 3-NRTI regimen ABC + 3TC + ZDV + TDF as 4-NRTI regimen DLV NFV SQV as sole PI (unboosted) TPV/r High incidence of toxicities d4T + 3TC ddI + TDF IDV/r RTV as sole PIARV Medications: Should Not Be Offered at Any Time: ARV Medications: Should Not Be Offered at Any Time ARV regimens not recommended: Monotherapy with NRTI* Dual-NRTI therapy 3-NRTI regimen (except ABC + 3TC + ZDV or possibly TDF + 3TC + ZDV, when other regimens are not desirable) * If ZDV monotherapy is being considered for prevention of mother-to-child transmission, see Public Health Service Task Force Recommendations for the Use of Antiretroviral Drugs in Pregnant HIV-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission.What NACO says???: What NACO says??? In their guidelines published in apr 2004 and revised in apr 2011FIRST LINE & SECOND LINE DRUG REGIMEN : FIRST LINE & SECOND LINE DRUG REGIMEN First-line ART: First-line ART is the initial regimen prescribed for an ART naïve patient when the patient fulfils national clinical and laboratory criteria to start ART. (Current NACO treatment guidelines for first-line ART recommends two classes of drugs for initial treatment ie 2 NRTI + 1 NNRTI.)PowerPoint Presentation: Second-line ART: Second-line ART is the next regimen used in sequence immediately after first line therapy has failed. (Current NACO treatment guidelines recommend that the protease inhibitor (PI) class is reserved for, and therefore characterizes second-line ART. Ritonavir boosted protease inhibitors (bPIs) are recommended, supported by two agents from the NRTI class.)ARV Components in Initial Therapy: NNRTIs : ARV Components in Initial Therapy: NNRTIs ADVANTAGES Long half-lives Less metabolic toxicity (dyslipidemia, insulin resistance) than with some PIs PIs and II preserved for future use DISADVANTAGES Low genetic barrier to resistance – single mutation Cross-resistance among most NNRTIs Rash; hepatotoxicity Potential drug interactions (CYP450) Transmitted resistance to NNRTIs more common than resistance to PIsARV Components in Initial Therapy: PIs : ARV Components in Initial Therapy: PIs ADVANTAGES Higher genetic barrier to resistance PI resistance uncommon with failure (boosted PI) NNRTIs and II preserved for future use DISADVANTAGES Metabolic complications (fat maldistribution, dyslipidemia, insulin resistance) GI intolerance Potential for drug interactions (CYP450), especially with RTVARV Components in Initial Therapy: Dual-NRTI Pairs: ARV Components in Initial Therapy: Dual-NRTI Pairs ADVANTAGES Established backbone of combination therapy Minimal drug interactions DISADVANTAGES Lactic acidosis and hepatic steatosis reported with most NRTIs (rare)PowerPoint Presentation: SACS-standardized account code structurePowerPoint Presentation: Ref- NACOHence………………..: H ence ………………..PowerPoint Presentation: Consider the patient’s comorbidities, mental health and lifestyle. Educate, educate, educate: Adherence and ways to improve it Side effects Controlling comorbiditiesPowerPoint Presentation: HIV is preventable………… What about availability of HIV Vaccine??? Ref- Harrisons text book of medicine 18 th edition.Why we are tempted to develop vaccine?: W hy we are tempted to develop vaccine? There are elements of host defense or HIV specific immune response that have the potential to be protective. Some are long term non progressors or elite controllers. Number of individuals who are exposed to HIV multiple times but remain uninfected.A Preventive vaccine against HIV infection: A Preventive vaccine against HIV infection It is a critical modality for preventing the spread of HIV infection is the development of a safe & effective vaccine. Historically, vaccines has provided us a safe cost effective & efficient means of preventing illness, disability & death from infectious diseases. But this is not the case with HIV , since natural immune response to HIV infection is unable to clear the virus from the body and cases of super infection have been reportedProblems for development of HIV Vaccine: Problems for development of HIV Vaccine High mutability of vaccine Infection can be transmitted by cell free or cell associated virus. Latent forms are known , which are unexposed to immune system.Development of vaccine: Development of vaccine Vaccine using envelop protein gp120 aimed at inducing neutralizing antibodies in humans were performed which is based on induction of neutralizing antibodies in nonhuman primates. But recent trials suggests that vaccine is failed to protect human from HIV infection. No. of studies in monkeys using vaccines that induce CMI ( T cell vaccine), have not protected these animals against infection but have lowered initial burst of viremia as well as it decreased viral set point temporarilyContd…: Contd… As there is initial burst of viremia following acute infection or during advanced stage of disease when viral load is high, thus by decreasing viral load vaccine could have benefits for both patient and his/her sexual partner.Failure till date….: Failure till date…. In human clinical trials T cell vaccine failed to lower either the initial burst of viremia or viral set point after acquisition of infectionCurrant studies…: Currant studies… Vaccine using a pox virus vector prime : expressing various viral protein followed by an enveloped protein boost, was tested in 16000 persons in Thailand among predominantly heterosexuals, showing 31% protection against infection, but evidence is not sufficient for clinical use of vaccine, but it serves as an important first step in the direction of development of safe and effective vaccine against HIV infectionPrevention : Prevention Education, counseling & behavior modification are the cornerstones of an HIV prevention strategy. Major problem is that most of the infected persons don’t know that they are infected. In this regard CDC recommended HIV testing as a part of routine medical care between the age group 13 to 64 yrs be informed of the testing & no need of consent. The practice of safer sex is the most effective way for sexually active uninfected individuals & infected individuals.Contd…: Contd… Abstinence from sexual relations is the only absolute way to prevent sexual transmission of HIV infection. When 1 of the partner is infected then options are a: Use of condoms but they are not 100% safe. b: avoid multiple sexual partners.Thank you for being awake…. : T hank you for being awake …. You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.