LATEST TREATMENT IN HIV-AIDS

Dr. K.Kantharaj

Goals of Therapy & Tools to Achieve Goals                    

• Improvement of quality of life
• Reduction of HIV-related morbidity and mortality
• Restoration and/or preservation of immunologic function
• Maximal and durable suppression of viral load
• Selection of ARV regimen
• Preservation of future treatment options
• Rational sequencing of therapy
• Maximizing adherence
• Use of resistance testing in selected clinical settings

Considerations for Discontinuing Therapy

                           

• Patients begun on HAART at CD4 count >350 cells/µL
• No clinical data on safety of treatment discontinuation
• Potential benefits: decreased toxicity, drug interactions, and drug resistance
• Potential risks: rebound in viral replication, immunologic deterioration

 

        Current Antiretroviral Medications

       NRTI 

• Abacavir                   ABC
• Didanosine               DDI
• Emtricitabine            FTC
• Lamivudine               3TC
• Stavudine                  D4T
• Zidovudine                ZDV
• Zalcitabine                DDC
• Tenofovir                   TDF

NNRTI

• Delavirdine               DLV
• Efavirenz                   EFV
• Nevirapine                 NVP

PI

• Amprenavir               APV
• Atazanavir                 ATV
• Fosamprenavir         FPV
• Indinavir                     IDV
• Lopinavir                   LPV
• Nelfinavir                   NFV
• Ritonavir                    RTV
• Saquinavir                 SQV
• soft gel                      SGC
• hard gel                      HGC
• tablet                          INV
• Tipranavir                  TPV

ANTIRETROVIRAL COMPONENTS IN INITIAL THERAPY

   NNRTIs

ADVANTAGES

• Less dyslipidemia and fat maldistribution than in PI-based regimens
• PI options preserved for future use

    DISADVANTAGES

• Resistance - single mutation
• Cross-resistance among NNRTIs
• Rash; hepatotoxicity
• Potential drug interactions (CYP450)

PIs

ADVANTAGES

• Longest prospective data
• NNRTI options preserved for future use

DISADVANTAGES

• Metaboliccomplications (fat maldistribution, dyslipidemia, insulin resistance)
• Greater potential for drug interactions (CYP450), especially with ritonavir

 NRTIs

        ADVANTAGES

• Established backbone of combination therapy
• Minimal drug interactions
• PI and NNRTI preserved for future use

 DISADVANTAGES

• Lactic acidosis and hepatic steatosis reported with most NRTIs (rare)
• Triple NRTI regimens show inferior virologic response compared with efavirenz- and indinavir-based regimens*

 Treatment-Experienced Patients: ARV Treatment Failure

• Causes of treatment failure include:
• Patient factors(CD4 nadir, VL, comorbidities, etc)
• Suboptimal adherence
• ARV toxicity and intolerance
• Pharmacokinetic problems
• Suboptimal drug potency
• Viral resistance