HIV Lecture 20 PDF

HIV  OVERVIEW uHIV is a sexually transmitted infection (STI) uSeveral methods for transmission. uRapid spread throughout the world. uAcquired immunodeficiency syndrome (AIDS). uFirst discovered in central Africa in 1959. uHIV-1 group M: western world uHIV-2 found...

HIV  OVERVIEW uHIV is a sexually transmitted infection (STI) uSeveral methods for transmission. uRapid spread throughout the world. uAcquired immunodeficiency syndrome (AIDS). uFirst discovered in central Africa in 1959. uHIV-1 group M: western world uHIV-2 found in mostly in western Africa  HIV PATHOGENESIS Entrance into human cells: CD4 attachment. Two major chemokine receptors: chemokine (C–C motif) receptor 5 (CCR5) and chemokine (C–X–C motif) receptor 4 (CXCR4) Release after replication  HIV š Moods of Transmission š Sexual š Parenteral Exposure to Blood š Universal Precautions š Perinatal  HIV Clinical Presentation More: Fever, headache, sore throat, fatigue, GI upset (diarrhea, nausea, vomiting), weight loss, myalgia, morbilliform or maculopapular rash usually involving the trunk, lymphadenopathy, night sweats Less: Aseptic meningitis, oral ulcers, leukopenia Other; High viral load (may exceed 1,000,000 copies/mL or 109 /L) Persistent decrease in CD4 lymphocytes HIV o HIV infection goes into 3 phases: Acute, Chronic Terminal (AIDS). o The hallmark of untreated HIV infection is Profound CD4 T-lymphocyte depletion Severe immunosuppression Ø Significant risk for infectious diseases caused by opportunistic pathogens > Opportunistic infections (OIs). HIV o Diagnosis o ELISA – initial test o Western Blot – confirmation o Rapid HIV tests o HIV RNA (copies/ml) o Signal amplification nucleic acid probe o Reverse transcriptase PCR o Nucleic acid sequence based amplification  HIV o HIV RNA test indications: o Acute infection o Newly diagnosed o Every 3-4 months (on or off therapy) o 2-8 weeks after starting or changing therapy o 3-4 months after starting therapy o Following a clinical event or decreasing CD4  HIV Treatment Goals š Decrease morbidity and mortality, š Improve quality of life restore š Preserve immune function š Prevent further transmission. General Approach to treatment š Combinations of three active antiretroviral agents from two pharmacologic classes potently inhibit HIV replication to undetectable plasma levels, prevent and reverse immune deficiency, and substantially decrease  HIV treatment š The same principles of ART apply to both HIV-infected children and adults, although treatment of HIV-infected children involves unique pharmacologic, virologic, and immunologic considerations. š Women should receive optimal ART regardless of pregnancy status HIV Care Process Collect Follow up, monitor & Asses evaluate HIV Care Process Implement plan HIV treatment o Nucleoside Reverse Transcriptase Inhibitors o Nucleotide Reverse Transcriptase Inhibitors o Non-Nucleoside Reverse Transcriptase Inhibitors o Protease Inhibitors o Entry Inhibitors o Integrase Inhibitors  HIV Treatment Principles š Antiretroviral therapy (ART) is recommended for everyone with HIV regardless of CD4 counts š Conditions increasing the urgency to start ART: š Pregnancy š AIDS-defining conditions, including HIV-associated dementia (HAD) and AIDS-associated malignancies š Acute opportunistic infections š Low CD4 counts (< 200 cells/mm) š HIV-associated nephropathy š Acute/early infection š HIV/hepatitis B virus coinfection š HIV/hepatitis C virus coinfection  Antiretroviral Classes Antiretroviral Class Drugs Nucleoside reverse transcriptase inhibitors Abacavir, didanosine, emtrictiabine, (NRTIs) lamivudine, stavudine, tenofovir, zidovudine Non-nucleoside reverse-transcriptase Efavirenz, delavirdine, ertavirine, inhibitors nevirapine, ripivirine NNRTIs Protease Inhibitors Atazanavir, darunavir, fosamprenavir, Pis indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranivir Integrase strand transfer inhibitor Dolutegravir, raltegravir INSTI Fusion inhibitor Enfuviritide CCR5 antagonist Maraviroc  *in -negative patients) In patients with HIV RNA < 100,000 copies/mL and CD4 > 200 cells/mm3: (*in -negative patients) (*in -negative patients and HIV RNA < 100,000 copies/mL) (*in -negative patients and HIV RNA < 100,000 copies/mL) in patients with HIV RNA < 100,000 copies/mL and CD4 > 200 cells/mm ) 3  HIV š Important aspects in HIV management š Adherence š Efficacy š Resistance  HIV Special Populations Ø Pregnancy Dolutegravir problem. should be avoided, if possible, Zidovudine is recommended Ø Infants born to HIV-infected mothers Zidovudine should receive (± several doses of nevirapine) prophylaxis for 4 to 6 weeks after birth. Ø Breastfeeding is not recommended HIV š Change therapy for: q Toxicity if significant q Virologic failure § Not achieving HIV RNA < 400 copies/ml by 24 weeks or