Treatment Modalities In HIV/AIDS Patients

POST-EXPOSURE PROPHYLAXIS :
  1. Basic (2 drug) regimen (for low risk)
  2. Zidovudine 300 mg + Lamivudine 150 mg - Twice daily for 4 weeks
  3. Expended (3 drug) regimen (for high risk)
  4. Zidovudine 300 mg + Lamivudine 150 mg - Twice daily+ Indinavir 800 mg (or another PI) Thrice daily All for 4 weeks. 
DRUGS AGAINST HIV: Attachment inhibitor
  • Dextrin 2 SO4 (D2S) Inhibit the binding of HIV-1 gp 120 with CD4 cells.
Coreceptor antagonists CCR5 is a coreceptor involved in the entry of the HIV virus into the cell
  • Maraviroc binds to CCR5, preventing HIV from binding to this receptor.
  • Vicriviroc
  • Aplaviroc
Fusion inhibitors
  • Enfuvirtide - targets multiple sites in gp 41 and gp 120.
  • Tifuvirtide - 2nd generation HIV fusion inhibitor.
lntegrase inhibitors
  • Raltegravir first integrase inhibitor (FDA approved)(used in combination with other antiretroviral agents in treatment of patients with ongoing HIV-1 replicaiton.)
  • Elvitegravir
 Maturation inhibitors inhibit the development of HIV's internal structures in a new virus.
  • Bevirimat
  • Vivecon
Zinc finger inhibitors
  • Azodicarbonamide
Monoclonal antibodies restrict HIV entry - CD4 blocker:
  • Ibalizumab
Non-nucleoside reverse transcriptase inhibitor:
  • Efavirenz
Protease inhibitors:
  • Potent inhibitors of CYP3A4 
  • Ritonavir and lopinavir
  • Saquinavir is a weak inhibitor of CYP3A4
  • Most HIV protease inhibitors are substrates for P-glycoprotein drug transporter (P-gp), which is an efflux pump encoded by the mdr 1 gene
  • Indinavir and atazanavir can cause indirect hyperbilirubinemias with overt jaundice.
TREATMENT MODALITIES FOR HIV RELATED DISEASES:
Drug of choice for diarrhea in AIDS :

  • Octreotide(Somatostatin analogue) inhibits the release of hormones (triggered by rapid passage of food into the small intestine) that are responsible for distressing local and systemic effects.
  • Octreotide has been used, with varying success, in other forms of secretory diarrhea such as
Chemotherapy-induced
  1. Diarrhea associated with human immunodeficiency virus (HIV)
  2. Diabetes-associated diarrhea.
  3. Its greatest utility is in the "dumping syndrome" 
  4. seen in some patients after gastric surgery and pyloroplasty
  5. Used in carcinoid tumors and VIP–secreting tumors, as well as in the treatment of acromegaly.
  • Interferon is a Glycoprotein, produced by many mammalian cells, and used in the treatment of hepatitis, papillomaviruses, hairy-cell leukemia and AIDS-related Kaposi's sarcoma
 New drugs in HIV infection
  • Etravirine is recently approved NNRTI. This is second generation NNRTI and is effective against HIV resistant to first generation NNRTI (Efavirenz, Delaviridine, Nevirapine).
 Fusion inhibitors (Entry inhibitors)
  • Enfluviritide binds to Gp41 subunit of HIV envelop protein and inhibits the fusion of viral and host cell membrane.
  • Maraviroc is a CCRS Co-receptor antagonist and is only active against "CCR - 5 - tropic virus" which tends to predominate early in infection.
Treatment during Pregnancy
  • HIV infected mother can transmit the virus to fetus/infant during pregnancy, during delivery or by breast feeding.
  • Early diagnosis and antiretroviral therapy to mother and infant significantly decrease the rate of intrapartum and perinatal transmission (vertical transmission) of HIV infection.
  •  Zidovudine treatment of HIV infected pregnant women from the beginning of second trimester through delivery and of infant for 6 weeks following birth decreases the rate of transmission from 22.6% to < 5%.
  • Single dose of nevirapine given to the mother at the onset of labor followed by a single dose to the newborn within 72 hours of birth decreased transmission by 50%. 
  • For the prevention of parent to child transmission of HIV, the NACO's recommendation is to give Niverapine 200 mg in active about to mother and syrup niverapine 2 mg/kg body weight to newborn with 72 hours of delivery

Antiretroviral agents in pregnancy
Recommended AlternativeNRTIs
Zidovudin Diadanosine
Lamivudine  Emtricitabine
Stavudine
AbacavirNNRTIs
NepirapinePis
Nelfinavir Indinavir
SquinavirLopinavir/ritonavir
AIDS with bronchiolitis:
  • Antibiotics are not usually used in the treatment Bronchiolitis who are previously healthy but Ribavarin shortens the duration of treatment in patient who have —> Immunodeficiency, Congenital heart disease, Chronic lung disease
  • AIDS patient presents with fistula - in- ano can be treated with seton
CMV infection in AIDS patients:
  • HIV positive persons are most at risk, especially when the CD4 cell count decreases.
  • It is usually treated by antivirals such as ganciclovir or foscarnet, which can be taken orally, intravenously, injected directly into the eye (intravitreal injection). Fomivirsen is the first antisense drug as an intraocular injection for the treatment of cytomegalovirus retinitis.
Exam Question
  • Octreotide is the drug of choice for diarrhea in AIDS
  • Interferon is a Glycoprotein, produced by many mammalian cells, and used in the treatment of hepatitis, papillomaviruses, hairy-cell leukemia and AIDS-related Kaposi's sarcoma Raltegravir is an integrase inhibitor which is used in combination with other antiretroviral agents in treatment of patients with ongoing HIV-1 replicaiton.
  • The drug efavirenz inhibits HIV 1 reverse transcriptase
  • Ritonavir, Didanosine, Zidovudine comes under anti-HIV agents
  • Rifampicin is contraindicated in AIDS as it induces metabolism of ritonavir, indinavir and saquinavir
  • Protease inhibitor in HIV is Potent inhibitors of CYP3A4 
  • Saquinavir is a weak inhibitor of CYP3A4
  • All protease inhibitors are substrates for P glycoprotein coded by MDR gene.
  • Zidovudine given for HIV in preganancy because Decreases the risk of vertical transmission
  • For the prevention of parent to child transmission of HIV, the NACO's recommendation is to give Niverapine 200 mg in active about to mother and syrup niverapine 2 mg/kg body weight to newborn with 72 hours of delivery
  • Ribavarin is the drug of choice for bronchitis with HIV 
  • AIDS patient presents with fistula - in- ano can be treated with seton
  • The drug of choice for cytomegalovirus retinitis in HIV patients are ganciclovir or foscarnet
  • Post exposure prophylaxis [PEP] for HIV should be given for a minimum period of 4 weeks 
  • Nevirapine drug is given as a single dose to prevent mother to child HIV transmission
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