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HIV
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1 4 3
Reverse transcription
5- In the cytoplasm of the cell,
Integration
6- The newly made HIV DNA moves to the cell's nucleus, where it is spliced into the host's DNA with the help of HIV integrase. HIV DNA that enters the DNA of the cell is called a provirus.
Transcription
7- For a provirus to produce new viruses, RNA copies must be made that can be read by the host cell's protein-making machinery. These copies are called messenger RNA (mRNA), and production of mRNA is called transcription, a process that involves the host cells own enzymes. Viral genes in concert with the cellular machinery, control this process. Genomic RNA is also transcribed for later incorporation in the budding virion.
Translation 8- After HIV mRNA is processed in the cell's nucleus, it is transported to the cytoplasm. The protein encoded by the HIV's rev gene is critical to this process. Without the rev protein, structural proteins are not made. In the cytoplasm, the virus co-opts the cell's proteinmaking machinery (like ribosomes) to make long chains of viral proteins and enzymes, using HIV mRNA as a template. Assembly and budding 9-Newly made HIV proteins and genomic RNA gather inside the cell and an immature viral particle forms and buds off from the cell, acquiring an envelope that includes both cellular and HIV proteins from the cell membrane. During this part of the viral life cycle, the core of the virus is immature and the virus is not yet infectious. The precursor proteins (gag and pol) that make up the immature viral core are now cut into smaller functional proteins by the viral protease. This step results in infectious virions.
Current Treatment
The theoretical possibility of viral eradication is now improbable, so that treatment, once started, must be maintained indefinitely.
4. 5. 6. 7. 8.
World Health Organization (WHO) Clinical Staging of HIV/AIDS For Adults and Adolescents (2005)
Primary HIV infection
Asymptomatic Acute retroviral syndrome
Clinical stage 1
Asymptomatic Persistent generalized lymphadenopathy
Clinical stage 2
Moderate and unexplained weight loss (<10% of presumed or measured body weight)
Recurrent respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis)
Herpes zoster Recurrent oral ulcerations Papular pruritic eruptions
Angular cheilitis
Seborrhoeic dermatitis Fungal finger nail infections
Clinical stage 3
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations
Unexplained chronic diarrhoea for longer than one month Unexplained persistent fever (intermittent or constant for longer than one month)
Clinical stage 4
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or simple investigations
HIV wasting syndrome Pneumocystis pneumonia Recurrent severe or radiological bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal of more than one months duration) Oesophageal candidiasis Extrapulmonary Tuberculosis Kaposis sarcoma Central nervous system toxoplasmosis HIV encephalopathy
HIV-infected adults should start ART when HIV infection has been confirmed and one of the following conditions is present:
Clinically advanced HIV disease; WHO Stage IV HIV disease, irrespective of the CD4 cell count; WHO Stage III disease with consideration of using CD4 cell counts less than 350/l to assist decision making; WHO Stage I or II HIV disease with CD4 cell counts less than 200/l.
Block reverse transcriptase's enzymatic function and prevent completion of synthesis of the doublestranded viral DNA.
Retrovir
Didanosine (ddI) Zalcitabine (ddC) Stavudine (d4T) Lamivudine (3TC) Abacavir (ABC) Emtricitabine (FTC)
Videx, Videx EC Hivid Zerit, Zerit XR Zeffix and Epivir Ziagen Emtriva
Peripheral neuropathy
Hyperuricemia Pancreatitis
Peripheral neuropathy,,
Protease inhibitor
Protease inhibitors
Active principle Saquinavir Ritonavir Indinavir Trade name Invirase Norvir Crixivan Side effects
Sleep disorder, paresthesia, peripheral neuropathy, dizziness, dysgeusia, headache, dyspnea, muscle spasms, nausea, increased ALT, AST Headache, lipodystrophy, increased triglycerides, total cholesterol, GGT, amylase, AST, ALT, circumoral and peripheral paresthesia Nephrolithiasis. Gastrointestinal intolerance. Hyperbilirubinemia. Hyperglycemia. Dyslipidemia. Lipodystrophy. skin rash, increased AST, ALT, CK, Neutropenia diarrhea, headache, lipodystrophy, increased triglycerides, total cholesterol, GGT, amylase, AST, ALT elevation of total bilirubin, lipase, CK, ALT, AST, rash, jaundice oral paresthesia, eurpcion skin, dizziness, increased ALT, AST, lipase and triglycerides urticaria, rash, increased AST, ALT, amylase, cholesterol, neutropenia insominio, pruritus, increased cholesterol, triglycerides, AST, ALT and serum amylase, rash,
Nelfinavir
Lopinavir Atazanavir Fosamprenavir Tipranavir Darunavir
Viracept
Kaletra Reyataz Lexiva, Telzir Aptivus Prezista
peripheral neuropathy
Combination of antiretroviral drugs has dramatically improved the prognosis of individuals with HIV infection. However, their long-term benefit is limited by two main factors:
The selection of drug-resistant strains. Side effects.
Mitochondrial damage
Nucleoside analogue reverse transcriptase inhibitors (NRTI), which lack the hydroxyl group needed for further DNA chain elongation, block HIV reverse transcriptase. These nucleosides can be mistaken as natural substrates by the polymerase , the enzyme responsible for the replication of mitochondrial DNA (mtDNA).
Toxicity
Active principle
Didanosine (ddI) NRTI
Trade name
Videx, Videx EC
Side effects
Peripheral neuropathy
Hyperuricemia Pancreatitis Diarrhea Lactic acidosis with nausea Hepatic steatosis Lipodystrophy
Hivid
Zerit, Zerit XR
Etravirine NNRTI
Intelence
Darunavir PI
Prezista
neuropathy
Is dose dependent. Usually appears as a distal symmetric polyneuropathy. Predominantly sensory, manifesting with paresthesia, dysesthesia, numbness, decreased pain sensitivity and thermal or distal pain. Examination with an abolition or reduction of tendon reflexes. Moderate muscle weakness.
Clinical procedures
Make a good medical history. To know:
How are the characteristics of the symptoms? Is the patient taking antiretroviral drugs? Since when? Are the symptoms linked with taking antiretroviral drugs? Is the patient taking abusive alcohol?
Clinical characteristics of the disease are very obvious, and could be diagnosed by medical history.
Pain treatment
Bibliography (articles)
E. Santos Corraliza, A. Fuertes Martn. Efectos adversos de los frmacos antirretrovirales. Fisiopatologa, manifestaciones clnicas y tratamiento. An. Med. Interna (Madrid) v.23 n.7 Madrid jul. 2006. Soto Ramrez, L.E; Prez Saleme et al, L. Gua para el tratamiento antirretroviral de las personas adultas que viven con VIH/SIDA, Rev Invest Cln 2004; Vol. 56(2):253-271. R.Rubio, J.Berenguer et al; Recomendaciones de GESIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en pacientes adultos infectados por el virus de la inmunodeficiencia humana en el ao 2002. Enferm Infecc Microbiol Clin 2002;20(6):244-303. P. Casanova-Sotolongo a, P. Casanova-Carrillo b, C. Casanova-Carrillo; Enfermedades del sistema nervioso perifrico y visual durante la infeccin por el virus de inmunodeficiencia humana; REV NEUROL 2003; 37 (5): 481-485. C.de Mendoza, F.Blanco, V.Soriano. Toxicidad mitocondrial de los antirretrovirales: diagnstico y monitorizacin. Med Clin (Barc) 2003;121(8):310-5. Kallianpur AR, Hulgan T. Pharmacogenetics of nucleoside reverse-transcriptase inhibitorassociated peripheral neuropathy. Pharmacogenomics. 2009 Apr;10(4):623-37. E.Santos Corraliza y A.Fuertes Martn. Tratamiento antirretroviral y toxicidad mitocondrial. Med Clin (Barc). 2007;128(8):311-6 Taylor & Francis. The epidemiology of human immunodeficiency virusassociated neurological disease in the era of highly active antiretroviral therapy. Journal of NeuroVirology, 8(suppl. 2): 115121, 2002. E.Santos Corraliza y A.Fuertes Martn. Side Effects of Antiretroviral Therapy. Fisiopathology, Clinical Manifestations and Treatment. Med Clin (Barc) 2008; 58-182. K.Ng, K, kumar. Axonal excitability in viral polyneuropathy and nucleoside neuropathy in HIV patients. J Neurol Neurosurg Psychiatry 2011;82:978-980
Bibliography (books)
Bradley, W. G. Neurologa clnica. Diagnstico y tratamiento. 4 ed. Madrid : Elsevier,. 2005 Bradley, W. G. Neurologa clnica.Transtornos neurolgicos. 4 ed. Madrid : Elsevier,. 2005 Gatell Artigas, Josep M. Gua prctica del SIDA clnica, diagnstico y tratamiento.4 ed. Barcelona. Masson. 1996 DeVita, Vincent T. SIDA etiologa, diagnstico, tratamiento y prevencin. 1ed. Barcelona. Salvat. 1986.