Hiv Aids

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Hiv Aids

  1. 1. HIV- AIDS By Dr. Osman Sadig
  2. 2. <ul><li>Epidemiology </li></ul><ul><li>- HIV, za cause of AIDS is now za 4 th commonest cause of death world-wide. </li></ul><ul><li>- In 2000, 34.5 million were infected wz HIV, of whom 24.5 in Sub-Saharan Africa </li></ul>
  3. 3. <ul><li>- The human & economic costs are high because of high mortality & fall in life expectancy. </li></ul><ul><li>- Despite that HIV can be isolated from a wide </li></ul><ul><li>range of body fluids & tissue, the majority of </li></ul><ul><li>infections are transmitted via semen, cervical </li></ul><ul><li>secretions & blood. </li></ul><ul><li>1- Sexual transmission ( vaginal & anal): </li></ul><ul><li>Commonest route & coexistent STDs , sp </li></ul><ul><li>those causing genital ulceration, enhance </li></ul><ul><li>transmission. Transmission is more efficient </li></ul><ul><li>from men to women & to za passive partner </li></ul><ul><li>in anal intercourse. </li></ul>
  4. 4. <ul><li>2- Mother to Child (vertical): Commonest route in children. Transmission occur during pregnancy, </li></ul><ul><li>during delivery or after delivery through breast feeding. Most infections occur perinatally. Advanced dis. & high viral load in the mother, prolonged & premature rupture of membranes & chorioamnionitis increase za risk of transmission. </li></ul><ul><li>Interventions to reduce transmission include use antiretroviral agents, delivery by CS and avoidance of breast feeding. </li></ul><ul><li>3- Contaminated blood, blood products & organ </li></ul><ul><li>donations if not screened. </li></ul><ul><li>4- Contaminated needles & instruments . The risk </li></ul>
  5. 5. <ul><li>of acquiring HIV following a single needle-stick injury contaminated wz HIV is 0.3%. </li></ul><ul><li>*** No evidence of HIV transmission by social or household contact or by blood sucking insects. </li></ul><ul><li>The virus </li></ul><ul><li>- HIV belongs to retroviral family . </li></ul><ul><li>- 2 types: HIV-1 & HIV-2 ( West Africa. ? India). </li></ul><ul><li>HIV-2 is more indolent in nature. </li></ul><ul><li>- RNA virus & needs a living cell to multiply. </li></ul><ul><li>-The target cells for HIV are CD4 T-lymphocytes </li></ul>
  6. 7. <ul><li>1- HIV binds to za host CD4 via za envelope glycoprotein ( gp120 ) </li></ul><ul><li>2- Reverse transcriptase converts viral RNA to ssDNA and host cell polymerase leads to formation of dsDNA which enters za nucleus of CD4 & inserted into its genome via integrase . </li></ul><ul><li>3- With za help of za protease enzyme new viral particles are assembled in za cytoplasm and are budded out of za cell ready to infect other CD4 cells. </li></ul><ul><li>- Virus production lasts 2 days & is limited by the death of za cell due to direct effect of za virus. The half life of za virus is only 6 hrs, but its </li></ul>
  7. 10. <ul><li>turnover is very high (10 to za power 9 each day) - Immunosuppression is due to progressive and severe depletion of CD4 T-lymphocytes causing both CM & humoral immune def. </li></ul><ul><li>- HIV also has a direct effect on za nervous tissue, lymphoid tissue & testes. </li></ul>
  8. 11. <ul><li>Diagnosis of HIV infection </li></ul><ul><li>1- Detection of virus specific Abs: </li></ul><ul><li>a/ Abs to gp 120 : - detects Abs against envelop glycoprotein gp 120 </li></ul><ul><li>- Routine test for screening & based on ELIZA . </li></ul><ul><li>- Window period or serological latency is 3/12 </li></ul><ul><li>- Abs have no protective fn & persist for life. </li></ul><ul><li>- Abs cross za placenta & not reliable indicator of active infection in za baby & in uninfected babies will be gradually lost over za 1 st 18/12 of life </li></ul>
  9. 12. <ul><li>- b/ Abs to p24 ( core protein): detected early </li></ul><ul><li>in infection & lost as dis progresses. </li></ul><ul><li>2- Ag assays by : a/ HIV DNA PCR assay : used in diagn of HIV in babies borne to infected mothers & in the </li></ul><ul><li>window period </li></ul><ul><li>b/ HIV RNA PCR assay : superseded za above test. </li></ul><ul><li>It measures za amount of HIV RNA in za blood </li></ul><ul><li>( viral load ). Higher viral load is predictive of </li></ul><ul><li>faster dis progression. This test is also used to </li></ul><ul><li>assess za response to anti-viral therapy . </li></ul><ul><li>The viral load can also be measured by c/branched DNA tehneque . </li></ul>
  10. 13. <ul><li>3- Western blot : </li></ul><ul><li>- confirmatory test </li></ul><ul><li>- detects Abs against Ag coded by 3 diff viral </li></ul><ul><li>genes. </li></ul><ul><li>4- Isolation of virus in culture for research. </li></ul><ul><li>*** NACO guidelines for diagn HIV infection is based on 3 diff ELIZA/rapid tests using 3 diff Ags. AIDS is diagn by using 2 diff ELIZA/rapid </li></ul><ul><li>tests on diff Ags in za presence of AIDS-related </li></ul><ul><li>opportunistic infections. </li></ul>
  11. 14. <ul><li>Clinical features of HIV infection </li></ul><ul><li>- It is za result of both direct HIV infection and associated immune dysfn . </li></ul><ul><li>- AIDS is defined as individuals wz CD4 < 200 with AIDS defining conditions in USA while in Europe it is defined without CD4 level. Both need positive HIV test . </li></ul><ul><li>- IP is 2-4Ws immediately following infection and is both clinically & serologically silent. </li></ul><ul><li>1- Primary HIV infection/ seroconversion </li></ul><ul><li>2- Asymptomatic infection/clinical latency </li></ul><ul><li>3- Symptomatic infection (ARC) </li></ul><ul><li>4- AIDS </li></ul>
  12. 15. Acute pry infection CD4>500/microlit . Asymp infection CD4 200->500 Symp infection (ARC) CD4 200-500 AIDS CD4 <200 Acute seroconversion Illness in some pts. PGL in some pts. Oro/vulvovaginal candidiasis, ITP, P. neur Hairy leukopl, constitutional symp (fever, Diah > 1/12, mucocutaneous manifestation Constitutional symp ( Wt loss> 10%, Diah >1/12), neurological dis (dementia, myelopathy, P, neuropath), Kaposi's, NHL and Opportunistic infections .
  13. 16. <ul><li>** Seroconversion illness is a self-limiting non-sp </li></ul><ul><li>illness occurring 6-8Ws after exposure (sore throat, fever, arthralgia, myalgia, lethargy, LN, </li></ul><ul><li>mucosal ulcers, +/- MP rash, HA, photophobia, </li></ul><ul><li>myelopathy, neuropathy & rarely encephalopat) </li></ul><ul><li>It lasts up to 3Ws & recovery is usually complet . </li></ul><ul><li>There is cytopenia, CD4 lym depleted, raised liver enzymes, Abs absent early, high viral RNA </li></ul><ul><li>levels. Pts experiencing seroconversion illness may have a more rapidly progressive course of infection. </li></ul>
  14. 17. <ul><li>** Asymp stage have a median time of 10 years </li></ul><ul><li>( period from infections to AIDS). Older age and those experiencing seroconversion have </li></ul><ul><li>a rapid progression. </li></ul><ul><li>** AIDS defining conditions :- </li></ul><ul><li>1- Tracheal, bronchial or lung candidiasis </li></ul><ul><li>2- Oesophageal candidiasis </li></ul><ul><li>3- Invasive cervical Ca. </li></ul><ul><li>4- Coccidioidomycosis, disseminated or extrapulmonary </li></ul><ul><li>5- Extrapulmonary cryptococcosis, e.g meningitis </li></ul><ul><li>6- Cryptosoridiosis, chr intestinal (> 1/12) </li></ul>
  15. 18. <ul><li>7- CMV dis other than liver, spleen or LN. </li></ul><ul><li>8- CMV retinitis (wz loss of vision) </li></ul><ul><li>9- Encephalopathy, HIV related </li></ul><ul><li>10- Herpes simplex, chr ulcers (>1/12), or bronchitis, pneumonitis or oessophagitis. </li></ul><ul><li>11- Hitsplasmosis, disseminated or extrapulmon </li></ul><ul><li>12- Isosporiasis, chr intestinal (>1/12) </li></ul><ul><li>13- Kaposi's sarcoma </li></ul><ul><li>14- Lymphoma, NHL or Burkett's </li></ul><ul><li>15- Pry lymphoma of za brain </li></ul><ul><li>16- Mycobact Tb, any site </li></ul><ul><li>17- Mycobact avium complex or kansasi, dissem </li></ul><ul><li>or extrapulm </li></ul>
  16. 19. <ul><li>18- Pneumocystic carinii pneumonia </li></ul><ul><li>19- Recurrent pneumonia </li></ul><ul><li>20- Progressive multifocal leucoencephalopathy </li></ul><ul><li>21- Salmonella septicemia, recurrent </li></ul><ul><li>22- Toxoplasmosis of za brain </li></ul><ul><li>23- Wasting syndrome, due to HIV </li></ul><ul><li>*** Clinical case definition for AIDS : </li></ul><ul><li>An individual wz +ve test for HIV infection </li></ul><ul><li>by 2 tests based on 2 diff Ags PLUS any </li></ul><ul><li>AIDS defining condition </li></ul>
  17. 20. <ul><li>*** Common opportunistic infections : </li></ul><ul><li>- Tb, both M. Tb & atypical mycobact. </li></ul><ul><li>- candidiasis </li></ul><ul><li>- Herpes zoster </li></ul><ul><li>- Diarrhoeal: </li></ul><ul><li>- protozoal: amoeba, giardia, isospora, </li></ul><ul><li>cryptosporidium.. </li></ul><ul><li>- Helmiths: strongyloidosis </li></ul><ul><li>- Viral: CMV </li></ul><ul><li>- Toxoplasmosis </li></ul><ul><li>- Cryptococcal meningitis </li></ul><ul><li>- CMV retinitis </li></ul><ul><li>- VL ? </li></ul>
  18. 21. <ul><li>Management of HIV positive patient </li></ul><ul><li>Treatment approach involves : </li></ul><ul><li>- Inhibiting viral replication & decrease viral load by antiretroviral drugs. </li></ul><ul><li>- Treatment & prophylaxis of opportunistic infections </li></ul><ul><li>- Psychological support. </li></ul><ul><li>1- Antiretroviral therapy : </li></ul><ul><li>- Inhibit viral replication & decrease viral load. </li></ul><ul><li>- Preserve immune fn by increasing CD4 count. </li></ul>
  19. 22. <ul><li>- Prevent dis progression </li></ul><ul><li>- Decrease za incidence of opportunistic infections. </li></ul><ul><li>- Reduce dis progression </li></ul><ul><li>- Prolong survival & improve quality of life. </li></ul><ul><li>- Possibly reduces za risk of transmission </li></ul><ul><li>** The goal of antiretroviral therapy is to bring down za viral load to <50 by triple drug therapy over Ws & Ms. </li></ul>
  20. 23. <ul><li>Classes of antiretrovirals </li></ul><ul><li>Antiretrovirals target two key enzymes, protease </li></ul><ul><li>and reverse transcriptase: </li></ul><ul><li>1- Reverse transcriptase inhibitors </li></ul><ul><li>a/ nucleoside reverse transcriptase </li></ul><ul><li>inhibitors (NRTs) </li></ul><ul><li>b/ non-nucleoside reverse transcriptase </li></ul><ul><li>inhibitors (NNRTs) 2- Protease inhibitors (PIs) </li></ul>
  21. 24. <ul><li>NRTIs NNRTIs PIs </li></ul><ul><li>Zidovudine Nevirapine Indinavir </li></ul><ul><li>Stavudine Efavirenz Nelfenavir </li></ul><ul><li>Lamivudine Delavirdine Ritonavir </li></ul><ul><li>Didanosine Saquinavir </li></ul><ul><li>Zalcitabine Amprenavir </li></ul><ul><li>Abacavir Lopinavir </li></ul><ul><li>When to initiate antiretrovirals? </li></ul><ul><li>1- Asym pts = CD4 goes below 350 or HIV RNA </li></ul><ul><li>above 30-55000 copies/ml </li></ul><ul><li>2- All sym pts irrespective of CD4 count or plasma viral load. </li></ul>
  22. 25. <ul><li>Combination therapy </li></ul><ul><li>- 3 drugs should be used in combination to prevent drug resistance ( HAART). </li></ul><ul><li>- Initiate therapy using: a-2 NRTIs with either one PI or one NNRTIs e.g </li></ul><ul><li>Zidovudine + Lamivudine + Indinavir </li></ul><ul><li>Stavudine + Lamivudine + Nevirapine </li></ul><ul><li>b- 2 PIs + 2 NRTIs, but za following NRTIs </li></ul><ul><li>combinations should be avoided because of </li></ul><ul><li>antagonism or overlapping toxicity </li></ul><ul><li>Zidovudine + Stavudine </li></ul><ul><li>Zalcitabine + Stavudine or Didanosine </li></ul>
  23. 26. <ul><li>How long should za HIV-infected pt </li></ul><ul><li>continue taking antiretrovirals? </li></ul><ul><li>- Antiretrovirals should continue indefinitely </li></ul><ul><li>because they are only suppressive and not </li></ul><ul><li>curative </li></ul><ul><li>- The pt should be committed to lifelong therapy. </li></ul><ul><li>- The virus remain latent in za long lived resting </li></ul><ul><li>memory CD4 cells & antiretrovirals are not </li></ul><ul><li>effective against these cells which are not </li></ul><ul><li>actively multiplying. </li></ul>
  24. 27. <ul><li>Follow up of HIV +ve patients using antiretroviral therapy </li></ul><ul><li>Follow up pts regularly every 3-6/12 by monitoring: </li></ul><ul><li>- CD4 counts </li></ul><ul><li>- Viral load using HIV RNA PCR test </li></ul><ul><li>- Clinically: look for Wt gain & reduction in the No of opportunistic infections. </li></ul><ul><li>- Adherence (drug combin) </li></ul><ul><li>- Drug interactions </li></ul><ul><li>- Drug side effects - Drug access. </li></ul>
  25. 28. <ul><li>Patients counselling </li></ul><ul><li>Before initiating antiretroviral therapy discuss </li></ul><ul><li>following points wz za pts </li></ul><ul><li>- Therapy is only suppressive but za pt can lead </li></ul><ul><li>healthy productive life. </li></ul><ul><li>- Long life therapy </li></ul><ul><li>- Drugs free or at low cost </li></ul><ul><li>- Side effects & drug interactions </li></ul><ul><li>- The NO of pills taken is large, but can be reduced by combination therapy </li></ul><ul><li>- Adherence </li></ul><ul><li>- Avoid blood donation. Protected sex. </li></ul>
  26. 29. <ul><li>2- Treatment of common opportunistic infections </li></ul><ul><li>1- Tb = Anti-Tb drugs + ciprof in resist. cases </li></ul><ul><li>2- MAC = Azith + ETB +/- RIF </li></ul><ul><li>3-Oropharyngeal candidiasis= topical anti-fungal </li></ul><ul><li>4- Oesophageal or tracheal candidiasis= system </li></ul><ul><li>ketoconazole or fluconazole </li></ul><ul><li>5- Herpes simplex/Zoster= Acyclovir </li></ul><ul><li>6- CMV retinitis= Ganciclovir </li></ul><ul><li>7- Pneumocystic carinii= Co- trimoxazole </li></ul><ul><li>8- Toxoplasmosis= pyrimeth & sulfadiazine </li></ul>
  27. 30. <ul><li>9- Cryptococcal meningitis= Amph-B + flucytosin </li></ul><ul><li>OR Fluconazole + flucytosine & maintain on fluconazole </li></ul><ul><li>10- NHL= Chemotherapy </li></ul><ul><li>11- Kaposi's sarcoma= Chemotherapy depending on za extent of za dis. </li></ul><ul><li>12- Diarrhoea due to: </li></ul><ul><li>- Salmonella/ shigella= Ciprof, Co- trimoxazole </li></ul><ul><li>- Campylobacter= erythro/ Azith </li></ul><ul><li>- Clostridium difficile= metronidazole </li></ul><ul><li>- Amoeba & giardia= Metronidazole </li></ul><ul><li>- Isospora= Co- trimoxazole </li></ul>
  28. 31. <ul><li>- Stronyloides= Mebendazole </li></ul><ul><li>- CMV= Ganciclovir </li></ul><ul><li>- HSV= Acyclovir </li></ul><ul><li>- VL= SSG. </li></ul>
  29. 32. <ul><li>Pediatric HIV infection </li></ul><ul><li>- ELIZA testing is reliable only after za age of 18/12 since maternal Abs cross za placenta. </li></ul><ul><li>- HIV DNA PCR is recommended for diagn in children < 18/12 . </li></ul><ul><li>- Antiretroviral therapy is recommended in all children wz clinical symptoms or evidence of immune suppression regardless of age or viral </li></ul><ul><li>load </li></ul><ul><li>- In asym children <1 year start TR soon after diagn regardless of clinical or immune status or viral load. </li></ul>
  30. 33. <ul><li>- In asym children aged 1 year or above, start TR immediately or defer if immune status is normal wz regular follow up. </li></ul><ul><li>- triple therapy is recommended. </li></ul><ul><li>Maternal transmission of HIV </li></ul><ul><li>(Vertical transmission) </li></ul><ul><li>- It is za pry means for infants infection </li></ul><ul><li>- The risk is 7-40%. 50-70% of transmission occur in late pregnancy or during labour and delivery. </li></ul><ul><li>- Transmission occurs in utero, during labour and delivery or via breast feeding. </li></ul>
  31. 34. <ul><li>- Increased risk of maternal HIV transmission is associated with: </li></ul><ul><li>- high maternal viral load - low CD4 count </li></ul><ul><li>- advanced clinical dis - pry infection </li></ul><ul><li>- chorioamnionitis - mode of delivery - - >4 hr ruptured membr. - breast feeding </li></ul><ul><li>- Decrease risk of transmission by : </li></ul><ul><li>- Prophylactic antiretroviral therapy for mother and child to prevent maternal HIV transmission </li></ul><ul><li>- Use of formula feeding reduces risk of transmis </li></ul><ul><li>via breast milk as delivery by CS. </li></ul><ul><li>** Zidovudine & nevirapine are effective </li></ul>
  32. 35. <ul><li>Post-exposure prophylaxis for healthcare personal (PEP) </li></ul><ul><li>- Contact wz blood or bloody fluids or other potentially infectious fluids (CSF, synovial, pleural, pericardial and amniotic fluid) from HIV +ve pts is hazardous </li></ul><ul><li>- The risk of infection after percutaneous exposure is 0.3% & depends on za size & type of needle, depth & severity of exposure, volume of blood involved & viral load of pt. The risk after mucus membr exposure is 0.09% </li></ul><ul><li>- Semen, vaginal secretions & fluids wz visible blood potentially transmit HIV. </li></ul><ul><li>- PEP aborts infection by inhibiting HIV replication </li></ul>
  33. 36. <ul><li>1- Consider expanded regimen for severe percutaneous exposure. Consider basic regimen if source HIV status unknown </li></ul><ul><li>2- For large volume splash over mucosa or non intact skin or less severe percutaneous exposure recommend expanded or basic regimen if source is HIV +ve. Basic regimen if source HIV status unknown. </li></ul><ul><li>3- For small volume splash over mucosa & non intact skin consider basic regimen if source is HIV +ve. Basic regimen if source HIV status unknown. </li></ul><ul><li>4- For exposure to intact skin PFP is not needed. </li></ul>
  34. 37. <ul><li>*** Basic regimen (28 days): </li></ul><ul><li>Zidov 300 mg tid + lamiv 150 mg bid OR </li></ul><ul><li>Stavu 750 mg bid + Lamiv 150 mg bid </li></ul><ul><li>*** Expanded regimen (28 days): </li></ul><ul><li>As above + indinavir 800 mg tid OR </li></ul><ul><li>Efavirenz od at bedtime OR </li></ul><ul><li>Nelfinavir 750 mg tid. </li></ul>

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