HIV- AIDSHIV- AIDSBy Dr. Osman SadigBy Dr. Osman Sadig

EpidemiologyEpidemiology - HIV, za cause of AIDS is now za 4- HIV, za cause of AIDS is now za 4thth

commonest cause of death world-wide.commonest cause of death world-wide.

- In 2000, 34.5 million were infected wz - In 2000, 34.5 million were infected wz HIV, of whom 24.5 in Sub-Saharan AfricaHIV, of whom 24.5 in Sub-Saharan Africa

- - The human & economic costs are highThe human & economic costs are high because because of high mortality & fall in life expectancy.of high mortality & fall in life expectancy.

- Despite that HIV can be isolated from a wide- Despite that HIV can be isolated from a wide range of body fluids & tissue, the majority ofrange of body fluids & tissue, the majority of infections are infections are transmitted via semen, cervicaltransmitted via semen, cervical secretions & blood.secretions & blood. 1- 1- Sexual transmissionSexual transmission ( vaginal & anal): ( vaginal & anal): Commonest route & Commonest route & coexistent STDscoexistent STDs, sp, sp those causing genital ulceration, enhancethose causing genital ulceration, enhance transmission. Transmission is transmission. Transmission is more efficientmore efficient from from men to womenmen to women & to za & to za passive partnerpassive partner in anal intercourse.in anal intercourse.

2- 2- Mother to Child Mother to Child (vertical): Commonest route (vertical): Commonest route in children. Transmission occur during pregnancy,in children. Transmission occur during pregnancy,

during delivery or after delivery through breast during delivery or after delivery through breast feeding. feeding. Most infections occur perinatally. Most infections occur perinatally. Advanced dis. & high viral load in the mother, Advanced dis. & high viral load in the mother, prolonged & premature rupture of membranes & prolonged & premature rupture of membranes & chorioamnionitis increase za risk of transmission.chorioamnionitis increase za risk of transmission.

Interventions to reduce transmissionInterventions to reduce transmission include use include use antiretroviral agents, delivery by CS and antiretroviral agents, delivery by CS and avoidance of breast feeding.avoidance of breast feeding.

3- 3- Contaminated blood, blood products & Contaminated blood, blood products & organorgan

donations if not screened.donations if not screened.

4- 4- Contaminated needles & instrumentsContaminated needles & instruments. The . The risk risk

of acquiring HIV following a single needle-stick of acquiring HIV following a single needle-stick injury contaminated wz HIV is 0.3%.injury contaminated wz HIV is 0.3%.

*** No evidence of HIV transmission by social *** No evidence of HIV transmission by social or household contact or by blood sucking or household contact or by blood sucking insects.insects.

The virusThe virus - HIV belongs to - HIV belongs to retroviral familyretroviral family..

- 2 types: - 2 types: HIV-1 & HIV-2HIV-1 & HIV-2 ( West Africa. ? India). ( West Africa. ? India).

HIV-2 is more indolent in nature.HIV-2 is more indolent in nature.

- - RNA virusRNA virus & needs a living cell to multiply. & needs a living cell to multiply.

-The target cells for HIV are -The target cells for HIV are CD4 T-CD4 T-lymphocyteslymphocytes

1- HIV binds to za host CD4 via za envelope 1- HIV binds to za host CD4 via za envelope glycoprotein (glycoprotein (gp120gp120))

2- 2- Reverse transcriptaseReverse transcriptase converts viral RNA converts viral RNA to ssDNA and to ssDNA and host cell polymerasehost cell polymerase leads to leads to formation of dsDNA which enters za nucleus formation of dsDNA which enters za nucleus of CD4 & inserted into its genome viaof CD4 & inserted into its genome via integraseintegrase..

3- With za help of za 3- With za help of za proteaseprotease enzyme new enzyme new viral particles are assembled in za cytoplasm viral particles are assembled in za cytoplasm and are budded out of za cell ready to infect and are budded out of za cell ready to infect other CD4 cells.other CD4 cells.

- Virus production lasts 2 days & is limited by - Virus production lasts 2 days & is limited by the death of za cell due to direct effect of za the death of za cell due to direct effect of za virus. The half life of za virus is only 6 hrs, virus. The half life of za virus is only 6 hrs, but its but its

turnover is very high (10 to za power 9 turnover is very high (10 to za power 9 each day) each day) - -ImmunosuppressionImmunosuppression is due to is due to progressive and severe depletion of CD4 progressive and severe depletion of CD4 T-lymphocytes causing both CM & T-lymphocytes causing both CM & humoral immune def.humoral immune def.

- - HIV also has a direct effectHIV also has a direct effect on za on za nervousnervous tissue, tissue, lymphoid tissuelymphoid tissue & & testes.testes.

Diagnosis of HIV infectionDiagnosis of HIV infection 1- 1- Detection of virus specific Abs:Detection of virus specific Abs:

a/ a/ Abs to gp 120Abs to gp 120: - detects Abs against : - detects Abs against envelop glycoprotein gp 120envelop glycoprotein gp 120

- Routine test for - Routine test for screeningscreening & based on & based on ELIZAELIZA..

- - Window periodWindow period or serological latency is 3/12 or serological latency is 3/12

- - Abs have no protective fnAbs have no protective fn & persist for life. & persist for life.

- - Abs cross za placentaAbs cross za placenta & not reliable indicator & not reliable indicator of active infection in of active infection in za baby & in uninfected babies will be za baby & in uninfected babies will be gradually lost over za 1gradually lost over za 1stst 18/12 of life 18/12 of life

- b/ - b/ Abs to p24Abs to p24 ( core protein): detected early ( core protein): detected early

in infection & lost as dis progresses.in infection & lost as dis progresses.

2- 2- Ag assays byAg assays by: : a/ a/ HIV DNA PCR assayHIV DNA PCR assay: used in diagn of : used in diagn of HIV in babies borne to infected mothers & in theHIV in babies borne to infected mothers & in the

window periodwindow period

b/ b/ HIV RNA PCR assayHIV RNA PCR assay: superseded za above : superseded za above test.test.

It measures za amount of HIV RNA in za bloodIt measures za amount of HIV RNA in za blood

( ( viral loadviral load). Higher viral load is predictive of). Higher viral load is predictive of

faster dis progression. This test is also used tofaster dis progression. This test is also used to

assess za assess za response to anti-viral therapyresponse to anti-viral therapy..

The viral load can also be measured by The viral load can also be measured by c/branched DNA tehnequec/branched DNA tehneque. .

3- 3- Western blotWestern blot: :

- - confirmatory testconfirmatory test

- - detects Abs against Ag coded by 3 diff detects Abs against Ag coded by 3 diff viralviral

genes.genes.

4- 4- Isolation of virus in cultureIsolation of virus in culture for for research.research.

*** *** NACO NACO guidelines for diagnguidelines for diagn HIV infectionHIV infection is is based on 3 diff ELIZA/rapid tests using 3 diff based on 3 diff ELIZA/rapid tests using 3 diff Ags. Ags. AIDSAIDS is diagn by using 2 diff ELIZA/rapid is diagn by using 2 diff ELIZA/rapid

tests on diff Ags in za presence of AIDS-tests on diff Ags in za presence of AIDS-relatedrelated

opportunistic infections. opportunistic infections.

Clinical features of HIV Clinical features of HIV infectioninfection

- It is za result of both - It is za result of both direct HIV infectiondirect HIV infection and and associated immune dysfnassociated immune dysfn..

- AIDS is defined as individuals wz - AIDS is defined as individuals wz CD4 < CD4 < 200200 with with AIDS defining conditionsAIDS defining conditions in in USAUSA while in while in EuropeEurope it is defined without CD4 it is defined without CD4 level. Both need level. Both need positive HIV testpositive HIV test..

- - IPIP is 2-4Ws immediately following infection is 2-4Ws immediately following infection and is both clinically & serologically silent.and is both clinically & serologically silent.

1- Primary HIV infection/ seroconversion1- Primary HIV infection/ seroconversion 2- Asymptomatic infection/clinical latency 2- Asymptomatic infection/clinical latency 3- Symptomatic infection (ARC)3- Symptomatic infection (ARC) 4- AIDS4- AIDS

Acute pry Acute pry

infectioninfection

CD4>500/CD4>500/microlitmicrolit..Asymp Asymp infectioninfection

CD4 200-CD4 200->500>500Symp Symp infectioninfection

(ARC)(ARC)

CD4 200-500CD4 200-500

AIDSAIDS

CD4 <200CD4 <200

Acute Acute seroconversionseroconversion

Illness in some pts.Illness in some pts.

PGL in some pts.PGL in some pts.

Oro/vulvovaginal candidiasis, ITP, P. Oro/vulvovaginal candidiasis, ITP, P. neurneur

Hairy leukopl, constitutional symp Hairy leukopl, constitutional symp (fever,(fever,

Diah > 1/12, mucocutaneous Diah > 1/12, mucocutaneous manifestationmanifestationConstitutional symp ( Wt loss> 10%, Constitutional symp ( Wt loss> 10%, Diah >1/12), neurological dis Diah >1/12), neurological dis (dementia, myelopathy, P, (dementia, myelopathy, P, neuropath), Kaposi's, NHL and neuropath), Kaposi's, NHL and Opportunistic infections .Opportunistic infections .

****Seroconversion illnessSeroconversion illness is a self-limiting non-sp is a self-limiting non-sp

illness occurring illness occurring 6-8Ws after exposure6-8Ws after exposure (sore throat, (sore throat, fever, arthralgia, myalgia, lethargy, LN,fever, arthralgia, myalgia, lethargy, LN,

mucosal ulcers, +/- MP rash, HA, photophobia,mucosal ulcers, +/- MP rash, HA, photophobia,

myelopathy, neuropathy & rarely encephalopat)myelopathy, neuropathy & rarely encephalopat)

It It lasts up to 3Wslasts up to 3Ws & & recovery is usually completrecovery is usually complet..

There is cytopenia, CD4 lym depleted, raised liver There is cytopenia, CD4 lym depleted, raised liver enzymes, Abs absent early, high viral RNAenzymes, Abs absent early, high viral RNA

levels. levels. Pts experiencing seroconversion Pts experiencing seroconversion illness may have a illness may have a more rapidly progressive more rapidly progressive course of infection.course of infection.

** ** Asymp stageAsymp stage have a median time of 10 years have a median time of 10 years

( period from infections to AIDS). Older age ( period from infections to AIDS). Older age and those experiencing seroconversion have and those experiencing seroconversion have

a rapid progression.a rapid progression.

** ** AIDS defining conditionsAIDS defining conditions:-:-

1- Tracheal, bronchial or lung candidiasis1- Tracheal, bronchial or lung candidiasis

2- Oesophageal candidiasis2- Oesophageal candidiasis

3- Invasive cervical Ca.3- Invasive cervical Ca.

4- Coccidioidomycosis, disseminated or 4- Coccidioidomycosis, disseminated or extrapulmonaryextrapulmonary

5- Extrapulmonary cryptococcosis, e.g 5- Extrapulmonary cryptococcosis, e.g meningitismeningitis

6- Cryptosoridiosis, chr intestinal (> 1/12)6- Cryptosoridiosis, chr intestinal (> 1/12)

7- CMV dis other than liver, spleen or LN.7- CMV dis other than liver, spleen or LN. 8- CMV retinitis (wz loss of vision)8- CMV retinitis (wz loss of vision) 9- Encephalopathy, HIV related9- Encephalopathy, HIV related 10- Herpes simplex, chr ulcers (>1/12), or 10- Herpes simplex, chr ulcers (>1/12), or

bronchitis, pneumonitis or oessophagitis.bronchitis, pneumonitis or oessophagitis. 11- Hitsplasmosis, disseminated or 11- Hitsplasmosis, disseminated or

extrapulmonextrapulmon 12- Isosporiasis, chr intestinal (>1/12)12- Isosporiasis, chr intestinal (>1/12) 13- Kaposi's sarcoma13- Kaposi's sarcoma 14- Lymphoma, NHL or Burkett's14- Lymphoma, NHL or Burkett's 15- Pry lymphoma of za brain15- Pry lymphoma of za brain 16- Mycobact Tb, any site16- Mycobact Tb, any site 17- Mycobact avium complex or kansasi, 17- Mycobact avium complex or kansasi,

dissemdissem or extrapulmor extrapulm

18- Pneumocystic carinii pneumonia18- Pneumocystic carinii pneumonia

19- Recurrent pneumonia19- Recurrent pneumonia

20- Progressive multifocal leucoencephalopathy20- Progressive multifocal leucoencephalopathy

21- Salmonella septicemia, recurrent21- Salmonella septicemia, recurrent

22- Toxoplasmosis of za brain 22- Toxoplasmosis of za brain

23- Wasting syndrome, due to HIV23- Wasting syndrome, due to HIV

*** *** Clinical case definition for AIDSClinical case definition for AIDS::

An individual wz An individual wz +ve test for HIV infection+ve test for HIV infection

by 2 tests based on 2 diff Ags by 2 tests based on 2 diff Ags PLUSPLUS any any

AIDS defining conditionAIDS defining condition

*** *** Common opportunistic infectionsCommon opportunistic infections::

- Tb, both M. Tb & atypical mycobact.- Tb, both M. Tb & atypical mycobact.

- candidiasis- candidiasis

- Herpes zoster- Herpes zoster

- Diarrhoeal:- Diarrhoeal:

- protozoal: amoeba, giardia, isospora, - protozoal: amoeba, giardia, isospora,

cryptosporidium..cryptosporidium..

- Helmiths: strongyloidosis- Helmiths: strongyloidosis

- Viral: CMV- Viral: CMV

- Toxoplasmosis- Toxoplasmosis

- Cryptococcal meningitis- Cryptococcal meningitis

- CMV retinitis- CMV retinitis

- VL ?- VL ?

Management of HIV positive Management of HIV positive patientpatient

Treatment approach involvesTreatment approach involves:: - Inhibiting viral replication & decrease viral - Inhibiting viral replication & decrease viral

load by antiretroviral drugs.load by antiretroviral drugs.

- Treatment & prophylaxis of opportunistic - Treatment & prophylaxis of opportunistic infectionsinfections

- Psychological support.- Psychological support.

1- 1- Antiretroviral therapyAntiretroviral therapy:: - Inhibit viral replication & decrease viral - Inhibit viral replication & decrease viral

load.load.

- Preserve immune fn by increasing CD4 - Preserve immune fn by increasing CD4 count.count.

- Prevent dis progression- Prevent dis progression

- Decrease za incidence of opportunistic - Decrease za incidence of opportunistic infections.infections.

- Reduce dis progression- Reduce dis progression

- Prolong survival & improve quality of life.- Prolong survival & improve quality of life.

- Possibly reduces za risk of transmission- Possibly reduces za risk of transmission

** ** The goal of antiretroviral therapy is to The goal of antiretroviral therapy is to bring down za bring down za viral load to <50viral load to <50 by by triple drug therapy over Ws & Ms.triple drug therapy over Ws & Ms.

Classes of antiretroviralsClasses of antiretrovirals Antiretrovirals target two key enzymes, Antiretrovirals target two key enzymes,

proteaseprotease

and reverse transcriptase:and reverse transcriptase:

1- 1- Reverse transcriptase inhibitorsReverse transcriptase inhibitors

a/ nucleoside reverse transcriptase a/ nucleoside reverse transcriptase

inhibitors (NRTs)inhibitors (NRTs)

b/ non-nucleoside reverse transcriptaseb/ non-nucleoside reverse transcriptase

inhibitors (NNRTs) inhibitors (NNRTs) 2- 2- Protease inhibitorsProtease inhibitors (PIs) (PIs)

NRTIsNRTIs NNRTIs PIsNNRTIs PIs Zidovudine Nevirapine IndinavirZidovudine Nevirapine Indinavir Stavudine Efavirenz NelfenavirStavudine Efavirenz Nelfenavir Lamivudine Delavirdine RitonavirLamivudine Delavirdine Ritonavir Didanosine SaquinavirDidanosine Saquinavir Zalcitabine AmprenavirZalcitabine Amprenavir Abacavir LopinavirAbacavir Lopinavir

When to initiate antiretrovirals?When to initiate antiretrovirals? 1- 1- Asym ptsAsym pts= CD4 goes below 350 or HIV = CD4 goes below 350 or HIV

RNARNA above 30-55000 copies/mlabove 30-55000 copies/ml 2- 2- All sym ptsAll sym pts irrespective of CD4 count or irrespective of CD4 count or

plasma viral load.plasma viral load.

Combination therapyCombination therapy - 3 drugs should be used in combination to - 3 drugs should be used in combination to

prevent drug resistance ( HAART).prevent drug resistance ( HAART). - Initiate therapy using: - Initiate therapy using:

a-2 NRTIs with either one PI or one NNRTIs a-2 NRTIs with either one PI or one NNRTIs e.ge.g

Zidovudine + Lamivudine + IndinavirZidovudine + Lamivudine + Indinavir Stavudine + Lamivudine + NevirapineStavudine + Lamivudine + Nevirapine b- 2 PIs + 2 NRTIs, but za following NRTIsb- 2 PIs + 2 NRTIs, but za following NRTIs combinations should be avoided because combinations should be avoided because

of of antagonism or overlapping toxicityantagonism or overlapping toxicity Zidovudine + StavudineZidovudine + Stavudine Zalcitabine + Stavudine or Didanosine Zalcitabine + Stavudine or Didanosine

How long should za HIV-infected ptHow long should za HIV-infected pt

continue taking antiretrovirals?continue taking antiretrovirals? - Antiretrovirals should continue - Antiretrovirals should continue indefinitelyindefinitely

because they are only because they are only suppressive and notsuppressive and not

curativecurative

- The pt should be committed to - The pt should be committed to lifelong lifelong therapy. therapy.

- The virus remain latent in za long lived - The virus remain latent in za long lived restingresting

memory CD4 cells & antiretrovirals are not memory CD4 cells & antiretrovirals are not

effective against these cells which are noteffective against these cells which are not

actively multiplying. actively multiplying.

Follow up of HIV +ve patients Follow up of HIV +ve patients using antiretroviral therapyusing antiretroviral therapy

Follow up pts regularly every 3-6/12 by Follow up pts regularly every 3-6/12 by monitoring:monitoring:

- CD4 counts - CD4 counts

- Viral load using HIV RNA PCR test- Viral load using HIV RNA PCR test

- Clinically: look for Wt gain & reduction in - Clinically: look for Wt gain & reduction in the No of opportunistic infections.the No of opportunistic infections.

- Adherence (drug combin) - Adherence (drug combin)

- Drug interactions- Drug interactions

- Drug side effects - Drug side effects - Drug access. - Drug access.

Patients counsellingPatients counselling Before initiating antiretroviral therapy Before initiating antiretroviral therapy

discussdiscuss following points wz za ptsfollowing points wz za pts - Therapy is only suppressive but za pt can - Therapy is only suppressive but za pt can

leadlead healthy productive life.healthy productive life. - Long life therapy - Long life therapy - Drugs free or at low cost- Drugs free or at low cost - Side effects & drug interactions- Side effects & drug interactions - The NO of pills taken is large, but can be - The NO of pills taken is large, but can be

reduced by combination therapyreduced by combination therapy - Adherence- Adherence - Avoid blood donation. Protected sex. - Avoid blood donation. Protected sex.

2- 2- Treatment of common Treatment of common opportunistic infectionsopportunistic infections

1- Tb = Anti-Tb drugs + ciprof in resist. cases1- Tb = Anti-Tb drugs + ciprof in resist. cases

2- MAC = Azith + ETB +/- RIF2- MAC = Azith + ETB +/- RIF

3-Oropharyngeal candidiasis= topical anti-3-Oropharyngeal candidiasis= topical anti-fungalfungal

4- Oesophageal or tracheal candidiasis= 4- Oesophageal or tracheal candidiasis= systemsystem

ketoconazole or fluconazoleketoconazole or fluconazole

5- Herpes simplex/Zoster= Acyclovir5- Herpes simplex/Zoster= Acyclovir

6- CMV retinitis= Ganciclovir6- CMV retinitis= Ganciclovir

7- Pneumocystic carinii= Co- trimoxazole7- Pneumocystic carinii= Co- trimoxazole

8- Toxoplasmosis= pyrimeth & sulfadiazine8- Toxoplasmosis= pyrimeth & sulfadiazine

9- Cryptococcal meningitis= Amph-B + 9- Cryptococcal meningitis= Amph-B + flucytosinflucytosin

OR Fluconazole + flucytosine & maintain on OR Fluconazole + flucytosine & maintain on fluconazolefluconazole

10- NHL= Chemotherapy10- NHL= Chemotherapy

11- Kaposi's sarcoma= Chemotherapy 11- Kaposi's sarcoma= Chemotherapy depending on za extent of za dis.depending on za extent of za dis.

12- Diarrhoea due to:12- Diarrhoea due to:

- Salmonella/ shigella= Ciprof, Co- - Salmonella/ shigella= Ciprof, Co- trimoxazoletrimoxazole

- Campylobacter= erythro/ Azith- Campylobacter= erythro/ Azith

- Clostridium difficile= metronidazole- Clostridium difficile= metronidazole

- Amoeba & giardia= Metronidazole- Amoeba & giardia= Metronidazole

- Isospora= Co- trimoxazole- Isospora= Co- trimoxazole

- Stronyloides= Mebendazole- Stronyloides= Mebendazole

- CMV= Ganciclovir- CMV= Ganciclovir

- HSV= Acyclovir- HSV= Acyclovir

- VL= SSG.- VL= SSG.

Pediatric HIV infectionPediatric HIV infection - ELIZA testing is reliable only after za age of - ELIZA testing is reliable only after za age of

18/12 since maternal Abs cross za placenta.18/12 since maternal Abs cross za placenta.

- - HIV DNA PCR is recommended for diagn in HIV DNA PCR is recommended for diagn in children < 18/12children < 18/12..

- Antiretroviral therapy is recommended in all - Antiretroviral therapy is recommended in all children wz clinical symptoms or evidence of children wz clinical symptoms or evidence of immune suppression regardless of age or immune suppression regardless of age or viralviral

loadload

- In asym children <1 year start TR soon after - In asym children <1 year start TR soon after diagn regardless of clinical or immune status diagn regardless of clinical or immune status or viral load.or viral load.

- In asym children aged 1 year or above, - In asym children aged 1 year or above, start TR immediately or defer if immune start TR immediately or defer if immune status is normal wz regular follow up.status is normal wz regular follow up.

- triple therapy is recommended.- triple therapy is recommended.

Maternal transmission of HIV Maternal transmission of HIV (Vertical transmission)(Vertical transmission) - It is za - It is za pry means for infants infectionpry means for infants infection - The risk is 7-40%. 50-70% of - The risk is 7-40%. 50-70% of

transmission occur in transmission occur in late pregnancy or late pregnancy or during labour and delivery.during labour and delivery.

- Transmission occurs - Transmission occurs in utero, during in utero, during labour and delivery or via breast feeding.labour and delivery or via breast feeding.

- - Increased risk of maternal HIV transmissionIncreased risk of maternal HIV transmission is is associated with:associated with:

- high maternal viral load - low CD4 count- high maternal viral load - low CD4 count

- advanced clinical dis - pry infection- advanced clinical dis - pry infection

- chorioamnionitis - mode of delivery - chorioamnionitis - mode of delivery - - >4 hr ruptured membr. - breast - - >4 hr ruptured membr. - breast feedingfeeding

- - Decrease risk of transmission byDecrease risk of transmission by::

- Prophylactic antiretroviral therapy for mother - Prophylactic antiretroviral therapy for mother and child to prevent maternal HIV transmissionand child to prevent maternal HIV transmission

- Use of formula feeding reduces risk of transmis- Use of formula feeding reduces risk of transmis

via breast milk as delivery by CS.via breast milk as delivery by CS.

** ** Zidovudine & nevirapine are effectiveZidovudine & nevirapine are effective

Post-exposure prophylaxis for Post-exposure prophylaxis for healthcare personal (PEP)healthcare personal (PEP)

- Contact wz blood or bloody fluids or other - Contact wz blood or bloody fluids or other potentially infectious fluids (CSF, synovial, potentially infectious fluids (CSF, synovial, pleural, pericardial and amniotic fluid) from HIV pleural, pericardial and amniotic fluid) from HIV +ve pts is hazardous+ve pts is hazardous

- The risk of infection after percutaneous - The risk of infection after percutaneous exposure is 0.3% & depends on za size & type exposure is 0.3% & depends on za size & type of needle, depth & severity of exposure, volume of needle, depth & severity of exposure, volume of blood involved & viral load of pt. The risk of blood involved & viral load of pt. The risk after mucus membr exposure is 0.09%after mucus membr exposure is 0.09%

- Semen, vaginal secretions & fluids wz visible - Semen, vaginal secretions & fluids wz visible blood potentially transmit HIV.blood potentially transmit HIV.

- - PEP aborts infection by inhibiting HIV replicationPEP aborts infection by inhibiting HIV replication

1- Consider expanded regimen for severe 1- Consider expanded regimen for severe percutaneous exposure. Consider basic percutaneous exposure. Consider basic regimen if source HIV status unknownregimen if source HIV status unknown

2- For large volume splash over mucosa or 2- For large volume splash over mucosa or non intact skin or less severe percutaneous non intact skin or less severe percutaneous exposure recommend expanded or basic exposure recommend expanded or basic regimen if source is HIV +ve. Basic regimen regimen if source is HIV +ve. Basic regimen if source HIV status unknown.if source HIV status unknown.

3- For small volume splash over mucosa & 3- For small volume splash over mucosa & non intact skin consider basic regimen if non intact skin consider basic regimen if source is HIV +ve. Basic regimen if source source is HIV +ve. Basic regimen if source HIV status unknown.HIV status unknown.

4- For exposure to intact skin PFP is not 4- For exposure to intact skin PFP is not needed.needed.

*** Basic regimen (28 days):*** Basic regimen (28 days):

Zidov 300 mg tid + lamiv 150 mg bid Zidov 300 mg tid + lamiv 150 mg bid OROR

Stavu 750 mg bid + Lamiv 150 mg bidStavu 750 mg bid + Lamiv 150 mg bid

*** Expanded regimen (28 days):*** Expanded regimen (28 days):

As above + indinavir 800 mg tid ORAs above + indinavir 800 mg tid OR

Efavirenz od at bedtime OREfavirenz od at bedtime OR

Nelfinavir 750 mg tid.Nelfinavir 750 mg tid.