management of aids-3[3] (vaibhav)

8/6/2019 Management of Aids-3[3] (Vaibhav)

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-VAIBHAV THAKKAR

FINAL B.D.S

ROLL NO.78

2008-2009


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Management of HIV involves both treatment of virus andprevention of opportunistic infections. The aims of HIVtreatment are to reduce the viral load to an undetectable levelfor as long as possible; improve the CD4 count (above 200 cells/mm3) ;increase the quantity and improve qualit y o f lifewithout unacceptable drug related side-effect s o r lifestyle

alteration; and reduce transmission (mother-to-child and post-exposure).


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DRUGS

1. Nucleoside Reverse Transcriptase Inhibitors(NRTIs)

Thefirstdrugtoenter clinicalpracticewasZidovudine(ZDV,AZT) in 1987 followingdemonstrationthat itsignificantlyreduced AIDS- associateddiagnosesanddeathsover 6 months.

Other drugs in this class:

Didanosine(ddI),Zalcitaline(ddc),Stavudine(d4T)and Abacavir.

Mechanism of action:NRTIsactthrough intercellularphosphorylationtotriphosphateand incorporate into DNAwheretheyfurther inhibit

lengtheningofcomplementarystrandtotheviral RNAtem late.


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Each drug competes with specific nucleoside:

ZDV and d4T with thymidine

3TC and ddC with cytidine

The inclusion of 2 NRTIs remains the cornerstone ofhighly active anti-retroviral therapy(HAART) combination

therapy.

CNS penetration is good with all NRTIs

Resistance occurs to all NRTIs:

Rapid to 3TC

Intermediate for ZDVto a lesser degree for ddI, d4T and Abacavir


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Multidrug resistance to all NRTIs is now being

recognized

Dosage of NRTIs:

i. Zidovudine(AZT) : 200mg t.d.s or 250mg b.d

ii. Lamivudine (3TC) : 150mg b.d

iii. Stavudine (d4T) : 30-40mg b.d

iv. Zalcitabine (ddC) : 0.75mg b.d

v. Didanosine(ddI) : 125-200mg b.d


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2. Protease Inhibitors (PIs)

The first PI to enter clinical practice was saquinavir (hard

gel formulation) in 1995 followed by indiavir, ritonavir,amprenavir and lopinavir.

Mechanism of Action:PIs prevent post-translational cleavage of polypeptidesinto functional viral proteins. Given with two NRTIs thecombination controls viral replication.


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PIs inhibit the p450 cytochrome system giving rise topotential for multiple drug interactions. Adequate

plasma levels are necessary for ,and predictive of,successful treatment. Monitoring the levels(therapeutic drug monitoring) and adjusting the doseaccordingly may be necessary to optimize the antiviral

effect and reduce toxicity.

Dosage ofPIs:

i. SAQUINAVIR: 600mg t.d.s

ii. RITONAVIR: 600mg b.d

iii. INDINAVIR: 800mg t.d.s


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3. Non-Nucleoside Reverse Transcriptase Inhibitors(NNRTIs)

There are 3 main NNRTIs:a. Nevirapineb. Delavirdine

c. Efavirenz

Mechanism of Action:Inhibits reverse transcriptase by binding near to theactive enzyme site.

The major disadvantage is potential for development ofcross-resistance to all current drugs in this class througha single mutational change.


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Dosage of NNRTIs:

i. Nevirapine: 200mg b.d

ii Delavirdine: 300-400mg t.d.s

4. Newer Drugs

Many drugs are presently in trial or earlier stagesof development are improvements on the currentlyavailable compounds and either have increased

potency, activity against resistant virus or easiercompliance, or are likely to reduce short and longterm complications.

E.g.:- T-20,SCH-C,AMD-3100,S-1360


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Table 1. ANTIRETROVIRAL DRUGS:

NRTIsNRTIs PIsPIs NNRTIsNNRTIs OthersOthers

1. Zidovudine(ZDV)1. Zidovudine(ZDV) SaquinavirSaquinavir NevirapineNevirapine HydroxyureaHydroxyurea

2. Lamivudine(3TC)2. Lamivudine(3TC) RitonavirRitonavir EfavirenzEfavirenz TT--2020

3. Stavudine(d4T)3. Stavudine(d4T) IndinavirIndinavir DelavirdineDelavirdine FusionFusionInhibitorsInhibitors

4. Zalcitabine(ddC)4. Zalcitabine(ddC) LopinavirLopinavir

5. Didanosine(ddI)5. Didanosine(ddI) NelfinavirNelfinavir


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Table 2. ANTI-RETROVIRAL DRUG SIDE EFFECTS:

Drug ClassDrug Class SideSide--EffectsEffects

NRTIsNRTIs

Peripheral neuropathyPeripheral neuropathy AnaemiaAnaemia

MyopathyMyopathy

CardiomyopathyCardiomyopathy

Hepatic SteatosisHepatic Steatosis Lactic AcidosisLactic Acidosis

PancreatitisPancreatitis

Extremity fat lossExtremity fat loss


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PIsPIs Fat redistributionFat redistribution

HyperlipidaemiaHyperlipidaemiaCoronary artery diseaseCoronary artery disease

Insulin resistanceInsulin resistance

HyperglycemiaHyperglycemia

NRTIsNRTIs RashRash

CNS sideCNS side--effects likeeffects likedizziness,insomnia,vivid dreamsdizziness,insomnia,vivid dreams

Stevens Johnson SyndromeStevens Johnson Syndrome

HAARTHAART Bone DemineralisationBone Demineralisation


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Treatment

The nave patient

The decision to start therapy is major one.It is dependent upon:

Symptoms status of patient

CD4 count

Viral load (VL)

Wishes of the patient


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Currently, there is no clear move to delay therapy untilthere are clinical or immunological indications to

commence and not just the basis of a high VL.

Table 3. INDICATION TO START HAART

CD4 Count (cells/mmCD4 Count (cells/mm33 )) DecisionDecision

Seroconversion > 350Seroconversion > 350 Monitor 2 monthlyMonitor 2 monthly

200200--350350 Monitor/Drugs therapyMonitor/Drugs therapybased on VLbased on VL

< 200< 200 Recommended drug therapyRecommended drug therapy

The risk of HIV-related opportunistic infection increasesand treatment is less effective when CH4 count is < 200cells/mm3 .Also, higher the VL, faster the CD4 count falls.


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A potent combination (HAART:Highly Active Antiretroviral Therapy) should always be

used.

Table 4. * COMBINATION TREATMENTS FOR THE NAVE PATIENTS

Standard ( 2NRTIs + PI / NNRTIs)

2NRTIs d4T + 3TC ZDV + 3TC

d4T + ddC ZDV + ddI

PI / NNRTIs Saquinavir Lopinavir

Indinavir Nevirapine

Ritonavir

Nelfinavir

Other Regimens

Equal Potency ZDV + 3TC + Abacavir

NNRTI + PI + NRTI

2 PI + 2NRTI

Uncertain Potency NNRTI + PI

2 NNRTI + 2 NRTI


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When starting treatment certain factors need to beconsidered.

Table 5. Factors to be Considered:

Ease of complianceFit of drug regimen around patients lifestyleWishes of the patientStages of diseasesCo-existing / past medical historyPossibility of side-effects

Potential for drug interactionCNS penetrationPossibility of acquisition of resistance virusAntagonistic NRTI combinations (ZDV / d4T and ddC /3TC)


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Despite careful and appropriate choice of HAART, thechances of a VL of < 50 copies / mm3 at 24 weeks areonly approximately 75%.

Factors that reduce the probability of achievingprolonged viral suppression are:

1.Suboptimal potency of the regimen

2. High baseline VL

3. CD4 count of < 200 / mm3

4. Poor adherence

5. Prior exposure to antiretroviral drugs

6. Resistance virus


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MEDICAL INTERVENTION FOR MANAGEMENT OFHIV:

1) Anti- retroviral therapy

2) Prophylactic therapy against Pneumocystis Cariniiand Cereberal Toxoplasmosis

3) Ancillary care , including earlier diagnosis and

better treatment of opportunistic infections.


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ENHANCING THE IMMUNE SYSTEM

In the knowledge that HAART alone will not cure thepatient of HIV, focus has now turned towards possibilityof bolstering immune system with the hope thatvirological control without drugs may be achievable. Thiscan be achieved by:

o STI: Structured Therapeutic Interruption

o Direct anti-HIV cytotoxic T-cell stimulation through

immunisation with viral proteins.

Whether either approach will prove to be beneficial inlong term is unknown.


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IMPACT OF HIV AND AIDS

Epidemiologists anticipated that AIDS would decimate

the workforce population in dentistry.

Public alarm was intense when a Florida dentist withclinical AIDS transmitted his unique strain of HIV to 6patients in his large dental practice. This could havebeen prevented by conscientious use of infectioncontrol procedures.

OSHA(Occupational Safety and Health Administration)regulations have provided an intense impetus tostrengthen and control aseptic standards in all healthcare disciplines.


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Infection control is now accepted as a standard of careby dentists

Infection control programmes,such as those by CDC (

Centres for Diseases Control and Prevention) and ADAare designed to protect patients and personnel

Exposure is defined in the OSHA regulations as:-specificeye,mouth,other mucous membrane, on-intact skin, orparental contact with blood or OPIM (Other PotentiallyInfectious Materials) that results from performance of anemployees duties.


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Only in dentistry is saliva considered a potentiallyinfectious material because oral manipulations and dentaltreatments routinely cause saliva to become

contaminated with patients blood .In dental practice, allpatients must be treated with standard precautions toreduce the risk of disease transmission.

Dentists should obtain and read a copy of the FinalOSHA Rule on Blood borne Pathogens.


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HIV RISKS FOR CLINICAL PERSONNEL

Testing for evidence of prior HIV infection at time ofexposure was not commonly performed in dentistry until1990s.

HIV infection has developed in a nurse and a technician

spattered with HIV- infected blood. Other medicalpersonnel have acquired HIV infections related to spatterof infected blood to their non-intact skin.

Personal are required to protect eyes,mucosa,skin andhands from spatter and direct contact with blood andblood contamination body fluids during treatment of allpatients.


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Precaution also must be made to minimize risks ofinjuries with sharp instructions.

HIV is killed by all methods of sterilization. When used

properly all disinfectants (except some quaternaryammonium compounds) are said to inactivate HIV in lessthan 2 mins.


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EXPOSURE ASSESSMENT PROTOCOL

Dental students are required to follow some exposureincident protocol plan as dental employees, in case of anaccidental exposure.

If possible, patients potential to transmit and the

students susceptability is determined.

The attending physician who helps with thesedeterminations provides anti-HIV testing and counseling.


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HIV INFECTION CONTROL

It can be described under 3 headings:

1. Universal Precautions2. Measures at time of Surgery3. Measures for Health Care Workers (HCWs)

1.Universal Precautions

Infection control strategies reduce the risk oftransmission of infectious diseases.

All infected patients cannot be identified on the basis ofmedical history, examination and lab investigations,hence,philosophy is to consider all patients infected andfollow certain basic infection control procedures referred

to as universal precautions.


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Universal precautions for dental team entail:

i) Employment of various personal protectivebarrier techniques such as:-

Gowns Face masks Protective eyewear Gloves Handwashing and care of hands Clinical attire Head caps No refreshments in clinical areas Protective over-garments


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ii) Disposal of clinical waste

iii) Needle disposal

iv) Precautions to avoid Injury Exposure

v) Contaminated items to be discarded;protected by disposable covers; or removed,cleaned and sterilized.


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2. Measures at Time of Surgery

A protocol to be followed in OT. Special precautions: when dealing with HIV positive or

high risk patients, special precautions are to be taken:-

i) In operation theaterii) For personneliii) Surgery techniques ( no touch technique)iv) At end of surgeryv) OT waste disposal

vi) Reusable instruments to be autoclaved and washedvii) Non-Autoclavable to be disinfected in 2 %

Glutraldehyde solutionviii) Laboratory specimensix)Equipments and surfaces


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3. Measures for Health Care Workers(HCWs)

Transmission of HIV infection from patient to HCW hasbeen reported.

The risk of acquiring HIV three needle stick injury isapprox.0.4% and three exposure of mucous membrane is0.04%

Needle Stick Injury is the most common cause of

contracting HIV infection in HCWs.

The risk of acquiring HIV infection can be negligible ,ifthe HCWs observe adequate safety measures andobserve universal safety precaution mentioned above.


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*NEEDLE STICK INJURY

Measures forPreventions:

1.Ensuring needles and surgical blades are sheathed /covered, when not in use

2.Keeping full control of sharp instruments and retain fullconcentration while handling it.

3.Keeping gloved fingers behind the edge of blades or

points of needles.

4.Adequate retraction of tissues


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5.Placing needles in sharp safe box

6.Taking care when clearing away surgical sharps

7.Over-gloving or using double gloves,wheneverindicated.

*POST ACCIDENTAL MANAGEMENT

Measures to be taken are:

a) Remove gloves

b) Wash the site of injury under running water withsoap and water

c) Avoid scrubbing and encourage bleeding and then

protect


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d) It is controversial whether or not to apply antisepticprecautions

e) Inform the patient about incident

f) Usually,it is necessary to take blood samples of both

patient and the injured person and tested for HIV.


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In case, patient is seropositive, has AIDS, or refusesthe tests, the HCWs should be :

i. Counseled about risk of infection and evaluated

clinically and serologically as soon as possible.

ii. A baseline HIV test should be carried.

iii.Adviced to report for any febrile illness that mayoccur within 12 weeks of exposure.


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iv. HIV test should then should be repeated approx. 6 to12 weeks after exposure

v. Advice to follow the steps to prevent transmission ofHIV.

vi. Advice regarding domestic relationships andprocedures at workplace


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Table. 6 HIV,PEP for HCWs

TypeType DrugsDrugs RegimenRegimen

Basic (28 days)Basic (28 days) ZidovudineZidovudine ++LamivudineLamivudine

600mg/ day +600mg/ day +150mg/ day150mg/ day

ExpandedExpanded(28 days)(28 days)

As above +As above +

IndinavirIndinavir

oror

NelfinavirNelfinaviroror

NevirapineNevirapine

800mg800mg--8 hourly,8 hourly,

750mg750mg t.d.st.d.s,,

200mg200mg b.db.d..


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The first dose should be given as soon as possible.However, protection is not absolute and healthcare

workers have been reported to seroconvert despite takinga full course of three drugs started within hours ofexposure.

PEP is also being used for non-occupational settings

such as condom breakage in HIV serodiscordant partners,victims of rape, relapses in injecting drug users, andsharps-related home exposures in families of HIVpatients.

As for occupation PEP, a careful risk assessment bemade. Benefits will be greatest in those presenting early,where the risk of transmission is high and whereadherence is likely.


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References

1) Textbook of ORAL MEDICINE Anil GovindraoGhom.

2) Davidsons Principles & Practice ofMedicine

3) Barlett J.G Medical Management of HIV infection www.hopkins-aids.edu

4) Medicine for Students ASPI . F . GOLWALLA

5) Textbook of Oral &Maxillofacial Surgery NeelimaAnil Malik.

6) Sturdevants Art & Science of Operative Dentistry.


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