OPPORTUNISTIC INFECTIONS

1
OPPORTUNISTIC INFECTIONS IN HIV/AIDS
PATIENTS ITS MANAGEMENT.

Dr.K.SREEKANTHAN,
ASSOCIATE PROFESSOR HEAD DPT.OF
INFECTOUS DISEASES
2
HISTORY

• ACQUIRED IMMUNODEFICIENCY SYNDROM (AIDS)
•     FIRST DESCRIBED IN 5 YOUNG HOMOSEXUAL MEN IN
  U.S.A.IN I981.
•   PNEUMOCYSTIS CARINII PNEUMONIA KAPOSI'S
  SARCOMA WERE DETECTED.
•   THE DISEASE IS CHARACTERIZED BY DEPLETION OF
  THE IMMUNE CELLS.
• CD4 LYMPHOCYTES,THE BANDMASTER OF IMMUNE
  SYSTEM.

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• THE CAUSATIVE AGENT WAS IDENTIFIED IN 1983-84 IN
  FRANCE AND USA.
• FIRST CALLED AS HTLV-III BY ROBERT HALLOW OF
  USA.
• THE VIRUS SUBSEQUENTLY NAMED AS HUMAN
  IMMUNODEFICIENCY VIRUS(HIV)
• IN 1985,THE DIAGNOSTIC KITS BASED ON DETECTION
  OF ANTIBODIES AGAINST HIV WAS DISCOVERED.

4

• THE FIRST DRUG ZIDOVUDINE AFFECTING THE VIRUS WAS
  DISCOVERED IN 1987.
• IN INDIA ,THE DISEASE WAS DETECTED IN 1986.
• THE LATEST ESTIMATE DECEMBER 2003. 40 MILLION
  PEOPLE LIVING WITH IV/AIDS. 95 OF THEM IN
  DEVELOPING COUNTRIES.
• ABOUT 14,000 NEW INFECTIONS OCCUR DAILY.

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COMMON OI'S IN AIDS PATIENTS

• TUBERCULOSIS BOTH PULMONARY AND EXTRA PULMONARY.
• OROPHARYNGEAL CANDIDIASIS
• HERPES ZOSTER.
• TOXOPLASMOSIS.
• CRYPTOCOCCAL MENINGITIS
• PNEUMOCYSTIS CARINII PNEUMONIA.
• CYTOMEGALOVIRUS RETINITIS.
• CRYPTOSPORIDIAL DIARRHOEA

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THE COURSE OF INFECTION

• MAY VARY-SOME INDEVIDUALS DEVELOPING
  IMMUNODEFICIENCY WITHIN 2 TO 3 YEARS.
• OTHERS REMAINING AIDS FREE FOR 10-15 YEARS.
• THE MANIFESTATIONS OF INFECTIONS IN HIV/AIDS
  PATIENTS DEPEND ON THE LEVEL OF IMMUNITY.
• THIS IS REFLECTED BY THE CD4 T CELL COUNT.
• MAJORITY OF INFECTIONS OCCUR WHEN THE CD4 COUNT
  FALLS BELOW 500 CELLS/ MM3.

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EARLY DISEASE.(CD4 COUNT gt500 CELLS/CMM)

• MAJORITY GENERALLY NO SYMPTOMS.
• SEBORRHIC DERMATITIS
• PRURITIC FOLLICULITIS
• RARELY HSV,VZV, EBV INFECTIONS.

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MIDDLE STAGE DISEASE ( CD4 COUNT 200-500 CELLS/
CMM)

• MAJORITY ASYMPTOMATIC OR ONLY MILD DISEASE
  MANIFESTATIONS.
• SEBORRHIC DERMATITIS
• FOLLICULITIS.
• RECURRENT HERPES SIMPLEX INFECTIONS
• ORAL HAIRY LEUKOPLAKIA.
• SHINGLES.

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• OROPHARYNGEAL OR VAGINAL CANDIDIASIS.
• BACTERIAL INFECTIONS LIKE SINUSITIS,BRONCHITIS,
  OR PNEUMONIA
• TUBERCULOSIS
• SALMONELLOSIS.
• RARELY PCP.

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LATE DISEASE ( CD4 COUNT 50-200 CELLS/CMM)

• ALL PATIENTS IN THIS GROUP ARE
• DEFINED AS HAVING AIDS.
• PATIENTS ARE AT HIGH RISK OF DEVELOPING
• TUBERCULOSIS.
• PCP.
• TOXOPLASMA GONDI ENCEPHALITIS
• ESOPHAGEAL CANDIDIASIS.
• CYTOMEGALOVIRUS INFECTION.

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• CRYPTOSPORIDIASIS
• ISOSPORIASIS.
• HUMAN PAPILLOMA VIRUS ASSOCIATED MALIGNANCIES.
• CERVICAL CANCER IN WOMEN CARCINOMA RECTUM IN
  MEN.
• MYCOBACTERIUM AVIUM COMPLEX (MAC).
• CRYPTOCOCCUS
• HISTOPLASMOSIS
• NOCARDIA
• ASPERGILLUS
• LYMPHOMA,KAPOSIS SARCOMA,
• PROGRESSIVE MULTIFOCAL LEUCOENCEHALOPATHY(PML)
  -J.C VIRUS.

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ADVANCED HIV DISEASE. CD4 COUNTS lt 50 CELLS/ CMM.

• CYTOMEGALOVIRUS RETINITIS.
•  DISSEMINATED MYCOBACTERIUM AVIUM
• COMPLEX  DISEASE CRYPTOCOCCAL
• MENINGITIS.
•        PROGRESSIVE MULTIFOCAL
• LEUCOENCEPHALOPATHY.
•        INVASIVE ASPERGILLOSIS.
•        DISSEMINATED HISTOPLASMOSIS
•        DISSEMINATED COCCIDIOIDOMYCOSIS.
•        INVASIVE PENICILLIUM MARNEFFI DISEASE.

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COMMON OI'S IN AIDS PATIENTS

• TUBERCULOSIS BOTH PULMONARY AND
• EXTRA PULMONARY.
• OROPHARYNGEAL CANDIDIASIS
• HERPES ZOSTER
• HERPES SIMPLEX.
•  TOXOPLASMOSIS.
•  CRYPTOCOCCAL MENINGITIS
•  PNEUMOCYSTIS CARINII PNEUMONIA.
•  CYTOMEGALOVIRUS RETINITIS

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    PNEUMOCYSTIS CARINII PNEUMONIA

• INITIALLY DESCRIBED IN 1909 BY CHAGAS.
• INITIALLY CONSIDERED AS A PROTOZOA
• NOW INCLUDED UNDER FUNGUS ASCOMYCETES YEASTS.
• UNTIL 1980 OCCURED SPORADICALLY IN
• IIMMUNOCOMPROMISED PATIENTS ON CANCER
  CHEMOTHERAPY,LYMPHOMAS, MARASMIC CHILDREN ,
  B.M.TRANSPLANTS.
• WITH THE BEGINNING OF AIDS IN 1981 AN EXPLOSION
  OF CASES OF PCP.

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PATHOGENESIS

• AIR-BORN TRANSMISSION.
• NO CLINICAL INFECTION IN IMMUNOCOMPETENT.
• ATTACHES TO TYPE1 PNEUMOCYTES OF ALVEOLI AND
  CAUSE
• EXUDATIVE REACTION IMPAIRING GAS EXCHANGE.

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INCIDENCE

• COMMONEST RESPIRATORY INFECTION EARLIER IN AIDS
• INCIDENCE CAME DOWN WITH P.PROPHYLAXIS A.R.T.

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CLINICAL PRESENTATION

•   FEVER,COUGH,DYSPNOEA,SPUTUM,
• CHEST PAIN.

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RADIOLOGY

• DIFFUSE ALVEOLAR OR INTERSTITIAL PULMONARY
  INFILTRATES
• HRCT FINE DIFFUSE ALVEOLAR CONSOLIDATION WITH
  BRONCHIAL WALL THICKENING.

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DIAGNOSIS.

• BRONCHO ALVEOLAR LAVAGE
•    SPUTUM INDUCTION.
• TRANSBRONCHIAL BIOPSY.
• STAINIG FOR P.CARINII.
•    MOLECULAR IDENTIFICATION.

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TREATMENT-FIRST LINE.

• TMP-SMX- IS THE DRUG OF CHOICE.
• TRIMETHOPRIM 20MG/KG/D
• SMX100MG/KG/D IN 3-4 DEVIDED DOSE.x 21 DAYS.
  ROUTE ORAL OR IV.
• ORAL 5-6 DS TABLETS DAILY FOR ADULTS

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SECOND LINE  
PENTAMIDINE4MG/KG/D, INFUSED OVER 1H
ONCE DAILY X 21 DAYS.
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ALTERNATIVE THERAPIES

• TRIMETHOPRIM-DAPSONE
• TRIMETHOPRIM20MG/KG/D IN 3 DEVIDED DOSE
  DAPSONE 100MG x 21DAYS ORAL.
• CLINDAMYCIN 600-900 MG IV EVERY 6-8H OR 300-450
  MG ORALLY PRIMAQUIN,15-30 MG ORALLY x 21DAYS
• ATAVAQUONE 750MG TIDx21 DAYS ORALLY.
• TRIMETHOTREXATE45MG/M2X21 DAYS IV LEUCOVORIN 20
  MG /M2 4 TIMES DAILY

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CORTICOSTEROIDS

• ORAL OR IV STEROIDS SHOULD BE GIVENT O ALL HIV
  PATIENTS WITH MODERATE OR SEVERE PCP (WITH A
  PO2lt70mmHg).
• 4 CONTROLLED STUDIES ESTABLISHED
• THAT ADDITION OF STEROIDS WITHIN 72H OF
  BEGINNING CONVENTIONAL THERAPY IMPROVES OUTCOME
  AND REDUCES MORTALITY.
• BETTER TO START WITH INITIATION OF ANTI PCP
  THERAPY
• PREDNISOLONE 40MG ORALLY BD/D x 5d THEN 20MG BD/D
  x5d THEN 20MG OD UNTIL COMPLETION OF ANTI PCP
  THERAPY   .
• IF PARENTERAL THERAPY IS INDICATED
• METHYLPREDNISOLONE 75 OF ABOVE RECOMMENDED
  DOSE.

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PROPHYLAXIS-

• PRIMARY PROPHYLAXIS
• SECONDARY PROPHYLAXIS.

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INDICATIONS FOR PROPHYLAXIS

• CD4 COUNT lt 200CELLS/Cmm.
•    UNEXPLAINED FEVER gt100DF FORgt2W.
•    HISTORY OF OROPHARYNGEAL CANDIDIASIS.
•    PRIOR EPISODE OF PCP.

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PREFERRED REGIMEN

• TMP-SMX IS THE DRUG OF CHOICE.
•   1 DOUBLE STRENGTH TABLET
• DAILY (160mg OF TMP 800mg SMX).

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TUBERCULOSIS

• THE MOST COMMEN OI IN HIV/AIDS PATIENT
•  THE AIDS PANDEMIC HAS STALLED THE
• ELIMINATION OF TB IN USA.
•  HIV MOST SIGNIFICANT RISK FACTOR FOR
• PROGRESSION OF LATENT M.TUBERCULOSIS
• INFECTION TO ACTIVE TB.
• 10 OF PERSONS INFECTED WITH M.TB WILL
• DEVELOP ACTIVE TB IN LIFE TIME.
• IN HIV INFECTED AS MANY AS 50 WILL
• DEVELOP ACTIVE TB DURING A SHORTENED
• LIFETIME

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CLINICAL PRESENTATION

• ASSOCIATED WITH INCREASED TUBERCULOUS
  DISSEMINATION.
•   AN INCREASE IN THE NUMBER SEVERITY OF
  SYMPTOMS.
•   RAPID PROGRESSION TO DEATH UNLESS TREATMENT IS
  BEGUN.

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SITES OF DISEASE

• PULMONARY TB IN 70-90 OF HIV PTS. MOSTLY
  ASSOCIATED WITH EXTRA PULMONARY.
•   DISSEMINATED TB AND LYMPHADENITIS ARE THE
  MOST COMMON EXTRA PULMONARY.
•   CERVICAL AXILLARY COMMONLY AFFECTED WITH
  TENDENCY TO CASEATE.
•   INTRATHORACIC INTRAABDOMINAL TB
• LYMPHADENITIS ARE PARTICULARLY
• COMMON
•    CNS TB OCCURS IN 5-10 AS MENINGITIS
• TUBERCULOMAS.

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OTHER SITES

• PLEURA, PERICARDIUM, B.MARROW
• SKIN, G.U TRACT, LIVER, ADRENALS.

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RADIOLOGY

• RATHER THAN HAVING APICAL DISEASE AND CAVITY
  DISEASE MAY REVEALADENOPATHY-(HILAR,MEDIASTINAL,PA
  RATRACHEAL),
•   ATYPICAL INFILTRATES,P.EFFUSIONS, MILIARY
  DISEASE, OR NO ABNORMALITY AT ALL.
•   SPUTUM SMEARS MAY LESS COMMONLY BE AFB VE.

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DIAGNOSIS

• DEMONSTRATION OF AFB IN SPUTUM. RESULT MAY VARY
  FROM 20-80
•   CULTURE OF SPUTUM, URINE, BLOOD, CSF, P.FLUID,
  PURULENT MATERIAL, BIOPSY MATERIAL.
•   DNA PROBES. PCR.

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TREATMENT

• HIV-RELATED IMMUNOSUPPRESSION DOES NOT INTERFERE
  WITH THE INITIAL EFFECTIVENESS OF ANT-TB THERAPY.
•    TREATMENT OF HIV-INFECTED TB PATIENTS IS
  IDENTICAL TO THAT OF HIV-NEGATIVE.
•   BECAUSE OF WEAKER IMMUNE SYSTEM, IT IS
  PARTICULARLY IMPORTANT THAT TREATMENT
  RECOMMENDATIONS BE FULLY ADHERED TO.
•   ALSO APPEAR MORE SUSCEPTIBLE TO DEVELOPING
  DRUG RESISTANT STRAINS OF THE DISEASE.
•   FOR THESE REASONS, PATIENTS WITH HIV SHOULD
  RECEIVE TREATMENT WITH DOTS.

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CAUSES OF FAILURED THERAPY

•   DRUG RESISTANCE.
•      POOR ADHERENCE TO THERAPY.
•      MALABSORPTION OF ANTI TB DRUGS.
•      FAILURE TO DRAIN TUBERCULOUS
• ABSCESSES.
•      UNEXPLAINED TREATMENT FAILURE
• RELAPSE.

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PREFERRED REGIMEN

• SHORT COURSE CHEMOTHERAPY INCLUDING
• INH, RIFAMPICIN, ETHAMBUTOL, PZA, STREPTOMYCIN IS
  THE PREFERRED ONE.
•   DIRECTLY OBSERVED TREATMENT (DOT) SHOULD BE
  CONSIDERES FOR ALL PATIENTS WITH TB.
•   DURATION OF TREATMENT 6-9 MONTHS.
•   THE DURATION OF THERAPY CAN BE INDEVIDUALIZED
  DEPENDING ON THE SEVERITY OF TB,SEVERITY OF
  IMMUNO-DEFICIENCY, INITIAL RESPONSE TO THERAPY,
• DROG TOXICITY CONSEQUENCES TO THE PATIENT.

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MOST OF THE PATIENTS WITH HIV AND TB COME UNDER
CATEGORY I.

• NEW SMEAR -POSITIVE.
•   NEW SMEAR-NEGATIVE.(SERIOUSLY ILL).
•   EXTRA-PULMONARY(SERIOUSLY ILL).
•   THESE ARE MENINGITIS, DISSEMINATED TB,

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• TUBERCULOUS PERICARDITIS, PERITONITIS,
•   BILATERAL OR EXTENSIVE PLEURISY,
•   SPINAL TB WITH NEUROLOGICAL COMPLICATIONS, AND
  INTESTINAL GENITO-URINARY TB.
•                

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RNTCP TREATMENT REGIMEN
                     INTENSIVE PHASE
2(HRZE)3.             CONTINUATION PHASE
4(HR)3.                     H ISONIAZID
(600MG),                     R RIFAMPICIN (450
MG),                     Z PYRAZINAMIDE
(1500MG),                     E ETHAMBUTOL
(1200MG).     TREATMENT FOR 2 MONTHS 3
DOSES PER WEEK FOLLOWED BY 4 MONTH TREATMENT WITH
ISONIAZID AND RIFAMPICIN.
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DRUG TOXICITY AND INTERACTIONS

•   AS MANY AS 20-30 MAY DEVELOP ADVERSE
  REACTIONS PROMPTING A CHANGE IN THERAPY.
•                     RASH HEPATITIS .
•                     GIT DISTURBANCES.
• RIFAMPICIN IS APOTENT INDUCER OF THE HEPATIC
  CYTOCHROME P450 ENZYME SYSTEM IN HUMANS.
•   RIFAMPICIN THUS REDUCES THE ACTIVITY OF
  SEVERAL MEDICATIONS COMMONLY USED IN HIV INFECTED
  PATIENTS( FLUCONAZOLE,ART)
• 
  

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FUNGAL INFECTIONS

• A MAJOR CAUSE OF MORBIDITY MORTALITY
• IN PATIENTS WITH HIV INFECTION.
•       CANDIDA AND CRYPTOCOCCUS ARE THE MOST
• COMMON CAUSES OF MYCOTIC DISEASES.
• CANDIDIASIS-
•       MOST COMMON FUNGAL INFECTION OBSERVED
• IN HIV-INFECTED PATIENTS.
•       DISEASE OF M.MEMBRANE OCCURS INgt90 OF
• PATIENTS AT SOME POINT IN THEIR ILLNESS.

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C.MANIFESTATIONS

• ORAL CANDIDIASIS-ONE OF THE INITIAL
• MANIFESTIONS.
•   INCIDENCE INCREASES WHEN CD4 COUNT FALL BELOW
  200-300/CMM.
•    CAN OCCUR REGARDLESS OF CD4 COUNT ALSO.
•    OESOPHAGEAL CANDIDIASIS-AN AIDS DEFINING
  ILLNESS. OCCURS MOSTLY IN PATIENTS WITH CD4lt
  100/CMM.
•    MAY BE ASYMPTOMATIC,BUT MORE COMPLAIN OF
  ODYNOPHAGIA,

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OTHER MANIFESTATIONS

• VAGINAL CANDIDIASIS.
•    PULMONARY INVOLVING, TRACHEA, BRONCHI, AND
  LUNG CAN OCCUR AS A LATE OR TERMINAL
  MANIFESTION.
•    INVASIVE CANDIDIASIS IS RARE IN HIV
• INFECTED PATIENTS.
•    RARELY HEART,CNS EYES AFFECTED.

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DIAGNOSIS

• CHARACTERISTIC APPEARANCE.
•     DEMONSTRATION OF THE ORGANISM.

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TREATMENT

• TOPICAL CLOTRIMAZOLE.
•     SYSTEMIC TREATMENT IS PREFERRED IN
• MANY PATIENTS.
•     ORALFLUCONAZOLE 100-200MG DAILY
• ORALLY.
•     ITRACONAZOLE 200 MG DAILY.
• USUALLY GIVEN FOR 10-14 DAYS.

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  ESOPHAGEAL AND ADVANCED INFECTION

• INITIAL IV FLUCONAZOLE 200-400 MG DAILY  FOLLOWED
  BY ORAL TREATMENT FOR 14-28DAYS.
•   IN ADVANCED DISESE AND RESISTANT CASES,
  AMPHOTERICIN MAY BE NECESSARY.
•   0.5MG/KG 20-30MG/DAY IV INFUSION FOR 7-14
  DAYS.

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PROPHYLAXIS

• ROUTINE PROPHYLAXIS FOR ORAL AND VAGINAL
  CANDIDIASIS IS NOT RECOMMENDED BECAUSE OF THE
  EMERGENCE OF DRUG RESISTANCE.
•   IF RECURRENCE IS FREQUENT OR SEVERE TOPICAL OR
  ORAL TREATMENT MAY BE USED.
•   OESOPHAGEAL CANDIDIASIS AND VERY LOW CD4 COUNT
  MAY BE PUT ON FLUCONAZOLE 100MG/DAY.

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CRYPTOCOCCOSIS

• A LEADING CAUSE OF MORBIDITY
• MORTALITY.
•      ORGANISM CRYPTOCOCCUS NEOFORMANS.
• CLINICAL MANIFESTATIONS
•       MENINGITIS -MOST COOMON INITIAL
• MANIFESTATION.
•       PULMONARY-FOCAL AND DIFFUSE,
•       SKIN LESIONS,ENDOPHTHALMITIS,
• DISSEMINATION ARE OTHER MANIFESTATIONS.

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DIAGNOSIS

• CT MRI OF BRAIN TO EXCLUDE SOL.
•  CSF STUDY.ANTIGEN DETECTION, INDIA INK STAIN,
  CULTURE.
•  CAN BE DETECTED FROM SERUM, URINE OR SPUTUM
  ALSO.

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TREATMENT

• DRUGS USED ARE AMPHOTERICIN-B, BOTH CONVENTIONAL
  AND LIPOSOMAL
•   FLUCYTOSINE AND FLUCONAZOLE.
•  MANY COMPARATIVE STUDIES DONE.

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BEST RECOMMENDED REGIMEN.

• AMPHOTERICIN 0.7MG/KG/DAY FLUCYTOSINE
  100MG/KG/DAY FOR AT LEAST 2 WEEKS.
•   IF THE PATIENT HAS IMPROVED FLUCONAZOLE 400
  MG/DAY FOR FURTHER 8-10 WEEKS.
•   IN PATIENTS WHO ARE NOT RESPONDING DURING
  INITIAL COURSE, AMPHOTERICIN CAN BE GIVEN FOR
  UPTO 6 WEEKS. IF TOXICITY DEVELOPS ONE OF THE
  LIPOSOMAL PREPARATION CAN BE USED IF AVAILABLE
  AND AFFORDABLE.

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OTHER REGIMENS

• FLUCONAZOLE 400MG/DAY OR
•    ITRACONAZOLE 400MG/DAY.
•    BUT RESPONSE RATE LOWER THAN THAT
• CONTAINING INITIAL AMPHOTERICIN.
•    FLUCONAZOLE 400MG/DAY FLUCYTOSINE
• 150MG/KG/DAY-
•    ENCOURAGING RESULT IN SMALL NUMBER OF
• PATIENTS.
•    ALL TREATED PATIENTS SHOULD BE PUT ON
  FLUCONAZOLE 200 MG/D TO PREVENT RELAPSE.

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• MAINLY CAUSY TOXOPLASMA ENCEPHALITIS MANIFESTED
  AS A FOCAL LESION.
•   INCIDENCE INCREASES AS CD4 CELL COUNT REACHES
  AROUND100-200/CMM.
•   SEIZURE FOCAL NEUROLOGICAL SYPTOMS OCCUR.
•   IT IS THE COMMONEST CAUSE OF A SPACE OCCUPYING
  LESION IN A PATIENT WITH AIDS.

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ADJUNCTIVE TREATMENT-

• INTRACRANIAL PRESSURE MAY INCREASE DUE DUE TO
  REDUCED REABSORPTION OF CSF BY ARACHNOID VILLI
  BLOCKED BY YEAST CELLS LEADS TO HYDROCEPHALUS.
  
• THIS CAN CAUSE BLINDNESS CAN BE PREVENTED TO
  SOME EXTEND BY
•               FREQUENT LUMBAR PUNCTURE.
•               ACETAZOLAMIDE 250MG QID.
•               HIGH DOSE CORTICOSTEROIDS.
•               VENTRICULAR SHUNTING.

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TOXOPLASMOSIS

• TOXOPLASMOSIS REFERS TO THE CLINICAL AND/OR
  PATHOLOGICAL EVIDENCE OF DISEASE CAUSED BY
  TOXOPLASMA GONDII.
•   AN OBLIGATE INTRACELLULAR PATHOGEN.
•   CAUSES ASYMPTOMATIC OR MILDLY SYMPTOMATIC
  INFECTIONS IN NORMAL HOSTS.
•   CAUSES RAPIDLY PROGRESSIVE FATAL DISEASE IN
  IMMUNOCOMPROMISED PATIENTS.
•   ZOONOTIC DISEASE.
•   DEFINITIVE HOST CAT.

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TRANSMISSION TO HUMANS

• ORAL ROUTE.
•   BY EATINGPOORLY COOKED MEAT
• CONTAINING TISSUE CYSTS
•   FOOD CONTAMINATED WITH SOIL CONTAINING
  OOCYSTS EXCRETED BY CATS.
•   ACUTE ACQUIRED TOXOPLASMOSIS IS MOST
• COMMONLY ASYPTOMATIC.
•   IN HIV-INFECTED PERSONS CAUSE A REACTIVATION
  OF THE DISEASE WHEN IMMUNITY FADES.

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• MAINLY CAUSY TOXOPLASMA ENCEPHALITIS MANIFESTED
  AS A FOCAL LESION.
•  INCIDENCE INCREASES AS CD4 CELL COUNT REACHES
  AROUND100-200/CMM.
•  SEIZURE FOCAL NEUROLOGICAL SYPTOMS OCCUR.
•  IT IS THE COMMONEST CAUSE OF A SPACE OCCUPYING
  LESION IN A PATIENT WITH AIDS.

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D. DIAGNOSIS

• LYMPHOMA,TUBERCULOMA, PML, FUNGAL
• ABSCESS, CVA, HSV ENCEPHALITIS.
• DIAGNOSIS
•       MRI AND CT SCAN WITH CONTRAST.
•       DEMONSTRATION OF LATENT INFECTION BY
• RAISED SERUM IgG TITRES. BRAIN BIOPSY FOR
• HISTOLOGICAL CONFIRMATION

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TREATMENT-

• THE GENERAL TREND IS TO RELY ON THERAPEUTIC TRIAL
  FOR A DIAGNOSIS, RESERVING BRAIN BIOPSY FOR
  TREATMENT FAILURES OR ATYPICAL PATIENTS WHO ARE
  SERO NEGATIVE.
• REGIMEN OF CHOICE-
•            SULFADIAZINE AND PYREMETHAMINE.
•            SULFADIAZINE- INITIAL DOSE IS1-1.5G
• ORALLY EVERY 6H.
•            IN COMATOSE PATIENT S.D.CAN ALSO BE
• GIVEN 1G ( 75mg/Kg IN 4 DEVIDED
  DOSES) IN
• 500 ML SALINE EVERY 6HRS.

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SIDE EFFECTS

•    NAUSEA,VOMITING,DIARRHOEA,
•              NEUTROPENIA,
•              INTERSTITIAL NEPHRITIS,
•              CRYSTALLURIA, AND
• NEPHROLITHIASIS,
•              ACUTE RENAL FAILURE
•              SKIN RASH.

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PYREMETHAMINE

• INITIAL LOADING DOSE OF 200Mg FOLLOWED by 50-100
  mg ORALLY/D.
•   TO REDUCE INCIDENCE OF PANCYTOPENIA, 10MG OF
  FOLINIC ACID DAILY.

62
ALTERNATIVE THERAPIES-

• FANSIDAR (PYREMETHAMINE25MG SULFADOXINE500mg)
  6-8 TABLETS DAILY IN DIVIDED DOSES FOR FIRST 2
  DAYS FOLLOWED BY 2-3 TABLET DAILY. FOLINIC ACID
  AS ABOVE.
•   DAPSONE100MG ORALLY,PYREMETHAMINE AND FOLINIC
  ACID AS ABOVE.
•   TRETMENT IN THIS DOSE TO BE CONTINUED FOR 6
  WEEKS.
•   PYREMETHAMINE 100-200MG PO LOAD THEN 50-75
  MG/D ORAL OR IV CLINDAMYCIN 600MG QID
  LEUCOVORIN 10MG OD.

63

• AZITHROMYCIN 1200-1500 MG QD PYREMETHAMINE
  LEUCOVORIN.
•   CLARITHROMYCIN 1000MG PO BID PYREMETHAMINE
  LEUCOVORIN              
•   ATOVAQUONE 750MgPO TID PYREMETHAMINE
  LEUCOVORIN.
•   MAINTENANCE TREATMENT
•   FULL DOSE THERAPY TO BE GIVEN FOR 6-8
  WEEKS,WEEKS,WITH FOLLOW UP IMAGING SHOWING
  DECREASE IN SIZE OF LESION, THEN
• CONTINUETHERAPY
•   SD.2GM PMN 25-50 MG, OR
•   FANSIDAR 1 OD, OR 2 THRICE WEEKLY,
•   CO TRIMOXAZOLE DS 1OD,

64
CRYPTOSPORIDIASIS

• PREFERRED REGIMEN
•   PARAMOMYCIN 500 MG PO TID OR 100MG PO BID WITH
  FOOD X 14-28 DAYS.THEN 500MG PO BID.
•   PARAMOMYCIN 1GM BID/ AZITHROMYCIN600MG QD x 4
  WEEKS,
•   THEN PMN ALONE x 8 WEEKS.

65
ALTERNATIVE REGIMENS

• NITAZOXANIDE 500Mg PO BID.
•     OCTREOTIDE (SANDOSTATIN) 50-500 MicGm TID
• SC/ IV AT 1Mic Gm/HR.
•     AZITHROMYCIN 1200MG X2 PO 1ST DAY,1200Mg/D X
  27 D,
• THEN 600 Mg/D
•     ATOVAQUONE 750 Mg PO SUSPENSION WITH MEAL
  BID.
•     OF THESE ONLY PMN AZN SHOWED GOOD RESPONSE
  IN
• TERMS OF CLINICAL SYMPTOMS AND OOCYST
• EXCRETION.
•     HEART WITH IMMUNE RECONSTITUTION IS THE MOST
• EFFECTIVE TREATMENT.

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CYTOMEGALOVIRUS RETINITIS

• SYMPTOMS VISUAL DISTURBANCE, FLOATERS, FLASHING
  LIGHTS, FEVER.
•   Dx OPHTHALMOLOGIC EXAM WITH CHARACTERESTIC
  LESIONS.,CD4 lt100.
•   Rx GANCYCLOVIR 5Mg/Kg IV Q 12 HRS INDUCTION
  DOSE FOR 2 WEEKS FOLLOWED BY LIFE LONG
  GANCYCLOVIR 5Mg/KG IV QD.
•   TOXICTYNEUTROPENIA 20-40,
•   THROMBOCYTOPENIA- 5.
•   GIT SYMPTOMS,RASHNEPHROTOXOCITY RARELY.

67

• ALTERNATIVE FOSCARNET 90Mg/Kg IV Q12Hrs
  INDUCTION FOR 2 Wks THEN QD DOSING.
•   TOXICITY MOST COMMON-NEPHROTOXICITY,
  RARE-HYPOCALCEMIA, HYPOKALEMIA, HYPOMAGNESEMIA,
  NAUSEA, SEIZURE, ANAEMIA.
•   CIDOFOVIR 5MG/KG IV Q WEEK FOR 2 WEEKS THEN
  EVERY 2 WEEKS THEREAFTER WITH PROBENECID 2GM PO 3
  HR BEFORE AND 1GM PO 2 AND 8HRS AFTER INFUSION.
• TOXICITY NEPHROTOXICITY.
•   LIFELONG THERAPY WITH CONTINUED FOLLOWUP.

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DISSEMINATED MAC

•   Dx CD4 lt100,BLOOD CULTURE, OR BM BIOPSY VE.
•   Rx CLARITHROMYCIN 500 MGPO BID OR
  AZITHROMYCIN 500MG PO QD PLUS ETHAMBUTOL 15-25
  MG/KG/D PLUS RIFABUTIN 300 MG PO QD.
• SIGNS AND SYMPTOMS FEVER, WT LOSS NIGHT SWEATS.

69
         ALTERNATIVES TO ADD IF NO RESPONSE OR
SIDE EFFECTS TO ABOVE

• CIPROFLOXACIN 750MG PO BID, OFLOXACIN 400MG PO
  BID, AMIKACIN 7.5-15MG/KG IV QD FOR 1-2 MKONTHS.
•   DURATION OF THERAPY IS LIFELONG.

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PRIMARY PROPHYLAXIS OF OPPORTUNISTIC INFECTIONS
IN ADULTS ADOLESCENTS WITH HIV.

• PNEUMOCYSTIS CARINII
• INDICATION
•                     CD4 COUNT lt200/MicL OR
•                     OESOPHAGEAL CANDIASIS.
•                     FIRST CHOICETMP-SMZ,1DS
  ORALLY OD.
•                     ALTERNATIVE DAPSONE 50Mg BD
  OR 100Mg OD, DAPSONE 50 Mg OD PYREMETHAMINE50
  Mg/WEEK LEUCOVORIN25Mg /WEEK.
•  
•   AEROSOLIZED PENTAMIDINE,300MG EVERY MONTH VIA
  RESPIGARD 11 NEBULIZER.
•   ATOVAQUONE. 1500MG MG ORALLY OD.
•   TMP-SMZ,1DS ORALLY 3 TIMES/WEEK.

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TOXOPLASMA GONDII

• IgG Ab TO TOXOPLASMA CD4 COUNTlt100/MicL.
•   CO-TRIMOXAZOLE DS TABLET I DAILY.

72
MYCOBACTERIUM AVIUM COMPLEX

• CD4 COUNT lt50 /MicL.
•     AZITHROMYCIN 1200M ORALLY / WEEK.
•     OR CLARITHROMYCIN 500MG BID OD.

73
CRYPTOCOCCUS NEOFORMANS

• CD4 COUNT lt50/Cumm.
•        FLUCONAZOLE 100-200MG OD.
•        A.RITRACONAZOLE 200MG OD

74
CYTO MEGALO VIRUS

• CD4 lt50/Cumm CMV Ab ve.
•   ORAL GANCYCLOVIR 1GM TID.