Causal Organism: Aetiology

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HIV INFECTION
AETIOLOGY
Causal organism
 HIV ( Human Immunodeficiency Virus )
Mode of transmission
 Sexual ( Heterosexual – major route > 75% )
 Blood exposure
 Mother to child
VIROLOGY
 RNA virus
 Family – Retrovirus
 Subfamily – Lentivirus
 Types
1. HIV-1 – world wide divided into three subtypes
 “M” ( Major ) – nine sub-types ( A-D, F-H, J & K )
 “O” ( Outlier )
 “N” ( Non-major & Non-outlier )
2. HIV-2  almost entirely confined to West Africa
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NATURAL HISTORY & STAGING OF HIV
Stages of HIV infection

I. Primary Infection & Seroconversion phase ( CDC category A or WHO Stage1 )
 IP = 2-4 wks after exposure
 Symptomatic in >50% of cases
Clinical features
 Fever with rash
 Pharyngitis with cervical lymphadenopathy
 Myalgia / arthralgia
 Headache
 Mucosal ulcerations ( Oral & Genital )
 Diarrhea
 Rarely neurological features  meningo-encephalitis, Bell’s palsy
 Seroconversion
 Appearance of specific Anti-HIV abs in serum
 Occurs 2-12wks after the development of symptoms ( window period )
 Window period is prolonged when PEP has been used
II. Asymptomatic Infection phase ( CDC Category B or WHO Stage1 )

 Patient remain well with no evidence of disease
 Persistent Generalized Lymphadeopathy ( PGL )
 Enlarged L/N at ≥2 extra-inguinal sites ( symmetrical, firm, mobile & non-
tender )
 Size = typically < 2cm
 Duration > 3months
 No other cause of lymphadenopathy
 Nodes may disappear with disease progression
 Median time from infection to development of AIDS is about 9yrs in adults
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 Viremia peaks during primary infection & then drops reaching plateau in about
3months
 Level of viremia post-seroconversion is predictor of the rate of decline in CD4 count
III. Minor HIV-associated disorders ( CDC category B or WHO stage 2 & 3 )

 Mildly symptomatic diseases which are not AIDs defining
 Oral hairy leucoplakia ( EB virus )
 Herpes Zoster > 1episode / dermatome
 Oropharyngeal candidiasis
 Recurrent vaginal candidiasis
 Bacillary angiomatosis ( Bartonella )
 Severe pelvic inflammatory disease
 Listerosis
 Cervical dysplasis
 ITP ,Peripheral neuropathy
 Weight loss >10%
 Chronic diarrhea >1month
 Low-grade fever/night sweats
IV. AIDS ( CDC category C or WHO stage 4 )

 Development of AIDS-defining conditions ( Oppotunistic infections & Tumors )
Protozoa
 Chronic Cyrptosporidial diarrhea ( > 1month )
 Chronic Isosporiasis ( >1month )
 Cerebral toxoplasmosis
Fungus
 Esophageal / respiratory tract Candidiasis
 Extrapulmonary Cryptococcosis
 Pneumocystis jirovecii ( carinii ) pneumonia
 Disseminated Mycosis – Coccidiodomycosis or Histoplasmosis
Bacteria
 Non-tuberculous Mycobacterial infection
 Tuberculosis – pulmonary or Extrapulmonary
 Recurrent non-typhi Salmonella septicemia
 Recurrent bacterial pneumonia
Virus
 Cytomegalovirus disease
 Herpes simplex – chronic mucocutaneous or visceral
 Progressive multifocal leukoencephalopathy ( JC virus )
Neoplasm
 Invasive cervical canver
 Lymphoma – B-cell NHL or Cerebral
 Kaposi’s sarcoma
Others
 HIV wasting $ ( HIV-associated wasting )
 HIV encephalopathy ( HIV-associated dementia )
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INVESTIGATIONS
 Serum or salivary HIV-Ab by ELISA
 Confirmation by Western blot
 For recent infection
 PCR – for HIV RNA
 Plasma core p24 antigen
 Repeating ELISA 6wks & 3mnoth
th
 4 generation test kit  test both HIV Ab & p24 Ag
( Rapid test kits  give results in 30min but must be confirmed by ELISA )
 Other Baseline Invx
 CD4 count
 Viral load
 HBsAg & HCV Ab
 LFT
 FBC
 Urinalysis & serum Cr
 Syphilis serology
 Cervical smear in women
 Serum Cryptococcal antigen ( if CD4 < 100 )
 STI screen
 Tuberculin skin test etc …………
MANAGEMENT
1. Anti-retroviral therapy ( HARRT )
2. Prevention of Opportunistic infection
3. Counselling & support
ANTI-RETROVIRAL THERAPY / HARRT (Highly Active Anti-Retroviral Therapy)

Aims of Therapy
 Reduce the viral load to an undectable level for as long as possible
 Improve the CD4 count to > 200 cells/ml so that severe HIV-related disease is unlikely
 Improve the quantity & quality of life without unacceptable drug-related side-effects or
lifestyle alteration
 Reduce transmission
Indications for initiating ART

 All patients with HIV infection, regardless of CD4 count or Clinical status
Commonly used ART drugs

Classes Drugs
1. Nucleoside Reverse Transcriptase Inhibitors Abacavir, Emtricitabine, Lamivudine, Tenofovir,
( NRTIS ) Zidovudine
2. NNRTIs Efavirenz, Nevirapine, Etravirine
3. Protease Inhibitors ( PI ) Lopinavir, Atazanvir, Darunavir
4. Integrase Inhibitors Raltegravir
5. Chemokine R/c Inhibitor Maraviroc
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Anti-retroviral Regimens
 2NRTI + 1NNRTI or 1 PI or 1 INTEGRASE INHIBITOR
Side-Effects of ART
1. NRTIs
 Peripheral neuropathy, Pancreatitis, Hepatic steatosis, latic acidosis
 Extremity fat loss, anemia, neutropenia
 Myopathy, cardiomyopathy
2. NNRTIs
 Rash, Stevens-Johnson syndrome
 Hepatitis
3. PIs
 GI intolerance, Fat redistribution, Hyperlipidemia, Insulin resistance, Hyperglycemia
 Bleeding in hemophilia, Liver enzyme derangement

Monitoring of ART
 CD4 count – 6monthly Opportunistic infections reduced
 Viral load ( HIV RNA ) – 4 wks after starting ART  by Co-trimoxazole
should be at least 10-fold decrease  then 6 monthly  Pneumocystis jirovecii
 Serum U&E, Cr pneumonia
 Serum Bilirubin + LFT  Cerebral toxoplasmosis
 Full blood count  Isosporiasis
 Fasting lipid profile & glucose  Malaria
 Bacteremia + Bacteria
PREVENTION OF OPPOTUNISTIC INFECTIONS pneumonia
 Immunize with hepatitis A & hepatitis B vaccines
 Give pneumococcal & influenza vaccines to all patients
 Avoid live-attenuated vaccines ( eg: BCG or oral polio vaccines ) but MMR vaccine is safe &
can be given
Pneumocystic pneumonia Primary prophylasix when CD4 count <200cells/mm3 OR

WHO stage3 or 4
 First-line = Co-trimoxazole 960mg daily
 Second-line = Dapsone / atovaquone
Toxoplasmosis Co-trimoxazole 960mg daily
Cryptococcosis Fluconazole 200mg daily
CMV infection Valganciclovir 900mg daily
MAC Clarithromycin 500mg twice daily + Ethabutol 800mg daily
Isospora belli infection Co-trimoxazole 960mg daily
POST-EXPOSURE PROPHYLASIX ( PEP )

 Combination therapy
 For low-risk exposure  dual NRTIs
 For high-risk exposure  add either PI or Efavirenz
 First dose should be given as soon as possible preferably within 6-8hours
( There is no point in starting PEP after 72hours )
 Duration of Tx = 4 weeks
 HIV Ab testing = performed at 0, 6, 12 & 24 weeks after exposure
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Causal Organism: Aetiology

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NATURAL HISTORY & STAGING OF HIV

Stages of HIV infection

II. Asymptomatic Infection phase ( CDC Category B or WHO Stage1 )

III. Minor HIV-associated disorders ( CDC category B or WHO stage 2 & 3 )

IV. AIDS ( CDC category C or WHO stage 4 )

ANTI-RETROVIRAL THERAPY / HARRT (Highly Active Anti-Retroviral Therapy)

Indications for initiating ART

Commonly used ART drugs

Pneumocystic pneumonia Primary prophylasix when CD4 count <200cells/mm3 OR

POST-EXPOSURE PROPHYLASIX ( PEP )

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