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HIV/AIDs (Signs/Symptoms (Pneumocystis carinii (now jiroveci) pneumonia…
HIV/AIDs
Signs/Symptoms
Pneumocystis carinii (now jiroveci) pneumonia (PCP)
Oesophageal candidiasis
Kaposi’s sarcoma
Herpetic ulcer > 1 month
Cerebral toxoplasmosis
Cryptococcal
meningitis
Cryptosporidium,
Microsporidium
TB
CMV retinitis
Clinical Latency - lymphadenopathy, splenomegaly,Neurological disease
- infection of nervous tissue occurs at an early stage but neurological involvement increases as HIV advances
- ADC - AIDS dementia complex , sensory polyneuropathy, aseptic meningitis
- sensory polyneuropathy - advanced HIV infeciton
- autonomic neuropathy - postural HTN, diarrhea
Eye:
- CMV retinitis (cotton wool)
- anterior uveitis
Mucocutaneous manifestations:
- skin - common site for HIV related pathology as function of dendritis and Langerhan's cells
- pruritus - common complaint at all stages of HIV
- generalised dry, itchy, flaky skin
- eosinophilic folliculitis presents with urticarial lesions
Haematological Complications:
- lymphopenia
- neutropenia
- isolated thrombocytopenia
- pancytopenia
Gastrointestinal effects
- weight loss, diarrhea
- hypochlorhydria
- rectal lymphoid tissue celsl - targets for HIV infection during penetrative anal sex - may be a reservoir for infection to spread through the body
Renal Complications:
- HIV associated nephropathy
- nephrotic syndrome - focal glomerulosclerosis - usual pathology --> renal epithelium
- nephrotoxic drugs - management of HIV associated pathology
Resp
- sinus - chronic inflammation
- lymphoid interstitial pneumonitis (LIP) - paediatric HIV infeciton
Endocrine
Cardiac complication- morbidity in people with HIV
- lipid dysregulation - antiretroviral mediation
-
Mx of HIV
HAART - triple therapy + 2 nucleoside analogues + protease inhibitor or NNRTI or 3 nucleoside analogues
SE- enhanced toxicity, lipodystrophy, lactic acidosis, other mitochondrial toxicities, drug interactions Complications:
Virological failure:
- viral resistance
- poor adherance
- intercurrent illness
- pharmacokinetic problems --> absorption, not taking at therapeutic levels (allowing virus to replicate/mutate)
- swarms of quasi species
Prophylaxis:
- PCP: cotrimoxazole, pentamidine
- Oesophageal candidiasis: fluconazole
- Kaposi’s sarcoma: ART, Liposomal daunorubicin
- Herpetic ulcer > 1 month: aciclovir
- Cerebral toxoplasmosis: Sulphadiazine
- Cryptococcal meningitis: Amphotericin then fluconazole
- TB: isoniazid +/- rifampicin
- CMV retinitis: valganciclovir
Definition/Epidemiology
Epidemiology- 36.7 million people infected with HIV worldwide, 70% in sub-Saharan Afric
- Caribbean
- globally - 2.1 mill
- 6000 newly diagnosed with HIV in UK in 2013
- 2.8 per 1000 population
Routes of Transmission: blood, blood products, sexual fluids, other fluids containing blood (breast milk)
- most common route - sexual contact, before birth or during delivery, during breast feeding, sharing contaminated needles and syringes
Genome - 10, 000 bp, 3 open reading frames --> protein --> cleaved to yield gag - nucleocapsid (p24, p7- nucleocapsid) - long
- pol - reverse transcriptase, protease - 2nd largest
- env - gp 120, gp 41
- accessory proteins - shortest RNA
Four groups of HIV-1: M, N, O, P
M (main) - 10 genotypes - CRFs (circulating recombinant forms)
-
CD4 - closely linked to CCR5/CXCR4, gp41 - allows virus to fuse
provirus -
HIV 1 variants:
Dual tropic- both
TCL- T cells
M- tropic - macrophage
Risk factors
Eastern Europe/Middle East -less except homosexuality, IV drug users, mother-baby, oral sex - depending on country
-
Routes of transmission
HIV1, HIV - transmitted through same routes, similar opportunistic infections
- transmission of HIV - transmitted by - direct contact with infected blood, sexual contact - ral, anal or vaginal
- direct contact with semen, vaginal or cervical secretions
- HIV-infecte
Natural History of HIV infection
- Serovonversion
- Asymptomatic - no signs of HIV, immune system controls virus production
- Symptomatic -
- AIDS- opportunistic infections, end-stage
Diagnosis
Immunological - CD4+ absolute CD4 count - % of total lymphocytes falls as HIV progresses
500 - asymptomatic
- <350 - substantial immune suppression
- <200 - defines AIDS
Virological monitoring
- Viral load (HIV RNA)
- bDNA
- RT-RCT
- nucleic acid sequence based amplificaiton (NASBA)
- serum HIV ELISA
- serum HIV rapid test
- HIV non invasive tests
- serum western blot
- serum p24 antigen
- serum HIV DNA PCR