HIV / AIDS
Disease caused by an infectious
agent:
A Retrovirus
H Human
I Immunodeficiency
V Virus
A Acquired
I Immuno
D Deficiency
S Syndrome
HIV and AIDS
History of an infectious agent
In Los Angeles 1967-1978: only two cases of
Pneumocystis carinii pneumonia
• 1979 - 5 cases of Pneumocystis carinii
pneumonia
Dot-like intracystic bodies of
Pneumocystis carinii in lung
Cytologic preparation from a
bronchoalveolar lavage –
Giemsa stain
Pneumocystis jiroveci
HIV and AIDS
an infectious agent – Kaposi’s Sarcoma
Early 1981 MMWR: 5 cases of Kaposi’s
sarcoma
Hitherto: rare (immunocompromization)
Elderly - Non-aggressive
1981 - 26 cases of Kaposi’s sarcoma
• Young
• Male
• San Francisco and New York
• All Homosexuals
HIV and AIDS
an infectious agent – Kaposi’s Sarcoma
Before 1981: 40 - 120 cases per year in United States
1981-1999: 46,684 definite cases in United States
HIV and AIDS
In 1981, it was clear that AIDS was present in the homosexual
male communities of several major metropolitan areas in
United States- mode of spread was by sexual contact.
By 1982, another mode of transmission was apparent-
Infected blood and blood products-
Disease arose in
Hemophiliacs
Blood transfusion recipients
Intravenous drug users
HIV and AIDS
1983: people were talking of the 4H club for the likelihood
of getting AIDS:
• Homosexuality among males
• Hemophilia
• Heroin use (drug use that may involve shared needles)
• Haitian origin
HISTORY OF HIV
1978 unusual Pneumonia in young homosexuals –death-
Sanfransisco Gen hospital
1981 Increased incidence of Kaposi sarcoma & PCP
in homosexual men in USA
1983 Virus Isolated
Dr.Luc Montagneir Institute Pasteur, Paris
Dr. Robert C Gallo National Cancer Institute, USA
1984 - Human Immunodeficiency Virus
1986 - First case in India
1988 - First case in Karnataka
Prevalence of HIV in adults
37.8 (34.6 – 42.3) million
HIV and AIDS
Obvious agent:
A virus……that is now in the blood
supply
Primary route of transmission: Sex
AIDS is a sexually-transmitted viral disease
HIV and AIDS
The Cellular Picture
Loss of one cell type throughout the course of the disease
CD4+ T4 helper cells
A fall in the CD4+ cells always precedes disease
In advanced disease: the loss of another cell type
CD8+ cytotoxic killer cells
Suggests an infectious agent
A virus
But initially difficult to grow
Rapidly kills cells on which it grows
AIDS Definition
• AIDS is currently defined as the presence of one of 25
conditions indicative of severe immunosuppression
OR
• HIV infection in an individual with a CD4+ cell count
of 10% in 1 month)
Chronic Diarrhea (Intermittent / persistent)
Prolonged fever (> 1 month Intermittent / continuous)
Disseminated, miliary, extra-pulmonary, extensive tuberculosis
Neurological impairment
Oro-pharyngeal candidiasis
Life threatening or recurrent pneumonia
Cryptococcal meningitis
Neurotoxoplamosis
Cytomegalovirus retinitis
Recurrent or multi-dermatomal Herpes zoster
Penicillium marnefei
Disseminated molluscum
Kaposi’s sarcoma
Clinical Findings
The clinical picture of HIV infection can be divided into
three stages:
An early- acute stage;
A middle- latent stage; and
A late- immunodeficiency stage
The acute stage: -begins 2–4 weeks after infection. A
mononucleosis-like picture of fever, lethargy, sore throat, and
generalized lymphadenopathy seen. A maculopapular rash on
the trunk, arms, and legs (but sparing the palms and soles) is
also seen. Leukopenia occurs, but the number of CD4 cells is
usually normal. A high-level viremia typically occurs, and the
infection is readily transmissible during this acute stage. This
acute stage typically resolves spontaneously in about 2 weeks.
The middle stage: a long latent period, measured in years, usually
ensues. In untreated patients, the latent period usually lasts for 7–
11 years. The patient is asymptomatic during this period. Although
the patient is asymptomatic and viremia is low or absent, a large
amount of HIV is being produced by lymph node cells but
remains sequestered within the lymph nodes. This indicates that
during this period of clinical latency, the virus itself does not enter
a latent state.
A syndrome called AIDS-related complex (ARC) can occur during
the latent period. The most frequent manifestations are persistent
fevers, fatigue, weight loss, and lymphadenopathy. ARC often
progresses to AIDS.
The late stage: of HIV infection is AIDS, manifested by a decline
in the number of CD4 cells to below 400/L and an increase in the
frequency and severity of opportunistic infections.
Early symptoms
• Weight loss
• Fever
• Night Sweats
• Diarrhea
• Skin disorders early
– Fungal
Grant AD et al BMJ 2001
Overview: Infections
Mucocutaneous
Gastrointestinal
Respiratory
CNS & Eye
Miscellaneous
Blood
Renal
Cardiac
Endocrinal
MALIGNANCIES
Kaposi sarcoma
Non Hodgkin's lymphoma
Primary lymphoma of CNS
Anogenital neoplasia
OPPORTUNISTIC INFECTIONS
Bacterial: Mycobacterrium spp (Tuberculosis), Salmonellae,
Listeria, Pneumococci, Campylobacter
Viral : HSV, VZV, CMV, EBV, Adeno
Fungal
Candida, Cryptococcus,
Histoplasma, Penicillium marneffii
Parasitic
Pneumocystis carinii ,Toxoplasma,
Isospora, Cryptosporidium, Microsporiridia,
Giardia, Strongyloides
Mucocutaneous infections
Common
Most patients affected
Atypical presentation
Difficult to treat
Rashes:
type and severity depend on CD4 count
Skin conditions
Fungal infections
Xerosis and pruritus
Seborrheic dermatitis-A yeast called Malassezia furfur
causes Seborrhea dermatitis .
Viral infections
Herpes simplex
Varicella zoster (HZ)
Molluscum contagiosum
Bacterial & parasitic infections
Staph. aureus
Bacillary angiomatosis – caused by Bartonella
Syphilis
Seborrheic dermatitis:
dry scaly patches on face
Herpes simplex: perioral
Herpes zoster: thoracic dermatome
Molluscum contagiosum
Molluscum contagiosum
Bacillary angiomatosis
Oral conditions
Candidiasis
Oral hairy leukoplakia
GASTROINTESTINAL DISEASE
Oesophageal candidiasis
CMV infection
Cryptosporidiosis
Microsporidium
Isospora
Hepatitis B & C Oesophageal candidiasis
M. avium intracellulare (MAI)
Respiratory disease
Pneumocystis carnii pneumonia
M. tuberculosis
Bacterial pneumonias
PCP…
PCP is usually reactivation of latent infection
Air-borne transmission
Risk inversely related to CD4
Rare if CD4>200
If CD4200/mm3
Improve quality of life
Less drug adverse effects
Less lifestyle alterations
Reduce transmission
Antiretroviral agents
HAART (Highly active antiretroviral therapy)- is effective .
Antiretroviral drugs include -
Reverse transcriptase inhibitors (RTI)
Nucleoside analogue RTIs (NRTI)
Non-nucleoside RTIs (NNRTI)
Protease inhibitors (PI)
NRTIs
Adverse Effects
Zidovudine
Peripheral neuropathy
Didanosine Pancreatitis
Zalcitabine Myopathy
Lamivudine Mucosal ulcers
Stavudine
Abacavir
NNRTIs
Adverse Effects
Nevirapine
Rash
Delavirdine Sjogren’s syndrome
CNS adv. Effects
Loviride Dizziness
Insomnia
Vivid dreams
PIs
Adverse Effects
Indinavir
Fat redistribution
Saquinavir Hyperlipidemia
Insulin resistance
Ritonavir GI intolerance
Management of HIV infection
Multiple drug therapy
Indications to start:
Recommended
CD4<200
Considered
Seroconversion
CD4 200-350
Usual combinations
2 NRTIs
Stavudine+ lamivudine
Zidovudine + lamivudine
Plus
1 NNRTI or PI
Nevirapine
Indinavir
Efavirenz
VACCINE APPROACHES
Several strategies have been explored for vaccine-
Recombinant subunit vaccine
Live recombinant vaccine
Whole inactivated vaccine
Pseudovirions and virus like particles
Peptide based vaccine
DNA vaccine
References:
Jawetz-
Levenson-
MIMS-