HIV AND AIDS
Structure of HIV
Surface pro-
teins
gp 120, gp
41
Lipid Mem-
brane
outer sur-
face
Reverse tran-
scriptase
enzyme in
life cycle
Etiology
Human retroviruses HIV-1 and HIV-2
• Family of human retroviruses (Retroviridae)
• Subfamily of lentiviruses
• RNA viruses whose hallmark is the reverse transcription
of its genomic RNA to DNA by the enzyme reverse tran-
scriptase
• HIV-1 is the most common cause of AIDS worldwide.
• HIV-2 has been identified predominantly in western
Africa.
o Small numbers of cases have also been reported in
Europe, South America, Canada, and the U.S.
o Has ~40% sequence homology with HIV-1
Definition
HIV disease
An infectious disease caused by HIV, a human retrovirus
HIV disease should be viewed as a spectrum ranging from
primary infection, with or without the acute syndrome, to an
asymptomatic stage, to advanced disease characterized by
profound immunodeficiency and susceptibility to opportunistic
infections.
AIDS
Late stage of infection with HIV
Current case definition
Any HIV-infected person with a CD4+ T-cell count <200/μL
Epidemiology
• Prevalence worldwide
o A global pandemic, with cases reported from virtually every
country
o ~38 million adults were living with HIV/AIDS as of the end of
2005.
Two-thirds of these adults are in sub-Saharan Africa.
~50% are women.
o ~2.3 million children <15 years are living with HIV/AIDS.
o In 2005, there were ~5 million new cases worldwide.
o Through 2005, the cumulative number of AIDS-related deaths
worldwide exceeds 25 million.
HIV/AIDS is the second leading infectious cause of death
Pathophysiology and im-
munopathogenesis
• Hallmark of HIV disease is a profound immun-
odeficiency.
• Results from a progressive deficiency of the
subset of T lymphocytes (CD4+ T cells), referred
to as helper or inducer T cells.
o The CD4 molecule serves as the primary cellu-
lar receptor for HIV.
o A co-receptor must be present with CD4 for ef-
ficient entry of HIV-1 into target cells.
o The 2 major co-receptors for HIV-1 are CCR5
and CXCR4.
• Although the CD4+ T lymphocyte and CD4+
Risk Factors
• Sexual transmission
o Homosexual and heterosexual contact with an infected person
44% of new HIV/AIDS diagnoses in 2001–2004 were attrib-
uted to male-to-male sexual contact.
34% of new HIV/AIDS diagnoses in 2001–2004 were attributed
to heterosexual contact.
o Male-to-female transmission is 8 times more efficient than fe-
male to male.
o The presence of other sexually transmitted diseases significantly
increases the risk of transmission, especially those with genital ul-
ceration.
o Lack of circumcision carries an increased risk of HIV infection.
.. Transmission by blood and blood products
o Transmission by HIV-tainted blood transfusions, blood products,
or transplanted tissue
o Intravenous drug users
Exposed to HIV while sharing injection paraphernalia, such as
needles, syringes, the water in which the drugs are mixed, or the
cotton through which drugs are filtered
Subcutaneous (skin popping) or intramuscular (muscling) injec-
tions can transmit HIV.
• Occupational transmission of HIV (health
care workers and laboratory personnel)
o Risk of HIV transmission after skin puncture from a needle or a
sharp object that was contaminated with blood from a person with
documented HIV infection is ~0.3%, and after a mucous membrane
exposure it is 0.09%.
o Transmission after nonintact skin exposure has been docu-
mented.
o The risk is estimated to be less than the risk for mucous mem-
brane exposure
• Maternal-fetal/infant transmission
o Can be transmitted intrapartum, perinatally
(most commonly), or via breast milk
o In the absence of prophylactic antiretroviral
therapy to the mother during pregnancy, labor,
and delivery, and to the fetus following birth, the
probability of transmission of HIV from mother
to infant/fetus ranges from:
15–25% in industrialized countries
25–35% in developing countries
• Transmission by other body fluids
o Although the virus can be identified from vir-
tually any body fluid, there is no evidence that
HIV can be transmitted as a result of exposure
to saliva, tears, sweat, or urine.
o Transmission of HIV by a human bite can oc-
Stages of HIV infec-
tion
Viral transmission 2-3 wks.
Acute Retroviral syndrome 2-3 wks.
Recovery + Seroconversion 2-4 wks.
Asymptomatic chronic HIV infection
Avg. 8 yrs
Symptomatic HIV infection / AIDS
Avg. 1.3 yrs
WHO staging for HIV infection & dis-
ease in adults and adolescents
Clinical stage 1
1. Asymptomatic
2. Generalized lymphadenopathy
Performance scale 1 asymptomatic, normal activ-
ity
Clinical stage 2
• Weight loss <10% of body weight
• Minor mucocutaneous manifestations
(seborrhoeic dermatitis, prurigo, fun-
gal nail infections, recurrent oral ul-
cerations)
• Herpes Zoster within the last 5 yrs
• Recurrent URTI (i.e bacterial sinusi-
tis)
Clinical stage 3
• Weight loss >10% of body weight
• Unexplained chronic diarrhea, >1
month
• Unexplained prolonged fever (in-
termittent or constant), >1 month
• oral candidiasis (thrush)
• Oral hairy leucoplakia
• Pulmonary tuberculosis
• Severe bacterial infection (i.e.
pneumonia)
• And/or performance scale 3 bedrid-
den <50% of the day during last
month
Clinical stage 1V
• HIV wasting syndrome
• Pneumocystic carinii pneumonia
• Toxoplasmosis of the brain
• Cryptosporidiosis with diarrhoea- 1
month
• Cryptosporidiosis extrapulmonary
• Cytomegalovirus disease of an organ
other than liver, spleen or lymph
node (e.g. retinitis)
• Herpes simplex virus infection, mu-
cocutaneous (>1 month) or visceral
Contd..
• Progressive multifocal leucoencephalopa-
thy
• Any disseminated endemic mycosis
• Candidiasis of oesophagus, trachea,
bronchi
• Atypical mycobacteriosis, disseminated
or pulmonary
• Non-typhoid Salmonella septicaemia
• Extrapulmonary tuberculosis
• Lymphoma
• Kaposi’s sarcoma
• HIV encephalopathy
Baseline evaluation (1)
History esp. prior ARV use, high risk
behaviour
Physical examination esp oppurtunis-
tic infection.
Laboratory
Essential-
Absolute leucocyte count
CD 4 count
Viral load
Chest x ray
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Sputum AFB
Baseline evaluation (2)
Laboratory
Before starting HAART-
LFT
Hb %
Optional –
HbsAg
Pap smear.
JAPI 2006;54:57-74
When to initiate: Patient
discussion
• ART is not curative, but prolongs life
• Treatment is lifelong
• Treatment is expensive
• Adherence is critical
• Potential toxicities
• Drug interactions
• Safer sex still essential
Patient can take some time to think
JAPI 2006;54:57-74
HIV infected patient
History and
Physical examination
AIDS defining No symptoms
Illness/some
Non-AIDS
defining illness CD4 counts
Stabilize OIs
CD4 <200 CD4 200-350 CD4>350
CD4 counts
CD4 200-250 CD4 250-350
Recommend Monitor Defer
Confirm 4 wks
HAART PVL>100000
HCV/HIVAN
Treatment of HIV
HAART (Highly active
anti retro viral therapy)
Goals of ART
Reduction of HIV related morbidity
and mortality
Improvement of quality of life
Restoration and/or preservation of
immunological function
Maximal and durable suppression of
viral replication
Current Antiretroviral Med-
ications
NRTI PI
Abacavir Indinavir IDV
ABC
Didanosine Lopinavir LPV
DDI
Emtricitabine Nelfinavir NFV
FTC
Lamivudine Ritonavir RTV
3TC
Stavudine Saquinavir SQV
D4T
Zidovudine hard gel HGC
ZDV
tablet INV
Tenofovir TDF Tipranavir TPV
Amprenavir APV
NNRTI Atazanavir ATV
Delavirdine DLV Darunavir DRV
Efavirenz EFV Fosamprenavir FPV
Nevirapine NVP
Etravirine Fusion Inhibitor
Enfuvirtide T-20
Entry Inhibitors - CCR5 co-receptor
antagonist HIV integrase strand transfer in-
Maraviroc hibitors
Raltegravir
HAART
“ Use of combination of 3 antiretroviral agents
for
treatment of HIV infection ”
Combination Regimens
NNRTI based (1 NNRTI + 2 NRTI )
PI based 1 – 2 PI + 2 NRTI
Triple NRTI based regimens
Most experienced in India - NNRTI based
regimen
What to start?
NRTI
Recommended
Zidovudine NNRTI
NRTI • Nevirapine
Tenofovir • Lamivudine • Efavirenz
Alternative
Stavudine
Abacavir
Didanosine
JAPI 2006;54:57-74
Conditions to start
HAART
Pregnant women.
Patients
with HIV-associated
nephropathy.
Treat Oppurtunistic
infections
Septran DS 1 tab
daily for primary pro-
phylaxis.
ARTis not an emer-
gency treatment
Patientmust be ready
to take tablets
OPPURTUNIS-
TIC INFECTIONS
OPPURTUNISTIC INFECTIONS
BRAIN – Toxoplasmosis
Cryptococcal meningitis
EYES - Cytomegalo virus
MOUTH, THROAT – Candidiasis
LUNGS – Pneumocystic jinoveci
pneumonia
Pulmonary TB
GUT – CMV
Cryptosporidiosis
Mycobacterium avium com-
plex
SKIN – Herpes simplex
Shingles
GENITALS – Genital herpes
Human papilloma
virus
Extrapulmonary Tuberculosis
Pleural effusion
Miliary tuberculosis
Lymph nodes
Pericardial effusion
Abdominal tuberculosis
Splenic micro abscess
TB meningitis
Tuberculoma
Isospora Cryptosporidium
