hiv epidemology,mode of transmission,pathogensis treatment, opportunistic infections

1. HIV AND
OPPURTUNISTIC
INFECTIONS.

2. • The AIDS is the state of profound
immunosuppression produced by chronic
infection with HIV.
EPIDEMIOLOGY
• In june 1981, 5 cases of pneumocystis jiroveci
pneumonia were derived in homosexual men in
the USA. Universal conditions like Kaposis’s
Sarcoma followed shortly. Also a marked
impairment of similar immune response. So the
term Acquired immune deficiency syndrome was
coined.

3. • In 1984, a new human retro virus named human
immuno deficiency virus was isolated and
identified as the cause of AIDS.
• PCP (pneumocystic pneumonia) was the
indicator disease in more than 60% of newly
diagnosed cases.
MODE OF TRANSMISSION
• Virus has been isolated from body fluids
including blood, semen, vaginal secretions,
saliva, breast milk, tears, urine, peritoneal fluid
and CSF.
1. Sexual intercourse
2. Sharing of unsterilized needles or syringes,
blood or blood products that are not screened.

5. • Profound immuno suppression affecting cell
mediated immunity is the hallmark of AIDS.
• This results from infection and a severe loss of
CD4+ T cells and the impairment in the function
of surviving helper T cells.
• Macrophages and monocytes are also targets of
HIV infection.
The HIV envelop contains 2 glycoproteins,
• Surface gp120 that is non covalently attached to
transmembrane gp41.

7. CD4+ molecule is a high affinity receptor for HIV.
The binding to CD4 is not sufficient for infection.
HIV gp120 must also bind to other cell surface
molecule CCR5 and CXCR4 receptor.
• Initial step is the binding of the gp120 envelop
glycoprotein to CD4+ molecule. This binding
leads to an imp. Conformational change that
results in the formation of a new recognition site
on gp120 for the receptors CCR5 and CXCR4.
• Next step involves conformational changes I n
the gp41, which results in the insertion of a
fusion peptide at the tip of gp41 into the cell
memb. of the target T cells or macrophages.

8. • After fusion the virus core containing the HIV genome
enters the cytoplasm of the cell, after shedding its
outer coat.
• Once internalized, the viral genome undergoes reverse
transcription, with reverse transcriptase enzyme,
leading to the formation of CDNA (proviral DNA)
• In quiescent T cells, HIV CDNA may remain in the
cytoplasm in a linear episomal form. In dividing T cells
the CDNA circularizes, enters the nucleus and is then
integrated into the host genome.
• After this integration, the provirus may remain locked
into the chromosome for months or years and
hence the infection may become latent.

9. • Alternatively proviral DNA may be transcribed
with the formation of complete viral particles that
bud from the cell membrane. Finally maturing
into infectious virions under the influence of the
protease enzyme. Such productive infection
when associated with extensive viral budding
leads to cell death.
• Although HIV can infect resting T cells, the
initiation of proviral DNA transcription (productive
infection) occurs only when the infected cell is
activated by an exposure to antigens or
cytokines.
Physiologic stimuli that promote activation and
growth of normal T- cells leads to the death of HIV
infected T cells.

11. In addition to this, infection of monocytes and
macrophages is also important.
• The majority of the macrophages that are
infected are found in the tissues and not in the
peripheral blood.
• Infected macrophages bud relatively small
amount of virus from the cell surface of these
cells but these cells contain large number of
virus particles in intracellular vacuoles.
• Macrophages allow viral replication, but are
resistant to the cytopathic effects of HIV.

12. HIV INFECTION OF MACROPHAGES HAVE 3
IMP IMPLICATIONS.
• Monocytes and macrophages represent a
varitable virus factory and reservoir, whose
output remains largely protected from host
defenses.
• They provide a safe vehicle for HIV to be
transported to various parts of the body,
particularly the nervous system.
• In late stages of HIV infection, when the CD4+ T
cells number decline, macrophages may be the
major site of continued viral replication.
The number of monocytes in circulation infected by
HIV is low.

13. Two types of dendritic cells are also imp targets for
the initiation and maintanance of HIV infection.
Mucosal and
Follicular dendritic cells.
• The mucosal dendritic cells or langerhan cells
capture the virus and transport it to regional
lymph nodes where CD4+ T cells are infected.
• The follicular dendritic cells in the germinal
centres of lymph nodes are imp. reservoir of HIV.
Some of them gets infected.
AIDS also display profound abnormalities of B cell
function. These patients have hypergamma
globulinemia and circulating immune complexes
owing to polyclonal B cell activation.

14. The sequelae of untreated HIV infection can be considered
in 4 categories.
• Opportunistic infections- infections that would not
normally cause disease in an immunocompetent host.
E.g. PCP and cytomegalovirus.
• Infections that can occur in immuno competent patients,
but tend to occur more frequently , severly and atypically
in the context of underlying HIV infection.
E.g. Salmonella, herpes simplex and M. tuberculosis.
• Malignancies , particularly those that occur rarely in
immunocompetent population.
E.g. KS and non hodgkin’s lymphoma.
• Direct manifestations of HIV infections.
E.g. HIV encephalopathy, HIV myleopathy and HIV
enteropathy.

15. • Approx. 50% of individuals develop a flu like
illness at seroconversion. This primary HIV
infection is characterized by fever, arthralgia,
pharyngitis, rash and lymphadenopathy.
• The degree of associated CD4 count depletion
result in development of oppurtunistic illness
such as oropharyngeal or oesophageal
candidiasis or PCP.
Oppurtunistic infections generally fall into 2
categories.
• DNA viruses
E.g. CMV and JC virus.
• Intracellular pathogens.

16. • Patients can be classified into one of 3 groups
according to the clinical status.
1. Asymptomatic
2. Symptomatic
3. AIDS
• Symptomatic disease is characterised by fever,
night sweats, lethargy, weight loss or by
complications including oral candidiasis, oral
hairy leucoplakia and recurrent herpes simplex
or herpes zoster infections.
• AIDS is defined as the diagnosis of one or more
specific conditions such as PCP, M.tuberculosis
and CMV disease.

17. HIV infection is diagnosed by finding antibodies to
HIV in the plasma using various serological testing
methods.
The initial screening test is ELISA.
• As a false +ve test can occur in those with
collagen vascular diseases, chronic hepatitis,
pregnancy etc, it should be confirmed with
western blot. The accuracy and sensitivity is
excellent.
• A false negative test can occur in an HIV infected
patient if the ELISA and WB are obtained during
the window period or before antibody production
has occurred after primary HIV infection. It may

18. • In a high risk patient with a negative WB,
elevated plasma viral RNA levels greater than
50,000 copies per ml or the detection of the P24
antigen can establish the diagnosis of an acute
HIV infection. But a positive WB is essential to
conform HIV infection.
• A major disadv. Of HIV testing by ELISA and WB
is that the 1-2 weeks delay or more for test
results.
A rapid HIV assay for use with blood or oral
fluids, the OraQuick Advance Rapid HIV1/2
Antibody Test can detect antibodies to HIV-1 and
HIV-2 within 20 minutes of testing.
No further confirmatory test is needed if the test is

21. • To perform the test with oral liquid, the person
uses a device and gently swab completely
around the outer gums, both upper and lower,
one time around. The appearance of 2 reddish
purpile line in a small window in the device
indicates a preliminary positive test that requires
confirmation with WB.
Urine test may be possible. The sentinel HIV-1
urine EIA is the test. Sensitivity and specificity is
less. A repeatedly +ve urine EIA should be
conformed with serum WB.
Home acess HIV-1 test system- user pricks
finger tip with a supplied lancet to collect blood
specimen and sent to a central testing lab. Once

22.  CD4 count.
 The level of immunosuppression is most easily
estimated by monitoring a patients CD4 count.
This measures the no. of CD4 +ve lymphocytes
in a sample of peripheral blood.
 The normal range is 500-1500 cells/mm3. as HIV
progress no of cells falls. It is often used to
determine if HAART should be started.
 Lower than 200 cells, offered prophylaxis against
PCP. Below 50 cells, prevalence of other
infections like M. avium, CMV etc increases.

23. Viral load assays.
• Estimates the amount of circulating virus in the
blood plasma.
• Higher viral load predicting faster disease
progression.
• A reduction in viral load after commencement of
therapy is associated with clinical benefit.
• The 3 RNA assays include
1. RT polymerase chain reaction (RT-PCR)
2. In vitro signal amplification nucleic acid probe
assay or branched DNA (bDNA)
3. Nucleic acid sequence based amplification
(NASBA)

24. Can be classified as
• Antiretroviral therapy
• Management of opportunistic infections or
malignancies
• Symptom control.
Treatment goals
• Improve the quality and duration of life
• Prevent deterioration of immune function and
restore immune status.
• Treat and prevent opportunistic infections
• Relieve symptoms.

25. HAART
• More superior and beneficial.
• The treatment of opportunistic infections
comprises an induction phase of high dose
therapy followed by indefinite maintenance or
secondary prophylaxis using lower doses.
• This is due to high risk and rate of relapse or
progression after a first episode of disease such
as p.jiroverci pneumonia, cerebral
toxoplasmosis, systemic cryptococcosis and
CMV rhinitis.

26. • Discontinuation of prophylaxis both primary and
secondary is now usually possible in individuals
who demonstrate immunological restoration on
HAART
• This may result in apparent clinical deterioration
with oppurtunistic infection during the first few
weeks after the initiation of HAART.
• This is known as Immune reconstitution
inflammatory syndrome. (IRIS)

27. 1. A combination of 3 anti retroviral agents
selected on the basis of treatment history and
resistant tests should be prescribed to increase
the efficacy and reduce the development of
drug resistant virus.
2. Regimen should contain a drug that penetrates
the CNS and provides protection against HIV
related encephalopathy or dementia.
3. Treatment strategies should be adopted that
sequence drug combinations mindful of
potential cross resistance and future therapy
options.
4. Given the critical imp of a high level of

28. The British HIV association (BHIVA) and the
international AIDS society provide regularly
updated guidelines on the use of antiretroviral
therapy.
This includes.
• When to start therapy
• What to start with
• How to monitor, including use of TDM and
resistance testing.
• When to switch therapy
• What to switch to
• Treating individuals who have been highly
exposed to multiple agents.
• Managing individuals with comorbidities
(TB or hepatitis B/C)

29. 1. Nucleoside reverse transcriptase inhibitors
(NRTIs) zidovudine, didanosine, stavudine,
lamivudine, abacavir, trizivir, zalcitabine,
emtricitabine, tenofovir
2. Non nucleoside reverse transcriptase inhibitors
(NNRTIs)
Nevirapine, efavirenz, delavirdine.
3. Protease inhibitors
ritonavir, indinavir, lopinavir, atazanavir,
darunavir,nelfinavir, saquinavir, amprenavir,
foramprenavir, tiprinavir.
4. Fusion inhibitors
enfuvirtide

30. • PEP involves the use of antiretroviral drugs to
prevent infection with HIV after possible
exposure which may be recommended after
occupational injuries or sexual exposure.
• Usually commenced as a 3-5 day regimen of 2
nucleotide/ nucleoside analogue and as protease
inhibitor followed by an ongoing course for a total
of 4 weeks post exposure.
• Aim is to suppress local viral replication prior to
dissemination so that the infection is aborted.
• Should be started ASAP within 1-2 hrs of
exposure, likelyhood of preventing infection
declines with the delay.

31. • The national AIDS control org. recommends 2
types of regimen.
1. For low risk
Zidovudine 300mg twice daily+
lamivudine 150 mg twice daily
Both for 4 weeks
1. For high risk
Zidovudine 300mg twice daily +
lamivudine 150 mg twice daily+
indinavir 800mg thrice daily.
All for 4 weeks.

32. HIV may be trasmitted from mother to child either
through placenta/ during delivery/ by breast
feeding.
• In the HIV+ve women who are not receiving ART,
zidovudine (300mg BD) started during 2nd
trimester and continued through delivary to post
natal period with treatment of the neonate for 6
weeks has found to reduce the chances of mother
to child transmission by 2/3rd.
• Even 3 drug ART after the first trimester can be
given.
• Breast feeding should be discouraged as it can

33. • Combination of 2 NRTIs and 1 NNRTI or
2 NRTIS and a boosted protease inhibitor.
• Boosted PI refers to a combination of 1 PI
combined with a low dose (100-200 mg OD/BID)
of ritonavir, another PI.
(ritonavir is used as a pharmacokinetic enhancer
of the other PI generally by increasing the Cmax
and extending t1/2)
• Triple NRTI therapy is no longer recommended
as it is associated with unacceptable rates of
virological failure.

34. • The aim of initial therapy is to achieve viral load
suppression in the plasma to levels below the
detection limit (40 copies/ml)
• Elevation in CD4 count and clinical evidence of
immune reconstitution.
• Sustained suppression over years is possible,
viral rebound may occur and is usually
accompanied by the development of resistance
to 1 or more agents in the combination.
• A 2nd line regimen is then given using a new
class of drug to which the individual has not
previously been exposed.

35. Zidovudine ( Thymidine analogue)
• MOA: phosphorylated in the host cell to
zidovudine triphosphate which inhibits reverse
transcriptase enzyme (by acting as a false
substrate) and so viral RNA to viral DNA
conversion is inhibited.
• Thus prevents infection of new cells by HIV but
has no effect on virus directed DNA that has
already integrated into host chromosome.
• Zidovudine gets integrated into growing DNA and
terminates chain elongation.

36. DOSE
• 250 mg BD
• Can be taken with or
after food to reduce GI
side effects.
SIDE EFFECTS
• Nausea, vomiting,
headache, fatigue and
muscle pain.
• More common in first 2
weeks and then wear
off.
• Hematological toxicities
like neutropenia and
anemia may develop
after 6 weeks.
• Myopathy may be
associated with long
term therapy.
• Lactic acidosis.

37. MOA & DOSE
• Guanosine analogue
• Potent drug that acts
after intracellular
conversion to
carbovir
triphosphate.
• 300 mg bd
• 600 mg od
• Taken with or with
out food.
SIDE EFFECTS
• Rash, headache,
nausea and vomiting,
reduced appetite
• Hypersensitivity
• Lactic acidosis.

38. MOA:
• Purine nucleotide analogue
• Which after intracellular conversion to didanosine
triphosphate
• Competes with ATP for incorporation in viral DNA
• Inhibits reverse transcriptase
• And terminates proviral DNA.

39. • If > 60 kg-
400 mg OD
(with tenofavir- 250 mg
OD)
If < 60 kg-
250mg OD
( with tenofavir- 200 mg
OD)
Must be taken on an
empty stomach.
• Nausea
• Bloating
• Diarrhoea
• Dry mouth
• Pancreatitis
• Peripheral neuropathy
• Hyperuricaemia
• Lactic acidosis

40. • 200 mg OD
• Taken with or without
food
• Headache
• Nausea
• Diarrhoea
• Dizziness
• Harmless skin
discolouration
• Lactic acidosis

41. MOA: Gets phosphorylated intracellularly and
inhibits HIV reverse transcriptase.
• Its incorporation into DNA results in chain
termination
• It is also active in Hepatitis B virus (inhibits
hepatitis B virus DNA polymerase)
DOSE: 150 mg BD, 300 mg OD,
• taken with or without food
SIDE EFFECTS: generally well tolerated
• GI disturbance, headache, anaemia, neutropenia
& lactic acidosis.

42. DOSE
If > 60 kg,
• 40 mg BD
• Taken with or without
food.
If < 60 kg,
• 30 mg BD
SIDE EFFECT
• Zidovudine
antagonises the action
of stavudine.
• Perpheral neuropathy
• Pancreatitis
• Lactic acidosis
• Lipoatropy
• Hyperlipidemia

43. DOSE
• 300 mg OD
• Tinofovir disoproxil
245mg tablet is
equivalent to tenofovir
disoproxil fumarate
300mg
SIDE EFFECT
• Diarrhoea
• Nausea
• Vomiting
• Headache
• Flatulence
• Renal impairment
• Hypophosphataemia

44. • CAMBIVIR
300 mg zidovudine +
150mg lamivudine
(One tablet BD)
• KIVEXA
600 mg abacavir +
300 mg lamivudine
(One tab OD)
• TRIZIVIR
300 mg abacavir +
300 mg lamivudine +
300 mg zidovudine
(One tab BD)
• TRUVADA
200 mg emtricitabine +
245 mg tenofovir
disoproxil.
(One tab OD)

45. • Most antiretroviral regimens will include 2 NRTIS
and a PI or an NNRTI
• Combination formulations like KIVEXA and
TRUVADA have the benefits of once daily
administration and improved toxicity profile.
• A no of combinations should be avoided.
1. Zidovudine + stavudine
(intracellular competition resulting in
antagonism)
2. Stavudine + didanosine
(unacceptable toxicity)
3. Tenofovir + didanosine

46. • They inhibit the reverse transcriptase enzyme by
binding to its active site.
• Do not require prior phosphorylation and can act
on cell free virions as well as infected cells.
• They are more potent than zidovudine on HIV-1
but do not inhibit HIV-2.
• They include- efavirenz & nevirapine.
• Resistance to NNRTIs occurs rapidly in
incompletely suppressive regiments & it is
therefore essential that they are prescribed with
atleast 2 NRTIs or in a combination of NRTI & PI.

47. • Cross resistance between these agents is high.
• Efavirenz and nevirapine have much longer
plasma half lives than NRTI & PI, so when
stopping an NNRTI containing combination,
consideration should be given to either
1. Continuing the other agents for a period after
cessation of the NNRTI or
2. Switching to a booster PI prior to regimen
discontinuation.
• 2nd generation NNRTI Eg: etravirine that are
active against virus resistant to the currently
available agents are in clinical development.
• The combination therapy with an NNRTI has
successfully reduced the HIV-RNA levels when
an early regimen has failed.

48. DOSE
• 600 mg OD usually at
night.
• Oral solution has
lower bioavailability
than tablets or
capsules, equivalent
dose 720 mg OD.
• Increase to 800 mg
OD with rifampicin.
• Can be taken with or
without food.
• Taken with fatty food
may increase
bioavailability and
toxicity.
• Taken at night to
minimize sedative
effect, but can be
taken during day if
preferred.

49. • CNS disturbance
ranging from sedation,
dizzy & impaired
concentration to vivid
dreams, mood swings
& hallucinations.
• Advise not to drive if
affected.
• Caution in patients
with previous or
current psychartic
illness.
• Mild rash, raised LFTs
more common if
hepatitis B & C co-
infected.
• Hyperlipidemia, hence
cholesterol level
should be monitored.
• Avoid during
pregnancy-
teratogenic.

50. DOSE & SIDE EFFECTS
• 200 mg OD for first 14
days.
• 200 mg BD or 400 mg
OD
(only after >= 6 weeks
to reduce risk of liver
toxicity)
• Taken with or with out
food.
• Rashes, raised LFTs,
hepatitis. ( check every
2 -weeks for 1st two
months)
CAUTION:
• On retaining
nevirapine if prev.
discontinued due to
rash or hepatitis or
raised LFTs.
• Greater risk of rash
associated hepatic
events if starting in
women with CD4>
250 cells/mm3 or men
with CD4> 400
cells/mm3.
• Hence avoid in such
patients.

51. • An aspartic protease enzyme encoded by HIV is
involved in the production of structural proteins
and enzymes (including reverse transcriptase) of
the virus.
• The large viral polyprotein is broken into various
functional components by this enzyme.
• This enzyme protease acts at a late step in HIV
replication, i.e. maturation of new virus particles
when the RNA genome acquires the core
proteins and enzymes.
• PI bind to the protease molecule, interfere with
its clearing function and are more effective viral
inhibitors than zidovudine.

52. • Because they act at late step of viral cycle they
are effective in both newly and chronically
infected cells.
• Under their influence, HIV infected cells produce
immature non infectious viral progeny, hence
prevent further rounds of infection.
• The major e.g. are
1. Atazanavir
2. Darunavir
3. Foramprenavir
4. Indinavir
5. Lopinavir
6. Nelfinavir and ritonavir

53. • Monotherapy with one of these drugs in
previously zidovudine treated patients reduced
HIV viral levels, increased CD4 cell count and
improved the clinical condition.
• Combination of NRTIs with PIs has been found
more effective than either drug given alone, and
the triple therapy is more effective than double
therapy.
• Current recommendations are to use a PI in
combination with either 2 NRTI or 1 NRTI +
1NNRTI
• In case of different PIs 6-18 tablets are to be
taken daily. Some on empty stomach, but others
with meals and this has to go on for months and
years.

54. • One of the strategies adopted to reduce the dose
of IDV, LPV and SQV is to combine them with a
low and sub therapeutic dose (100mg) of
ritonavir.
• By reducing first pass metabolism, ritonavir
increases the bioavailability of the companion PI.
• This boosted PI regimen permits reduction in the
number/ frequency of tablets to be taken each
day.
• Lopinavir is marketed only in combination with
ritonavir.
• Nelfinavir is not to be combined with ritonavir.

55. • GI intolerance
• Asthenia
• headache
• Dizziness
• Limb and facial tingling
• Numbness and
• Rashes.
• Lipodystrophy-
abdominal obesity,
buffalo hump with
wasting of limbs and
face.
• Dyslipidemia – raised
TG and cholesterol
• Diabetes- may be
exacerbated
• Indinavir -crystallises in
urine and hence
increases the risk of

56. DOSE
• 300 mg with 100 mg
ritonavir OD
• 400 mg with 100 mg
ritonavir OD with
enzyme inducers
• 400 mg OD without
ritonavir (not
recommended)
• Taken with or after
food to enhance
bioavailability.
SIDE EFFECT
• Nausea
• Diarrhoea
• Headache
• Rash
• Jaundice
• Hyperbilirubinaemia
• Raised LFTs
• More common in
hepatitis B or C co-
infection
• Lipodystrophy

57. DOSE
• 600 mg BD with
ritonavir 100 mg BD
• Taken with food to
improve bioavailability.
SIDE EFFECTS
• Nausea
• Diarrhoea
• Vomiting
• Constipation
• Abdominal pain
• Headache
• Hyperlipidemia
• Raised LFTs
• Lipodystrophy

58. DOSE
• 700 mg BD with 100
mg BD ritonavir
• Taken with or with out
food.
SIDE EFFETCS
• Nausea
• Vomiting
• Diarrhoea
• Rash
• Fatigue
• Raised LFTs
• Hyperlipidaemia
• Lipodystrophy
syndrome

59. DOSE
• 800 mg 8 hourly with
ritonavir.
• 800 mg with 100 or
200 mg ritonavir BD
• 400 mg with
400 mg ritonavir BD
1. Should be taken on an
empty stomach > 1hr B/F
or > 2 hr A/F food.
2. May take with light, low fat
snacks.
3. No food interaction if with
ritonavir.
4. Drink > 1.5 L water/day
even if taking with ritonavir.
SIDE EFFECTS
• Nephrolithiasis
• Hyperbilirubinaemia
• Increased LFTs
• Rash
• Dry skin
• Pruritis
• Hair loss
• In grown toe nails
• Haemolytic anaemia
• Lipodystrophy
• Taste perversions

60. DOSE
• 1250 mg BD
• 750 mg tds
• Taken with or after
food to increase
bioavailability.
SIDE EFFECTS
• Diarrhoea
• Flatulence
• Nausea
• Hyperglycemia
• Diabetes
lipodystrophy
syndrome.

61. DOSE
• 600 mg BD, escalate
dose over 2 weeks
• E.g. 300 mg BD 4
days,
400 mg BD 4 days,
500 mg BD 4 days,
600 mg thereafter.
• Normally used to
boost other PIs at
doses of 100-200
mg OD or BD.
• Take with or after food
if possible to reduce
SIDE EFFECTS
• Asthenia
• Nausea
• Vomiting
• Diarrhoea
• Anorexia
• Abdominal pain
• Taste perversion
• Circumoral and peripheral
parasthesiae
• Lipodystrophy
Do not administer liquid
formulation with disulfuram
or metronidazole due to
high alcohol content.

62. DOSE
• 1000 mg with 100 mg
ritonavir BD.
• 400 mg with 400 mg
ritonavir BD
• 1500-2000 mg OD
with 100 mg ritonavir
OD.
• Take with or 2 hours
after a full meal.
SIDE EFFECTS
• Diarrhoea
• Nausea
• Abdominal dyscomfort
• Raised LFTs
• Lipodystrophy

63. DOSE
• 500 mg BD with 200
mg ritonavir BD
• Take with or after food
to improve GI
tolerance.
COMBINATIONS
• Lopinavir + ritonavir
2 tab BD
3 tab BD
• Oral solutions contain
alcohol hence donot
take with disulfuram or
SIDE EFFECTS
• Diarrhoea
• Nausea
• Vomiting
• Fatigue
• Headache
• Elevated LFTs
• Lipodystrophy

64. Commonly 2 types
• Fusion inhibitors - enfuvirtide
• CCR5 inhibitors – maraviroc
ENFUVIRTIDE
Administered SC and is largely used in heavily
treatment experienced persons with the best
results seen with when it is used with at least 2
other active agents.
MOA:
Acts by binding to HIV-1 envelope glycoprotein
(gp41) & preventing fusion of viral & cellular
membrane. Entry of virus into the cell is thus

65. • 90 mg BD ideally
every 12 hr. between
dosing interval of 8-16
hrs. allowed.
• i.e., 4 hr. flexibility for
each dose.
• Mainly infection site
reactions like pain,
erythema, nodules
and cysts.
• Insomnia
• Headache
• Lymphadenopathy
• Eosinophilia
• Increased rate of
bacterial infections
• Hypersensitivity
reactions

66. • Attachment blockers
• Integrase inhibitors
(raltegravir)
• Maturation inhibitors
• Immunomodulatory therapies
( IL-2, granulocyte macrophage colony
stimulating factor)
• Adjustive therapeutic vaccines

68. 1.PNEUMOCYSTIS JIROVERCI PNEUMONIA
Symptoms:
• Insidious onset of a non productive cough,
shortness of breath on exertion and an inability
to take a deep breath, Fever, anorexia and
weight loss.
• Most common cause of morbidity and mortality in
HIV+ve patients.
• Markedly immunosuppressed.
• CD4 counts < 200 cells/mm3.

69. Pneumocystis
jirovecii
Pneumocystis jirovecii
cysts from
bronchoalveolar lavage,
stained with Toluidin blue
O stain

70. • Presence of exercise induced oxygen desaturation.
• Typhical chest radiographic appearance of bilateral
intestitial shadowing.
• Demonstration of the organism by
immunofluorescence or silver staining of samples
obtained by sputum induction or bronchoalveolar
lavage.
TREATMENT
• Oxygen is essential for patients with compromised
respiratory function.
• Trimethoprim-sulfamethoxazole (TMP-SMX) is
widely considered the drug of choice. No other
drug or drug combination has been
demonstrated to be superior to TMP-SMX in
efficacy.

71. • In mild case, a combination of oral trimethoprim
(10-15 mg/kg/day in 2 divided doses) + dapsone
(100 mg daily) may be effective.
• In moderate to severe cases, combination of
clindamycin (600 mg, 4 times a day IV or oral)
and primaquine (30 mg OD orally)
• IV pentamidine (4mg/kg/day) is another
alternative. It should be given in nebulised form.
• Oral Atovaqnone suspension (750 mg BD) for
mild to moderate case, but must be taken with
food esp fatty food to be effective.

72. • Moderate to severe infections- adjunctive
corticosteroid therapy is required.
Prednisolone 75 mg daily for 5 days
50 mg daily for 5 days
25 mg daily for 5 days
• Cotrimoxazole confers protection against
toxoplasmosis and some bacterial infections.
960 mg daily or 3 times a week
480 mg daily
• Prophylactic therapy reduces both the incidence and severity
of this infection.
Primary prophylaxis is recommended for those individuals with a
previous AIDS defining illness or a CD4 count < 200-300
cells/mm3.

73. • Frequent manifestations and occurs easily.
SYMPTOMS
• White plaques on the oral mucosa, but may present
as erythematous plaques or an angular cheilitis.
• If swallowing is difficult or painful, oesophageal
involvement may be suspected.
THERAPY
• Ist line therapy is topical and includes nystatin
suspension, amphotericin lozenges or suspension,
with miconazole gel for patients with dentures.
• Good oral hygiene- smoking cessation
• Adjunctive therapy- chlorhexidine or H2O2
mouthwashes.

74. • For severe cases, systemic agents such as
fluconazole (200 mg OD)
• For oesophageal candidia – fluconazole 100 mg
OD for 2 weeks.
(Contiouous use can cause azole resistance in
which an alternative azole or caspofungin may
be used or higher doses of the original agent,
fluconazole 400mg daily.)

75. • Causes a disseminated infection usually with meningeal
involvement.
• Patients present with fever, headaches often without the
symptoms of meningism such as photophobia and neck
stiffness.
• Diagnosis – CSF analysis, serum cryptococcal antigen
and blood cultures.
• Moderately or severe case- IV amphotericin is generally
administered in 500ml or 1 L of buffered glucose 5% over
4 – 8 hrs.
The dose is increased from 0.25mg/kg to 0.7-1mg/kg as
tolerated.
• Renal function and serum electrolytes particularly K and
mg should be monitered closely.
Sodium loading (NaCl 0.9%) may help to reduce

76. • Administration of corticosteroids or
antihistamines may reduce the severity of
infusion related reactions.
• The usual duration of amphoterricin and
flucytosine treatment is 2 weeks, after which high
dose fluconazole (400 mg daily orally) should be
continued further for 10 weeks.
• Maintainence therapy- fluconazole 200mg daily.
Continued for life or until immune function is
restored.
Milder cases-
• Fluconazole (may be given for the entire duration
of treatment.)
• Amphoterricin (liposomal or lipid complexed
formulations, expensive, but less nephrotoxic.)

78. 1.TOXOPLASMOSIS
Toxoplasma gondii – CNS disease in patients with
AIDS
• Headache, fever, confusion, seizures or focal
neurological symptoms and signs.
• Diagnosis – appearance of ring enhancing lesions
on CT scan, brain biopsy.
First line treatment
• Sulfadiazine- 1-1.5 g iv/po 4 times daily for atleast 6
weeks and a maintanance dose of 2g PO daily in
divided doses + pyrimethamin with folic acid to
prevent myelosuppression.
• Clindamycin+ pyrimethamine with folinic acid. 600mg
IV/PO 4 times daily for atleast 6 weeks .

81. 2. CRYPTOSPORIDIOSIS
• Crptosporidium parvum- common cause of
diarrhoea in immunocompetent patients.
• In immunocompromised patients – abdominal
pain, wt loss and severe diarrhoes
• Diagnosis- stool analysis
• Optimal treatment is to increase immunological
function with HAART.
• Management in patients who are not willing to
take HAART is to remain symptomatic control
with nutritional suppliments, adequate hydration
and antidiarrhoel agents.

82. • Recurrent bacterial pneumonia, streptococcal
pneumonia and diarrhoel illness associated with
salmonella, shigella or campylobacter.
MYCOBACTER
In HIV +ve individuals M.tuberculosis is
characterised by
• Increased likelihood of reactivation of latent
disease.
• More freq. extrapulmonary manifestations of Tb.
• Rapid progression of HIV disease (patients not
receiving HAART)
• Diagnosis- culture of organism from biological

83. • Initiate treatment empirically ( due to atypical
clinical features and reduced response to
tubercular testing)
• Managing TB and HIV co infection is complicated
by Drug- drug interactions and overlapping
toxicities of both treatments and risk of
developing immune reconstitution.
HAART is usually started
• after 2 weeks of TB treatment (CD4 <100
cells/mm3)
• After 2 months (btw 100-200 cells/mm3)
• At 6 month or on completion of TB treatment
(>200 cells/mm3)

84. • Mycobacterium avium intracellulase (MAI or
MAC) infections is a frequent manifestation of
late stage HIV but is rare now as HAART is
followed.
• Symptoms: fever, wt loss, diarrhoea,
hepatomegaly
• Diagnosis: culture of the organism
• Drugs: Rifabutin, azithromycin, ethambutol.
Aternatively quinolones & amikacin.
Corticosteroids for symptomatic control.
• Rifabutin:
prophylaxis - 300 mg OD
MAI treatment - 300- 400 mg po od with other
drugs

86. CYTOMEGALOVIRUS
• Once infection has occurred, the virus remains
dormant, but in people with advanced
immunosuppression reactivation may occur and
cause disease.
• Common sites of infection are retina and
gastriontestinal tract though neurological
involvement and pneumonitis are reported.
• Diagnosis of CMV. retinitis- clinical appearance,
blurred vision, visual field defects & if untreated
progressed rapidly to blindness and substantial
treatment reduces the morbidity.
• Prev. life long treatment is recommended where

87. • Requires an initial induction period of high dose
therapy for 2-3 weeks until the retinitis is quiescent
followed by lowerdose maintenance with reinduction
if disease progresses.
• Commonly given ganciclovir IV/Orally as prodrug
valganciclovir.
• Administered 5mg/kg via a central line over 1 hr.
• Side effects- neutropenia and thrombocytopenia.
• Maintenance therapy- IV 6 mg/kg on 5 days a week
or orally valganciclovir 900 mg OD.
• Alternative- foscarnet ( if treatment failure with
ganciclovir, less toxicity profile)
• Side effects: elctrolytic abnormalities, nephrotoxicity
and ulceration esp in genitalis
(prevented by personal hygiene after micturation)

88. Cidofovir requires less frequent administration
• 2 doses at weekily intervals for induction and
fortnightly for maintainance IV route.
• Nephrotoxic and cause metabolic disturbance.
• Strict regimens of IV hydration and oral
probenecid (2g given 3 hours prior to infusion
and 1g 2hr and 8 hr post cidofovir)
CMV disease of the GIT
• usually affects the oesophagus/ colon causing
dysphagia and abdominal pain with diarrhoea.
• Diagnosis- histological analysis of biopsy
specimens
• treatment- as for CMV retinits induction therapy.

89. • Loss of > 10% of body weight with diarrhoea and
fever.
• HIV patient has significant weight loss.
• Pathogenic mech: hypermetabolism, hormonal
imbalance, HIV infection of enterocytes &
reduced oral intake.
• Therapeutic interventions: appetite stimulants
(megastrol, medroxyprogesterone acetate,
anabolic agents and recombinant human growth
hormone) with intensive nutritional support.

90. 1. KAPOSI’S SARCOMA
• Most common malignancy and may be triggered
by infection with human herpes virus 8 (HHV-8).
• Majority of lesions affect the skin and appears as
raised purple papules.
• May be single/multiple and in severe cases may
result in odema, ulceration and infection.
• Some cases treatment is not necessary and
cosmetic camouflage may be sufficient.
• Treatment with antiretroviral results in
improvement & sometimes complete restoration
of kaposis sarcoma.

91. • When individual lesions become troublesome local
radiotherapy/intralesional chemotherapy (vincristine)
may be beneficial.
• Newer approaches using topical agents- retinoic acid
derivatives.
• The lipososmal formulation of doxorubicin and
daunorubicicn have supersided the combination of
vincristine & bleomycin being less toxic and more
efficient.
• Etoposide and Paclitaxel have used in recurrent
cases.

92. • 2. LYMPHOMAS
• Common type is high grade B cell (non-hodgkin’s)
types.
• Primary CNS lymphomas, more common in HIV
infection (uncommon in general population).
• The advent of HAART has dramatically reduced the
incidence of all lymphomas but not the primary CNS
lymphoma.
• Even palliative radiotherapy/corticosteroids confer
little benefit
• For CNS disease a regimen involving
cyclophosphamide, doxorubicin, vincristine &
prednisolone was used.
• Cyclophosphamide, doxorubicin & etoposide-
recently used.

93. • CIN & AIN are both associated with human
papillomavirus infection, common in HIV infected
patients and may progress to cervical cancer and anal
cancer.
• HAART reduces the progression of CIN but not AIN.
• Incidence of this malignancy may increase with
improvements in HIV survival.
• Early diagnosis, surgery, chemotherapy and
radiotherapy.
• Screening by smear tests & easily treatment with
imiquinod may reduce the need for such aggressive

94. • Neurological symptoms may be due to
appurtunistic infections, tumours or the primary
neurological effects of HIV.
• HIV encephalopathy or AIDS dementia complex
(ADC) results from direct infection of the CNS,
with HIV.
• The patients have profound cognitive dysfunction
and amnesia.
• Any other causes can be ruled out by brain
scanning and CSF analysis.
• Psychometric test results are usually suggestive
of the underlying aetiology.

95. • HAART reduce the incidence of ADC.
• One agent with good penetration of the CNS is
included in most HAART regimen because CNS
penetration of some antiretroviral agents is better
than others particularly in individuals with
cognitive impairment.
• Progressive multifocal levoencephalopathy
(PML) is caused by JC virus and may at
presentation appears similar to cerebrovascular
accident, but will have characteristic white matter
lesions on an MRI scan, with or without the
presence of JC virus in the CSF.
• HAART prevents the disease progression, but do
not reverse the functional deficit.

96. Number of ways by which HIV can impact on HBV
infection.
• Hepatitis B vaccination is less successful.
• Hepatitis b is less likely to be cleared hence
more likely to be chronic.
• HBV infection is likely to be associated with
higher hepatitis B DNA levels.
• Progression to cirrhosis is rapid
• Hepatocellular carcinoma is more common.
Although many individuals with HIV will have
hepatitis B, serological markers suggestive of
previous infection, 6-10% have active hepatitis B
infection.

97. • Management requires an understanding of both
viruses and is complicated by
immunosuppression and the availability of drugs
with dual HIV & hepatitis b activity.
• Hepatitis B treatment- interferon α or adefovir
should be used.
• If treatment of both viruses is indicated then the
HAART regimen should include 2 agents with
antihepatitis activity usually tenofovir with either
emtricitabine or lamivudine.
• If HIV develops resistance to these agents, they
can be continued for their anti Hepatitis B
activity.

98. HIV can impact on hepatitis C in a no. of ways.
• Hepatitis c is less likely to be cleared
spontaneously
• Higher levels of hepatitis c RNA are seen.
• Hepatitis c progresses to cirrhosis more rapidly.
• Hepatocellular carcinoma occurs more
frequently.
• Response to hepatitis c therapy is poor.
• If treatment for hepatitis C is needed for
someone on HAART the antiretrovirals used
must be compatible with hepatitis C therapy-
pegylated α interferon and ribavirin.

99. • Didanosine, abacavir, stavudine and zidovudine
– avoided.
• Treat individuals with co- infection for a longer
duration
• Side effects of hepatitis c therapy tend to be
more frequent and severe in the infected
population.
• The proactive use of the colony stimulating
factors erythropoetin, and G-CSF may enable
optimal doses of hepatitis C therapy and thereby
improve outcome.

100. DECREASED INCIDENCE OF OPPURTUNISTIC
INFECTIONS
• Consequent reduction in mortality rates and
requirement for hospital admission.
WITHDRAWAL OF PROPHYLAXIS
• The rise in CD4 count associated with HAART
has lead to an improvement in functional
immunity.
• In individuals on successful HAART if the CD4 is
>200 cells/mm3, withdrawal of prophylaxis of
PCP, toxoplasmosis, cryptococcosis or 100
cells/mm3 for M.avium intracellulase and CMV is

101. EFFECTS OF TREATMENT OF OPPURTUNISTIC
INFECTIONS
• Some difficult to treat infections like cryptosporidiosis &
microsporidiosis appear to resolve with significant CD4
count improvements associated with HAART.
• In upto 30% individuals initiation of HAART has caused a
clinical deterioration known as immune reconstitution
inflammatory syndrome or IRIS.
• This occurs in the first 2-6 weeks after starting HAART
and presents as fever and localised symptoms pertaining
to a recently treated or previously undiagonised
oppurtunistic pathogen.
• Most frequently seen in mycobacteria (lymphadenitis with
both mycobacterium TB and MAL) and CMV (vitritis, iritis
and retinal odema)
• Corticosteroids, NSAIDs and immunomodulatory