Lecture notes and very simplified

1. HIV/AIDS
Dr Arina Odawa,
MB,ChB (NBI), M.MED/STD,HIV,AIDS (SYDNEY),
Chest Medicine (Tel Aviv & Japan)
Consultant Physician STD/HIV/AIDS, Chest & Skin
Medicine

2. Introduction
AIDS was first recognized in the United States in
the summer of 1981, when the U.S. Centers for
Disease Control and Prevention (CDC) reported
the unexplained occurrence of Pneumocystis
carinii pneumonia in five previously healthy
homosexual men in Los Angeles and of Kaposi’s
sarcoma (KS) in 26 previously healthy
homosexual men in New York and Los Angeles.

3. Introduction cont-
Within months, the disease became recognized
in male and female injection drug users (IDUs)
and soon thereafter in recipients of blood
transfusions and in hemophiliacs.
As the epidemiologic pattern of the disease
unfolded, it became clear that a microbe
transmissible by sexual (homosexual and
heterosexual) contact and blood or blood
products was the most likely etiologic agent of
the epidemic.

4. Introduction cont-
In 1983, human immunodeficiency virus (HIV)
was isolated from a patient with
lymphadenopathy, and by 1984 it was
demonstrated clearly to be the causative agent
of AIDS.
In 1985, a sensitive enzyme-linked
immunosorbent assay (ELISA) was developed,
which led to an appreciation of the scope and
evolution of the HIV epidemic at first in the
United States and other developed nations and
ultimately among developing nations throughout
the world (see below).

5. Definition
With the identification of HIV in 1983 and its
proof as the etiologic agent of AIDS in 1984, and
with the availability of sensitive and specific
diagnostic tests for HIV infection, the case
definition of AIDS has undergone several
revisions over the years.
The current CDC classification system for HIV-
infected adolescents and adults categorizes
persons on the basis of clinical conditions
associated with HIV infection and CD4 T
lymphocyte counts.

6. Defn cont
The system is based on three ranges of CD4 T
lymphocyte counts and three clinical categories and is
represented by a matrix of nine mutually exclusive
categories A1, A2, A3, B1, B2, B3, C1, C2 and C3.
Using this system, any HIV-infected individual with a CD4
T cell count of 200/L has AIDS by definition, regardless
of the presence of symptoms or opportunistic diseases.
Once individuals have had a clinical condition in
category B, their disease cannot again be classified as
category A, even if the condition resolves; the same
holds true for category C in relation to category B.

7. AIDS surveillance case definition for Adults & Children
Clinical Categories
A B C
CD4 cell
categories
Asymptomatic
or PGL or
Acute HIV
infection
Symptomatic AIDS indicator
condition
>500
>29% A1 B1 C1
200-499
14-28%
A2
B2 C2
<200
<14%
A3 B3 C3

8. Mode of Transmission
HIV is transmitted by both homosexual
and heterosexual contact; by blood and
blood products; and by infected mothers to
infants either intrapartum, perinatally, or
via breast milk.
After 20 years of scrutiny, there is no
evidence that HIV is transmitted by casual
contact or that the virus can be spread by
insects, such as by a mosquito bite.

9. Sexual Transmission
HIV infection is predominantly a sexually
transmitted disease (STD) worldwide.
Although in the United States 42% of new HIV
infections are among men who have sex with
men and 33% of new HIV infections are by
heterosexual transmission, the most common
mode of infection worldwide, particularly in
developing countries, is clearly heterosexual
transmission.

10. Transmission cont
HIV has been demonstrated in seminal fluid both
within infected mononuclear cells and in the cell-
free state.
The virus appears to concentrate in the seminal
fluid, particularly in situations where there are
increased numbers of lymphocytes and
monocytes in the fluid, as in genital inflammatory
states such as urethritis and epididymitis,
conditions closely associated with other STDs.
The virus has also been demonstrated in cervical
smears and vaginal fluid.

11. Transmission cont
There is a strong association of transmission of
HIV with receptive anal intercourse, probably
because only a thin, fragile rectal mucosal
membrane separates the deposited semen from
potentially susceptible cells in and beneath the
mucosa and trauma may be associated with
anal intercourse.
Anal douching and sexual practices that
traumatize the rectal mucosa also increase the
likelihood of infection.

12. Transmission cont
It is likely that anal intercourse provides at
least two modalities of infection:
(1) Direct inoculation into blood in cases of
traumatic tears in the mucosa; and
(2) infection of susceptible target cells, such
as Langerhans cells, in the mucosal layer
in the absence of trauma.

13. Transmission by blood & blood
products
HIV can be transmitted to individuals who receive HIV-
tainted blood transfusions, blood products, or
transplanted tissue as well as to IDUs who are exposed
to HIV while sharing injection paraphernalia such as
needles, syringes, the water in which drugs are mixed, or
the cotton through which drugs are filtered.
Parenteral transmission of HIV during injection drug use
does not require intravenous puncture; subcutaneous
(“skin popping”) or intramuscular (“muscling”) injections
can transmit HIV as well, even though these behaviors
are sometimes erroneously perceived as low-risk.

14. Transmission cont
Among IDUs, the risk of HIV infection increases
with the duration of injection drug use; the
frequency of needle sharing; the number of
partners with whom paraphernalia are shared,
particularly in the setting of “shooting galleries”
where drugs are sold and large numbers of IDUs
may share a limited number of “works”.
Comorbid psychiatric conditions such as
antisocial personality disorder; the use of
cocaine in injectable form or smoked as “crack”;
and the use of injection drugs in a geographic
location with a high prevalence of HIV infection
also increase the risk of infection.

15. Transmission cont
Transfusions of whole blood, packed red blood cells, platelets,
leukocytes, and plasma are all capable of transmitting HIV
infection.
Currently, in most developed countries, the following
measures have made the risk of transmission of HIV infection by
transfused blood or blood products extremely small:
(1) the screening of all blood for HIV nucleic acid, p24 antigen,
and/or anti-HIV antibodies;
(2) the self-deferral of donors on the basis of risk behavior;
(3) the screening out of HIV-negative individuals with positive
surrogate laboratory parameters of HIV infection, such as
hepatitis B and C;
(4) serologic testing for syphilis.

16. TRANSMISSION OF HIV:
HEALTH CARE WORKERS AND
LABORATORY
WORKERS
There is a small, but definite, occupational
risk of HIV transmission to health care
workers, laboratory personnel and others
who work with HIV-containing materials,
particularly when sharp objects are used.

17. MATERNAL-FETAL/INFANT
TRANSMISSION
HIV infection can be transmitted from an infected mother to
her fetus during pregnancy, during delivery, or by breast-
feeding.
This is an extremely important form of transmission of HIV
infection in developing countries, where the proportion
of infected women to infected men is 1:1.
Proportions of mother to-child transmissions is 23 to
30% before birth, 50 to 65% during birth, and 12 to 20% via
breast-feeding.

18. 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 to 25% in industrialized countries and
from 25 to 35% in developing countries.
These differences may relate to the adequacy of prenatal care as
well as to the stage of HIV disease and the general health of the
mother during pregnancy.
Factor that is associated with higher rates of transmission is the
presence of high maternal levels of plasma viremia.
Low maternal CD4 T cell counts have also been associated with
higher rates of transmission; since low CD4 T cell counts are often
associated with high levels of plasma viremia.
A prolonged interval between membrane rupture and delivery is
another well-documented risk factor for transmission.

19. ARV treatment of HIV-infected pregnant women from the
beginning of the second trimester through delivery and of the
infant for 6 weeks following birth dramatically decreased the rate
of intrapartum and perinatal transmission of HIV infection from
22.6% in the untreated group to 5%.
The rate of mother-to-child transmission is approaching 1% or
less in pregnant women who are receiving combination
antiretroviral therapy for their HIV infection. Such treatment,
combined with cesarean section delivery, has rendered mother-to-
child transmission of HIV an unusual event in the United States
and other developed nations.
In developed countries, current recommendations to reduce
perinatal transmission of HIV include universal voluntary HIV
testing and counseling of pregnant women, antiretroviral
prophylaxis with ARV drugs in cases in which the mother
does not require therapy, combination therapy for women who do require
therapy, obstetric management that attempts to minimize exposure of the
infant to maternal blood and genital secretions, and avoidance of breast-
feeding.

20. Breast-feeding is an important modality of transmission of HIV
infection in developing countries, particularly where mothers
continue to breast feed for prolonged periods.
The risk factors for mother-to child transmission of HIV via breast-
feeding are detectable levels of HIV in breast milk, the presence
of mastitis, low maternal CD4 T cell counts, and maternal vitamin
A deficiency.
The risk of HIV infection via breast-feeding is highest in the early
months of breast-feeding.
In addition, exclusive breast-feeding has been reported to carry a
lower risk of HIV transmission than mixed feeding.
Certainly, in developed countries breast-feeding by an infected
mother should be avoided.
In certain developing countries, breast milk is the only source of
adequate nutrition as well as immunity against potentially serious
infections for the infant. Absolute breast feeding is practised with
risk due to poverty.

21. TRANSMISSION BY OTHER BODY FLUIDS
Although HIV can be isolated typically in low titers from saliva of a
small proportion of infected individuals, there is no convincing
evidence that saliva can transmit HIV infection, either through
kissing or through other exposures, such as occupationally to
health care workers.
Saliva contains endogenous antiviral factors such as HIV-specific
immunoglobulins of IgA, IgG, and IgM isotypes which are detected
readily in salivary secretions of infected individuals.
A number of soluble salivary factors also inhibit HIV to various
degrees in vitro, probably by targeting host cell receptors rather
than the virus itself.
Secretory leukocyte protease inhibitor (SLPI), blocks HIV infection
in several cell culture systems, and it is found in saliva at levels
that approximate those required for inhibition of HIV, higher
salivary levels of SLPI in breast-fed infants were associated with a
decreased risk of HIV transmission through breast milk.

22. Although virus can be identified, if not isolated, from virtually any
body fluid, there is no evidence that HIV transmission can occur
as a result of exposure to tears, sweat, and urine.
Natural History & Classification of HIV Infection
1 Viral transmission
2-3 weeks
2 Acute retroviral syndrome
2-3wks
3 Recovery + seroconversion
2-4wks
4 Asymptomatic chr HIV infection
Avg 8yrs
5 Symptomatic HIVinfection/AIDS
1-3yrs

23. Initial Event
Acute retroviral syndrome
Fever 96%, Myalgias 54%, Hepatosplenomegaly 14%,
Adenopathy 74%, Pharyngitis 70%, Rash 70%, Diarhoea 32%,
Thrush 12% weight loss13%, Headache 32%, N/vomiting 27%,
Neurologic symptoms 12%.
Clinical recovery is accompanied by a reduction in plasma
viraemia due to development of cytotoxic T cell response.
CD4 decrease is due to HIV induced cell death.
The rate of CD4 cell decline depend on the viral load.
HIV RNA concentration in plasma show an initial burst increase
during acute infection and then decline to a set point as a result of
seroconversion and immune response.
With continued infection, HIV RNA levels gradually increase.
Late stage disease is characterised by a CD4 count of
< 200cells/ml.

24. and the development of opportunistic infections and tumors,
wasting and neurological complications.
In untreated patient the median survival after CD4 has fallen
200cells/ml is 3.7yrs.
The median survival after an AIDS defining illness is 1.3yrs.
Correlation of complications with CD4 cell count
CD4 cell count/ml Complications
>500 Acute retroviral syndrome, candidal
vaginitis
200-500 Pneumoccocal & other bacterial pneu-
monia, PTB, H. zoster, thrush, Kaposi
sarcoma
<200 PCP, M/PTB, wasting, dementia, neuro-
pathy, cardiomyopathy, lymphomas.

25. < 100 Disseminated herpes simplex, Toxoplasmosis
Cryptococcosis, Cryptosporidiosis, candidal
oesophagitis.
< 50 Disseminated CMV, disseminated MAC
Diagnosis of Primary HIV infection
HIV RNA >10000 copies /ml + indeterminate or HIV negative
serology or recent seroconversion.
Diagnosis of Chronic HIV infection & AIDS
Rapid tests – Unigold, Oraquick, Clearview, Reveal G2, Multispot
Vitros, Determine, Colloidal, Orasure in saliva,
Calypte test for urine.
ELISA, Western blot, PCR and Viral load. CD4 count in serum.

26. Factors increasing the risk of acquisition of HIV
Common to all transmission categories
• High viral load
• Lower CD4 cell count
• AIDS
• Seroconversion
Vertical transmission
• Older gestational age
• Prolonged rupture of membranes
• Chorioamnionitis
• Fetal trauma (e.g. scalp electrodes)
• Lower birth weight
• Vaginal vs. elective caesarean delivery
• No peripartum prophylaxis
• First-born twin

27. Breastfeeding
• Longer-duration feeding
• Lower parity
• Younger age
• Mastitis
Sexual transmission
• STIs, especially genital ulcers
• Cervical ectopy
• Receptive vs. insertive anal sex
• Rectal or vaginal trauma
• Menstruation
• Male–male vs.heterosexual sex
• Non-circumcised
• Increased number of partners

28. Injection drug use transmission
• Sharing equipment
• Frequency of use
• Linked commercial sex
• Lower income
• Intravenous use
• Cocaine use
• Incarceration
Occupational transmission
• Deep injury
• Visible blood on device

29. Virology and immunology
HIV is a single-stranded RNA retrovirus from the Lentivirus
family.
After mucosal exposure, HIV is transported to the lymph nodes via
dendritic, CD4 T lymphocytes or Langerhans cells, where infection
becomes established.
Dendritic cells express various receptors (e.g. DC–SIGN)
that facilitate capture and transport of HIV-1.
Free or cell associated virus is then disseminated widely through
the blood with seeding of ‘sanctuary’ sites (e.g. central nervous
system (CNS) and latent CD4 cell reservoirs.
Each mature virion is spherical and has a lipid membrane
lined by a matrix protein that is studded with glycoprotein (gp) 120
and gp41 spikes surrounding a cone-shaped protein core.
This core houses two copies of the single-stranded RNA genome
and viral enzymes.

30. The virus infects the CD4 cell in a complicated sequence of
events beginning with engagement of the viral gp120 and
the CD4 cell receptor (stage 1), which results in a conformational
change in gp120.
This permits interaction with one of two chemokine co-receptors
(CXCR4 or CCR5: stage 2), which is followed by membrane
fusion and cellular entry involving gp41 (stage 3).
Monocyte macrophages,follicular dendritic cells and microglial
cells in the central nervous system also express the CD4
cell receptor and are permissive to infection.
After penetrating the cell and uncoating, a DNA copy
is transcribed from the RNA genome by the reverse transcriptase
(RT) enzyme (stage 4) that is carried by the infecting virion.
Reverse transcription is an error-prone process and multiple
mutations arise with ongoing replication (hence the rapid
generation of viral resistance to drugs).

31. This DNA is transported into the nucleus and integrated randomly
within the host cell genome via integrase enzyme (stage 5).
Integrated virus is known as proviral DNA.
On host-cell activation, this DNA copy is used as a template to
transcribe new RNA copies (stage 6), which are processed and
exported from the nucleus, viral mRNA then being translated into
viral peptide chains (stage 7).
The precursor polyproteins are then cleaved by the viral protease
enzyme to form new viral structural proteins and viral enzymes
such as the reverse transcriptase and protease (8).
These then migrate to the cell surface and are assembled using
the host cellular apparatus to produce infectious viral particles.
These bud from the cell surface, incorporating the host cell
membrane as their own lipid bilayer coat, and cell lysis occurs
(stage 9).

32. Once maturation is complete, the new infectious virus
(virion) is then available to infect uninfected cells and
repeat the process.
All of these processes are enabled by three viral genes (Gag, Pol
and Env ), as well as the products of six regulatory genes (Vif,
Vpr, Vpu, Nef, Tat and Rev ).
Each day more than 1010 virions are produced and 109 CD4 cells
destroyed.
This represents a daily turnover of 30% of the total viral burden
and 6–7% of the total body CD4 cells.
A small percentage of T cells (< 0.01%) either produce small
quantities of virus or enter a post-integration latent phase and
represent the main reservoir of HIV.
Together with virion-associated immune complexes bound to
follicular dendritic cells, they refuel infection if host defences
fail or HAART is discontinued.

33. There is ongoing low-level replication within these cells, even
when plasma levels of HIV are below the level of detection as a
result of antiretroviral treatment.
They are important as sanctuary sites from antiviral therapy, as
continuing sources of virus (including the generation of drug-
resistant strains) and as eventual targets for eradication
strategies.
The half-life of the virus is 1–2 hours in plasma, 1.5 days in
productively infected CD4 cells and over 12 months in latently
infected CD4 cells.
With time, there is gradual attrition of the CD4 cell population and,
as CD4 cells are needed in initiating the immune response,
any depletion renders the body susceptible to opportunistic
infections and oncogenic virus-related tumours.

35. The predominant opportunistic infections seen in HIV disease are
intracellular parasites (e.g. Mycobacterium tuberculosis) or
pathogens susceptible to cell-mediated rather than antibody-
mediated immune responses.
The exact mechanism underlying the CD4 decline is not fully
understood, but it is not restricted to virus-infected cells and is
linked to the height of plasma viral load.
Both are monitored closely in patients and used as measures of
disease progression.
Virus-specific CD8 cytotoxic T lymphocytes develop rapidly after
infection and are crucial in recognising, binding and lysing infected
CD4 cells, thus attempting to controlling HIV replication after
infection and the subsequent rate of disease progression.

36. On the basis of DNA sequencing, HIV-1 can be subdivided
into group M (‘major’, world-wide distribution), group O (‘outlier’,
divergent from group M) and group N (‘non-major and non-outlier’,
highly divergent) types.
Groups O and N are restricted to West Africa and may screen
weakly positive or negative on routine antibody testing.
Group M can be subdivided further into subtypes; 9 are currently
recognised (A–K), with numerous subsubtypes (e.g. A1–A4) and
circulating recombinant forms (e.g. CRF01_AE).
Globally, subtype C (Africa and India) accounts for half of strains.
Subtype A (Africa, Asia and Eastern Europe) and subtype B
(Western Europe, the Americas and Australia) are responsible for
approximately 10% each, and in many countries, more than one
subtype or recombinant exists, or is emerging in restricted groups
(e.g. West Africa, South-east Asia, southern Europe, and Russia).

37. Increased HIV diversity has implications for diagnostic tests,
treatments and vaccine development.
It may also influence transmission (more frequent with subtype
C), disease progression (faster with subtypes A and D), co-
receptor usage (CXCR4 used early with subtype D) and emergent
resistance patterns (subtype C).
In Europe, the prevalence of non-B subtypes is increasing
because of migrants (predominantly from Africa) and now
accounts for a significant proportion of newly diagnosed infection.
HIV-2 is an important but separate retrovirus which has at least
five subtypes.
The virus differs from HIV-1 in that patients have lower viral loads,
slower CD4 decline, lower rates of vertical transmission and 12-
fold lower progression to AIDS.

38. Antiretroviral Drugs Used in the Treatment of HIV Infection
Drug Class, Names, Doses & Side effects
I. Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTI)
1. Zidovudine (AZT, azidothymidine, Retrovir, 3'azido-3'-deoxythymidine)
Dose: 200 mg q8h or 300 mg bid
Side effects: Anemia, granulocytopenia, myopathy, lactic acidosis,
hepatomegaly with steatosis, headache, nausea, nail pigmentation, lipid
abnormalities, lipoatrophy, hyperglycemia
2. Didanosine (Videx, Videx EC, ddI, dideoxyinosine, 2',3'-dideoxyinosine
Dose: Buffered: Requires 2 tablets to achieve adequate buffering of stomach
acid; should be administered on an empty stomach
60 kg: 200 mg bid
<60 kg: 125 mg bid
Enteric coated:
60 kg: 400 mg qd
< 60 kg: 250 mg qd
Side effects: Pancreatitis, peripheral neuropathy, abnormalities on liver
function tests, lactic acidosis, hepatomegaly with steatosis, optic neuritis,
nausea, hyperglycemia

39. 3. Zalcitabine (ddC, HIVID, 2'3'-dideoxycytidine)
Dose: 0.75 mg tid
Side effects: Peripheral neuropathy, pancreatitis, lactic acidosis,
hepatomegaly with steatosis, oral ulcers
4. Stavudine (d4T, Zerit, 2'3'-didehydro-3'-dideoxythymidine)
Dose: >60 kg: 40 mg bid
<60 kg: 30 mg bid
Side effects: Peripheral neuropathy, pancreatitis, lactic acidosis,
hepatomegaly with steatosis, ascending neuromuscular weakness,
lipodystrophy, lipid abnormalities, hyperglycemia
5. Lamivudine (Epivir, 2'3'-dideoxy-3'-thiacytidine, 3TC)
Dose: 150mg bd or 300mg od
Side effects: Flare of hepatitis in HBV-coinfected patients who discontinue
drug
6. Emtricitabine (FTC, Emtriva)
Dose: 200mg od
Side effects: Hepatotoxicity in HBV-coinfected patients who discontinue drug,
skin discoloration

40. 7. Tenofovir (Viread) Dose: 300mg od
Side effects: Renal osteomalacia, flare of hepatitis in HBV-coinfected
patients who discontinue drug
8. Abacavir.
II. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)
1. Delavirdine (Rescriptor) Dose: 400mg tid. Side effects: Skin rash,
abnormalities in liver function tests
2. Nevirapine (Viramune) Dose: 200mg/day for 2 wks then 200mg bd or
400mg/day.
Side effects: Skin rash, hepatotoxicity
3. Efavirenz (Sustiva) Dose: 600mg nocte
Side effects: Rash, dysphoria, elevated liver function tests, drowsiness,
abnormal dreams, depression, lipid abnormalities, potentially teratogenic
4. Etravirine Dose 200mg bd
Side effects: Rash, nausea, hypersensitivity reactions
5. Rilpivirine Dose: 25mg od
Side effects: Nausea, dizziness, somnolence, vertigo, less CNS toxicity and
rash than Efavirenz

41. III Protease Inhibitors(PI)
1. Saquinavir mesylate (Invirase—hard-gel capsule)
Dose: 1000 mg + 100 mg ritonavir bid
Side effects: Diarrhea, nausea, headaches, hyperglycemia,
fat redistribution, lipid abnormalities, PR and QT interval
prolongation
2. Ritonavir (Norvir) Dose 600mg bd or 100mg as booster
Side effects: Nausea, abdominal pain, hyperglycemia, fat
redistribution, lipid abnormalities, may alter levels of many
other drugs including saquinavir, paresthesias, hepatitis
3. Indinavir sulfate (Crixivan) Dose: 800 mg q8h or 800 mg + 100
mg ritonavir bid or 1000 mg q8h when used with efavirenz or
nevirapine
Side effects: Nephrolithiasis, indirect hyperbilirubinemia,
hyperglycemia, fat redistribution, lipid abnormalities, nausea,
transaminase elevations, headache.

42. 4. Nelfinavir mesylate (Viracept) Dose: 750 mg tid or 1250 mg bid
Side effects: Diarrhea, loose stools, hyperglycemia, fat
redistribution, lipid abnormalities, transaminase elevations
5. Amprenavir (Agenerase)
Dose: Amprenavir 1200 mg bid or 600 mg + 100 mg ritonavir bid
or 1200 mg + 200 mg ritonavir qd
Side effects: Nausea, vomiting, diarrhea, rash, oral
paresthesias, elevated liver function tests, hyperglycemia, fat
redistribution, lipid abnormalities, headache, nephrolithiasis
6. Lopinavir/ritonavir (Kaletra, Aluvia) Dose 400/100mg
Side effects: Diarrhea, hyperglycemia, fat redistribution, lipid
abnormalities, nausea, pancreatitis, elevated liver function
tests, PR and QT interval prolongations
7. Atazanavir (Reyataz) Dose: 400 mg qd or 300 mg qd
+ ritonavir 100 mg qd when given with efavirenz

43. Side effects: Hyperbilirubinemia, PR prolongation, nausea,
vomiting, hyperglycemia, fat maldistribution, rash
transaminase elevations.
8. Tipranavir (Aptivus) Dose: 500mg / 200mg retonavir bd
Side effects: Diarrhea, nausea, fatigue, headache, skin rash,
hepatotoxicity, intracranial hemorrhage, hyperglycemia, lipid
abnormalities, fat redistribution.
9. Darunavir (Prezista) Dose 600mg/100mg retinavir bd with food
Side effects: Diarrhea, nausea, headache, skin rash,
hepatoxicity, hyperlipidemia, hyperglycemia.
IV. Entry Inhibitors
1. Enfuvirtide (Fuzeon) Dose: 90 mg SC bid
Side effects: Local injection reactions, hypersensitivity
reactions, increased rate of bacterial pneumonia.

44. 2. Maraviroc (Selzentry) Dose: 150–600 mg bid depending on
concomitant medications
Side effects: Hepatotoxicity, nasopharyngitis, fever, cough,
rash, abdominal pain, dizziness, musculoskeletal symptoms.
V. Integrase Inhibitor
1. Raltegravir (Isentress) Dose: 400mg bd
Side effects: Nausea, headache, diarrhea, CPK elevation,
muscle weakness and rhabdomyolysis.
2. Elvitegravir Dose: 150 mg qd pharmacoenhancing agent.
3. Dolutegravir
4. Cabotecavir