Chapter 51
RETROVIRUSES: HIV
I. RETROVIRUSES
These are RNA viruses that belong to family
Retroviridae. Members of this family possess reverse
transcriptase (RNA directed DNA polymerase)
enzyme which prepares a DNA copy of the RNA
genome in host cell. The presence of enzyme reverse
transcriptase is a characteristic feature.
II. HUMAN IMMUN ODEFIC IENCY
VIRUS (HIV)
HN occurs in two main types, HIV-1 an.ct HIV-2.
A. Morphology
HN is a spherical enveloped virus, about 90-120 nm in
diameter (Fig. 51. 1). It contains two identical copies
of single stranded RNA genome. In association with
viral RNA is the reverse transcriptase enzyme. The
fig . 51.1 Structure of Human immunodeficie ncy virus
305
virus core is surrounded by a nucleocapsid composed
of protein. The virus contains a lipoprotein envelope.
The major virus coded envelope glycoproteins
are the projecting spikes on the surface and the
anchoring transmembrane pedicles.
)¥.'Modes of Transmission
There are three modes of transmission: sexual
contact, parenteral and perinatal.
1. Sexual contact: This is the most important mode
of transmission. Sexual transmissio n occurs
among both homosexual as well as heterosexu al
individuals.
2. Parenteral transmissi on: It may occur through
blood after receiving infected blood transfusions,
blood products, sharing contamina ted syringes
and needles as in intravenou s drug abusers or
accidental inoculation.
Envelope glycoprotein spike (gp 120)
~
Envelope
RNA
Nucleocapsid (p24)
Outer shell of nucleocapsid (p 18)
Reverse transcriptase
Transmembrane pedicle
glycoprotein (gp 41)
 ,/"'fafile ITT.::::: u pporr orusn c IDiec tmns arm 1Vl3.ll-
gJtan~
lilV infects all cells expr essin g at their surfa ce the
CD4
Comm only Asso ciate d with HIV lntec ti~ ~ 3
antig en, whic h is the recep tor for the virus . It infec I. Bacte rial
ts
prim arily the CD4+ lymp hocytes. The Cent re / Myco bacte ria l infec tio ns-T ube rculo sis and
for
Disea se Cont rol (CDC) in Atlan ta, USA has class ified non-tuberc ulous infecti ons
the clinic al cours e of HIV infection into vario us grou
ps ~ M. avium comp lex
(Tab le 51.1). / . Salm onell osis
-~---~ II. Viral
Table 51.1: Class ificat ion Syste m for HIV
1. CMV
Infec tion and AIDS
J V 'Herp es simp lex
(Cen tre for Disea se Cont rol , USA)
~ arice lla-zo ster
Grou p I Acute HIV infec tion
· / Epste in-Ba rr· (EB) virus
Group II Asymptom atic infec tion
III. Mycotic
Group ill Persi stent gener alised lymp haden opath y 1. Pneu mocy stis j irove ci pneu moni a
Group IV Y. Candidiasis
Subgr oup A Cons titutio nal disea se -ARC y.· Cryp tococ cosis
Subg roup B Neurological disea ses Y Aspe rgillo sis
Subg roup C Secon dary infect ious disea ses y Histo plasm osis
Cl & C2 6. Cocc idioid omyc osis
Subgr oup D Secon dary cance rs IV. Paras itic
Subgroup E Other condi tions y Toxo plasm osis
P rypto spori diosi s
1. Grou p I-Acute HIV infec ti on: The illne ss is
characteri sed by acute onse t of fever, mala ise,
Y
Isosp orias is
4. Gene ralise d stron gyloi diasis
sore throa t, mylagia, arthralgia, skin rash and
V. Malig nanci es
lymphadenopathy.
~ Kapo si's sarco ma
2. Group II-As ympt oma tic infec tion: This
includes all infec ted perso ns who are usua lly Y. B-cell lymp homa or non-H odgk in's lymp homa
well. They show posit ive lilV antib ody tests , and
are infectious. 4,-al Manifestations
3. Group III-P ersis tent gene ralis ed lymp ha- Patie nts with AIDS are at grea ter risk for bacte
de?wpathy (PGL): This grou p is char acter ised rial,
viral and fung al infec tions of the mout h. Dent
by enlar ged node s. al
carie s and gingivitis may occu r. Acut e nee
4. Group IV-S ympt oma tic HIV infec tion: Whe · · u
n @ce ranv e gingivitis)pay act as ~ m cato r that tne
CD4+ T lymp hocy te coun t falls belo w 400 per patie nt may have AIDS.
mrn 3, the patie nt may deve lop symp toms like
Herp es simp lex infec tions may be prese nt as
fever, diarThoea, weig ht loss, nigh t swea ts and multiple, deep er, more painf ul ornl lesio ns in patie
oppo rtuni stic infec tions. nts
with AIDS. Thes e lesio ns heal slowe r than the he
Wh.en CD4+ ceHs fall belo w 200 per mm 3, the titre ~
simp lex lesio ns in immunco mpe tt•nt persous.
of virus increases markedly and there is irrev ersib
le Hair le ukop lakia sl_~\ of
breakdown of immune defence mech anism s. Most immu nocteflciency. t appe ars to be i.nduet'<i
of the pacient'f with HIV disease dJe of infec tions Y
Epstein-b arr ( EB) virus, poss ibly ln comb inati
on
 witll papillomavirus or Candida in patients with 1
infection. TI1e lesions are generally @ ate ral.)whik,
0 , hairy excrescences on the lat eral margins of_
tJ1e tongue. However, t m1 ateral co ated lesion
may
__:-
also occur elsewhere on tlte tongl1e or oral
~
Candidiasis may bee-Present in most patients with
HIV infection. ~ is usually found on the_palatal
and buccal mucosae. Asymptomatic erythematous
lesions of candidiasis sometimes occur on the palatal
;;a lingmtl;;1ucosa~. Other oral manifestations inciude
angular chgiitis. (fissures and ulcers at the comer of
~ ) and mucocut.aneous candidiasis.
_,..JY.Laboratory Diagnosis -
J. Specific _Tests f or HIV Infections
(i) A11tigc11 detection
TI1e p24 antigen is the earliest virus marker to appear
-
in the blood. ELISA can be used for detection of this
antigen. It may be useful for diagnosis in window
period.
'\
(ii) Virus isolation)
For diagnosis, virus is not routinely isolated. It can
be isolated from CD4 lymphocytes of eripheral
bloo ,- bone-marrow and serum. V--ni.Is isolation is
an important ·test for diagnosis in window period
when antibodies are absent in serum of patient.
(iii) Detection of viral nucleic acid
Viral nucleic acid can be detected by polymerase
chain reaction (PCR). The test is highly sensitive
and specific. It is also useful for diagnosis in window
period.
(iv) Antibody detection
Demonstration of antibodies is the simplest and
. most commonly employed technique for diagnosis.
? ~ It may take several weeks to months for antibodies
fJ to appear after ~ection. IgM antibodies appear first
ually in about 3-4 weeks after infection, to be
followed by IgG antibodies.
HIV infected persons remain negative for
antibodies during w i ndow period, when initial viral
replication takes place for about 2-3 weeks.
There are two types of serological tests-
screening and supplemental (Table 51.3).
~ o, 7
r---- 51.&t · Luor~tery Test.a b>r Detection
8pe~ Afftllfedte'e lo lf1V tnfeCl'tto• j
L ScN>Pning (&IRIS) tests
(a) ELIS,\
(b) Rapid tests
- Dot blot assay
- Particle agglutination
- HJV spot and comb test.s
( c) Simple tests
ThPse are ba<;ed on ELISA principle.
2. Supplemental tests
- Western blot test
- Indirect immunofluorescence test
- Radio lmmuno Precipitation assay
Screening tests
(a) ELISA test: ELISA is the method most commonly
used. It is highly sensitive and specific test.
-ELISA ,test is an extremely good screening test
and most labora~ries use a::_:comrnercial ELISD
Jett that contains boffi Al Y-1 · and HIV-2. )
Saliva is an acceptable alternative to serum for
antibody testing by ELISA
(b Ra id tests: These tests take Gess lhan 3? J
d do not require expensive ent.
tests include dot-blot ·cle
·on HIV spot and comb tes
(c) Simple tesf,S: They take 1-2 hours and do not
require expensive equipment.
Supplemental tests
(a) Western blot test: In this test, HIV proteins are
· se'parated by polyacrylamide gel electr~oresjs... . .
The separated proteins are !!,lotted ,<>n t9 strips '
of nitr.ocelJnlase papt:r Thes.e strips are reac.ted
with test sera.. Antibodies to . HIV proteins,. if
present in test serum, . combin_e with different
fragments of ·HIV. .The position of the colour
band on the strip indicates- the fragment of
antigen with which antibodies have reacted
(Fig._51.2).
A positive result in any one screening test may
not be accepted without confirmation. It was
the practice to use the Westem blot test for
confirmation. As the test is cwnbersome, eostly
and not readily available, different stmtegies art'
 3. Blood: All blood and blood product s are to be
eC: e screened for HIV. This also applies to donation
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en treatmen t.
5. Control of inf ection: Screenin g of individuals
gp 160 - -
gp 120 - - within risk groups helps to identify the HIV
infected persons.
P 59 I
p 51 ::=::::
p41- F. Prophylaxis
No effective vaccine has yet been found out. High
p31-- rate of mutation of the virus has made difficulty in
developi ng the vaccine.

y.Antiretroviral Therapy (ART)

Fig. 51 .2 Diagramatic representation of Western blot
test for HIV
followed for confirmation. The practice now is
to perform either two different types of ELISA
or an ELISA witn any of the rapid tests. A serum
positive in both tests is consider ed positive.
(b) Indirect immunojtuorescence test: ijIY infected
cells are fixed onto glass slides and then reacted
~ th senun followed by fluorescein coajugat ed
antihuman gamma globulin. In _;:i positive
test, apple-green fluorescence appears when
examined under fluorescent microscope.
2. Non -specific Tests
Total and differential leucocyte count
AIDS, there is leucopen ia with a
· lymphocyte count less than 400 per mm3.
!-lympho cyte subset assays
The normal CD4: CDS T-cell ratio of 2 : 1
is reversed to O5 : 1 in cases of AIDS. The
count of CD4 lymphocytes falls below
per mm3. 200
::.s.- , infected matenal or an ins~e nt contami nated
~ with one of these material s may lead to risk of
E. Prevention
The following preventi ve
measure s are
recomm ended.
1. Sexual contact: The use of condom s can prevent
transmis sion of the virus.
2. Sharingneedles: Contami nated syringes or
needles should not be shared.
Specific treatmen t with_w tiretrovi ral drugs is the
mainstay ih the manage ment of HIV · infection.
Highly active antiretr ovi ral therapy (HAAR.'Ij
is effective in inhibitio n of HIV repli~ in-
inost of the HIV-infected individu als but major
drawbac k with this therapy is the selectio n of_
resistant mutants . Antiretr oviral ?rags include
both nucleosi de and non-nuc leoside inhibitor s
of enzyme reverse transcri ptase, viral pretease
inhibitors, fusion inhibito r, integras e inhibito r and-._
e ntry inhibitor (Table 51.4). These drugs have been
used as monothe rapy or in various combina tions.
. Adverse reaction s and high cost restrict their wide
use in developi ng countrie s.
Apart from specific antiretro viral therapy,
other measure s in the treatme nt of AIDS include
-~ (i) treatmen t and ·prophyl axis of opportu nistic
~e~tion s and tumours_(ii) ~nera). m-a,nagement and
(m)unm unoresto rative measure s. /
H. Postexposure Prophylaxis (P~ P)
Exposur e to· ~lood, body fluid other potentia lly
acquirin g HIV infection . The risk of infection varies
with the type of exposur e and other factors. Most
exposur es do not result in infection . Health workeIS
are .normall y at very low 1isk of acquirin g infe.ction
durmg manage ment of infectect patients. FollowiJlg
exposur e, postexp osm·e prophyl axis (PEP) may be
required dependi ng upon tl1e categOl'y of e:\."l)OSW""e
and HIV status of exposure source . Zidovudine
Table 51.4: Antiretroviral DrutPJ
Nu,cko1JiM rever1Je Non-nucleoslde rever•e ProteMe Fusion lntegraMt E~
tmnscrlptaae transcrlpta8e Inhibitors Inhibitors Inhibitor JnlrUnlor lnlil&ltor
inhibitors (NRTia) (NNRTls)
Zidomtdine (AZT, . Nevimpine (viramune) Saquinavir Enjuvirtide RaUegravir Maraviroc

azidothymidine) Delavi ridine (rescriptor) Ritonavir

Didanosine ( ddl) Efavirnez (sustiva) Lopinavir ,

Zalcitabine (ddc) lndinavir ,

StaVlldine ( d4n Nelfinavir

LamiVlldine (3TC) Amprenavir

'
Abacavir (1592) Ti.pranavir

Tenofovir At.a?.anavir

Emitricitabine (ITC) Fosamprenavir

300 mg BD and Lamivudine 15_0 _m g :JJD are used
in basic two drug regimen. In expanded three drug
PEP regimen, a protease inhibitor is added to this
combination of ~gs_.- Among protease inhibitors,
lopinayir 400 mg BD or 800 mg OD or ritonovir 100
mg BD ·or 200 mg OD are preferred as third drug/
To be effective these drugs must be started within
the first 72 hours and ideally within 2 hours. The
PEP should be continued for a period of four weeks.
Both risk of infection and possible side-effects of
antiretroviral drugs should be carefully considered
when deciding to start PEP Besides PEP, iajured site
on the wound should be thoroughly washed with
soap and water. Antiseptics may also be used.
I. Universal Precautions
Concerns about transmission of the hepatitis B virus
(HBV) and hwnan immunodeficiency virus (IIlV)
led to the introduction of 'universal precautions',
to minimise the infections in medical laboratory
workers and health care personnel. These universal
precautions include:
1. Assume that all specimens/patients are
potentially infectious for HIV and other blood
borne pathogens.
2. All blood specimens or body fluids should be
placed in a leak-proof impeIVious bags for
transporation to the laboratory.
3. Use gloves while handling blood and body fluid
specimens and other objects exposed to them.
If there is a likelihood of spattering, use face
masks with ~ s or goggles.
4. Wear laboratory coats or gowns while working
in the laboratory. Wrap-around gowns should be
preferred. The~ should not be taken outside.
5. Never pipette by mouth. Mechanical pipetting
devices should be used.
6. Decontaminate the laboratory work surfaces
with an appropriate disinfectant after the
spillage of blood or other body fluids and when
the procedures are completed.
7. Limit use of needles and syringes to situations
for which there are no other alternatives..
8. Biological safety hoods should be used for
laboratory work.
9. All the potentially contaminated materials of
the laboratory should be decontaminated before
disposal or reprocessing.
10. Always wash hands after completing laboratory
work and remove all protectiV"e clothings before
leaving the laboratory.