HIV / AIDS

James Nelson Okema, DCM, MBChB

Gulu College Of Health Sciences
DCM1, 2023
 STRUCTURE OF HIV VIRUS

fig1
 DEFINITIONS
HIV Infection is the state where the virus is in
the body. In most instances this is the
asymptomatic state, which is a prelude to AIDS.
AIDS stands for Acquired Immune Deficiency
Syndrome, a condition in which the immune
system begins to fail, leading to life threatening
opportunistic infections.
 Acquired” means it is transmissible.
“Immune-Deficiency” means it damages the
body defense system.
 Syndrome” refers to a group of illnesses.
Historical Background of HIV
• 1981 – Doctors in the United States recognized
Pneumocystis Carinii Pneumonia (PCP) in
homosexual males, a condition previously
unreported in healthy adults. Later they
recognized that all these patients were
immunosuppressed.
• 1983/4 – Scientists described the cause of this
acquired immunodeficiency syndrome (AIDS)
as a retrovirus: (Barré-Sinoussi 1983, Broder
1984, Gallo 1984).
o Lymphadenopathy Associated Virus (LAV).
o AIDs Associated Retrovirus (ARV).
o Human T-lymphotrophic Virus Ш (HTLV-Ш).
• 1986 – Human Immunodeficiency Virus
(HIV) was accepted as the international
designation for the retrovirus in a WHO
consultative meeting.
• 1996 – ARVs became available in the
world.
• 1984– The first case in Kenya was
described.
• 2006 - AIDS Epidemic Update", published
by the UNAIDS/World Health Organization
• Fourth biggest killer in the world
• About one-third of PLHA are between 15-24
years
• Most people are still unaware they are
infected
• Young women are more vulnerable(7.5%)
• Almost twice as high in urban
• Highest prevalence seen in central, Kampala
and North Central regions
• Thus, HIV pandemic remains the most
serious of infectious disease challenges to
public health.
 EPIDEMIOLOGY
• Its a pandemic infection with HIV1 in Europe
and HIV2 in West Africa.
• Mostly HIV1 group-M and subtype B is
pandemic.
• Subtype B is mostly in America and Europe and
subtype C in S. Africa
Epidemic Update: Sub-Saharan Africa:
• HIV is now the leading cause of death
• 10% (600 million) of world’s population live in
sub Saharan African.
• 70% of new HIV infections found in sub Saharan
Africa.
HIV PREVALENCE IN URBAN AND RURAL
AREAS DISAGGREGATED BY SEX
• Current epidemiologic assessment has
encouraging elements since it suggests:
– the global prevalence of HIV infection is
remaining level
– there are localized reductions in prevalence in
specific countries
– a reduction in HIV-associated deaths, partly
attributable to the recent scaling up of
treatment access
– a reduction in the number of annual new HIV
infections globally.
 ETIOLOGY
• IT’S A VIRAL INFECTION OF RNA GENOTYPE
WHICH IS CLASSIFIED AS:-
• GROUP: ssRNA-RT.
• ORDER: unassigned.
• FAMILY: retroviridae (Retrovirus, meaning it has
the exceptional ability to convert its genetic
material from RNA to DNA).
• SUBFAMILY: orthoretrovirinae
• GENUS: lentivirus
• SPECIES:HIV1 AND HIV2
• HIV1-Groups as M,N,O,P. and M subtypes are:-A,B.
C.D,F,G,H,J,K and CRF-circulating recombinant
form.
HIV – 2
Is mainly found in West Africa, Mozambique
and Angola.
Causes a similar illness to HIV – 1
Less efficiently transmissible rarely causing
vertical transmission
Less aggressive with slower disease
progression
• HIV targets vital cells of the immune system
possessing the CD 4+ (cluster of differentiation antigen
4) surface marker.
• These include CD 4+ T helper cells (most crucial
mediators of cellular immunity), macrophages and
dendritic cells.
• HIV infection leads to widespread destruction of these
cells, eventually rendering the body susceptible to
opportunistic infections that it would otherwise be
capable of handling.
• Individuals with advanced clinical infection often die
from these opportunistic infections (TB, Cryptococcal
meningitis, pneumocystic pneumonia, bacterial
pneumonias, diarrhoeal illnesses…) or malignancies
associated wit h progressive failure of immunity.
COMPONENTS OF THE IMMUNE
SYSTEM
Found in blood and tissues
White blood cells (WBC)- key players in immune
response (humoral and cellular)
Macrophages act as clearing cells
Neutrophils attack bacteria
Eosinophils attack helminths (and mediate allergies)
B-lymphocytes make antibodies
T-lymphocytes
Responsible for attacking viruses, fungi and some
bacteria
T helper cells central in orchestrating function of
other immune cells
T killer cells are able to destroy infected cells
HOW HIV AFFECTS THE IMMUNE
SYSTEM

HIV attaches to cells of the immune system with

special surface markers called CD4 receptors
Immune cells with CD4 receptors include:
T-helper Lymphocytes
Macrophages
Monocytes
Dendritic cells
Microglial cells
HOW HIV AFFECTS THE IMMUNE
SYSTEM

The hallmark of HIV/AIDS is profound

immunodeficiency as a result depletion of
CD4+ T lymphocytes.
The CD4+ T cell dysfunction is two fold
Reduction in numbers
Impairment in function
STRUCTURE OF THE HUMAN IMMUNODEFICIENCY VIRUS
• THE HIV LIFE CYCLE
1. BINDING AND FUSION: HIV begins its life cycle
when it binds to a CD4 receptor and one of two co-
receptors on the surface of a CD4+T- lymphocyte.
The virus then fuses with the host cell releasing its
RNA genetic material into the cell.
 2. REVERSE TRANSCRIPTON: An HIV enzyme called
reverse transcriptase converts the single- stranded
HIV RNA to double-stranded HIV DNA

3. INTEGRATION: The newly formed HIV DNA enters the

host cell's nucleus, where an HIV enzyme called integrase "
hides" the HIV DNA within the host cell's own DNA
 4. TRANSCRIPTION : When the host cell is activated, an enzyme
called RNA polymerase creates copies of the HIV genome, and
shorter strands of RNA called messenger RNA (mRNA). mRNA is
used as a blueprint to make long chains of HIV proteins.

5. ASSEMBLY: An HIV enzyme called protease cuts the long chains of HIV
proteins into smaller individual proteins. As the smaller HIV proteins come
together with copies of HIV's RNA genetic material, a new virus particle is
assembled.
6. BUDDING : The newly assembled virus pushes out ("buds") from
the host cell stealing part of the cell's outer envelope. It is
studded with protein/sugar combinations called HIV
glycoproteins necessary for the virus to bind CD4 and co-
receptors . The new copies of HIV can now infect other cells.
Budding
 MODES OF TRANSMISSION

• Person to person transmission through

unprotected (heterosexual or homosexual)
intercourse. 70-80 %
• The use of HIV-contaminated needles and
syringes, including sharing by intravenous
drug users 5-10 % .
• Transfusion of infected blood or its
components 3 – 5 % .
• Transplantation of HIV-infected tissues or
organs.
• Contact of abraded skin or mucosa with body
secretions such as blood, CSF or semen.

• HIV can be transmitted from mother to child (MTCT or

vertical transmission).

• From 15% to 35% of infants born to HIV-positive

mothers are infected through placental processes at
birth.
• MTCT is the main mode of transmission of HIV
infection to children.

• HIV-infected women can transmit infection to their

infants through breastfeeding and this can account for
up to half of mother-to-child HIV transmission.
• After direct exposure of health care workers
to HIV-infected blood through injury with
needles and other sharp objects, the rate of
seroconversion is less than 0.5%, much
lower than the risk of hepatitis B virus
infection after similar exposures (about 25%)
.
• Unsafe injections may account for up to 5%
of transmission.
• While the virus has occasionally been found
in saliva, tears, urine and bronchial
secretions, transmission after contact with
these secretions has not been reported.

• No laboratory or epidemiological evidence

suggests that biting insects have transmitted
HIV infection.
HIV TRANSMISSION IN UNITED STATES
AND REST OF THE WORLD
 ACUTE HIV INFECTION
• Transient symptomatic illness in 40-90%
• Usually mild but can be severe
• 2-6 weeks after infection
• Often not recognized by primary care clinicians
• Symptoms non-specific
• Often resembles influenza, mononucleosis
• “Cold symptoms” absent
• Can be asymptomatic
• Duration: 14 days
Asymptomatic Disease (Latency)
Patients then enter a stage of asymptomatic disease
phase lasting on average 2-10 years (clinical latency)

Characterized by gradual decline in CD4 count

Rate depends on viral load

Long term non-progressors

Rare
>10-15 year survival without ART
CD4>500; low viral load
Host genetic/immunological or viral factors may be
involved
WHO CLINICAL STAGING OF HIV DISEASE IN
ADULTS AND ADOLESCENTS
• CLINICAL STAGE 1
– Asymptomatic
– Persistent generalized lymphadenopathy(PGL)
Is enlarged non painful lymph nodes occurring in
a couple of different areas for more than 3-6
months for which no other reason can be found
OR enlarged non painful lymph nodes of more
than 2cm in size of two or more non contiguous
sites and persists for more than 3 months with no
other reason found.
WHO CLINICAL STAGING OF HIV DISEASE IN
ADULTS AND ADOLESCENTS
CLINICAL STAGE 2
Moderate unexplained weight loss
(<10% of presumed or measured body weight)a
Recurrent respiratory tract infections: sinusitis,
tonsillitis, otitis media and pharyngitis)
Herpes zoster
Angular cheilitis
Recurrent oral ulceration
Papular pruritic eruptions
Seborrhoeic dermatitis
Fungal nail infections
Varicella Zoster Virus Disease: Epidemiology

• Reactivation of VZV that had been latent in

dorsal root ganglia since original infection
with VZV (chickenpox)

• Can occur early in HIV disease

• Herpes zoster occurs in 3-5% of adults in

the United States; more prevalent in
immunocompromised and elderly
Varicella Zoster Virus Disease: Epidemiology

• Incidence 15-25 times greater in HIV-

infected than in general population
• Can occur at any CD4 count
• Advanced immunosuppression may
change manifestations but does not
substantially change incidence
Varicella Zoster Virus Disease: Clinical
Manifestations
• Herpes zoster (shingles): prodrome of pain in
affected dermatome, then characteristic skin
lesions in same dermatome
– Extensive skin involvement or visceral
involvement are rare
– Progressive outer retinal necrosis may be
seen, usually with CD4 count <50 cells/µL
• Rapid progression and vision loss
– Acute retinal necrosis due to peripheral
necrotizing retinitis may occur at any CD4
count (more often at higher CD4)
HERPES ZOSTER
 Multi-dermatomal, recurrences
 Risk of debilitating post herpetic neuralgia
(PHN more common in older patient)
 Disfiguring keloid formation
Varicella Zoster Virus Disease: Clinical
Manifestations

• Chickenpox: primary VZV infection, uncommon

in adults and adolescents
– Respiratory prodrome, then vesiculopapular
lesions (face and trunk > extremities)
– In advanced immunosuppression, may persist
for weeks
• Reports of transverse myelitis, encephalitis,
vasculitic stroke
VARICELLA ZOSTER VIRUS DISEASE:
DIAGNOSIS

• Clinical diagnosis based on

appearance of lesions
• Viral culture or antigen detection from
swabs from fresh lesion or tissue
biopsy
HERPES ZOSTER: MANAGEMENT
 Analgesics – for acute pain
 Paracetamol plus an NSAID (+/- an opiate)
 Apply calamine lotion regularly
 Reduces itch and secondary infection

 If presents with new lesions

 Give Aciclovir (the sooner the better)

 Reduces acute pain, duration of lesions, number

of new lesions and systemic complaints

 ACV does not alter the rate of PHN

 Aciclovir 800mg 5 times a day for 7-10 days

 If visceral/extensive or disseminated or ophthalmic
where possible give IV aciclovir (10mg/kg TDS)
POST HERPETIC NEURALGIA
 Difficult to treat
 Pain difficult for patients to define - pricking,
tingling, burning
 Treatment
 Amitryptiline 25-50mg at night
 Carbamezipine 100mg BD (up to 200mg TDS)
 Can be used in combination
 Warn patients that it takes up to weeks to notice the
benefit
 “Don’t give up on the tablets too soon”
HERPES ZOSTER
OPTHALMIC HERPES ZOSTER
HERPES ZOSTER (VALICELLA ZOSTER
INFECTIONS)
TYPES OF GENITAL HERPES
 First episode: primary infection, non-
primary infection
 Recurrent episode

 Asymptomatic episode
GENITAL HERPES
 Red, raised, tender
vesicles or lesions
may occur
anywhere on the
vulva, in the vagina,
or on the cervix or
anal area.
 Multiple vesicles
may occur.
GENITAL HERPES

 Vesicles coalesce,
become denuded
and form large
ulcers
GENITAL HERPES—RECURRENCE ON
THE CERVIX
HIV AND GENITAL HERPES
 More extensive disease
 Frequent recurrences
 Chronicity
 Lesions associated high genital HIV viral load
 Recurrences whether symptomatic or asymptomatic
increase HIV genital VL
 Important cofactor for transmission of HIV
 Treatment of fist episode as standard however
higher doses may be required for longer periods
especially in chronic cases
BACTERIAL SKIN INFECTION
(PRURITIC PAPURIC ERUPTIONS)
BACTERIAL SKIN INFECTION (PRURITIC
ECZEMATOUS ERUPTIONS)
SEBORRHEIC DERMATITIS
SEBORRHEIC DERMATITIS
WHO CLINICAL STAGING OF HIV DISEASE IN
ADULTS AND ADOLESCENTS
CLINICAL STAGE III
– Unexplained severe weight loss (>10% of
presumed or measured body weight)
– Unexplained chronic diarrhea for longer than
one month
– Unexplained persistent fever (above 37.6°C
intermittent or constant, for longer than
one month)
– Persistent oral candidiasis
– Oral hairy leukoplakia
• CLINICAL STAGE 3 cont;
– Pulmonary tuberculosis (current)
– Severe bacterial infections (such as pneumonia,
empyema, pyomyositis, bone or joint infection,
meningitis or bacteraemia)
– Acute necrotizing ulcerative stomatitis, gingivitis
or periodontitis
– Unexplained anaemia (<8 g/dl), neutropaenia
(<0.5 × 109 per litre) or chronic
Thrombocytopaenia (<50 × 109 per litre)
MUCOCUTANEOUS CANDIDIASIS:
EPIDEMIOLOGY

• Oropharyngeal and esophageal candidiasis are

common
– Most common in patients with CD4 count <200
cells/µL
– Prevalence lower in patients on ART
• Vulvovaginal candidiasis
– Occurs in non-HIV-infected women; does not
indicate immunosuppression
– In advanced immunosuppression, may be more
severe or recur more frequently
• Usually caused by Candida albicans; other species
(especially C glabrata) seen in advanced
immunosuppression, refractory cases
 MUCOCUTANEOUS CANDIDIASIS:
CLINICAL MANIFESTATIONS
Oropharyngeal (thrush):
• Pseudomembranous: painless, creamy white
plaques on buccal or oropharyngeal mucosa or
tongue; can be scraped off easily
• Erythematous: patches on anterior or posterior
upper palate or tongue
• Angular cheilosis
Esophageal: retrosternal burning pain or discomfort,
odynophagia( painful swallowing), fever; on
endoscopy, whitish plaques with or without mucosal
ulceration. Dehydration, malnutrition, wasting
 ORO-PHARYNGEAL CANDIDIASIS
 White pseudomembraneous
plaques, atrophic /erythematous,
angular cheilitis
 Treatment
 Nystatin drops or tablet

 500,000 IU QDS

 Miconazole Oral Gel

 60mg QDS

 Miconazole buccal Tablet

 OD for 7 days

 If unresponsive:
 Fluconazole 100mg OD for 7
days
CANDIDIASIS
 Vaginal
 Not strictly an OI unless chronic (>1month)
or unresponsive to treatment. Has been
removed from revised WHO staging
 Vulvovaginal: creamy discharge, mucosal
burning and itching
ESOPHAGEAL CANDIDIASIS
MUCOCUTANEOUS CANDIDIASIS:
DIAGNOSIS

Oropharyngeal:
Usually clinical diagnosis
KOH preparation, culture
Esophageal:
Clinical, with trial of therapy
Endoscopy with histopathology and culture
Vulvovaginal:
Clinical diagnosis, KOH(10% potassium
hydroxide) preparation
CAUSES OF ANAEMIA IN HIV

• DRUGS e.g zidovudine.

• NEOPLASMAS e.g lymphoma , k.s.
• MALNUTRITION.
• MALABSORPTION
• HIV ITSELF AS CHRONIC INFECTION.
• BONE MARROW SUPRESSION BY HIV
TREATMENT

 Fluconazole 200mg stat, then 100mg daily for 14 days

 Ketoconazole
 200mg daily for 14 days
 Maintenance therapy required unless immune
reconstitution occurs. All such patients should be
evaluated for ART
WHO CLINICAL STAGING OF HIV
DISEASE IN ADULTS AND ADOLESCENTS
• CLINICAL STAGE IV
– HIV wasting syndrome
– Pneumocystis pneumonia
– Recurrent severe bacterial pneumonia
– Chronic herpes simplex infection (orolabial, genital
or anorectal
– of more than one month’s duration or visceral at any
site)
– Oesophageal candidiasis (or candidiasis of trachea,
bronchi or lungs)
– Extrapulmonary tuberculosis
CLINICAL STAGE IV cont
 Kaposi’s sarcoma
 Cytomegalovirus infection (retinitis or infection of
other organs)
 Central nervous system toxoplasmosis
 HIV encephalopathy
 Extrapulmonary cryptococcosis including meningitis
 Disseminated non-tuberculous mycobacterial
infection
 Progressive multifocal leukoencephalopathy
 Chronic cryptosporidiosis (with diarrhoe)
 Chronic isosporiasis
 Disseminated mycosis (coccidiomycosis or
histoplasmosis)
• CLINICAL STAGE IV cont
• Recurrent non-typhoidal Salmonella
bacteraemia
• Lymphoma (cerebral or B-cell non-Hodgkin) or
other solid HIV-associated tumours
• Invasive cervical carcinoma
• Atypical disseminated leishmaniasis
• Symptomatic HIV-associated nephropathy or
symptomatic HIV-associated cardiomyopathy
DIAGNOSIS AND INVESTIGATIONS OF HIV

HIV testing in children less 18 months:

• Is virological (DNA-PCR) testing
• Antibodies passed to the child from the mother so the rest can give a
false positive.
• Do DNA-PCR at 6 weeks of age or at an earlier if the mother is positive.
HIV testing in adult and children > 18 months:
• Serological ( antibody) testing .
• Due to window period between infection and production of detectable
levels of antibodies, patients who are negative be re – tested after three
months if they had a possible exposure in the 3 months before the test.
Serial HIV Testing Algorithm for testing persons above 18months
Screening Test DETERMINE

NON - REACTIVE REACTIVE

Report HIV Negative Confirmatory Test : STAT - PAK

NON - REACTIVE REACTIVE

The-Breaking Test Report HIV

SD BIOLINE positive

NON - REACTIVE REACTIVE

Report as
Report HIV inconclusive
Negative

Re-Test after14 days

Other tests in HIV management:
• Measures the level of CD4 T lymphocytes, a subtype white blood cell. It
reflects the level of compromise of the immune system.
- It is used for initial assessment pre ART and monitoring of ART
effect.
• Measures the quantity of virus in the blood ( Viral Load )
- It is used to monitor the effect of ARVs.