Overview of HIV and

its Management

Caroline Mills-Davies
Emmanuel Fantevie
March, 2010
 Objectives
• To explain how HIV/AIDS emerged
• Describe the pathogenesis of
HIV/AIDS
• Describe the stages of HIV infection
• Describe how HIV infection is
diagnosed
• List the current methods of managing
HIV infection
 Layout
Introduction
Definition
History
Epidemiology
Pathogenesis
Diagnosis
Management
Counseling and education
 Introduction
• HIV…. Human immunodeficiency virus
(HIV) is a lentivirus (a member of the
retrovirus family) that causes acquired
immunodeficiency syndrome (AIDS)

• AIDS… a condition in humans in which the

immune system begins to fail, leading to life-
threatening opportunistic infections.
 Introduction
• The result of HIV infection is
relentless destruction of the immune
system.
• All HIV infected persons are at risk
of illness and death from
opportunistic infections
 The AIDS is characterized by:

• Immunosuppression
• Opportunistic infections
• Secondary neoplasms
• Neurological manifestations.
 Types of HIV

• HIV-I

• HIV-II
 Comparison of HIV species
Parameter Species
HIV-I HIV-II

Infectivity High Lower

Virulence High Low

Prevalence Global West Africa

Origin Chimpanzee Sooty
Mangabey
 “Some History…”
• Appeared in the early 1980s in the US among
gay men who were developing opportunistic
infections and cancers

• Initially called GRID

Gay Related Immunodeficiency Disease.
• Appeared in Ghana in 1985/6 in the Eastern
region in Agomenya Hospital
 “Some History…”
• Simian Immunodeficiency Virus (SIV)
is a lentivirus that affects monkeys
• Similarity in strains of SIV and HIV I &II

• HIV I ≡ SIVcpz in chimpanzees

• HIV II ≡ SIVsm in sooty mangabey

Alabama Vas .
Sooty mangabey chimpanzee

www.google.com/images
From lower primates to humans???
zoonosis
• SIVchimp HIV (h. sapiens)
• The 'Hunter' Theory
• The Oral Polio Vaccine (OPV) theory
• The Contaminated Needle Theory
• The Colonialism Theory
• The Conspiracy Theory
“The road to the pandemic”

Cameroon

Congo

Haiti

USA Globe
 Epidemiology
• Total Number of people living with HIV in
2008: 33.4 million [31.1–35.8 m]
………..UNAIDS

• Adults : 31.3 million [29.2 –33.7 m]

• Women: 15.7 million [14.2 –17.2 m]
• Men: 15.6 million
• Children under 15 years 2.1 million [1.2 –2.9 ]
………..UNAIDS
 Epidemiology cont…
• Newly infected with HIV in 2008
2.7 million [2.4–3.0 m]

• Adults: 2.3 million [2.0–2.5 m]

• Children under 15 years 430 000 [240 000–
610 000]
 Regional Overview
• Sub – Saharan Africa – most affected
• In 2008, sub Saharan Africa accounted for
- 67% of HIV infections worldwide,
- 68% of new infections among adults
- 91% of new HIV among children
- 72% of AIDS related deaths
60% of HIV infections in sub-Saharan Africa
are in women
 Our Own Statistics
• Prevalence in Ghana 1.7%
• IN KORLE-BU, 2008
• 512 newly diagnosed i.e. 8.9% increase with
respect to 2007
• Highest number of cases between 21 – 30yrs
 Routes of Spread
Three main routes:
• Sexual: genital, oral, or rectal mucous,

• Blood or blood product: blood transfusion,

tattoos, piercing

• Mother-to-child: in utero (during pregnancy),

intrapartum (at childbirth), or via breast
feeding.
 Transmission Myths
• Touching
• Eating together
• Shaking hands
• Sharing utensils
• Mosquito bites
However...
• Small amounts of the virus found in saliva,
tears and urine
 Structure and Genome
• Spherical
• Diameter120 nm
• single-stranded
RNA
• Conical capsid
 Pathogenesis
• Entry to the cell

• Replication and transcription

• Assembly and release

 Pathogenesis
• Binding - gp120
molecule linkage with a
CD4 receptor.
• Viral envelope fuses
with the host cell
• Viral RNA is uncoated
and reverse-transcribed
into proviral DNA by the
viral Reverse
Transcriptase enzyme
 HIV-I lifecycle
Entry

RNA Viral protease

RNA Proteins
Reverse RT
transcriptase
RNA
RNA
DNA
RT

DNA

DNA Provirus
Integrase
 Pathogenesis cont…
• Proviral DNA is integrated into the host's DNA
by viral Integrase enzyme.
• Integrated viral genes are transcribed into
genomic RNA and mRNA, which are
translated into viral proteins.
• Viral proteins are cleaved by HIV Protease
enzyme into new viral proteins and assembled.

• Released by budding.
“HIV CAUSES AIDS”… evidence

• Immunosuppression and AIDS-defining

illnesses occur exclusively in HIV-
infected individuals

• AIDS and HIV infection are almost

always linked in time, location, and
population subgroup
HIV CAUSES AIDS… evidence
• A persistently low CD4 T cell count is
extraordinarily rare in non-HIV-infected
individuals

• Almost everyone with AIDS shows

antibodies to HIV

• HIV can be detected in almost everyone

with AIDS
 Diagnosis
• Assess Risk factors

• Baseline physical examination should

cover all organ systems

• Voluntary Counselling and Testing

• Lab investigation
 Diagnosis
Constitutional Symptoms:
• Weight loss
• Fever
• Night sweats
• Anorexia
• Visual disturbances
• Persistent headaches
• Oral lesions
• Recurrent diarrhoea
• These call for Retro Screening
 LABORATORY
INVESTIGATIONS
Two main types;

 HIV Antibody Tests

 Virologic Tests
 HIV ANTIBODY TESTS
• Detects antibodies produced against HIV

– ELISA
– Western Blot
– Rapid HIV Test (OraQuick HIV-1/2)
 VIROLOGIC TESTS

• Used to detect the virus itself

• Effective in the ‘window period’ when

antibody tests are negative
 Virologic Tests
• Three main tests;
• Viral antigen detection test (P24 antigen
tests)
• Nucleic acid based tests (specialized tests that
look for genetic information on HIV
polymerase chain reaction or PCR)
• Virus culture (isolates the virus)
 Korle bu Reference Lab
• ELISA for screening
• Immunochromatography for differentiating
HIV I & II
• Line immunoassay (INNOLIA)
 FALSE POSITIVE
• In babies less than18 months
• HLA cellular antigens may cross react and
give a false positive result with ELISA
– Rheumatoid arthritis
– Chronic hepatitis
– Addison’s disease
– Severe kidney disease
– Flu vaccination within the last 30 days
– Recent transfusion or organ transplant
 FALSE NEGATIVE
• A person in the ‘window period’
• Infection with a variant of the virus that is less
detectable than the test kit being used
• HIV antibodies which may not react with the
specific antigen utilized in the assay.
• Handling of sample
 Monitoring Tests
• CD4
• Percentage CD4 - children
• Viral load
• White Blood Cell
WHO CLINICAL STAGING of
HIV
• Based on
 Clinical
 Laboratory parameters
• Important in
 prognosis
Strengthening Clinical diagnosis
Therapy
 STAGE 1

• Acute retroviral infection

• Asymtomatic
• Generalised lymphadenopathy
• CD4 >500
• Performance scale 1: Normal Activity
 Stage 2
• < 10% weight loss
• Minor skin infections, nail infections,
• Recurrent oral ulcerations
• Recurrent URTI
• CD4 < 500
• Performance Scale 2; symptomatic,
normal activity
 Stage 3
• Weight loss > 10% body weight
• Unexplained chronic diarrhoea > 1mth
• Unexplained prolonged fever > 1 mth
• Oral candidiasis
• Tuberculosis
• Severe bacterial infections ( pneumonia)
• CD4 200-500
• Performance scale ; Bed-ridden < 50%
 Stage 4
•Pnuemocystis carinii
•Toxoplasmosis
•Lymphoma
•Karposi’s sarcoma
•Extrapulmonary Tb
•CD4 < 200
•Performance scale
bed-ridden > 50%
 WHO staging - Paediatric
• Stage I: asymptomatic, persistent generalized
lymphadenopathy (PGL)
• Stage II: recurrent oral lesions, fungal nail
infection, herpes zoster, papular pruritic
eruptions
• Stage III: Pulmonary TB, diarrhea, persistent
fever
• Stage IV: Kaposi Sarcoma, extrapulmonary
TB, Pneumocystis pneumonia
 The “Retro Challenge”

• Genetic variability/multiple infection

• Stigmatization
• Failing “ABC” policy
• Culture
• Economy
• Religion
MANAGEMENT
 Outline
• Goals of therapy
• Drugs for HIV
• Opportunistic infections
• Counseling and education
 Goals of Therapy:
1. Improve & prolong the quality of life of
the patient
2. Reduce the viral load as much as possible,
for as long as possible,
3. To halt disease progression and prevent or
reduce resistant variants.
4. To provide psychosocial support to the
infected and affected
 Goals of Therapy

4. Provide an antiretroviral regimen that

a) achieves reduced viral loads
b) preserves future therapeutic options,
c) is relatively free of side effects and
d) is tailored to individual needs for
adherence.
 Approaches in Management

• Psychosocial support (counseling)

• Drugs
 Drugs
(Classes of Antiretrovirals)
• Fusion/Entry inhibitors
• Nucleoside reverse transcriptase
inhibitors (NRTI)
• Non-nucleoside reverse transcriptase
inhibitors (NNRTI)
• Integrase inhibitors
• Protease inhibitors (PI)
Site of Action of ARVs
Nucleoside reverse transcriptase
inhibitors (NRTIs)
 Zidovudine, AZT-300mg 12hrly
 Abacavir-300mg 12hourly or 600mg dly
 Didanosine,DDI -250mg to 400mg daily
 Lamivudine,3TC- 150mg 12hrly or 300mg
dly
 Stavudine,d4T-30mg 12hrly
 Tenofovir 300mg dly
 Emtricitabine. 200mg dly
 Nucleoside reverse transcriptase
inhibitors (NRTI)
Caution

• Chronic hepatitis B or C
• In hepatic impairment
• In renal impairment
• In pregnancy
 Non-nucleoside reverse
transcriptase inhibitors (NNRTIs)
• Efavirenz- up to 600mg daily

• Nevirapine-200mg 12hrly

• Etravirine 200mg bid after meals.

Caution: chronic Hepatitis B/C

 Protease Inhibitors
 Atazanavir 300mg dly with 100mg ritonavir
 Darunavir 600mg bid
 Fosamprenavir 700mg bid
 Indinavir 800mg tid
 Ritonavir 300mg bid for 3 days then adjust
 Saquinavir 1g bid
 Tipranavir 500mg bid
 Lopinavir with ritonavir 400/100mg bid
 Nelfinavir 1.25g bid
 Protease Inhibitors
Caution: DM, Haemophilia, hepatic impairment,
pregnancy.
Interraction:PIs metabolised by cytochrome
P450 enzymes thus risk for drug interactions

Contraindications: acute porphyria,

breastfeeding mothers
 others
Fusion inhibitors
• Enfuvirtide (T-20)- Fuzeon® Sc 90mg bid
• used for patients for whom other ARV’s have
not been effective

• Caution: chronic hepatitis B/C, renal

impairment
• Side effects: pancreatitis, gerd, anorexia
weight loss
 Integrase inhibitors

• Raltegravir 400mg bid

• Caution: chronic hepatitis B/C

• Side effects: diarrhea, nausea, vomiting.

Common Side Effects and Toxicities:
Nucleoside Reverse Transcriptase Inhibitors

Drug Side effect/toxicity monitoring

Zidovudine GI intolerance, asthenia, Full blood count
headache, anemia,
leukopenia
Didanosine GI intolerance: Foot pain,
pancreatitis, peripheral parasthesias, serum
neuropathy, lactic acidosis amylase, frank
abdominal pain

Stavudine peripheral neuropathy, Foot pain,

lipodystrophy paresthesias, lipid
profile
 NRTI
Drug Name Side effects and Monitoring
Toxicity
(toxicities italicized)
Lamivudine Generally well tolerated: Full blood count
Headache, nausea

Abacavir Hypersensitivity reaction Educate patient on

(HSR)— symptoms of signs and
symptoms of HSR
fever, rash, GI, and what to do;
respiratory problems, check history for
lactic acidosis prior reaction.
 Non nucleoside reverse
transcriptase inhibitors (NNRTI)
Drug Side effect/toxicity monitoring

Nevirapine Extensive rash, hepatitis, Liver function tests

Stephen Johnson
Syndrome

Efavirenz CNS— hallucinations, Liver function tests

drowsiness, teratogenic
 Protease inhibitors
Drug Side effects and Monitoring
Name Toxicity
Nelfinavir Diarrhea, lipodystrophy Liver function tests
Lipid profile

Lopinavir/ GI intolerance (esp. Liver function tests

ritonavir diarrhea), asthenia, Lipid profile
lipodystrophy

Indinavir GI intolerance, benign Lipid profile

increase in bilirubin, Liver function tests
lipodystrophy
 Therapy:
Initiation Criteria
• Confirm HIV status
• Identify past HIV related illness
• Identify current HIV related illness requiring
treatment
• Clinically stage patient
• Identify co-existing medical condition that
may influence choice of treatment
• Assess capacity to adhere
 Initiation of Therapy
• Therapy is initiated when:
– Patient’s CD4 falls below 350 cells/mm3
• In pregnant women; initiate prophylaxis at
28weeks if CD4 cell > 350cells/mm3

(WHO new guideline in pregnancy) initiate if

CD4 <350 cells/mm3 regardless of stage
CD4 >350 cells/mm3 and symptomatic
Initiation of Therapy - paediatric
Parameter < 11 12 to 35 36 to 59 > 5yrs
months months months

CD4% < 25% <20% < 15% < 15%

CD4 count < 1500 <750 <350 <200

TLC total
lymphocyt <4000 <3000 <2500 <2000
e count
 Some ARTs in Ghana
NRTI
• Zidovudine (AZT,ZDV)
• Stavudine ( d4T)
• Lamivudine ( 3TC)
• Didanosine (ddI)
• Abacavir
• Tenofovir
NNRTI
• Nevirapine (NVP) Efavirenz ( EFV)

PIs
Ritonavir, Lopinavir, nelfinavir
 Highly Active Antiretroviral
Therapy (HAART)
• Introduced in 1996.
• A combination of
Two (NRTIs) plus either a protease
inhibitor or (NNRTI).
• Potent regimen that drastically reduces
viral replication and prevent drug
resistance
HAART - Some ARV Combinations
• Lamivudine +Stavudine +Nevirapine
• Zidovudine +Lamivudine +Nevirapine
• Lamivudine +Stavudine +Efavirenz
• Zidovudine +Lamivudine +Efavirenz
• Zidovudine+Lamivudine+Indinavir
• Zidovudine+ Lamivudine+Lopinavir/rito.
• Stavudine + Lamivudine + Nelfinavir
• Didanosine + Lamivudine + Efavirenz
 Line of Treatment - New
Recommendation
1st line
• Zidovudine+ Lamivudine+ Nevirapine
• Zidovudine+ Lamivudine+ Efavirenz
• Tenofovir + Lamivudine+ Efavirenz
• Tenofovir + Lamivudine+ Nevirapine
• Tenofovir + Emtricitabine + Efavirenz
 2 line
nd

• A boosted protease inhibitor (PI/r) plus two

nucleoside analogues (NRTIs)
• E.g. lopinavir/ritonavir, atazanavir/ ritonavir

• With stavudine, ziovudine, tenofovir or

lamivudine
 Wrong Combinations

• Zidovudine +Stavudine: antagonism of

intracellular phosphorylation thus decrease in
activity
• Stavudine + Didanosine: additive/synergistic
activity but overlapping toxicities limit use
• Lamivudine +Emtricitabine: minimal
additive activity and similar resistance profiles
 Standard Regimens in Ghana
Category of Zido Lami Stav Nev Efa
patient
“Normal” + + - - +
Anaemic male - + + - +
Female repro. + + - + -
stage
Anaemic
fem.repr. Stage - + + + -
TB patient + + - - +
smoker/alcoholic + + - - +
 Mother-to-Child Transmission
• Transmission of virus to the child
During pregnancy (5 – 10%)
During labor and delivery (10 – 20%)
During breastfeeding (5 – 20%)

• Delivery by Cesarean Section reduces

exposure to cervico-vaginal secretions
 Prevention of Mother To Child
Transmission (PMTCT)

• To reduce the risk of toxicity to the fetus

• To reduce the viral load and disease
progression in the mother
• To reduce transmission to the neonate
• Need for formula feeding if affordable
 Prophylactic therapy for both mother and
child
 Mother
• At CD4 cell > 350, ARV initiated with Combivir® at
28weeks + single dose Nevirapine at labour
• At CD4 < 350 full HAART is started
 Child
• If mother had ARV > 4weeks, single dose Nevirapine
at birth & Combivir for 1 week
• If mother had ARV< 4 weeks, single dose Nevirapine
at birth & Combivir for 6 weeks
 PMTCT - New WHO guideline
Prophylaxis:
Option A:
 Antepartum daily Zidovudine;
sd-Nevirapine at onset of labour
Zidovudine + Lamivudine during labour
and delivery
Zidovudine + Lamivudine for 7 days
postpartum.
 Prophylaxis
Option B
• Triple ARV from 14 weeks until one week
after all exposure to breast milk has ended
• Zidovudine + Lamivudine + Lopinavir/rit
• Zidovudine + Lamivudine + Abacavir
• Zidovudine + Lamivudine + Efavirenz
 Full ART in pregnancy – new
guideline
• In pregnant women in need of ART for their
own health, the preferred first-line ART
regimen should include Zidovudine and
Lamivudine backbone:
• Zidovudine + Lamivudine + Nevirapine or
• Zidovudine + Lamivudine + Efavirenz
• Alternatively;
• Tenofovir+ Lamivudine + Nevirapine/
Efavirenz
 PAEDIATRIC HIV
MANAGEMENT
• In asymtomatic children < 1 year, ARV
started soon as diagnosis is made.
• Children ≥ 1 year, ARV started
immediately or deferred if immune
system is normal
• Based on %CD4 and WHO staging
• In children, a triple therapy with 2 NRTIs
+ 1 NNRTI / 1 PI is favorable
 PAEDIATRIC HIV
MANAGEMENT
• Stavudine / Zidovudine + Lamivudine +

• Nevirapine (< 3yrs, wt< 10kg)

• Nevirapine / Efavirenz (> 3yrs, wt > 10kg)
 Treatment Failure
• Virological, Immunological, Clinical
• Indicated if after 3-6 months of therapy
there’s no
– increase in CD4 count
– no improvement in physical wellbeing of
patient
– insufficient viral suppression
• Note!!
– Rule out non - adherence
 Post exposure prophylaxis, PEP

• Not all exposures end in HIV infections

• Assess risk
• Within 24-48hrs of exposure, ARV given may
prevent infection
• If possible, initiate therapy within 1-2hrs of
exposure (72hrs)
• Determine status of source of exposure
• Determine HIV status of staff/victim
 Management of PEP
• Wash wound & skin site with soap & water/ flush mucous
membrane with water. “Initiate ARV preferably as soon as
pssible.
• Low risk exposure
– Zidovudine 300mg/12h for 28 days +
– Lamivudine 150mg/12h for 28 days + counseling
• High risk exposure
– Zidovudine 300mg/12h for 28 days +
– Lamivudine 150mg/12h for 28 days +
– Nelfinavir 750mg/8h for 28 days/ Lpv/r 400/100 bd for
28days + counseling
 Opportunistic infections
Herpes simplex Acyclovir po 400mg 5x dly 5/7

Varicella-zoster virus Acyclovir po 800mg 5x dly 7/7

Candidiasis/ meningitis- Amphotericin B IV 5mg/kg dly 14/7

aspergillosis /crytococcosis Fluconazole po 200-400 dly (max
800) 8/52 or
Itraconazole/Ketoconazole po 200mg
dly 15/7
Toxoplasmosis Pyrimethamine 100mg str then 50mg
dly po and sulfadiazine 1gm 6hrly 6/52
+ folinic acid 10mg dly po
Alt, Pyrimethamine + Clindamycin/
Clarithromycin/ Azithromycin
 Opportunistic infections
Pneumocystic carinii Co-trimoxazole-960mg dly for
pneumonia proph. 960mg tid for treatment
Adjunct prednisolone 50-80mg
dly x 5/7, then reduced to
complete 21 days
Diarrhoea Ciprofloxacin 500mg bd

Malignancies-Kaposi’s Chemotherapy; Bleomycin

sarcoma, non-hodgkin’s Radiotherapy – Vincristine
lymphoma, invasive cervical
cancer, tumours of anus &
rectum

TB HRZE
CNS effects: neuropathy, Treat appropriately
neuropsychiatric disorders
 HIV/AIDS Counselling :
• Preventive intervention
• Discussion of sexual practices (i.e. promote safer
sexual practices)
• Pre and post test counselling and testing of spouse
• Use of OTCs and herbal medicines
• De-stigmatisation
• Virus can be transmitted on ART so safe sex
• Drug information
• Adherence
• Disclosure (monitor)
• Emotional and Social Support
 Role of the Pharmacist
• HIV education anywhere
• Assessment of readiness for ART
• Counseling on alcohol use, herbal preparations
over the counter drugs
• PEP counseling
• Data capturing
• Monitoring programme success
• Training human resource
 Role of the Pharmacist
• Adherence counseling:
 goal of Art
Mode of action of ART
Triple therapy combination
Expected side effects
Nutrition issues
Dosage, timing, food restrictions,
Dispensing, labeling, feedback
Watch dog for adverse effects
 Any hope???
• Cure for HIV
• Antelman Marvin US Patent No. 5676977
 Conclusion

Yes you
• Yes wecan,
can,
Don’t turn back on HIV
• Don’t turn
patients they back on HIV
are just
like u
• patients they are just like u
 References
• BNF
• UNAIDS
• www.wikepedia.com
• Range and Dale
• Handbook on paediatric AIDS in Africa
• Bailes et al. (2003) "Hybrid Origin of SIV in
Chimpanzees", Science, Vol. 300, p. 1713
• Wolfe, ND; Switzer, WM; Carr, JK; et al. (20 March 2004)
"Naturally acquired simian retrovirus infections in Central
African Hunters." The Lancet, Vol. 363, p. 932
• Cohen, John (October 2000) "
The Hunt for the Origin of AIDS" The Atlantic, Vol. 286
No. 4, p. 88-104
 Acknowledgment
Miss Elaine Awumee Dovi
Mr Raymond Tetteh
Mrs Francisca Zigah Hamah
Mrs Amah Nkansah
Mrs Obedia Seaneke
Mr Dennis Ocansey
Mr Tony Osei
thanks
 Case Study
• Mad TK, 25, female presented to the
clinic on 11/02/09.
• P/C: Difficulty swallowing, cough,
headache, thrush, amenorrhea , weight
loss
• PMH: Asthma, Surgery??, Skin rash

• DHx: Ventolin (inhaler)

• O/E: Enlarged mesenteric lymph nodes

 SHx: A single 25 yr old lady with one child
and works as a house help at lapaz .
• Lab results
HB: 6.8
WBC: 5.3
ESR:145
CD4: 124c/mm3
HIV I positive: MPS ++

∆ Disseminated TB,

Malaria
Rx:
HRZE (June to Dec 09)
Coartem full adult course
Amoxiclav, 1g bd
Selevite one daily
Galfer one daily
Cetirizine 10mg daily
25/05/09: ARV started:

Stavudine 30mg bd
Lamivudine 150mg bd
Efavirenz 600mg nocte
Vitafol one daily
Septrin 960mg dly
• 19/11/09: Desire to become pregnant
CD4 225cell/mm3, HB 10.8

• ARV changed to
Stavudine 30mg bd
Lamivudine 150mg bd
Nevirapine 200mg bd
• 8/02/10: Came back Presenting with;
• Stevens Johnson Syndrome(SJS)
• Pregnant CD4 184c/mm3, HB 12.0

ARV stopped!! SJS managed appropriately

IV fluids, Savlon, Ceftriaxone, IV flagyl, IV
Hydrocortisone, Morphine, metoclopramide,
Omeprazole, Chloramphenicol eye drop,

Had Miscarriage (complete abortion)

Back to ARV after SJS crises

• Current medication:

• Stavudine 30mg bd
• Lamivudine 150mg bd
• Nelfinavir 1.25g bd
• Vitafol one daily
• Septrin 960mg dly
 Questions
What are Madam TK’s risk factors?

Are there any concerns in her current

medications?

What monitoring parameters must be

considered based on her current
medication?

What counseling would you give Mad TK?