CURRENT NATIONAL
GUIDELINE IN THE
PHARMACOTHERAPY OF
HIV/AIDS
Pharm. Shomuyiwa Rasheed .T
(B.Pharm. Olabisi Onabanjo University)
FEDERAL MEDICAL CENTER ,LOKOJA, KOGI STATE.
Supervisor : Dr. (Mrs) Ugo Adaobi
Pharm.D (Uniben))

Outline
‒Introduction
‒Opportunistic infection
‒Hiv transmission
‒Hiv life cycle
‒ Laboratory Diagnosis of HIV Infection
‒Pharmacotherapy of Hiv
‒Baseline treatment of ARV’s
‒Classification of ARV’s
‒Recommend ART regimen for Adults, Adolescent
and children
‒Conclusion
‒Reference

Introduction
Human immunodeficiency virus (HIV) is an infection that
attacks the body’s immune system, specifically the white
blood cells called CD4 cells (500-1400 per cubic meter).
HIV destroys these CD4 cells, weakening a person’s
immunity against opportunistic infections, such as
tuberculosis and fungal infections, severe bacterial
infections and some cancers.
AIDS (acquired immune deficiency syndrome) is the name
used to describe a number of potentially life-threatening
infections and illnesses that happen when your immune
system has been severely damaged by the HIV virus.

Introduction
 Hiv was first recognized in 1981 and the virus was
identified in 1983.
 There are two main types, HIV-1 and HIV-2
─ HIV-1 is responsible for AIDS in America, Europe, and
Asia
─ HIV-2 occurs mainly in western Africa
 There were an estimated 38.4 million [33.9–43.8 million]
people living with HIV at the end of 2021
 Two thirds of whom (25.6 million) are in the WHO African
Region.

Opportunistic infections (OIs)
 Opportunistic infections (OIs) are illnesses that occur
more frequently and are more severe in people with HIV.
This is because they have damaged immune systems.
 Today, OIs are less common in people with HIV because
of effective HIV treatment.
 But some people with HIV still develop OIs because
─ They may not know they have HIV
─ They may not be on HIV treatment
─Their HIV treatment may not be working properly.

Common Opportunistic Infections
─ Candidiasis
─ Herpes simplex virus (HSV)
─ Encephalopathy, HIV-related
─ Kaposi’s sarcoma (KS)
─ Lymphoma
─ Tuberculosis (TB)
─ Pneumocystis pneumonia (PCP)

HIV Transmission
• Blood
• Semen
• Vaginal Secretions
• Breast milk
Comes into contact with:
mucous membranes, damaged
tissue, or is injected into the
body
Through:
Vaginal, anal, or oral sex
Contaminated needles
IV drug use

HIV Transmission
 HIV is NOT transmitted by casual contact
─ Working or playing with an HIV positive person
─ Closed mouth kissing
─ Shaking hands
─ Public pools
─ Hugging
─ Public toilet
 HIV is not transmitted by air, food, or mosquito and does
not survive long outside the body.

Laboratory Diagnosis of HIV Infection
Antibody Assays
Enzyme-Linked Immunosorbent Assay (ELISA) or Enzyme
Immunoassay (EIA) for blood Screening
Nucleic Acid-based Testing
─HIV DNA Polymerase Chain Reaction (PCR)
─Viral Load Assay- Reverse Transcriptase Polymerase Chain
Reaction (RT-PCR)

Staging of HIV Infection
The WHO classified HIV infection clinically
into:
Asymptomatic stage 1
Mild symptom stage 2
Advanced symptoms stage 3
Severe symptoms stage 4

Manifestations at the clinical stages
Stage 1 Asymptomatic, gneralised lymphadenopathy
Stage 2 weight loss <10%, fungal nail infection, herpes
zoster, recurrent UTIs, prurigo
Stage 3 weigh loss>10%, chronic diarrhoea, fever, oral
candidiasis, pulmonary TB, severe bacteria infections.
Stage 4 AIDS-defining illnesses such as brain
toxoplasmosis, candida oesophagitis, extra pulmonary
TB, Karposi sarcoma, non-hidgkin lymphoma.

Pharmacotherapy of HIV/AIDS
Antiretroviral therapy (ART) is the treatment of
HIV infection using a combination of
antiretroviral drugs (ARVs).
ART should be initiated in a patient if:
CD4+ cell count =<350cells/mm3 including
pregnant women irrespective of clinical
symptoms
WHO stage 3 or 4 irrespective of the CD4+ count

Pharmacotherapy of HIV/AIDS
Co-infected with TB as soon as possible
irrespective of CD4 count (within 8 weeks after the
start of TB treatment)
HIV patient who require treatment for HBV
infection irrespective of CD4 cell count or WHO
clinical staging
HIV positive pregnant women with CD4
count<350 ARV prophylaxis should be provided

Baseline Assessment for ART
The baseline assessment and preparation of patients for ART
should include:
Re-testing for HIV to verify HIV positive status
A comprehensive history and clinical examination
Assessment of patient's readiness for initiation of ART
(regimen, dosage, scheduling, benefits, adverse effects,
follow up, monitoring visits and age-appropriate disclosure)
Development of patient-centred adherence strategy
 Baseline laboratory assessment

Classification of Antiretroviral Drugs (ARVs)
CLASS DRUGS
Nucleoside/Nucleotide Reverse
Transcriptase Inhibitors (NRTIs)
Abacavir (ABC) , Emtricitabine (FTC);
Lamivudine (3TC)
Tenofovir Disoproxil fumarate (TDF);
Zidovudine (AZT, ZDV), Didanosine (ddI)
Stavudine (d4T)
Non-Nucleoside Reverse
Transcriptase Inhibitors (NNRTIs)
Efavirenz (EFV), Etravirine (ETR);
Nevirapine (NVP), Rilpivirine (RPV)
Protease Inhibitors (PI)
Atazanavir (ATV), Darunavir (DRV)
Lopinavir (LPV), Fosamprenavir (FPV);
Indinavir (IDV) Nelfinavir(NFV)
Protease Inhibitors (PIs) boosters Ritonavir (RTV), Cobicistat (COBI)
Integrase Strand Transfer Inhibitors
(INSTIs)
Dolutegravir (DTG), Elvitegravir (EVG);
Raltegravir(RAL), Cabotegravir (CAB)

Classification of Antiretroviral Drugs (ARVs)
CLASS DRUGS
Attachment Inhibitors Fostemsavir, Ibalizumab, Anti CD4
adnectin
Fusion Inhibitors Enfuvirtide; Anti-GP41 Adnectin; Combinectin
Chemokine receptor antagonists Maraviroc; Vicroviroc; Cenicriviroc

MECHANISM OF ACTION:NRTI’S
Interrupt HIV replication cycle via competitive
inhibition of HIV reverse transcriptase and
termination of the DNA chain
These compete with host nucleotides to serve as the
substrate for reverse transcriptase chain elongation.
 Absence of 3'OHgroup on sugar moiety prevents
the addition of another nucleotide, resulting in chain
termination, abortion of viral DNA chain elongation
and cessation of viral replication.

SIDE EFFECTS
DRUGS ( NRTI’S) SIDE EFFECTS
ABACAVIR Hypersensitivity reaction,
increase in cholesterol
DIDANOSINE Nausea, vomiting abdominal
pain, peripheral neuropathy,
EMTRICITABINE Rash and skin darkening of palms
or soles
LAMIVUDINE Skin rash
STAVUDINE Peripheral neuropathy and lactic
acidosis
TENOFOVIR DISIPROXIL
FUMARATE
Kidney and bone damage
ZIDOVUDINE Anemia, nausea, vomiting, lactic
acidosis, increase in cholesterol, fat
loss in arms, legs or face, fatty liver

MECHANISM OF ACTION:NNRTI’S
 NNRTI’s are generally hydrophobic molecules
that bind to an allosteric binding site.
Binding to this allosteric site locks the
neighboring substrate-binding site into an
inactive conformation.
Inhibit HIV reverse transcriptase by binding a
hydrophobic pocket close to the active site thereby
locking the site in an inactive conformation.

SIDE EFFECTS
DRUGS(NNRT’S) COMMON SIDE EFFECT
EFAVIRENZ Anxiety, depression, insomnia, skin
rash, liver damage
ETRAVIRINE Skin rash , Nausea
NEVIRAPINE Skin rash
CABOTEGRAVIR/RILPIVIRINE
Headache, tiredness, trouble
sleeping, nausea
Doravirine Skin rash, weight gain

MECHANISM OF ACTION:PI
HIV protease is a 99-amino-acid, aspartic acid
protein
Inhibit HIV protease by binding to its active site,
preventing the cleavage of gag and gag-pol
precursor.
Virions are produced but they are incomplete and
noninfectious.

SIDE EFFECTS: P.I
─ Nausea
─ vomiting
─ Diarrhea,
─ Jaundice
─ Gall bladder and kidney stones
─ liver damage
─ Skin rash
─ Increase in cholesterol
─ Changes in heart rhythm

Pharmacokinetic enhancers/ PI boosters
 These are drugs used in HIV treatment to increase
the effectiveness of certain classes of ARV drugs.
The PIs are metabolized by cytochrome P450
(CYP) 3A enzymes; and intentional inhibition of the
enzymes' lead to higher drug exposure, lower pill
burden and simplified dosing schedules.
 In HIV therapy, two pharmacokinetic enhancers or
boosting agents are used: ritonavir and cobicistat.
 These agents inhibit CYP3A4, with cobicistat
being a more specific CYP inhibitor than ritonavir.

INTEGRASE INHIBITORS
It’s also known as Integrase Strand Transfer
Inhibitors (INSTI).
HIV integrase Responsible for transport and
attachment of proviral DNA to host-cell chromosomes,
allowing transcription of viral proteins and subsequent
assembly of virus particles
 Raltegravir , Elvitegravir & Dolutegravir

Mechanisms of Action: Integrase Inhibitors
The INSTI mechanism of action is to prevent HIV
integrase from incorporating proviral DNA into the
human host cell, thus inhibiting the HIV-catalyzed
strand transfer step.
This step has no human homolog, making it a
specific and effective HIV drug target with excellent
tolerability and minimal toxicity

SIDE EFFECTS:INSTI
─ Insomnia
─ Depression
─ Skin rash
─ Weight gain
─ Fever
─ Fatigue
─ Muscle or joint ache
─ Swelling in eyes, mouth and face

Entry Inhibitors
Entry Inhibitors block the mechanisms by which HIV
gains access into the cytoplasm of CD4+ cell
molecule bearing cell. There are 3 classes:
Attachment inhibitors: These agents complex with
glycoprotein 120 and prevent it from interacting
with the CD4+ molecule thus, the attachment of the
virus to the cell is blocked.

Entry Inhibitors
 Chemokine Receptor Antagonists: These are
agents that complex with cell membrane receptors
that serve as fusion proteins i.e. CXCR4, CCR5.
Fusion inhibitors: These are agents designed to compete
with the viral GP41. GP41 is the viral protein that is capable
of fusing with cellular membrane molecules called
chemokine receptors. The interaction of fusion inhibitors
with GP41 blocks the fusion of viral membrane with
cellular membrane

Highly Active Antiretroviral Therapy (HAART)
Highly active antiretroviral therapy (HAART) are
medications used to treat HIV. These medications
may also be called antiretroviral drugs (ART),
antiretrovirals (ARVs), or anti-HIV drugs.
 HAART is used to describe a combination of
three or more anti-HIV drugs.
HAART prevents the HIV virus from making
copies of itself and limits how much virus is in the
body. The level of virus in the blood is called ‘viral
load’.

 Recommended ART Regimen for Adults, Adolescents and
Children
‒ First-line ART regimens for adults and adolescents
Two NRTIs + INSTI
Abacavir (600mg) | Lamivudine (300mg) + Dolutegravir (50mg)
ABC + 3TC (or FTC) +DTG

Alternatively
Tenofovir(300mg) | Lamivudine (300mg) | Dolutegravir(50mg)
TDF + 3TC +DTG

A switch to a second-line regimen is
recommended when
FIRST-LINE THERAPY
FAILURE
 Clinical failure is recognized
 Immunological failure is recognized
 Virological failure is recognized.

Adult & Adolescent Second Line ART regimens
TWO NRTIs + TWO PIs
Tenofovir (300mg) | Lamivudine (300mg) +Lopinavir 200mg
Ritonavir (50mg)
‒ Tenofovir (300mg) | Lamivudine (300mg) + Atazanavir
(300mg) | Ritonavir (50mg)

Adult & Adolescent Third Line ART regimens
TWO NRTIs + TWO PIs + INSTI
Tenofovir (300mg) | Lamivudine (300mg) + Darunavir
(800mg)| Ritonavir (100mg) + Dolutegravir (50mg)

Paediatric First Line (0-9yrs) < 20kg
─Tenofovir | Lamivudine 60mg | Dolutegravir (TLD)
─ Abacavir 120mg | Lamivudine 6omg + Dolutegravir
─ Abacavir 120mg | Lamivudine 60mg + Lopinavir |
Ritonavir - 100/25mg
─Zidovudine 6omg| Lamivudine 60mg + Lopinavir
|Ritonavir - 100/25mg
─Abacavir | Lamivudine + Lopinavir | Ritonavir -
40/10mg

Paediatric Second Line (0-9yrs)
‒Abacavir | Lamivudine + Raltegravir
‒ Zidovudine | Lamivudine + Raltegravir
‒Abacavir | Lamivudine + Lopinavir | Ritonavir
‒ Zidovudine | Lamivudine + Lopinavir | Ritonavir
 HIV-exposed infants
‒ Nevirapine Suspension 10mg/ml
‒ Zidovudine 10mg/ml + Nevirapine 10mg/ml

PROPHYLAXIS
Pre-Exposure Prophylaxis
Pre-exposure prophylaxis (PrEP) is the pre-emptive use of
ARVs to reduce the probability of HIV negative individuals
acquiring HIV infection, especially in persons who are
deemed at substantial risk.
Post-Exposure Prophylaxis
Post-Exposure Prophylaxis (PEP) is the short-term use of
ARVs to prevent HIV infection in persons accidentally
exposed to a potential risk of acquiring HIV infection.

Pre Exposure Prophylaxis (PrEP)
─ Tenofovir (300mg) | Emtricitabine(200mg)
─ Tenofovir (300mg) | Lamivudine (300mg)
Adult & Adolescent Post Exposure Prophylaxis
(PEP)
‒
‒ Tenofovir (300mg) | Lamivudine (300mg) | Efavirenz
(600mg)
‒ Tenofovir (300mg) | Lamivudine (300mg) |
Dolutegravir (50mg)

Paediatric Post Exposure Prophylaxis (PEP)
‒ Zidovudine | Lamivudine + Dolutegravir
‒ Abacavir | Lamivudine + Dolutegravir
 TB/HIV Prophylaxis
─Co-trimoxazole |Isoniazid |Pyridoxine
(960/300/25mg)
─ Isoniazid (INH) 300mg
─Isoniazid (INH) 100mg

HIV Treatment Adherence
Taking HIV medicines every day prevents HIV from
multiplying, which reduces the risk that HIV will
mutate and produce drug-resistant HIV.
Skipping HIV medicines allows HIV to multiply,
which increases the risk of Drug resistance and HIV
treatment failure.
Poor adherence to an HIV treatment regimen also
allows HIV to destroy the Immune system. A damaged
immune system makes it hard for the body to fight off
infections and certain cancers.

CONCLUSION
‒HIV attacks and weakens the immune system, reducing its
ability to fight infection.
‒Main transmission routes are sexual, parenteral, vertical.
‒The four phases of HIV disease are acute, asymptomatic,
symptomatic, and full-blown AIDS.
‒HIV is recognized mainly by testing antibodies formed to fight
the virus.
‒ART can prevent OIs and slow progression of AIDS.

REFERENCES
National guidelines for hiv prevention treatment and care
Nigeria. 2020
New Mexico AIDS Education and Training Center: "Taking
Current Antiretroviral Drugs."
U.S. Dept. of Health and Human Services: "Side Effects of
Anti-HIV Medications."
U.S. Dept. of Health and Human Services: "Enfuvirtide."
World Health Organization Fact Sheet . 2020. Global
Update on the Health Sector Response to HIV. Geneva
World Health Organization; Joint United Nations
Programme on HIV/AIDS (UNAIDS) and United Nations
Children Fund (UNICEF)