Human Immunodeficiency Virus (HIV) and opportunistic infections.pdf

Human immunodeficiency virus (HIV) is a retrovirus.
Retroviruses are enveloped RNA viruses defined by their mechanism of replication via reverse transcription to produce DNA copies that integrate into the host cell's genome.
Opportunistic infections (OIs) are infections that occur more often or are more severe in people with weakened immune systems than in people with healthy immune systems. Types of opportunistic infections in HIV patients
Fungal infections : P. jiroveci Pneumonia Oropharangeal Candiasis �
Protozoal infections: Toxoplasmosis ,Cryptospordiasis
Bacterial infection : Mycobacterium Tuberculosis

1. Human Immunodeficiency
Virus (HIV) and opportunistic
infections
Prepared By: Prabin Kusmy
(Tharu)
PharmD(PB)

2. •Humanimmunodeficiencyvirus(HIV)isaretrovirus.
•RetrovirusesareenvelopedRNAvirusesdefinedbytheir
mechanismofreplicationviareversetranscriptionto
produceDNAcopiesthatintegrateintothehostcell's
genome.
•Thereare2HIVtypes,HIV-1andHIV-2.
•HIV-1causesmostHIVinfectionsworldwide,HIV-1can
bedividedintogroups:M,N,OandP.Theepidemicis
dominatedbygroupM,whichiscomposedofsubtypes
A–K.
•HIV-2causesasubstantialproportionofinfections,
particularlyinpartsofWestAfrica.InsomeareasofWest
Africa,bothvirusesareprevalentandmaycoinfect
patients.HIV-2appearstobelessvirulentthanHIV-1.

3. Epidemiology of HIV infections
•GlobalHIVstatisticswereestimatedbytheWorldHealthOrganization(WHO)in
2022
•GlobalprevalenceofHIV–39million
•Children(0to14yearsofage)withHIV–1.5million
•PeoplenewlydiagnosedwithHIVinfection–1.3million;since2010,thenumber
ofpeopleacquiringHIVhasbeenreducedby38%,from2.1million
•MortalityfromHIV-relatedcauses–630,000;since2010,HIV-relateddeathshave
beenreducedby51%,from1.3million
•PeoplewithHIVreceivingantiretroviraltherapy–29.8million
•InNepal2020,Reportedcases:37,596
•AlivePLHIV:23,136

4. Transmission of HIV Infection
•Sexual:Directtransmissionthroughsexualactivity
•Needle-orinstrument-related:Sharingofblood-contaminated
needlesorexposuretocontaminatedmedicalinstruments
•Transfusion-ortransplant-related
•Vertical:Transmissionfromaninfectedmothertochildduring
pregnancy,childbirth,orthroughbreastmilk.

5. Pathophysiology of HIV
SimplifiedHIVLifeCycle
TheHIVlifecycleistheseriesofstepsHIVtakestomultiplyinthebody.It
consistsofsevenstages:
1.Binding:HIVattachestoaCD4cell
2.Fusion:HIVenterstheCD4cell
3.Reversetranscription:HIVcopiesitsRNAintoDNA
4.Integration:HIV'sDNAintegratesintotheCD4cell'sDNA
5.Replication:TheCD4cellproducesHIVRNAandproteins
6.Assembly:HIVproteinsassembleintonewHIVparticles
7.Budding:ImmatureHIVispushedoutofthecellandproteasesactivate
immatureintomatureinfectiousHIV

8. Symptoms and Signs of HIV Infection
•Initially,infectionmaybeasymptomaticor
causetransientnonspecificsymptoms(acute
retroviralsyndrome).
•Acuteretroviralsyndromebeginswithin1to
4weeksofinfectionandusuallylasts3to14
days.
•Nonspecificviralsyndromesandmay
includefever,malaise,fatigue,several
typesofdermatitis,sorethroat,
arthralgias, generalized
lymphadenopathy,andsepticmeningitis,
Whiteplaquesduetooralcandidiasis,
Diarrhea,Fatigue,Feverwithintermittent
sweats
Complications
•Pneumocystis pneumonia
•Tuberculosis
•Cytomegalovirus
•Cryptococcal meningitis
•Toxoplasmosis

9. Diagnosis and Monitoring of HIV Infection
Screening for HIV Infection:
•Primary Test: Enzyme-linked immunosorbent assay (ELISA) to detect
HIV-1 antibodies.
•Confirmation: A second enzyme immunoassay to differentiate between
antibodies for HIV-1 and HIV-2.
•Western blot
False-Positive Results:
•Possible in individuals with autoimmune disorders.
False-Negative Results:
•May occur during the "window period" before sufficient antibody or
antigen production.

10. Monitoring HIV Disease:
•CD4 Cell Count: Normal ranges : 500 and 1500 cells/mm3. As HIV
disease progresses, the number of cells falls.
•Viral Load Measurement
•Measures the amount of HIV RNA in the blood.
•Higher viral load = faster disease progression.
•Lower viral load after treatment = better clinical outcomes.
•Methods:
•Reverse transcriptase–coupled polymerase chain reaction (RT-PCR).
•Branched DNA (bDNA) assay.
•Transcription-mediated amplification (TMA).
•Nucleic acid sequence–based assay (NASBA).

11. Eclipse period. This period refers to the period of about 7–10 days following HIV infection, during which currently available
assays cannot detect any marker of HIV infection.
Nucleic acid test

12. Goals of HIV Therapy
•Improve quality and duration of life.
•Prevent immune deterioration and restore immune function.
•Treat/prevent opportunistic infections.
•Relieve symptoms.

13. Antiretroviral Therapy (ART)
❖When to Start Therapy
•Recommended when CD4 < 350 cells/mm³.
Choosing and Monitoring Therapy
First-line Therapy:
•2 NRTIs + 1 NNRTI OR
•2 NRTIs + 1 boosted PI (e.g., with ritonavir as a pharmacokinetic enhancer).
•Triple NRTI therapy is no longer recommended due to virological failure.
•Integrase inhibitors are now an alternative to NNRTIs or PIs.

18. 28 days

22. Toxicity monitoring for other ARV drugs
1.DTG(dolutegravir) : An increase of 3–5 kg in body weight in
individuals receiving DTG-based regimens at 48 weeks is noted,
greatest with the tenofovir alafenamide (TAF)+emtricitabine
(FTC)+DTG regimen.
2.ABC : Abacavir (ABC) increases the risk of a hypersensitivity
reaction and myocardial infarction in adults.
3.AZT( Zidovudine) : AZT is associated with a risk of
haematological toxicity( anaemia)
4.EFV(Efavirenz) : The main type of toxicity of EFV is central
nervous system (CNS) side-effects.

23. Immune reconstitution inflammatory syndrome (IRIS)
•This is a condition that can occur shortly after a person starts HIV therapy for the
first time. If the CD4 count rapidly increases due to effective treatment of HIV, a
sudden increase in the inflammatory response produces non-specific symptoms
such as fever and, in some cases, a paradoxical worsening of pre-existing
symptoms of infective or non-infective conditions.
Management of IRIS
▪Improved screening for OIs (opportunistic infections) before initiating ART,
especially TB, cryptococcal disease and CMV
▪If not severe, symptomatic treatment, e.g. NSAIDs, is required. Decrease the
immune response by:
➢Giving immunosuppressive agents, e.g. corticosteroids 1–2 mg/kg usually for 1–2
weeks, sometimes for up to 12 weeks;
➢Continuing ART and OI therapy + steroids;
➢Treating OIs for the standard period or longer.

24. Follow-up visits for ARV drug refills

26. Immunization
•Patients who have not received a conjugate pneumococcal vaccine or
whose previous vaccination history is unknown should be given PCV15 or
PCV20
•All patients should be given the influenza vaccine annually.
•All patients should be given the hepatitis B vaccine.
•Patients at risk of hepatitis A or desiring protection from it should be given
the hepatitis A vaccine.
•At the appropriate age, males and females should be given the human
papillomavirus (HPV) vaccine to prevent HPV-related cervical and anal
cancers.
•Adults who have not been previously vaccinated with the meningococcal
vaccine should be given a 2-dose.
•Patients who did not receive tetanus-diphtheria-pertussis vaccine (Tdap)
as part of their completed tetanus-diphtheria vaccine (Td) series should be
given Tdap for their next Td booster.

27. •All patients should be given the recombinant zoster vaccine.
•The varicella vaccine and the measles, mumps, and rubella (MMR) vaccine
may be given to patients with CD4 percentage ≥ 15% and CD4 count ≥
200/mcl, but these vaccines are contraindicated in patients with CD4
percentage < 15% or CD4 count < 200/mcl.
•People with HIV should receive the full series of a COVID-19 vaccine,
regardless of CD4 count or viral load because the potential benefits outweigh
potential risks (4).
•Mpox vaccination is recommended for people with HIV at risk for MPox..

28. Women with HIV
Specific issues for women with HIV include
1. Cervical Screening & Gynaecological Manifestations
•Annual cervical screening is recommended due to higher risk of HPV-related conditions.
2. Drug Toxicity & Gender-Specific Differences
•Nevirapine hypersensitivity occurs at a lower CD4 count in women.
•Lipodystrophy may present differently (e.g., breast hypertrophy in women).
The factors that need to be taken in Pregnancy & Contraception Considerations
•Drug interactions between antiretrovirals and oral/injectable contraceptives should be
considered.
•No interactions with the levonorgestrel-releasing intrauterine system (Mirena).
•Barrier methods should always be recommended for HIV & STI prevention.
•Teratogenicity & toxicity risks for both mother and child must be evaluated.

29. Prevention of Mother-to-Child Transmission (PMTCT)
•HAART + caesarean section + neonatal zidovudine + no breastfeeding
can reduce transmission from 35% to <1%.
•Timing of HAART initiation (based on viral load):
•<10,000 copies/mL → Start by 26 weeks.
•10,000–32,000 copies/mL → Start by 20 weeks.
•>32,000 copies/mL → Start immediately.
•Caesarean -section is recommended if viral load is detectable before
delivery.
•Breastfeeding should be avoided, and antiretrovirals given to the
newborn for 4 weeks.

30. Prevention of HIV Infection
1.Psychosocial counselling and support;
2.Disclosure and partner notification
3.TB counselling, screening and preventive therapy;
4.Prevention of common fungal infections;
5.Treatment of STIs and support for reproductive health needs, including
6.Prevention and screening for cervical cancer;
7.Preventing malaria (CTX, bed nets and particularly preventing malaria
among pregnant women);
8.The use of vaccines for the prevention of COVID-19, pneumococcal
disease, influenza, hepatitis B and yellow fever;
9.Provision of adequate nutrition;
10.Family planning services;
11.Elimination of vertical transmission;
12.Harm reduction program for people who inject drugs; and
13.Water, sanitation and hygiene.

31. Opportunistic infections
•Opportunistic infections (OIs) are infections that occur more often or
are more severe in people with weakened immune systems than in
people with healthy immune systems.
•People with weakened immune systems include people living with
HIV.
•About 90% of HIV-related morbidity and mortality is due to
opportunistic infections in World Most read 3 Epidemiology
• In one study it was found that Tuberculosis was the most frequent
opportunistic infections accounting for 50% of all opportunistic
infections, followed by Candidiasis in 49% of cases. Pneumocystosis
was seen in 16%,Cryptococcal infection in 09% and parasitic
diarrhoea in 15% in India.

32. Risk factors
•Elders
•Malnutrition
•Patients with HIV
•Patients with Inflammatory bowel disease
•Patients with Leukopenia
•Patients with diabetes mellitus
•Patients who uses immunosupressants

33. Types of opportunistic infections in HIV patients
•Fungal infections : P. jiroveci Pneumonia Oropharangeal Candiasis
•Protozoal infections: Toxoplasmosis , Cryptospordiasis
•Bacterial infection : Mycobacterium Tuberculosis

34. 1. Fungal infections
•P. jiroveci Pneumonia (PJP) in HIV-Positive Individuals
❖Symptoms: Non-productive cough, shortness of breath, fever,
anorexia, weight loss.
Pneumocystis pneumonia

35. OropharyngealCandidiasis
❖Treatment:
•First-line : Fluconazole 50 mg daily for 7 days.
❖Alternative: Itraconazole 200 mg daily (solution preferred over
capsules).
❖Topical therapies:
•Higher doses & longer duration: Fluconazole 100 mg daily for 2 weeks.
•Frequent azole use may lead to antifungal resistance.

36. 2. Protozoal Infections
❖Toxoplasmosis(T.gondii)
•Common CNS infection in AIDS patients.
❖Symptoms: Headache, fever, confusion, seizures, focal neurological
deficits.
❖Treatment:
•First-line: Sulphadiazine + Pyrimethamine + Folinic acid (to prevent
myelosuppression) for 6 weeks, then maintenance therapy until CD4 > 200
cells/mm³.
❖Alternative: Clindamycin + Pyrimethamine + Folinic acid.
•Other options: Atovaquone, Co-trimoxazole, Clarithromycin, Doxycycline
(limited data).
❖Adjunct therapy:
•Corticosteroids (for severe cerebral oedema).
•Anticonvulsants (for seizures).

37. 3. Bacterial Infections
1.MycobacterialInfections(Tuberculosis - TB)
Treatment:
•Phase 1: Four-drug regimen (Isoniazid, Rifampicin, Pyrazinamide,
Ethambutol) for 2 months.
•Phase 2: Two-drug regimen (Isoniazid, Rifampicin) for at least 4
months.
•Adjunct therapy: Corticosteroids (Dexamethasone or Prednisolone) for
all cases of TB meningitis.

38. 4. Viral infections
❖Cytomegalovirus(CMV) Common sites of infection: Retina, GI tract,
CNS, lungs.
❖Treatment:
•Induction therapy for 2–3 weeks with high-dose antivirals.
•Maintenance therapy at lower doses to prevent recurrence.
•Treatment Options
•First-line therapy: Ganciclovir (IV or oral valganciclovir).
•IV ganciclovir: 5 mg/kg via central line.
•Oral valganciclovir: 900 mg twice daily.
•Side effects: Neutropenia (may need colony-stimulating factors),
thrombocytopenia.
Alternative treatments:
•Foscarnet:
•Cidofovir:

39. 5. Cancers
•Kaposi's Sarcoma (KS) and Lymphomas
•Most common malignancy in HIV patients, linked to human
herpesvirus 8 (HHV-8).
•Skin lesions: Raised purple papules, single or multiple; severe cases
cause oedema, ulceration, and infection.
Treatment:
•HAART (Highly Active Antiretroviral Therapy) leads to improvement
or complete resolution.
•Local therapy: Radiotherapy, intralesional vinblastine, topical
alitretinoin
•Systemic chemotherapy (liposomal anthracyclines, taxanes) for
widespread or visceral disease

40. 6. Hepatitis
Hepatitis B
•Lower success rates of HBV vaccination.
Management:
•Use HAART regimen with at least two anti-HBV agents.
•Preferred drugs: Tenofovir + either emtricitabine or lamivudine.
Hepatitis C
Management:
•Direct-acting antivirals (DAAs): sofosbuvir + Velpatasvir , Sofosbuvir +
Ledipasvir……12 wks
•HAART must be compatible with HCV therapy (pegylated α-interferon + ribavirin).
•Avoid didanosine , abacavir, stavudine, and zidovudine because it causes Hepatotoxicity,
Increased Risk of Pancreatitis, Poorer Response to HCV Therapy, Increased Risk of
Anemia with Ribavirin

43. Reference
•Clinical-Pharmacy-and-Therapeutics-roger-walker-5th.pdf
•Nepal-national-hiv-testing-and-treatment-guidelines-2022.

44. Thank You