lecture on MANAGEMENT OF HIV-AIDS_080953.pptx

MANAGEMENT OF HIV-AIDS

1. MANAGEMENT OF HIV/AIDS PHARM ADENIYI AYODEJI JOHNSON (AUGUST, 2024)

2. INTRODUCTION HIV is a retrovirus possessing the enzyme reverse transcriptase which enables it to transcribe its genetic material from RNA to DNA. It attacks the body's immune system, specifically the white blood cells called CD4 cells. Individuals living with HIV are more susceptible to other diseases and infections. If HIV us left untreated, it continues to damage the immune system and over time leads to a syndrome known as AIDS. Without treatment, HIV infections progress to AIDS in about 10 years.

3. The virus is believed to have originated in non-human primates in West Africa in the early 20th century. AIDS was first recognized among homosexual men in the United States of America in 1981 and the organism causing it(HIV) was later identified in the year 1983. The history of HIV/AIDS in Nigeria dated back to 1985 when the first two HIV cases were identified and then reported at an international AIDS conference in 1986.

4. TYPES There are two notable types of HIV they are HIV-1 and HIV-2. HIV-1 is more virulent, easily transmitted, predominant and is the cause of majority of infections globally, the most widespread of its subtypes is B and C.   HIV-2 has less viral load, less transmitted with longer period between infection and illness, it is confined to West Africa and doesn't respond to Nevirapine.

5. EPIDEMIOLOGY Globally, in the year 2021 38.4 million people were living with HIV. Africa remains most affected region in the world. Nigeria had an estimated HIV burden of 1.9 million people in 2021, the fourth largest in the world of which women were the most affected group. Since the first case of AIDS was reported in the year 1986,national HIV prevalence increased from 1.8% in 1991 to 5.8% in 2001and has progressively declined to through 4.4 in 2005,3.4 in 2013. The current national prevalence if HIV in Nigeria is 1.4% ranked 4th in the world in 2021.

6. MODE OF TRANSMISSION Sexual contact which is the predominant mode of transmission e.g homosexual, heterosexual. Blood and blood products e.g blood transfusion, needle sharing. Vertical transmission e.g during labor/delivery, in utero, postpartum via breastfeeding. Note that HIV cannot be transmitted by insect bites and casual contact

7. HIV LIFE CYCLE Binding Fusion Reverse transcription Integration Transcription/Replication Assembly Budding

8. HIV PATHOGENESIS 1. Acute HIV Infection  Earliest stage of HIV infection, develop weeks after infection with HIV. Flu-like symptoms (fever, headache and rash) Symptoms are self limiting and resolve within 2 weeks HIV multiplies rapidly and spread throughout the body. Viral load peaks up and the risk of HIV transmission is greatly increased Virus attacks & destroys infection fighting CD4 cells of the immune system

9. 2. Chronic HIV infection (Asymptomatic)  Active viral replication and immune destruction. -There may not be any HIV-related symptoms. May last for 10 years or more. Still possible to transmit HIV to others during this stage

10. 3. Symptomatic  Fever, weight loss, persistent generalized lymphadenopathy skin and oral conditions (oral thrush, recurrerit herpes simplex)   4. AIDS Final and most severe stage Collapse of the body immune system Disease manifestation sets in (Opportunistic infections and infection-related cancer

11. SIGNS AND SYMPTOMS WHO CLINICAL STAGING  Patients are assigned to a particular stage when they demonstrate at least one clinical condition in that stage's criteria.  Stage 1:- Asymptomatic, normal activity Generalized lymphadenopathy Stage 2 Mildly symptomatic stage, normal activity Unexplained weight loss < 10% of body weight Dermatological conditions (recurrent oral ulcerations, angular cheilitis, fungal nail infections), Herpes zoster, Recurrent upper RTI (bacterial sinusitis)

12. Stage 3- Moderately symptomatic Weight loss 10% of body weight -Unexplained chronic diarrhea >1month, prolonged fever (intermittent/constant) >1mth, Oral candidiasis (thrush), Severe bacterial infections(pneumonia, pyomyositis), Pulmonary tuberculosis

13. Stage 4- Severely symptomatic stage (AIDS defining illnesses)  HIV wasting syndrome, Fungal illnesses ( Pneumocystic carinii pneumonia PCP, Candidiasis of eosophagus , trache bronchi), Viral infections-Herpes simplex virus, HIV encephalopathy, Cytomegalovirus disease, Bacteria Extrapulmonary TB, Non-typhoid Salmonella septicaemia , Protozoa-Toxoplasmosis of the brain, Cryptosporidiosis with diarrhea AIDS associated cancer-CNS lymphoma, Kaposi'ssarcoma )

14. MANAGEMENT OF HIV/AIDS There are 2 main t ypes of HIV tests: 1. Antibody tests:- screen patient's serum for the presence of HIV-specific antibodies. The body starts producing antibodies between 2-12 weeks after being infected Antigen/Antibody test detects the presence of the HIV antigen, called p24 as well as HIV antibodies. If a person has HIV, an antigen called p24 is produced before antibodies developed Nucleic acid test: checks for the presence of the viral RNA or DNA via DNA-PCR (polymerase chain reaction) It is not routinely used for laboratory diagnosis of HIV infection in adults and adolescent, it is used to detect HIV infection in neonates at birth, 6-8 weeks and 9 months. CURRENTLY THERE IS NO CURE FOR HIV INFECTION, HOWEVER THERE ARE TREATMENT OPTIONS THAT CAN HELP PEOPLE LIVING WITH HIV TO LIVE LONG LIVES.

15. ANTIRETROVIRAL THERAPY  Tx of HIV infection using a combination of antiretroviral drug . GOALS OF ART Clinical goals-Halt disease progression, prevention of opportunistic infections & decrease HIV related morbidity and mortality. Virological goals : Reduce Viral load (measure of amount of HIV in the blood) to <50copies/ml for as long as possible.  Immunological goals: Increase CD4 T cells count to more than 500 cells/mm helps reduction of Ols and reduce susceptibility to new infections.

16. Therapeutic goals: Provide a regimen that will preserve future therapeutic options with relatively few side effects, if any, and facilitating adherence. Epidemiologic goals: Decrease in transmission, reduction in mother to child transmission. Individual on HAART is less likely to transmit the virus transmission risk directly correlates to viral load burden.

17. ART COMBINATION THERAPY Combination antiretroviral therapy (CART) may also be called HAART (Highly Active ART). In managing HIV patients with ART, a combination of at least (3) ARVs from at least (2) different classes is essential.  Most current HAART regimens consist of three drugs: 2 NRTIs ("backbone") + a PI/NNRTI/INSTI ("base") ART regimens are generally classified as 1-, 2- or 3-line 1-line regimens are used in ARV naïve patients. 2- and 3 lines regimens are used in individuals who have failed 1- and 2- lines respectively 3- line consist of a cocktail of regimens and are currently not supported.

18. DISEASE MONITORING l ooking out for clinical improvement of pr's status by checking for wt gain, disappearance of existing Ois etc   Laboratory: Lab monitoring is important for early detection of ADRs and to diagnose and confirm ARV treatment failure  NOTE Virological suppression is the most important factor to conclude that a px has a good treatment outcome. Adherence monitoring is the baseline for successful treatment outcome. Px must adhere to drug pick up visit & lab appointments (CD4 and viral load)

19. SUBSTITUTION/SWITCH OF HAART REGIMEN Substitution is the replacement of one or two ARV drugs in a regimen with another drug of the same class usually because of the following: Toxicity/ adverse drug reactions, Co-morbidity, Pregnancy, or Drug interaction. Switching is the replacement of two or more ARV drug in a regimen with other drugs (from another class) due to treatment failure. HIV treatment failure may be defined as sub-optimal treatment outcomes following after at least 6 months of the initiation of ART.

20. Treatment failure is defined in terms of Clinical failure clinical disease progression with development of an Opportunistic infections or malignancy indicating severe immunodeficiency after 6 months of effective treatment. Immunological failure a fall in the CD4 counts higher than 30% from the peak value or a return to or below the pre therapy baseline or persistently below 100 cells/m Virological failure Plasma viral load >1000 copies/ml 6 months after starting ART on consecutive VL measurements indicative of incomplete viral suppression ( Fallure to achieve undetectable viral load levels.

21. COMMON OPPORTUNISTIC INFECTIONS (OIs)IN HIV INFECTION OIs are caused by a variety of organisms such as viruses, bacteria, fungi and parasites.   PLHIVs are at greater risk of OIs when their CD4 count falls below 200 , some occur at CD4 count just below 500  Examples of common opportunistic infections Tuberculosis, other bacterial infections ( Pneumocystie jirovecr , salmonella spp , Streptococcus),  Cryptosporidiosis, Toxoplasmosis

22. PROPHYLAXIS FOR OIS Prophylaxis is the use of drugs to prevent infection or disease 1.  Cotrimoxazole Preventive Therapy (CPT):-  This is effective prophylaxis against PCP, S pneumonia, toxoplasmosis, cryptosporidiosis etc  CPT should be initiated in all PLHIV regardless of CD4 count or WHO stage  -Adult dose (and >14yrs or 30kg):-960mg daily -Infants <6mnths/<5kg 120mg daily  -Children 6mnths-5yrs or 5-15kg:- 240kg daily -Children 6-14yrs or 15-30kg:- 480mg daily

23. 2. Isoniazid Preventive Therapy (IPT)  This is the use of INH in patients with latent TB infection  to prevent the development of active TB disease  It is not treatment for active TB Always exclude active TB b4 commencing a patient on IPT  Adult dose 300mg daily for 6months  Children: 10mg/kg/day to max of 300mg/day for 6months Give pyridoxine to treat side effects of INH (numbness/ tingling/burning sensation) If patient develops active TB during the course of IPT, discontinue and refer/ commence DOTS.

24. POST EXPOSURE PROPHYLAXIS (PEP) PEP is the use of antiretroviral medication to prevent HIV infection in an HIV-Negative person who has had a specific high-risk exposure to HIV.  Post exposure Prophylaxis is classified into two types, 1. Occupational HIV Post exposure Prophylaxis-This is recommended for healthcare personnel who have an occupational exposure to blood, tissue, or other body fluids that contain human immunodeficiency virus  2 . Non-occupational HIV PEP: This refers to the delivery of ART to persons who have experienced an exposure that represents a substantial risk for HIV transmission within the past 72hrs, in order to decrease the risk of HIV acquisition. Some of these exposures include; Condomless intercourse (receptive or insertive ; anal or vaginal), same gender sex, injection drug users & sex workers.  Regimen should contain 3 antiretroviral drugs for all exposures to HIV. A dual nucleoside/nucleotide reverse transcriptase inhibitor(NRTI) backbone plus an integrase inhibitor is given as a 28-day course.

25. The preferred regimen include;   Raltegravir 400mg twice daily plus tenofovir disoproxil fumarate/emtricitabine (300-200mg) once daily   Dolutegravir 50mg once daily plus tenofovir disoproxil fumarate/lamivudine (300mg-300mg) once daily. The rational for this regimen is that it is tolerable, potent, and conveniently administered and it has been associated with minimal drug interactions.

26. PRE EXPOSURE PROPHYLAXIS PrEP The World health organization (WHO) defines PrEP AS the use of an antiretroviral medication by HIV-negative people to reduce the risk of HIV acquisition. The Center for Disease Control and Prevention (CDC) recommends that PrEP be considered for people who are HIV negative and who have had anal or vaginal sex in the past 6 months and have a sexual partner with HIV ( Serodiscordant Couple) especially if the partner has an unknown or detectable viral load or have not consistently used a condom. PrEP is also given to people who inject drugs and share needles, syringes, or other equipment to inject

27. PrEP Regimen Emtricitabine 200mg/tenofovir disoproxil fumarate 300 mg tablets (Truvada) once daily Lamivudine 300mg/tenofovir disoproxil fumarate 300mg once daily.   NOTE: These drugs are only for people who are at risk of getting HIV; it is not used in management of HIV infection and also does not prevent other sexually transmitted infection or pregnancy.

28. PREVENTION OF MOTHER-TO- CHILD TRANSMISSION (PMTCT) HIV can be passed from mother-to-child anytime during pregnancy, childbirth and breastfeeding. This is called Perinatal transmission. Nevirapine only is adequate in babies whose mothers are stable on ART. If unavailable nevirapine is replaced with zidovudine (AZT) High risk infant (those whose mothers are not virally suppressed) should receive zidovudine in addition to nevirapine whether they are being breastfed or formular fed for 6 weeks. Breastfed high risk infants should receive an additional & weeks of dual ARV Prophylaxis.

29. ROLE OF PHARMACISTS IN MANAGEMENT OF HIV/AIDS PX EDUCATION/COUNSELLING Helping patients to understand their disease and their treatment Promoting proper use of medications. Teaching and reinforcing drug administration techniques Advice patients on adherence to their medication and its importance. Help reinforce the importance of adherence and offer adherence tools such as kit/pillboxes, reminder phone calls for refills.

30. 2. PHARMACOVIGILANCE  Monitoring for treatment responses and adverse effects and Evaluating regimens for potential drug-drug interaction or drug-disease interaction. 3. COLLABORATION WITH OTHER H/C PROVIDERS  Refer patients to other health care Professionals ( eg Psychologists, Support groups, Adherence counselors) Elimination of Structural barrier ( eg Location, Lack of transportation) by dispensing long term regimen. 5. Documentation. Recording of activities.

31. REFERENCES UNAIDS, Global AIDS Monitoring 2020, Country progress report-Nigeria Federal Ministry of Health National HIV & AIDs and Reproductive Health Survey 2012. NARHS plus II