1. Antiretroviral therapy and its complications

2. GOAL OF ANTIRETROVIRAL THERAPY
• maximally and durably suppress plasma HIV viral load,
• restore and preserve immunologic function (CD4),
• reduce HIV-associated morbidity and prolong
survival,
• improve quality of life, and
• prevent HIV transmission.
HIV suppression with antiretroviral therapy may also decrease inflammation and immune activation thought to contribute to higher rates of cardiovascular and other comorbidities

3. WHAT CAN NOT BE ACHIEVED WITH ARV THERAPY
cure
lack of infectivity of a person living with HIV
Reservoirs (sanctuaries) of the virus:
- central nervous system
- lymph nodes
- urogenitary tract

5. When to start ARV treatment? 2019 - all guidelines
All patients

6. Groups of ARV drugs Reverse transcriptase inhibitors nucleotide NtRTI
nucleoside NRTI
non nucleoside NNRTI
Protease inhibitors PI
Fusion inhibitors
Integrase inhibitors
Co-receptors inhibitors (CCR5)

7. ARV drugs Highly active antiretroviral therapy – HAART 1996
Basic regimens
2 NRTI + PI/r
2 NRTI + NNRTI
2 NRTI +InI
Salvage regimens
We give what we can

8. Nucleoside reverse transcriptase inhibitors (NRTI)
Generic name Abbreviation Trade name
Zidovudine AZT „ Retrovir”
Emtricitabine FTC „Emtriva”
Lamivudine TC „Epivir”
Didanosine ddI „Videx”
Stavudine d4T „Zerit”
Abacavir ABC „Ziagen”

9. NRTIs may cause mitochondrial toxicity
NRTIs may cause mitochondrial toxicity. The most serious symptom of mitochondrial toxicity is a life-threatening condition - lactic acidosis Other symptoms pancreatitis polyneuropathy, lipoatrophy bone marrow suppresion (pancytopenia) miopathy hepatotoxicity .

10. Nucleotide reverse transcriptase inhibitor (NtRTI)
Tenofovir TDF „Viread”
TAF Tenofovir Alafenamide („Descovy” : F/TAF)
Non nucleoside reverse transcriptase inhibitors (NNRTI)
Nevirapine NVP „Viramune”
Efavirenz EFV „Stocrin”
„Sustiva”
Etravirine „Intelence”
Rilpivirine „Edurant”

11. Non nucleoside reverse transcriptase inhibitors NNRTI Adverse effects: hepatitis rash (hypersensivity)

12. Protease inhibitors Saquinavir SQV „Invirase” Indinavir IDV „Crixivan”
Atazanavir ATV „Reyataz”
Fosamprenavir FPV „Telzir”
Ritonavir RTV „Norvir”
Lopinavir LPV „Kaletra” (LPVr)
Tipranavir TPV „Aptivus”
Darunavir DRV „Prezista”

13. Protease inhibitors may cause : - abnormal distribution of fatty tissue (lipodystrofy) - diabetes, increased cholesterol and TG concentration CHD - increased bleeding in hemophiliacs - diarrhoea, nausea, abdominal pains - hepatitis

14. Fusion inhibitor Enfuvirtide ENF „Fuzeon”
Administered subcutaneously, topical symptoms

15. Raltegravir „Isentress”
Integrase inhibitors
Raltegravir „Isentress”
Elvitegravir only with other drugs in one pill „Stribild or Genvoya ”
Dolutegravir „Tivicay”
Bictegravir „Bictervy”
Co-receptors antagonists (CCR5)
Maraviroc „Celsentri”

16. EACS

17. What is important in highly active antiretroviral therapy
Combined treatment with at least 3 drugs
Combining drugs from different groups
Lifelong treatment
Adherence > 95%

18. Importance of adherence
Adherence „Full” suppresion of the virus
>95 % %
90 – 95 % %
80 – 90 % %
70 – 80 % %
<70 % %
Paterson D et al Conference on retrovirus and Opportunistic Infections Chicago 1999

19. Evidence for efficacy of ARV
decrease in HIV viremia
< 20 copies/ml
increase in CD4 count
patient`s general condition improved

20. Failure of ARV therapy Increase in HIV viremia Decrease in CD4 count
Occurrence of opportunistic infections
Causes:
Too low drugs concentration
Immergence of the resistant strain of virus
- improper dosing, drug-drug interactions,
malabsorption
- poor adherence

21. Definition of Antiviral Drug Resistance
Presence of viral mutations that reduces drug susceptibility compared with the susceptibility of wild-type viruses.
Selection of resistance requires viral replication in the presence of sub-optimal drug concentrations

22. When do we switch to another ARV regimen
Therapeutic failure
Improve adherence
Resistance testing : genotyping
phenotyping
Toxicity of the drugs

23. Drug – drug interactions
ARV drugs have many interactions with other drugs and between themselves.
PIs and NNRTIs are inhibitors or substrats of CYP 450 and that results in increasing or decreasing plasma concentration of other ARVs or concomitant drugs.
E.g. Rifamycin decreases PI plasma concentration by 80 %
Some herbs have similar effect (St.John`s wort, garlic)