HIV by Amar a brief into hiv life cycle and managment

Hiv brief of lice cycle and management

1. HIV/AIDS By SSEBWANA AMARU OUTLINE INTRODUCTION EPIDEMIOLOGY TRANSMISSION VIROLOGY & PATHOGENESIS CLINICAL STAGING DIAGNOSIS ART & PROPHYLAXIS OPPORTUNISTIC INFECTIONS

2. INTRODUCTION HIV is a blood borne virus typically transmitted via sexual intercourse HIV refers to human Immunodeficiency virus. It belongs to lentivirus subgroup of retroviruses which causes slow infections with long incubation period ( retroviridae family, lentivirus genus ). HIV infects only CD4+ cells ( e.g lymphocytes, monocyte-macrophages, dendritic cells, microglial cells), resulting in immune suppression. Acquired Immunodeficiency syndrome (AIDS) is the most advanced stage of the disease. WHO now defines AIDS as CD4 cell count less than 200cells/mm3 or WHO stage 3 or 4 in adults and adolescents. All children with HIV younger than 5 years of age are considered to have advanced HIV disease. There is no cure for HIV infection.

3. EPIDEMIOLOGY HIV/AIDs begun in 1981 and is an ongoing worldwide public issue HIV remains a global public health issue, having claimed 40.4 million(32.9-51.3 million) lives so far with ongoing transmission in all countries globally; with some countries reporting increasing trends in new infections when previously on the decline. There were an estimated 39.0 million (33.1-45.7 million) people living with HIV (PLWHIV) at the end of 2022, 2/3 of whom (25.6 million) are in the WHO African Region. In 2022, 630 000 (480 000-880 000) people died from HIV-related causes and 1.3 million (1.0-1.7 million) people acquired HIV.

4. TRANSMISSION sexual contact. Transfusion of infected blood. Vertical transmission(EMTCT) Sharing sharps Needle prick injuries

5. VIROLOGY & PATHOGENESIS There are two subtypes of HIV-1 & HIV-2. • The most common cause of HIV disease throughout the world is HIV-1. • HIV-2 was first identified in 1986 in West African patients and was originally confined to West Africa. However, a number of cases that generally can be traced to West Africa or to sexual contacts with West Africans have been identified throughout the world There are three groups of HIV-1, representing three separate transmission events from chimpanzees: M (‘major’, worldwide distribution), O (‘outlier’) and N (‘non-major and non-outlier’). Groups O and N are restricted to West Africa. Group M consists of nine subtypes: A–D, F–H, J and K, but recombinants of subtypes occur frequently. Globally, subtype C (which predominates in sub-Saharan Africa and India) accounts for half of infections and appears to be more readily transmitted. Subtype B predominates in Western Europe, the Americas and Australia. In Europe, the prevalence of non-B subtypes is increasing because of migration. Subtypes A and D are associated with slower and faster disease progression respectively.

6. HIV can only infect cells bearing the CD4 receptor; These are T-helper lymphocytes, monocyte–macrophages, dendritic cells, and microglial cells in the central nervous system (CNS). Individuals who are homozygous for the CCR5 delta 32 mutation do not express CCR5 on CD4 cells and are immune to HIV infection

7. CLINICAL STAGING(WHO) Clinical Stage I:Asymptomatic 1. Asymptomatic. 2. Persistent generalized lymphadenopathy Clinical stage II: Mild 1. Moderate weight loss (< 10% of presumed or measured body weight) 2. Minor mucocutaneous manifestations (seborrheic dermatitis, prurigo, fungal nail infections, recurrent oral ulcerations, angular stomatitis/cheilitis) 3. Herpes zoster within the last 5 years 4. Recurrent upper respiratory tract infections (e.g. bacterial sinusitis, tonsillitis, otitis media, and pharyngitis)

8. Clinical stage III: Advanced. 1. Severe weight loss (more than 10% of presumed or measured body weight) 2. Unexplained chronic diarrhoea for longer than 1 month 3. Unexplained persistent fever, intermittent or constant, for longer than 1 month 4. Persistent oral candidiasis 5. Oral hairy leukoplakia 6. Pulmonary tuberculosis 7. Severe bacterial infections (such as pneumonia, pyomyositis, empyema, bacteraemia or meningitis) 8. Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis 9. Unexplained anaemia (< 8 g/dl), neutropenia (< 0.5×109 per litre ), or chronic thrombocytopenia (< 50× 109 per litre

9. Clinical stage IV: Severe 1. HIV wasting syndrome. 2. Pneumocystis jirovecii pneumonia (PJP) 3. Recurrent severe bacterial pneumonia 4. Toxoplasmosis of the brain 5. Cryptosporidiosis 6. . Kaposi sarcoma 7. Extrapulmonary cryptococcosis including meningitis 8. Cytomegalovirus infection (retinitis or other organs) 9. Herpes simplex virus (HSV) 10. Progressive multifocal leukoencephalopathy (PML)

10. 11. Any disseminated endemic mycosis such as histoplasmosis, coccidioidomycosis 12. Candidiasis of the oesophagus , trachea, bronchi, or lungs 13. Disseminated non-tuberculous mycobacterial infection 14. Recurrent septicemia (including non-typhoid salmonella) 15. Extra pulmonary tuberculosis 16. Lymphoma (cerebral or B-cell non-Hodgkin) 17. Invasive cancer of the cervix 19. HIV encephalopathy 20. Atypical disseminated leishmaniasis 21. Symptomatic HIV-associated nephropathy or symptomatic HIV associated cardiomyopathy

11. DIAGNOSIS OF HIV HIV can be diagnosed by detecting anti HIV antibodies or by direct identification of viral material.

12. PREVENTION ABC ( abstinence, be faithful to your partner, condom use). Not sharing needles. Discard donated blood that is contaminated with HIV. Use of Pre-Exposure Prophylaxis( PrEP ) and Post- Exposure Prophylaxis (PEP) • Elimination of mother-to-child transmission(EMTCT) • Safe male circumcision

13. Co-trimoxazole is used for primary prophylaxis

14. ANTIRETROVIRAL THERAPY GOALS OF ART In summary the goals of ART are to: • Reduce the viral load to an undetectable level for as long as possible • Improve the CD4 count to over 200 cells/mm3 so that severe HIV-related disease is unlikely(CD4 restoration) • Improve the quantity and quality of life without unacceptable drug toxicity • Reduction in HIV related morbidity and mortality.

15. There are 5 classes of antiretroviral drugs. – NRTIs.(ABC,ZDV,TDF,3TC,)(abacavir, zidovudine, tenofovir disoproxil, lamivudine) -NNRTIs.(EFV efavirenz, NVP nevirapine, etravirine, delavirdine) -PIs(LPV,RTV,ATV,DRV)(lopinavir, ritonavir, atazanavir, darunavir) -Integrase inhibitors(RTG,DTG)(dolutegravir) -Entry inhibitors( enfirvitide,maraviroc )

16. ART IN UGANDA The test and treat policy. The 90 90 90 strategy. First line regimen for adults and adolscents . TDF+3TC+DTG (2022 guidelines). ABC+3TC+DTG (2022 guidelines) If TDF is contraindicated. First line regimen for pregnant women. ABC+3TC+ATV/r If TDF and EFV are contraindicated.

17. ART for TB/HIV co- infection ART should be initiated in all TB/HIV co-infected people irrespective of their clinical stage or CD4 count. However, the timing of initiating treatment may differ based on whether the patient is diagnosed with TB before or after initiating ART. When to start ART in TB/HIV co-infection; If the patient is already on ART, start TB treatment immediately and adjust the ART regimen as recommended below (Table 27). If the patient is not on ART, initiate anti-TB treatment immediately and start ART two weeks after initiation of TB treatment. For adults with CD4 count less than 50 cells/mm3 ART should be initiated

18. First-line ART regimen for TB/HIV co-infected patients diagnosed with TB but not on ART There are situations when a patient is diagnosed with both HIV and TB. The recommended first line regimen for a TB patient initiating ART are as indicated: 8 ART regimen substitutions for patients diagnosed with TB while on ART Anti-TB treatment should be initiated immediately upon diagnosis while continuing ART. However, the ARV regimen should be reviewed and may need substitutions to ensure optimal treatment of both TB and HIV and to decrease the potential for toxicities and drug–drug interactions

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20. TB PREVENTION Isoniazid Preventive Therapy (IPT) IPT prevents the progression of TB infection to active TB disease. All PLWHIV with a negative TB symptom screen should be offered IPT for six months . IPT is NOT recommended for contacts of patients with MDR-TB. Eligibility for IPT; HIV-positive children (≥one year of age), adolescents and adults with no signs and symptoms of TB HIV-positive infants and children

21. ART COMPLICATIONS Immune Reconstitution Inflammatory Syndrome(IRIS) IRIS presents either with paradoxical deterioration of an existing opportunistic disease (including infections that are responding to appropriate therapy) or with the unmasking of a new infection. Lipodystrophy Long-term use of ART may cause changes in body fat distribution. This can present either with fat accumulation or with subcutaneous fat loss. Rashes

22. References Mediscape by Shelley A, MD, FACP, June 7 th 2024 Uganda Population based HIV Impact Assessment UPHIA 2020-2021 WHO HIV AND AIDS (13 JULY 2023)