Kembara Xtra - Medicine - HIV / AIDS

Kembara Xtra - Medicine - HIV / AIDS 
HIV is a retrovirus (subgroup lentivirus) that integrates into CD4 T cells, changing cell-mediated immunity and, if left untreated, leading to cell death, severe immunodeficiency, opportunistic infections, and cancer.
Viral transmission, acute retroviral syndrome, recovery and seroconversion, chronic asymptomatic HIV infection, and symptomatic HIV infection or AIDS are all parts of the natural course of untreated HIV infection.
The average patient develops AIDS without treatment 10 years after contracting HIV.
Persons with AIDS are defined as HIV-infected individuals with CD4 counts below 200 cells/mm3 or those who have diseases that meet the criteria for AIDS.

Prevention Incidence
37,000 new cases in the United States in 2019, a 9% decline in incidence from 2015. In 2018, there were roughly 1.7 million new HIV diagnoses worldwide.

Prevalence
38 million individuals worldwide are living with HIV, including 1.2 million people in the United States who are unaware they are infected. Sub-Saharan Africa accounts for 43% of all new diagnoses.

In 2019, AIDS-related illnesses claimed the lives of 690,000 people.


Pathophysiology and Etiology 

HIV most commonly affects CD4+ cells. HIV is an enclosed, single-stranded, positive-sense RNA virus. Following entry into target cells, viral RNA is reverse-transcribed to DNA, transported into the nucleus of the host cell, and integrated into the host DNA. The virus can create fresh viral RNA and proteins that are released to infect more CD4+ cells, or it can go latent. Within the context of the seroconversion response, host CD8+ cells are activated.
There are two distinct HIV strains. The majority of HIV infections are caused by HIV-1. HIV-2 is less contagious and mostly found in West Africa.

Risk Elements 
Sexual activity (>90% of transmission): The largest risk is receptive anal intercourse. Infection is facilitated by ulcerative urogenital lesions.

 Drug injection usage
Children of women with HIV: HIV-1 RNA in the mother's blood forecasts transmission.
– Breast milk can also be a source of HIV transmission. Women with HIV should avoid breastfeeding unless there is no other option. Consider antiretroviral therapy (ART) in this situation.

Prior to 1985, recipients of blood products
Workplace exposure (healthcare professionals)

Prevention 

Avoid high-risk, unprotected sex and injectable drug usage, particularly the use of shared needles.
Preexposure prophylaxis (PrEP) is advised for people who are at a high risk of contracting HIV by the WHO and USPSTF.
– general recommendations for PrEP: Before starting medication, one should (i) rule out acute or chronic HIV infection (ii) repeat HIV testing every three months (iii) and (iv) test the kidneys and liver for function at baseline, 2 to 8 weeks after starting PrEP, and every six months.
For HIV+ individuals on ART, maintaining HIV RNA levels 200 copies/mL decreases risk of transmission to sexual partners (treatment as prevention). Postexposure prophylaxis (PEP) should be started within 72 hours after exposure and sustained for 28 days with a three-drug regimen.

HIV testing should be done at least once in individuals between the ages of 15 and 65, and it should be done at least annually in patients who are at higher risk.

Accompanying Conditions 

Syphilis in people with HIV is more aggressive.
HIV and tuberculosis (TB) are co-epidemic; all patients should be tested for TB. Patients who have both TB and HIV infection are 100 times more likely to acquire active TB.
Patients who also have hepatitis B or C advance to cirrhosis more quickly.
Enhanced risk for skin cancer, lymphoma, and cervical cancer


Acute retroviral syndrome is diagnosed when the CD4 lymphocyte count decreases and the viral load increases one to four weeks after transmission. High HIV RNA is also detected in the absence of an HIV antibody.
Acute retroviral syndrome exhibits symptoms that are similar to those of mononucleosis, including fever, adenopathy, pharyngitis, rash, and myalgias/arthralgias.
Clinical latency (asymptomatic): lasts anywhere from 8 to 10 years on average and is characterized by a steady fall in CD4 cell numbers and generally constant HIV RNA levels (the viral "set point"). Patients frequently experience prolonged widespread lymphadenopathy and, if left untreated, may also experience fever, weight loss, myalgias, and gastrointestinal issues.
AIDS is characterized by a CD4 cell count below 200, a CD4 cell percentage of total lymphocytes below 14%, or an AIDS-related opportunistic infection such as Pneumocystis jiroveci (carinii) pneumonia, cryptococcal meningitis, recurrent bacterial pneumonia, Candida esophagitis, CNS toxoplasmosis, TB, non-Hodgkin lympho
HIV illness that is advanced: CD4 cell count 50. At this time, most AIDS-related deaths take place.


Providing a complete medical history that includes risk exposures, sexual, social, and occupational histories, injectable drug usage, receiving blood products (before 1985), using PEP or PrEP in the past, and medication use.

 A thorough system review A review of the immunization record.

clinical assessment 
Focus on weight (weight loss is common), skin, retinal exam, oropharynx, lymph nodes (generalized lymphadenopathy is common), lung, liver, spleen, mental status, neurologic, genital, and rectal examinations, as well as weight (weight loss is common).
DISTINCTIVE DIAGNOSIS
Herpes simplex, influenza, lymphoma, mononucleosis, TB, toxoplasmosis, candidiasis, CMV, coccidioidomycosis, Cryptococcus,

Initial test results from the laboratory and imaging
The 4th generation of HIV testing incorporates HIV-1 and HIV-2 antibody/antigen immunoassays (4).[A].
- Within 2 to 3 weeks of exposure, results may be positive.
- Quantitative PCR can get HIV RNA and detect acute HIV infection within 12 days of exposure; Western blot confirmation, once considered a confirmatory test, is no longer advised. - CD4 cell count and percentage. - Plasma HIV RNA viral load.
Chemistry, transaminase levels, fasting blood glucose, lipid levels, creatinine (Cr), blood urea nitrogen (BUN), total bilirubin, and CBC with differential Check for chlamydia, gonorrhea, and syphilis as well as hepatitis A, B, and C.
Cervical cytology; PPD or interferon-release assay (IGRA) to check for latent TB infection; chest x-ray (CXR) if pulmonary symptoms are present or the PPD is positive; HLAB*5701 testing if abacavir is the intended course of treatment; genotypic tests for antiretroviral resistance for patients with pretreatment HIV RNA levels below 1,000 copies/mL; transmitted resistance to at least one drug is seen in 6–1
Tests in the Future & Special Considerations

If care is sought within 72 hours of a potential exposure and there is a significant risk of exposure, non-occupational PEP (nPEP) is advised:
If nPEP is necessary, a 28-day three-drug regimen should be initiated. Sources known to be HIV+, exposure to blood, semen, vaginal or rectal secretions, and breast milk.[A]. - Daily doses of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg also include:
 Dolutegravir 50 mg daily OR raltegravir 400 mg BID
Encourage PrEP use and offer preventative advice to patients who have completed multiple courses of nPEP.

Complete HIV, hepatitis B, and hepatitis C testing at baseline, 4–6 weeks, 3 months, and 6 months following exposure in cases with nPEP.

Get gonorrhea, chlamydia, and pregnancy tests for people who have been sexually exposed at the time of presentation and 4 to 6 weeks after exposure. Syphilis serology should be done 6 months after exposure. 


Management 

 Start ART in qualified patients. Resistance testing should be used to choose or modify regimens.
Dosing frequency, pill burden, toxic effect profiles, comorbidities, and drug interactions should all be taken into account.

The need for immediate treatment is made more urgent by the following factors: pregnancy, AIDS-defining conditions, acute opportunistic infections, CD4 count 200, HIV-associated nephropathy, acute/early infection, hepatitis B or C coinfection, rapidly declining CD4 counts (>100 cells/mm3 per year), and high viral loads (>100,000 copies/mL).

General Actions 
The purpose of ART is to postpone immune suppression and lower viral load (below limits of detection; HIV RNA 200).
The most significant marker of ART response is viral load.
Genotypic testing is advised to direct treatment in patients new to ART.
Prior to beginning ART, it is important to evaluate drug resistance, substance misuse, economic conditions (such as insecure housing and food security), social support, mental illness, comorbid conditions, and high-risk behaviors.
Use an ART regimen in women of reproductive age that reduces viral load with less teratogenicity.

 Vaccines and prophylactic antibiotics:
Treat for latent tuberculosis if positive PPD or positive IGRA if no prior prophylaxis or treatment, negative CXR, no recent TB contact, and no history of inadequately treated TB. P. jiroveci prophylaxis. Trimethoprim/sulfamethoxazole (TMP-SMX).
Mycobacterium avium complex prophylaxis: 20–40% risk with CD4 50 and no ART. Toxoplasma gondii prophylaxis: 33% per year risk of infection in untreated individuals with CD4 100 cells/mm3; prophylaxis: TMP-SMX 1 DS tab daily. It is best to use 1,200 mg of azithromycin every week.
- Streptococcus pneumoniae: pneumococcal conjugate vaccine (Prevnar) and pneumococcal vaccine polyvalent (Pneumovax 23) at least 8 weeks apart, repeat every 5 years, reduce risk of invasive infection by 50 to 100 times compared to general population.
- Hepatitis A and B vaccination, human papilloma virus vaccination, at least three Tdap shots throughout one's lifetime, and Td vaccination every ten years. - Annual influenza vaccination (no live vaccine).

First Line of Medicine
Integrase strand transfer inhibitor with two nucleoside reverse transcriptase inhibitors are the recommended regimens for the majority of HIV-positive individuals:
(50 mg/25 mg/200 mg PO daily) Bictegravir, Tenofovir Alafenamide, and Emtricitabine
 Only for patients who are HLA-B*5701 negative, dolutegravir/abacavir/lamivudine (50 mg/600 mg/300 mg PO daily).
Dolutegravir (50 mg PO daily) + lamivudine (300 mg PO daily) or tenofovir disoproxil fumarate (300 mg PO daily) or tenofovir alafenamide (25 mg PO daily) (right parenthesis)
- One nucleoside reverse transcriptase inhibitor and an integrase strand transfer inhibitor
 Dolutegravir/lamivudine (50 mg/300 mg PO daily), unless genotypic resistance testing findings are unavailable, HIV RNA > 500,000, or hepatitis B coinfection.
Dolutegravir is the recommended medication for women who are expecting or attempting to get pregnant.

The FDA has approved the combination drug Truvada (tenofovir/emtricitabine) 300 mg/200 mg PO daily for PrEP in individuals at high risk.


Patient Follow-Up Monitoring
2 to 8 weeks after starting treatment, check the HIV RNA viral load; if detectable, repeat testing every 4 to 8 weeks until the viral load is lowered to under 200 copies/mL. After that, test again every three to six months.
– It is regarded as a significant response when the HIV RNA viral load decreases by threefold.
For the first two years of ART, check HIV RNA viral load, CD4, and CBC every three to four months. If the CD4 count is below 300 cells/mm3, do the same.

 Verify that within the first year of ART, the CD4 count level has increased by 50 to 150 cells/mm3.
In patients who adhere to ART and have a persistently reduced viral load and are immunologically stable for more than 2 years, HIV RNA monitoring can be spaced out to every 6 months.

 Track the CBC along with each CD4 count.

 Extend CD4 monitoring to 12 months if viral load is controlled and CD4 is greater than 300 cells/mm3.

● Monitoring CD4 cell counts is not necessary once viral load has been persistently suppressed for more than two years and CD4 cell counts are consistently >500/L unless virologic failure occurs (or there are concurrent immunosuppressive diseases or therapies).
If normal at baseline, annual fasting lipids and fasting glucose
Annual cervical cytology (regardless of age), up until three negative screens, and thereafter every three years. Basic metabolic panel, AST/ALT, total/direct bilirubin, and every six months.
Urinalysis every six to twelve months or as necessary
In women of childbearing age, -hCG


Diet

 Promote healthy eating; stay away from raw eggs and unpasteurized dairy products.
Talk about supplement use's unknown and potentially dangerous side effects, such as medicine interactions.

Counseling for sex-positive prevention that is nonjudgmental and reviews high-risk behaviors and viral spread is provided.

Life expectancy associated with untreated HIV infection that results in the diagnosis of AIDS is approximately three years. The patient has a one-year life expectancy if they have an opportunistic infection.
Opportunistic infections that are specific to AIDS typically do not appear until CD4 > 200.
The most frequent reason for treatment failure—rather than drug resistance—is adherence failure.

Complications include lymphoma, cervical cancer, and anal cancer as well as immune dysfunction and opportunistic infections.

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