HIV Infection and AIDS

Definitions
HIV infection is a retrovirus infection that integrates into CD4 T lymphocytes, causing cell death and resulting in severe immunodeficiency, opportunistic infections (OI), and malignancies.


Epidemiology
Predominantly young adults: 25–44
Male > Female
Younger women and girls are particularly vulnerable
Ethnic and racial minorities make up a disproportionate number of new AIDS cases.
Worldwide 2007: 32.2 million living with HIV, 2.5 million per year newly infected, 2.1 million deaths attributable to AIDS

Aetiology
Human immunodeficiency Virus, a rotavirus
Commonly Associated Conditions

• Syphilis may be more aggressive in HIV-infected persons.
• Tuberculosis (TB) is coepidemic with HIV; test all persons with TB for HIV. Dually infected patients have a 100× greater risk of developing active TB disease, compared with non-HIV-infected people. They also have higher rates of multidrug-resistant TB.
• Hepatitis C–coinfected patients have more rapid progression to cirrhosis.

Classification

Species	Virulence	Infectivity	Prevalence
HIV-1	High	High	Global
HIV-2	Lower	Low	West Africa

Pathophysiology

Transmission	Sexual Genital 75%, oral in 3-7% or rectal Condoms and male circumcision reduce risk Blood transfusion IV drug abuse Hemophiliacs Recipients of blood transfusions Mother-to-child: in utero (during pregnancy) intrapartum (at childbirth/vertical transmission) breast feeding.
Immunology	HIV binds, via its gp120 envelope glycoprotein, to CD4 receptors on helper T-lymphocytes, monocytes, macrophages, neural cells. CD+ve cells migrate to the lymhoid tissue where the virus replicate producing  billions of new virions. They are released, and in turn infect new CD4+ve cells. Infection progresses and impairs immune system
Virology	HIV(RNA retrovirus) enters the cell Viral reverse transcriptase makes a DNA copy of the RNA genome Viral integrase enzyme integrates the copy into the host DNA Viral protease cleaves the core viral proteins into building blocks of the virus Completed virions are released by budding Number of circulating viruses (viral load) predicts progression to AIDS

Presentation
Depends on phase of infection

Window period	Time between infection & enough antibodies for a +ve HIV test Duration: approximately 3 months HIV test is negative, Virus is multiplying rapidly - viral load is high No symptoms or signs of illness. Person is very infectious
Acute Seroconversion	Point at which HIV test becomes positive Happens about 3 months after infection HIV test is positive, very high viral load, CD4 count drops, Symptoms: often no asymptomatic, may have a transients ilness 2-3wk after exposure: fever , malaise, myalgia, pharyngitis, maculopapular rash or meningoencephalitis(rare). Afterwards, the person is well again
Asymptomatic HIV infection	Time period between seroconversion and onset of HIV/AIDS-related illness Duration < 1 year to > 15 years. Mostly asymptomatic for 3 years The CD4 declines- count is above 500 cells/ml Symptoms- none/few. 30% will have persistent generalized lymphadenopathy (PGL)- nodes>1cm at 2 extra-inguinal site for 3months. AIDS related complex- a prodrome to AIDS with hyperactive B-cell immune responses, : symptoms T↑, night sweats, diarhhoea, leukoplakia, herpes zoster, recurrent herpes simplex, sebarrhoeic dermatitis, tinea infections
AIDS	Final phase Duration: without antiretroviral drugs, less than 2 years, with antiretrovirals, potentially many years CD4 count < 200 cells/ml, Viral loads are high, pt is veryinfectious HIV test may become -ve Symtopms: Symptomatic conditions (B symptoms): Fever or diarrhea >1 month, bacillary angiomatosis, thrush, persistent candidal vulvovaginitis, cervical dysplasia or carcinoma in situ, oral hairy leukoplakia, herpes zoster, idiopathic thrombocytopenic purpura, pelvic inflammatory disease, peripheral neuropathy, or myelopathy Other symptoms and conditions: Secondary cancers: Kaposi sarcoma, Hodgkin, non-Hodgkin, Burkitt, primary brain lymphoma, and invasive cervical cancer Cardiac: Myopathy, pericarditis Renal: HIV nephropathy Other conditions: Seborrheic dermatitis, severe chronic fatigue, chronic lymphoid interstitial pneumonitis, extraintestinal strongyloides, listeriosis, nocardioses HIV encephalopathy/dementia/minor cognitive-motor disorder Progressive multifocal leukoencephalopathy HIV wasting syndrome (>10% weight loss) AIDS-defining opportunistic infections: Candidiasis, coccidioidomycosis, cryptococcus, cryptosporidiosis, cytomegalovirus, herpes simplex, histoplasmosis, isosporiasis, mycobacterium avium complex, M. kansasii, M. tuberculosis, other mycobacterium, P. jiroveci, bacterial pneumonias (>2/yr), recurrent Salmonella septicemia, toxoplasmosis of brain

Investigation

Enzyme-linked immunoabsorbent assay (ELISA)	For screening: ELISA is  reported as reactive or nonreactive; sensitivity and specificity >98%:
Western blot (Confirmatory)	Results positive, negative, or indeterminate Positive test is reaction with 2 of these 3 bands: P24, gp41, and gp 120/160 If indeterminate, repeat test in 3–6 months.
New rapid/oral test	Eg. OraQuick, available over the counte, problem: false +ves
CD4 cell count and percentage	indicator for risk of opportunistic infections Normal: 500-2000 cells/μL
HIV-RNA viral load	Uses RT-PCR or nucleic acid sequence-based amplification (NASBA) Can often be suppressed to an undetectable level with therapy
Others	Complete blood count (CBC) with differential Serum chemistry Serologies: Hepatitis A, B, C; syphilis; CMV; toxoplasma Urine screen for sexually transmitted infections (N. gonorrhoeae, C. trachomatis) Cervical or anal cytology (for MSMs) PPD skin test to evaluate for tuberculosis infection Glucose-6-phosphate (G-6PD) levels At baseline and during highly active antiretroviral therapy (HAART): Fasting blood and lipids Genotypic and phenotypic tests for resistance to antiretrovirals; indicated if virologic failure on HAART or before initiation of therapy
Imaging	CXR- for TB

Management

Prevention	Lifelong safer sec, barrier contraception, reduce partent. Blood screening disposable equipment Perinatal antiretrovirals for HIV+ mothers + Caesarian birth + bottle feeding (may ↑ mortality if poor hygiene)
Post-exposure prophylaxis	Eg- needle-stick injury(seroconversion rate- 0.4%) split condom, HIV+, Wash well, encourage bleeding, don’t SUCK note details of donor- fill in accident form Store blood(HIV, HBV, HCV test), test recipient at 3,6, 8 months Question donor for risk, if +ve, ask about CD4, viral load Treatment: 4wks of drugs, possibly 1h post-exposure Low risk: no antivirals High risk: zidovidine 250mg/12h + lamivudine 150mg/12h Deep puncture case: indinavir 800mg/8h, all PO
Consideration	STD? Condom? What is the CD4 count/HIV RNA level? CMV & Toxoplasma titre? Recent CXR? Recent cervical smear
Highly active antiretroviral therapy, or HAART	Main goal of HAART is to reduce the viral load, ideally to <50 HIV1 RNA copies/mL) and delay immune suppression. Other goals: Prevent HIV-associated complications, short- and long-term adverse drug reactions, HIV transmission, HIV drug resistance, and preservation of HIV treatment options. Standard initial regimen includes: 2 nucleosides with a non-nucleoside reverse transcriptase inhibitor 2 nucleosides and a protease inhibitor (PI) or a ritonavir-boosted PI 3 nucleosides are not as effective. Some examples: (Make notes on antiretroviral) Nucleoside- Abacavir (ABC, Ziagen), didanosine (DDL, Videx) Non-nucleoside: Delavirdine (Rescriptor), efavirenz (Sustiva) Protease inhibitors: Amprenavir (Agenerase), atazanavir (Reyataz) -can cause metabolic syndrome (lipodystrophy, decreased HDL] increased triglycerides, high BP, and hyperglycemia) Indication: According to US Department of Health and Human Services, begin when CD4 count <200 or AIDS-defining illness and symptoms are present For other categories: Some debate about when to begin HAART; benefits must outweigh risks, such as side effects and medication resistance (if nonadherent). Side effects can lead to nonadherence. With prolonged use of HAART, virus may mutate; medication will be less effective, but resistant strains have more difficulty reproducing. (Medication less effective than in a nonresistant patient.)
Prophylactic antimicrobial agents and vaccines	P. jiroveci (former Pneumocystis carinii): TMP-SMX 1 DS/d or 1 SS/d indicated if CD4 <200/mm3, prior PCP, thrush, or unexplained fever for >2 weeks M. tuberculosis: Treat if PPD >5 mm induration without prior prophylaxis or treatment, recent TB contact, or history of inadequately treated TB that healed. Confirmed by culture. Treatment is based on susceptibility. Toxoplasma gondii: 33% per year risk of infection in untreated patients with CD4 <100/mm3. Prophylaxis: TMP-SMX DS/d. M. avium complex (MAC): 20–40% risk with CD4 <50 and no HAART. Preferred prophylaxis is clarithromycin, 500 mg p.o. b.i.d., or azithromycin, 1,200 mg p.o. weekly. Varicella (VZV): Seronegative and unexposed are at risk if exposed to chickenpox or shingles. Preferred regimen is VZIG 5 vials within 96 hours, preferably within 48 hours. S. pneumoniae: 50–100× increased risk of invasive infection compared with general population; Pneumovax every 5 years. Influenza vaccine each fall Hepatitis A and B vaccines for at-risk patients Tetanus: dT vaccine in adults
Follow-up	Determined by the patient's clinical status Every 3–4 months, perform careful physical exam, complete review of systems, CD4 counts, viral load; Pap every 6 months in female patients

Complications
Immunodeficiency
Opportunistic infections
Malignancy, including cervical or anal cancer

Prognosis
When untreated HIV infection leads to AIDS, the life expectancy is 3.7 years.
AIDS-defining opportunistic infections usually do not develop until CD4 <200.
In HIV-untreated infection, CD4 counts decline at a rate of 50–80/yr, with more rapid decline as counts drop <200.
Drug resistance most common cause of treatment failure