Diagnosis>Miscellaneous>

PATHOGENS

• HIV-1 and HIV-2 (HIV-2 predominantly found in West Africa).
• HIV-1 divided into 3 groups: M (Main) group (worldwide distribution); O (Outlier) group (primarily West Africa, and N (Non-O, Non-M) group (Cameroon).
• M group further divided into subtypes or clades designated A-K.
• HIV-1 group M subtype B is predominant cause of HIV-1 infection in U.S.
• Majority of HIV sexually transmitted with MSM the major mode in U.S. Heterosexual sex is the major mode globally. Injection drug use and mother-to -child transmission are also important modes of infection.
• A "primary HIV-like" syndrome can occur after discontinuation of ART in 5% of individuals.

CLINICAL

• Sx occur in up to 50-90% of pts within 1-4 wks of infection. Typically "flu-like" illness similar to other viral syndromes (e.g. influenza, mononucleosis) with low-grade fever, malaise, and headache. Additional symptoms may include lymphadenopathy, anorexia, and weight loss. Duration is usually 1 - 4 wks (median 2 weeks).
• Hx: fever +/- myalgias, arthralgias, rash, headache, pharyngitis, lymphadenopathy, oral or genital ulcers, thrush.
• Severity of presentation (& number of Sx) associated with peak HIV RNA level (VL).
• Exam: maculopapular rash that may extend to palms and soles (20-67%), pharyngeal erythema, oral ulcerations, oropharyngeal candidiasis, lymphadenopathy, & splenomegally (each 10-60%). 
• Most common lab abnormalities: thrombocytopenia, leukopenia, elevated liver enzymes, atypical lymphocytes. CD4 may be acutely suppressed, usually rises to near normal after acute illness.
• Rate of CD4 decline to AIDS (<200) from 2 to >20 yrs (without ART). Rate related to VL, multiple other factors are likely important.
• All individuals with acute HIV infection progress to chronic disease.

DIAGNOSIS

• ELISA negative or positive with previous negative test and VL>10,000 or p24 antigen positive. Seroconversion occurs 2-8 wks (avg. 25 days) after acute infection = test "window period." 97% seropositive by 3 mos.
• VL: sensitivity 100%, specificity 97%. False positive rates as high as 1%, but usually associated with low levels (<1000). Viral RNA can be detected as early as 9 days after infection. VL <100,000 unlikely during acute phase; suggests that pt approaching viral set point. VL<1000 rules our ARS but not HIV infection; retest in several wks with serology +/- VL.
• VL reaches peak of 100,000-10,000,000. Levels decrease spontaneously without treatment by 2 to 3 logs approx 2 wks after onset of Sx.
• p24 antigen: sensitivity 89%, specificity 100%, may be negative 1-2 mos following infection due to formation of Ag-Ab complexes. Can be detected as early as 2 wks after infection.
• Dx of HIV using VL or p24 antigen must be confirmed with WB, which may not be fully positive for several weeks.
• CD4 may be acutely decreased in primary HIV infection (rarely <200)
• Co-infection with STDs common (30%). Test for gonorrhea, Chlamydia, syphilis, and HSV.

TREATMENT

• Data currently insufficient to recommend routine use of ART for acute infection, however RCTs are ongoing to explore this issue.
• Treatment indicated in highly symptomatic acute infection with significant neurological disease.
• Inconclusive data that treatment during PHI results in reduction in disease progression compared to treatment during chronic infection.
• Potential risks of early treatment: (1) toxicity, (2) resistance, especially if treatment fails to suppress high viral replication seen in PHI.
• Consider referral to clinical trial if available.

• In Europe & North America 6 - 16% of transmitted HIV has 1 or more resistance mutations.
• Obtain resistance test (genotype) to determine if drug-resistant virus was transmitted for future use when ART is needed. Should be obtained promptly before wild-type HIV replaces mutant virus as dominant quasispecies.

• Risk of transmission highest during acute infection, approximately 10x higher than chronic. In some settings most transmission events occur during primary infection. 
• Educate & counsel on safer sex

FOLLOW UP

• Obtain CD4 at time of Dx to stage infection and level of immune suppression. Repeat every 3-6 mos. CD4 drawn during PHI may be lower than CD4 setpoint following resolution of acute syndrome.
• Obtain VL at time of Dx, and follow regularly (e.g. monthly until set point established, then every 3-4 mos).
• If ART initiated, obtain VL at initiation and repeat after 2-8 wks. Decrease of 1 log by 2-8 wks expected if regimen efficacious. Complete suppression (<50) expected by 16-20 wks. Once undetectable, repeat VL every 3-4 mos to evaluate effectiveness and durability of therapy.

REFERENCES

REFERENCED WITHIN THIS GUIDE

• Epstein-Barr virus