Diagnosis of acute HIV infection (AHI) prior to development of HIV antibodies (Ab) in blood can be challenging. In the earliest stages of AHI, diagnosis may be made solely by the detection of HIV RNA in plasma. Guidelines caution that HIV RNA <5,000 copies/ml may be a false positive result. However, those recommendations are based on data from >15 years ago, when testing methodologies were less specific than with current technology.
The RV254/SEARCH010 cohort has recruited participants with AHI in Thailand since 2009. A total 230,036 screening tests were done and 462 AHI cases enrolled through April 2017. We longitudinally examined participants diagnosed with HIV infection based on initial low viral load (LVL-detectable plasma HIV RNA <5,000 copies/ml) with HIV Ab tests negative or inconclusive. HIV RNA (qualitative and quantitative) and HIV antibody [4th-generation (4thG) and 3rd-generation (3rdG) immunoassays (IA)] were performed at baseline, 12 and 24 weeks. Antiretroviral therapy (ART) was started on all at baseline. Data are presented as median (range) unless noted otherwise.
There were 54 (12%) participants diagnosed with AHI based on LVL alone. Initial HIV RNA was 753 (29-4865) copies/ml; 57% were <1,000 copies/ml. Testing was repeated concurrently with starting ART after 3 (1-6) days with a median change of +1.3 (-0.4 to +3.4) log10 copies/ml. No false positive HIV RNA tests were identified; all tests were confirmed by repeat HIV RNA, of which 65% were >5,000 copies/ml. Only 3 participants had a fall in HIV RNA at the second test: all had started 3-drug post-exposure prophylaxis (PEP) on the day of the initial test. HIV RNA became undetectable at 4 (IQR 2-8) weeks on ART. Repeat HIV serology with 3rdGIA showed HIV Ab seroconversion in 90% (44/49) at 12 weeks and 88% (43/49) at 24 weeks. Surprisingly, 4thGIA was less sensitive: 63% (31/49) and 51% (25/49) positive at 12 and 24 weeks, respectively. Only 3 participants, 2 of whom received PEP, had both repeat HIV RNA <5,000 copies/ml and negative HIV Ab at 12 weeks.
Diagnosis of AHI based on HIV RNA <5,000 copies/ml alone had a positive predictive value of 100%: no false positive tests were identified. ART can safely be started in these individuals concurrently with confirmatory HIV RNA and Ab testing and sequentially thereafter. The diagnosis of HIV may be more challenging with the use of PEP, and potentially PrEP, which may blunt or delay the HIV Ab response.