Rare HIV-1 Controller with Antiretroviral Resistance

The 59- year-old controller (subject #1) was diagnosed with HIV-1 infection when he was treated in the hospital for recurrent epileptic seizures. Since an ischemic stroke seven years previously he had suffered from hemiparesis of his right leg and right arm. He was a smoker with hypertonic blood pressure. The time point of HIV-1 infection is not known but was established to have occurred prior to his severe neurological disability.
At diagnosis, he displayed a CD4 count of 1004 cells/µL and HIV-1-specific antibodies measured by ELISA (ARCHITECT HIV Ag/Ab Combo Assay, Abbott, Wiesbaden, Germany) and immunoblot (Geenius HIV 1/2 Confirmatory Assay, Bio-Rad laboratories, Feldkirchen, Germany). He maintained normal CD4 counts >800 cells/µL over the next 453 days post-diagnosis (Table 1). His viral load measured by real-time HIV-1 PCR (Abbott RealTime HIV-1 assay, Abbott, Wiesbaden) was 40 copies/mL at diagnosis. with subsequent low viral loads ranging between <20 and 20 copies/mL until day 293 post-diagnosis (Table 1). At day 383, four weeks after a traumatic subarachnoid hemorrhage and fracture of his right humerus, he displayed a transient increase of viral load to 250 copies/mL with spontaneous decline to <20 copies/mL at day 453. A resistance analysis from plasma obtained at day 383 post-diagnosis revealed the presence of several mutations in reverse transcriptase (RT, 41L, 210W, 215A) and protease (33F, 43T, 46L, 53L, 82A, 88D) which were associated with high-level resistance against zidovudine, stavudine and several protease inhibitors. This indicated the transmission of a drug-resistant virus as the patient has not been treated with antiretroviral drugs in the past.
At the time point of his first viral load measurement, he was treated with the following drugs: lamotrigine, levetiracetam, lacosamide, simvastatin, acetylsalicylic acid, ramipril, amlodipine, melperone, baclofen, citalopram and thiamine. The patient’s HLA-type was HLA A*11, B*52, B*57, C*6, C*12.
In addition to the controller (subject #1), we investigated 14 HLA-B*52-positive, HIV-1-infected patients (clinical characteristics shown in Table S1). All were on antiretroviral combination therapy (cART) for a median time of 75 months (range 3–315 months). They presented with a current median viral load of <20 copies/mL (range: <20 to 40 copies/mL) and a current median CD4 count of 872 (range 351–1434).