Acute HIV at the Time of Initiation of Pre-Exposure or Post-Exposure Prophylaxis

Impact on Drug Resistance and Clinical Outcomes

Kelly A. Johnson, MD, MPH; Miao-Jung Chen, PhD, MPH; Robert Kohn, MPH; Darpun Sachdev, MD, MPH; Oliver Bacon, MD, MPH; Sulggi Lee, MD, PhD; Stephanie E. Cohen, MD, MPH

Disclosures

J Acquir Immune Defic Syndr. 2021;87(2):818-825. 

In This Article

Results

From 2011 to 2018, 1758 and 2242 adult patients started PrEP and PEP, respectively, at SFCC. On the day of PrEP/PEP start, there were 7 cases of undiagnosed AHI among PrEP users (0.40%) and 6 among PEP users (0.30%). The details of each case are presented in Table 1, with summary statistics for numeric variables presented in Table 2. All 7 PrEP patients were prescribed TDF/FTC while 5 of the 6 PEP patients (83.3%) were prescribed 2-drug (rather than 3-drug) PEP with either TDF/FTC or zidovudine/lamivudine (AZT/3TC). The sixth and final PEP patient received 3-drug therapy. All 13 patients who had undiagnosed AHI on the date of PrEP/PEP start were gay-identified males with a median age of 29 years (IQR 26–34). Only 1 patient had symptoms of AHI with sore throat and body rash at the time of AHI diagnosis.

Two patients were diagnosed with bacterial STIs on the day they were later found to have AHI, both with rectal chlamydia (CT) and one with concurrent urethral gonorrhea (GC) and secondary syphilis. Within the year leading up to HIV acquisition (including the date of their AHI diagnosis), 9/13 patients (69.2%) were diagnosed with at least 1 bacterial STI, with the most common STIs being rectal CT and GC (7 and 5 patients, respectively) followed by syphilis (3 patients, one each with primary, secondary, and early latent disease).

The median number of total male sexual partners reported in the 3 months before HIV diagnosis was 9 (IQR 4–10); the median number of condomless anal receptive sex partners was 2 (IQR 1–6). Of the 11 patients with data available for this variable, 9 reported that their last sexual encounter occurred within 10 days of their AHI diagnosis (all 6 of the PEP patients and 3/5 of the PrEP patients). Five patients endorsed sex with an HIV-positive partner within the previous 3 days.

The median initial HIV viral load was 3655 copies/millimeter (IQR 587–345,616) with median CD4 count 576 cells/cubic millimeter (IQR 463–892). Only 1 patient had an initial CD4 count of less than 200 (CD4 = 129/22%). The median times from AHI diagnosis to linkage to HIV care, initiation of antiretroviral therapy, and viral suppression were, respectively, 7 (IQR 5–7), 12 (IQR 7–49), and 43 (IQR 23–182) days. The time lapse between initial diagnosis and linkage to care was likely driven in part by the fact that the laboratory turnaround time for our HIV RNA testing averages 5–10 days.

All 13 AHI patients had evidence of successful linkage to HIV care, 12/13 (92.3%) had evidence of starting antiretroviral therapy (ART), and 11/13 (84.6%) achieved viral suppression. Of the 2 patients who did not have documented viral suppression in California eHARS, 1 moved out of state shortly after his HIV diagnosis and 1 was lost to follow-up.

Genotypes were available on 11/13 (84.6%) of our AHI patients, all of which were performed within 2 months of each patient's PrEP or PEP initiation. The remaining 2 patients had initial HIV viral loads less than 500 copies/mL, and therefore, genotyping was unable to be performed. There were no tenofovir-associated K65R mutations. Of all 13 patients in our series, 3 patients (23%)—all of whom were diagnosed in 2012 or 2013—were found to have emtricitabine-related M184 (M184V or M184I) mutations at the time they initiated HIV care. All 3 had received TDF/FTC—1 for PrEP and 2 for PEP—which they had taken for 7, 8, and 12 days, respectively, before discontinuing. As evidenced by their date of linkage to care, the other 9 patients who had no evidence of developing resistance on PrEP or 2-drug PEP were on prophylactic therapy for 7 days or less before being asked to stop.

The 3 patients with the M184 mutation had additional genotyping performed on stored serum available from the date of their original PrEP/PEP initiation. These stored samples demonstrated wild-type virus before PrEP/PEP start, indicating that the M184 mutation had emerged within 7–12 days of PrEP/PEP exposure. One of these 3 patients acquired the M184I while participating in the US PrEP Demonstration Project; his case has been previously reported in the literature.[21]

All 3 patients with the M184 mutation were linked to HIV care, began ART, and achieved viral suppression within 6 months. Their initial treatment regimens were, respectively: (1) darunavir/ritonavir (DRV/r), raltegravir (RAL), and TDF/FTC; (2) DRV/r and TDF/FTC, and (3) DRV/r, rilpivirine (RPV), and TDF/FTC. As of 12/2020, these patients are most recently known to be on 2- or 3-class HIV treatment regimens, respectively, with (1) abacavir (ABC), 3TC, and DTG; (2) DRV/r and TDF/FTC; and (3) DRV/r plus elvitegravir/cobicistat/TAF/FTC.

Also as of 12/2020, 8 of our 13 patients in our case series continue to have HIV viral loads <40 copies/mL within the previous 12 months. Three additional patients had viral loads <40 copies/mL as of last available documentation in our electronic medical records (in 2014, 2017, and 2019, respectively). The final 2 patients either moved or were lost to follow-up in within the first year after their AHI diagnosis.

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