Wild-type HIV infection despite PrEP: a lot to learn from a case report

Abstract

We read with interest the case report by Hoornenborg and colleagues1Hoornenborg E Prins M Achterbergh RCA et al.Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report.Lancet HIV. 2017; 4: e522-e528Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar about the acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis (PrEP) despite high intracellular concentrations of tenofovir diphosphate. This case is all the more important given that PrEP roll-out is a work in progress, with regulatory approvals for its use for HIV prevention completed in 15 countries and dossiers under review in many others.2Hoornenborg E Krakower DS Prins M Mayer KH Pre-exposure prophylaxis for MSM and transgender persons in early adopting countries.AIDS. 2017; 31: 2179-2191Crossref PubMed Scopus (43) Google Scholar Despite its well demonstrated efficacy for the prevention of HIV acquisition,3Grant RM Lama JR Anderson PL et al.Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.N Engl J Med. 2010; 363: 2587-2599Crossref PubMed Scopus (3645) Google Scholar PrEP's widespred uptake means that this particular and unprecedented event might happen again. After seroconversion in the reported case, health-care workers decided to interrupt PrEP but not to start combination antiretroviral therapy (ART) because of the uncertainty on an actual infection. The atypical seroconversion pattern, with initially only gp160 detected in the western blot, contributed to questioning of the diagnosis of acute HIV infection. This strategy has the indisputable advantage of confirming what was strongly suspected. However, as suggested by the impossibility to detect any HIV proviruses in peripheral blood mononuclear cells, the HIV infection was probably mucosally contained. The HIV infection was thus characterised by an extremely low and localised viral reservoir and most likely a very limited viral diversity. This unique profile is associated with favourable outcomes such as a low or even absent immune activation.4Krebs SJ Ananworanich J Immune activation during acute HIV infection and the impact of early antiretroviral therapy.Curr Opin HIV AIDS. 2016; 11: 163-172Crossref PubMed Scopus (41) Google Scholar Limiting the viral reservoir size and diversity also could impede acquisition of mutations to evade cytotoxic T cells5Deng K Pertea M Rongvaux A et al.Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations.Nature. 2015; 517: 381-385Crossref PubMed Scopus (393) Google Scholar thereby conserving a better chance of response to potential cure strategies. Retrospectively, not starting ART at seroconversion was therefore a missed opportunity. We learned a lot from the case reported by Hoornenborg and colleagues and can use this knowledge to guide our therapeutic strategy should such cases arise again. Starting ART at seroconversion seems the best option considering all potential favourable outcomes. Concern about toxicity is a weak argument in the era of modern ART and for a patient already exposed to PrEP. If desired by the patient and considering the pros and cons, a structured treatment interruption might still be considered subsequently. We declare no competing interests. Wild-type HIV infection despite PrEP: a lot to learn from a case reportRecently, Hoornenborg and colleagues1 reported a case of transmission of HIV infection despite good adherence to pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine and high concentrations of tenofovir in dried blood spots. The diagnosis of the infection coincided with that of lymphogranuloma venereum in the anal canal. Previously the patient had presented episodes of proctitis caused by chlamydia and gonococcus. The number of sexual partners had increased with the start of PrEP. Full-Text PDF Wild-type HIV infection despite PrEP: a lot to learn from a case report – Authors' replyWe agree with Darcis and Moutchen that an early start of combination antiretroviral therapy (ART) might have been beneficial, allowing a reduction of the viral reservoir and diversity, and that toxicity is no longer an argument for withholding ART in case of HIV infection. However, stating that not starting ART at seroconversion was a missed opportunity does not take the complexity of this unprecedented case, with a very unusual seroconversion pattern, into account.1 To exclude a false positive result, a reactive HIV antibody–antigen test needs confirmation with western blot or HIV nucleic acid test. Full-Text PDF Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case reportTo our knowledge, this is the first detailed case report suggesting wild-type HIV-1 infection despite good adherence, evidenced by repeatedly high concentrations of tenofovir diphosphate in dried blood spots. PrEP providers need to be aware that infection can occur despite good adherence. Regular HIV testing and awareness of atypical patterns of seroconversion is highly recommended. Full-Text PDF