Centre Régional de Pharmacovigilance de Nice-Alpes-Côte d'Azur, Hôpital de Cimiez - Pavillon Victoria - CS 91179, 06003, Nice cedex 1, France.
Service des Maladies Infectieuses, Hôpital Sainte Musse, Toulon, France.
BMC Infect Dis. 2019 Jul 10;19(1):601. doi: 10.1186/s12879-019-4239-1.
Despite effective antiretroviral therapy developed over the last decade, HIV infection remains a major worldwide public health problem. Recently, a promising preventive treatment has been made available for HIV prophylaxis, PrEP for pre-ExPosure Prophylaxis. Indeed, it was shown to significantly reduce the risk of HIV infection in patients exposed to high risk of infection such as men having sex with men (MSM), heterosexuals and people who inject drugs. Several issues pertaining to PrEP remain uncertain including short and long-term adverse events, drug resistance, risk compensation and resurgence of other sexually transmitted infections.
We report a case of a 52-year-old MSM eligible for PrEP as he was exposed to a high risk of HIV infection, presented no clinical symptoms of HIV primary infection and was seronegative for HIV. PrEP therapy was then initiated with fixed association of emtricitabine-tenofovir disoproxil. One month later, HIV tests using two different assays were positive, despite perfect compliance reported by the patient and confirmed by plasma drug level. A retrospective search for plasma viral RNA in the blood sample before PrEP initiation turned out positive. Genotyping and treatment sensitivity performed on sample after one month of PrEP showed a virus resistance to lamivudine and emtricitabine. Similar cases in the literature and pivotal studies have reported HIV infections in patients initiating or undergoing PrEP. These patients where either infected but still seronegative, displaying no clinical symptoms upon enrollment, or became infected during PrEP. Reasons are mainly poor compliance to treatment, resistance to PrEP, and lack of diagnosis before PrEP. Guidelines advocate safe sex behavior before initiation, search for clinical signs of HIV primary infection and two different serologic tests performed with one-month interval.
Our patient newly HIV infected received PrEP as he was still seronegative. Current recommendations fail to screen recently HIV infected, but still seronegative patients who are initiating PrEP. This issue raises strong concerns regarding the lack of adequate selection for eligibility to PrEP and may contribute to exposing partners to HIV infection and select viral mutations. Infection risk could be minimized by search for plasma viral HIV RNA at pre-inclusion, at least for patients suspected of unsafe behaviors such as non-respect of the non-exposure period before PrEP initiation.
尽管过去十年中已经开发出有效的抗逆转录病毒疗法，但 HIV 感染仍然是全球主要的公共卫生问题。最近，一种有前途的预防性治疗方法已可用于 HIV 预防，即暴露前预防 (PrEP)。实际上，它已被证明可显著降低感染高风险（例如男男性行为者、异性恋者和注射毒品者）的患者感染 HIV 的风险。与 PrEP 相关的几个问题仍不确定，包括短期和长期不良事件、耐药性、风险补偿和其他性传播感染的复发。
我们报告了一例 52 岁男男性行为者 (MSM) 的病例，他符合 PrEP 条件，因为他面临 HIV 感染的高风险，但没有 HIV 原发感染的临床症状，并且 HIV 血清学检测为阴性。然后，他开始接受固定剂量的恩曲他滨-替诺福韦酯联合治疗。一个月后，尽管患者报告并通过血浆药物水平证实了完全依从性，但使用两种不同检测方法的 HIV 检测均为阳性。对 PrEP 开始前的血液样本进行回顾性搜索发现病毒 RNA 呈阳性。对 PrEP 一个月后样本进行基因分型和治疗敏感性检测显示病毒对拉米夫定和恩曲他滨耐药。文献和关键研究中报告了一些类似的病例，这些患者在开始或正在接受 PrEP 时感染了 HIV。这些患者要么已经感染但仍处于血清学阴性，在入组时没有临床症状，要么在 PrEP 期间感染。原因主要是治疗依从性差、对 PrEP 耐药以及 PrEP 前未诊断。指南主张在开始 PrEP 前进行安全性行为、搜索 HIV 原发感染的临床症状以及相隔一个月进行两次不同的血清学检测。
我们的新感染 HIV 的患者接受了 PrEP 治疗，因为他仍处于血清学阴性。目前的建议未能筛选新感染 HIV 但仍处于血清学阴性的正在接受 PrEP 的患者。这个问题引起了对 PrEP 资格选择不足的强烈关注，并可能导致暴露于 HIV 感染的伴侣和选择病毒突变。通过在入组前至少对疑似不安全行为（如不遵守 PrEP 开始前的非暴露期）的患者进行血浆 HIV RNA 检测，可以将感染风险降至最低。
