Background The introduction of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus-1 (HIV-1) prevention in Africa presents new challenges for health systems that are already overburdened because PrEP delivery requires frequent clinic visits (generally every 3 months) for HIV-1 testing and PrEP refills. HIV-1 self-testing (HIVST) has the potential to improve the efficiency of PrEP delivery by decreasing the number of clinic visits. Here, we describe the rationale and design of a randomized, noninferiority trial designed to test the effectiveness and safety of using HIVST to support PrEP delivery in Kenya. Methods The JiPime-JiPrEP (Kiswahili for ‘Test Yourself, PrEP Yourself’) study is a three-arm randomized trial taking place in Thika, Kenya. Participants ( n = 495) are eligible for enrollment if they are at least 18 years old, HIV-1 seronegative, and have been taking PrEP for 1 month. Three distinct participant types will be enrolled: men ( n = 165) and women ( n = 165) who are in mutually disclosed HIV-1 serodiscordant relationships, and women ( n = 165) who are at HIV-1 risk and not in a known serodiscordant relationship. Participants in each of these subpopulations will be 1:1:1 randomized to: 1) the standard of care, with quarterly clinic visits; 2) oral HIVST, with biannual clinic visits plus oral HIVSTs to use at the quarters between those visits; or 3) blood-based HIVST, with biannual clinic visits plus blood-based HIVSTs. All participants will complete quantitative surveys and provide blood samples for the objective measurement of PrEP adherence at baseline, 6 months, and 12 months. The primary outcomes are PrEP adherence, PrEP continuation, and HIV-1 testing, measured at 6 months and secondarily at 12 months. Discussion The findings from this trial can help to understand how HIVST—a new HIV-1 testing technology—can support health systems in sub-Saharan Africa. Additionally, the findings can inform policy aimed at improving the efficiency of PrEP implementation and scale-up in Kenya. Trial registration ClinicalTrials.gov, NCT03593629 . Retrospectively registered on 20 July 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3521-2) contains supplementary material, which is available to authorized users.

The early B cell repertoire is characterized by extensive interconnectivity, autoreactivity and multispecificity. Our preliminary sequence analysis of some of the idiotype specific antibodies is beginning to provide molecular clues to explain the observed multireactivity and the expression of shared idiotypic determinants on immunoglobulins of early B cells. The VH gene rearrangements analyzed are typical of the early pre-B cell and CD5 B cell repertoire. Some of these include shared or identical CDR3 regions resulting from the use of germline VH, D and JH gene segments in the absence of N region addition. As previously described, the most D proximal VH genes are also used most frequently. Collectively these genetic restrictions, together with the lack of somatic mutation, suggest that the characteristic self reactivity of the early B cell repertoire is related to the expression of germline gene segments and limited use of diversification mechanisms. It has also been possible for the first time to isolate hybridomas secreting functional IgM molecules which use the most D proximal VH gene, VH81X. These antibodies and another example from the VH7183 family have a broad multireactivity pattern possibly because of the presence of an unusually high number of charged amino acid groups present in the VH region. These findings are preliminary and more extensive studies are needed to establish if these groups are responsible for the highly cross-reactive nature of these antibodies. Nevertheless, these unusual characteristics signify a unique role for antibodies expressing this VH gene during B cell development. It is also clear that the observed anti-lymphocyte reactivity, another feature of the newborn repertoire, is the result of the prevalence of B cells using similar if not identical VHDJH genes and DJH joins. The development of these B cells appears to occur consistently in early ontogeny and, again, are not found in conventional splenic B cells obtained from the normal adult. Understanding the functional significance of the early appearance of these antibodies may help to clarify and understand their role during development as well as in autoimmunity. We propose that the unique self reactive nature of the early repertoire provides a pattern within which self-assertiveness develops and results in the establishment of the adult repertoire. In doing so, dominant clones are established which may or may not be within, but whose selection and differentiation is directed by the CD5 B cell subset.(ABSTRACT TRUNCATED AT 400 WORDS)

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