The uncertain future of lay counsellors: continuation of HIV services in Lesotho under pressure.

Between 2006 and 2011, when antiretroviral therapy (ART) was scaled up in a context of severe human resources shortages, transferring responsibility for elements in human immunodeficiency virus (HIV) care from conventional health workers to lay counsellors (LCs) contributed to increased uptake of HIV services in Lesotho. HIV tests rose from 79 394 in 2006 to 274 240 in 2011 and, in that same period, the number of people on ART increased from 17 352 to 83 624. However, since 2012, the jobs of LCs have been at risk because of financial and organizational challenges. We studied the role of LCs in HIV care in Lesotho between 2006 and 2013, and discuss potential consequences of losing this cadre. Methods included a case study of LCs in Lesotho based on: (1) review of LC-related health policy and planning documents, (2) HIV programme review and (3) workload analysis of LCs. LCs are trained to provide HIV testing and counselling (HTC) and ART adherence support. Funded by international donors, 487 LCs were deployed between 2006 and 2011. However, in 2012, the number of LCs decreased to 165 due to a decreasing donor funds, while administrative and fiscal barriers hampered absorption of LCs into the public health system. That same year, ART coverage decreased from 61% to 51% and facility-based HTC decreased by 15%, from 253 994 in 2011 to 215 042 tests in 2012. The workload analysis indicated that LCs work averagely 77 h per month, bringing considerable relief to the scarce professional health workforce. HIV statistics in Lesotho worsened dramatically in the recent era of reduced support to LCs. This suggests that in order to ensure access to HIV care in an under-resourced setting like Lesotho, a recognized and well-supported counsellor cadre is essential. The continued presence of LCs requires improved prioritization, with national and international support.

Cooperating pre-T-cell receptor and TCF-1-dependent signals ensure thymocyte survival.

Intrathymic T-cell maturation critically depends on the selective expansion of thymocytes expressing a functionally rearranged T-cell receptor (TCR) beta chain. In addition, TCR-independent signals also contribute to normal T-cell development. It is unclear whether and how signals from the 2 types of pathways are integrated. Here, we show that T-cell factor-1 (TCF-1), a nuclear effector of the canonical wingless/int (wnt)/catenin signaling pathway, ensures the survival of proliferating, pre-TCR(+) thymocytes. The survival of pre-TCR(+) thymocytes requires the presence of the N-terminal catenin-binding domain in TCF-1. This domain can bind the transcriptional coactivator beta-catenin and may also bind gamma-catenin (plakoglobin). However, in the absence of gamma-catenin, T-cell development is normal, supporting a role for beta-catenin. Signaling competent beta-catenin is present prior to and thus arises independently from pre-TCR signaling and does not substantially increase on pre-TCR signaling. In contrast, pre-TCR signaling significantly induces TCF-1 expression. This coincides with the activation of a wnt/catenin/TCF reporter transgene in vivo. Collectively, these data suggest that efficient TCF-dependent transcription requires that pre-TCR signaling induces TCF-1 expression, whereas wnt signals may provide the coactivator such as beta-catenin. The 2 pathways thus have to cooperate to ensure thymocyte survival at the pre-TCR stage.