Africa Health Research Institute (AHRI), Durban, South Africa.
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
JCI Insight. 2021 Nov 22;6(22):e146162. doi: 10.1172/jci.insight.146162.
HIV infection in the human gastrointestinal (GI) tract is thought to be central to HIV progression, but knowledge of this interaction is primarily limited to cohorts within Westernized countries. Here, we present a large cohort recruited from high HIV endemic areas in South Africa and found that people living with HIV (PLWH) presented at a younger age for investigation in the GI clinic. We identified severe CD4+ T cell depletion in the GI tract, which was greater in the small intestine than in the large intestine and not correlated with years on antiretroviral treatment (ART) or plasma viremia. HIV-p24 staining showed persistent viral expression, particularly in the colon, despite full suppression of plasma viremia. Quantification of mucosal antiretroviral (ARV) drugs revealed no differences in drug penetration between the duodenum and colon. Plasma markers of gut barrier breakdown and immune activation were elevated irrespective of HIV, but peripheral T cell activation was inversely correlated with loss of gut CD4+ T cells in PLWH alone. T cell activation is a strong predictor of HIV progression and independent of plasma viral load, implying that the irreversible loss of GI CD4+ T cells is a key event in the HIV pathogenesis of PLWH in South Africa, yet the underlying mechanisms remain unknown.
HIV 感染人体胃肠道（GI）被认为是 HIV 进展的核心，但对这种相互作用的了解主要局限于西方国家的队列研究。在这里，我们展示了一个从南非高 HIV 流行地区招募的大型队列研究，发现 HIV 感染者（PLWH）在 GI 诊所接受检查的年龄更小。我们发现 GI 道中存在严重的 CD4+ T 细胞耗竭，小肠中的耗竭程度大于大肠，且与抗逆转录病毒治疗（ART）时间或血浆病毒载量无关。HIV-p24 染色显示病毒持续表达，尤其是在结肠中，尽管血浆病毒载量得到完全抑制。黏膜抗逆转录病毒（ARV）药物的定量分析显示，十二指肠和结肠之间的药物渗透没有差异。无论 HIV 感染与否，肠道屏障破坏和免疫激活的血浆标志物均升高，但外周 T 细胞活化与 PLWH 肠道 CD4+ T 细胞的丢失呈负相关。T 细胞活化是 HIV 进展的一个强有力的预测指标，与血浆病毒载量无关，这意味着 GI CD4+ T 细胞的不可逆转损失是南非 PLWH HIV 发病机制中的一个关键事件，但潜在的机制尚不清楚。
