Poor immunological responders (PIR) are HIV-infected patients with virologic suppression upon antiretroviral therapy (ART) but persistently low CD4+ T cell counts. Early identification of PIR is important given their higher morbimortality compared to adequate immune responders (AIR). In this study, 33 patients severely lymphopenic at ART onset, were followed for at least 36 months, and classified as PIR or AIR using cluster analysis grounded on their CD4+ T cell count trajectories. Based on a variety of immunological parameters, we built predictive models of PIR/AIR outcome using logistic regression. All PIR had CD4+ T cell counts consistently below 500 cells/μL, while all AIR reached this threshold. AIR showed a higher percentage of recent thymic emigrants among CD4+ T cells; higher numbers of sj-TRECs and greater sj/β TREC ratios; and significant increases in thymic volume from baseline to 12 months of ART. We identified mathematical models that correctly predicted PIR/AIR outcome after 36 months of therapy in 77–87% of the cases, based on observations made until 2–6 months after ART onset. This study highlights the importance of thymic activity in the immune recovery of severely lymphopenic patients, and may help to select the patients that will benefit from closer follow-up or novel therapeutic approaches.

Background: Terms and criteria to classify people living with HIV on antiretroviral therapy who fail to achieve satisfactory CD4+ T-cell counts are heterogeneous, and need revision and summarization. Methods: We performed a systematic review of PubMed original research articles containing a set of predefined terms, published in English between January 2009 and September 2018. The search retrieved initially 1360 studies, of which 103 were eligible. The representative terminology and criteria were extracted and analyzed. Results: Twenty-two terms and 73 criteria to define the condition were identified. The most frequent term was “immunological nonresponders” and the most frequent criterion was “CD4+ T-cell count <350 cells/µL after ≥24 months of virologic suppression.” Most criteria use CD4+ T-cell counts as a surrogate, either as an absolute value before antiretroviral therapy initiation or as a change after a defined period of time. Distinct values and time points were used. Only 9 of the 73 criteria were used by more than one independent research team. Herein we propose 2 criteria that could help to reach a consensus. Conclusions: The high disparity in terms and criteria here reported precludes data aggregation and progression of the knowledge on this condition, because it renders impossible to compare data from different studies. This review will foster the discussion of terms and criteria to achieve a consensual definition.

BackgroundHIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality. Hence, a deeper knowledge of CNS-IRIS pathogenesis is needed.Case presentationA 37-year-old man was diagnosed with AIDS and cerebral toxoplasmosis. Anti-toxoplasma treatment was initiated immediately, followed by active antiretroviral therapy (HAART) 1 month later. At 2 months of HAART, he presented with progressive hyposensitivity of the right lower limb associated with brain and dorsal spinal cord lesions, compatible with paradoxical toxoplasmosis-associated CNS-IRIS, a condition with very few reported cases. A stereotactic biopsy was planned but was postponed based on its inherent risks. Patient showed clinical improvement with no requirement of corticosteroid therapy. Routine laboratorial analysis was complemented with longitudinal evaluation of blood T cell subsets at 0, 1, 2, 3 and 6 months upon HAART initiation. A control group composed by 9 HIV-infected patients from the same hospital but with no IRIS was analysed for comparison. The CNS-IRIS patient showed lower percentage of memory CD4+ T cells and higher percentage of activated CD4+ T cells at HAART initiation. The percentage of memory CD4+ T cells drastically increased at 1 month after HAART initiation and became higher in comparison to the control group until clinical recovery onset; the percentage of memory CD8+ T cells was consistently lower throughout follow-up. Interestingly, the percentage of regulatory T cells (Treg) on the CNS-IRIS patient reached a minimum around 1 month before symptoms onset.ConclusionAlthough both stereotactic biopsies and steroid therapy might be of use in CNS-IRIS cases and should be considered for these patients, they might be unnecessary to achieve clinical improvement as shown in this case. Immunological characterization of more CNS-IRIS cases is essential to shed some light on the pathogenesis of this condition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2159-x) contains supplementary material, which is available to authorized users.