Consequences of early treatment of HIV infection: identifying potential post-treatment controllers

Introduction: Post-treatment controllers (PTCs) are HIV-infected individuals who are able to spontaneously control the infection despite anti-retroviral therapy (ART) interruption. To date, the mechanisms underlying this control are still poorly understood. Several studies found an association between PTCs and with primary HIV infection (PHI), that is partially explained by the fact that the diagnosis of PHI often leads to an early treatment. It is well-established that acute and chronic infections exhibit important differences, however, it is yet unclear whether these differences can be employed for the identification potential PTCs and subsequently for selecting patients who could safely stop ART. Objectives: The primary objective of this thesis is to investigate potential statistically significant characteristics of patients diagnosed with a PHI, comparing them to patients with a chronic infection (CHI), with the ultimate goal of establishing a criterion for identifying potential post-treatment controllers. The adopted approach is the investigation of the immuno-virological parameters in these two groups, in association with the prevalence of comorbidities. Data collection and methods: In this study, we included patients diagnosed with PHI, particularly focusing on their immuno-virological parameters and comorbidities, in comparison to a control population (controls), matched according to the age, sex and ART duration. All individuals are older than 18 years old and were selected from patients treated and regularly followed at the “Amedeo di Savoia” Hospital in Turin. We analysed the two groups using Mann-Whitney test to compare continuous variables and Chi-squared test to compare categorical variables, by means of SPSS program. All laboratory measurements were carried out in laboratories at the “Amedeo di Savoia” Hospital. Results: We include 65 PHI and 64 controls. Age (40 vs. 39, p= 0.657), Sex (F=15.4% vs. F=14%, p= 0.832), and ART duration in years (7.5 vs. 8.1, p= 0.175) were well-balanced. PHI patients presented higher HIV-RNA zenith values [1413476 (139856;10000000) vs. 52468 (20436; 113689) copies/mL, p<0.00], lower CD4 cell baseline levels [478 (420; 535) vs. 554 (499; 608), p= 0.033] and significantly higher levels in HIV DNA [802 (239; 1876) versus 139 (21; 272), p= 0.007]. CD4/CD8 ratio was similar between the two groups (0.6 vs. 1.7, p=0.115) as well as virological control, as 44.6% vs. 57.8% (p= 0.570) remained constantly below the threshold of detectability. There was no relevant difference in terms of number of ART switches (p= 0.536) nor in terms of prevalence of dual therapy at the last observation (57% vs. 45%, p= 0.187). Concerning the comorbidities, they were collectively more prevalent in the control group (p= 0.001). The most significant included hypertension (4.6% vs. 18.8%, p= 0.012), psychiatric diseases (12.3 vs. 28.8, p= 0.025) and multimorbidity (4.6 vs 15.2, p= 0.038). PHI took less non-ART medications (p= 0.019), in particular antihypertensive (1.5% vs. 18.8%, p= 0.001), antipsychotics (0% vs. 10.9%, p= 0.006), vitamin D (58.5% vs. 81.3%, p= 0.005) and were less affected by polypharmacy (1.5% vs. 9.4%, p= 0.049). Discussions and conclusions: Despite several limitations (including a small sample size), the findings of this study identified clinical differences. The significantly lower prevalence of comorbidities in participants in the PHI group is a novel finding that may be explained by a lower level of systemic inflammation and/or by lower HIV reservoirs in the body tissues. Given the similar duration and number of changes in antiretroviral therapy, less drug toxicity in the former group is unlikely. Since no differences were observed in routine immunological and virological biomarkers, the identification of potential post-treatment controllers requires additional biomarkers (such as intact HIV DNA, HLA phenotypes and immune-activation biomarkers).