3.1. Baseline Characteristics of the Study Population
During the study period (January 2007–March 2011), 275 patients were diagnosed for the first time with HIV infection at our clinic. Characteristics of the 275 subjects at presentation are summarized in .
(a) Demographic and immunovirological characteristics of study population. (b) Peripheral T lymphocyte immune phenotypes of study population.
Overall, the majority of patients were male (225/275, 82%) with a median age of 37 (IQR 31–46) years and acquired HIV infection mostly through sexual contacts (homosexual transmission 152/275, 55%—heterosexual transmission 111/275, 40%) ().
A total of 16 (6%) patients displayed HCV coinfection. Most subjects were of white ethnicity, while 73 (26%) HIV-positive patients were born outside the European community.
The proportion of new HIV diagnosis remained stable over time (31% in 2007, 22% in 2008-2009-2010).
3.2. Immunovirological Parameters of the Study Population
Median CD4+ count at first presentation for HIV care was 396
L (IQR 234–555), and median viral load was 4.37
cp/mL (IQR 2.78–5.16). The other percentages (median, IQR) of peripheral T lymphocytes immune phenotypes were reported in .
3.3. Characteristics of Late Presenters
130 (47%) patients showed CD4+ T-cell counts <350
L and/or an AIDS defining event at presentation and were classified as late presenters (LPs) (). Compared to N-LPs, LPs were older (median age: LP 41, IQR 34–50—N-LP 36, IQR 30–43 years; P
= 0.0001), contracted HIV infection more frequently through heterosexual contacts (heterosexual transmission: LP 64, 49%—N-LP 47, 32%; homosexual transmission: LP 59, 45%—N-LP 93, 64%; intravenous drug users: LP 6, 5%—N-LP 4, 3%; P
= 0.020), and resulted more commonly migrants (LP 43, 33%—N-LP 30, 21%; P
= 0.020). No differences were observed between the two groups of patients regarding gender, coinfections, and calendar year of presentation ().
(a) Analysis of the association of demographic and HIV-related characteristics with late presentation. (b) Analysis of the association of T-cells subpopulations with late presentation.
Interestingly, analyzing the immune phenotypes of peripheral T lymphocytes, we found that LP were characterized by a significantly different immunological pattern in comparison to N-LP. In particular, LP displayed higher CD8+ T-cells percentages (LP 57, IQR 51–63—N-LP 45, IQR 38–54; P = 0.0001), lower IL-7 receptor (CD127) expression on CD4+ T cells (median CD127+CD4+%: LP 7, IQR 4–12—N-LP 19, IQR 12–24; P = 0.0001), and higher expression of CD95 receptor (median CD95+CD8+%: LP 3, IQR 2–5—N-LP 2, IQR 1–3; P = 0.0001), activated CD38+ (median CD38+CD8+%: LP 9, IQR 3–18—N-LP 5, IQR 2–9; P = 0.0001) and terminal-differentiated CD45R0+CD38+ (median CD45R0+CD38+CD8+%: LP 15, IQR 10–25—N-LP 9, IQR 5–16; P = 0.0001) on CD8+ T cells. The other immune phenotypes did not result significantly different between LP and N-LP ().
3.4. Characteristics of Patients Presenting Advanced HIV Disease
Using the second criteria to identify patients with a new diagnosis of HIV infection in a late stage of disease, 79 (29%) subjects presented advanced HIV disease (AHD) (). Similarly to the first definition, AHD patients resulted older (median age: AHD 42, IQR 34–52—N-AHD 36, IQR 31–44; P = 0.0001) and more frequently heterosexual (heterosexual transmission: AHD 41, 52%—N-AHD 70, 36%; homosexual transmission: AHD 34, 43%—N-AHD 118, 60%; intravenous drug users: AHD 4, 5%—N-AHD 6, 3%; P = 0.044). The proportion of HIV/HCV coinfection and migrants were comparable between the two groups of patients; in parallel, from 2007 to the first months of 2011, we did not register a substantial decrease of late diagnosis ().
(a) Analysis of the association of demographic and HIV-related characteristics with advanced HIV disease at presentation. (b) Analysis of the association of T-cells subpopulations with advanced HIV disease at presentation.
Diverse immune phenotype patterns were detected in AHD and N-AHD patients: AHD presented higher CD8+ (AHD: 59, IQR 51–66—N-AHD 48, IQR 41–57; P = 0.0001), lower CD127+CD4+ (median CD127+CD4+%: AHD 6, IQR 3–11—N-AHD 15, IQR 10–22; P = 0.0001), higher CD95+CD8+ (median CD95+CD8+%: AHD 3, IQR 2–6—N-AHD 2, IQR 1–3; P = 0.0001), CD38+CD8+ (median CD38+CD8+%: AHD 11, IQR 3–25—N-AHD 5, IQR 2–10; P = 0.0001), and CD45R0+CD38+CD8+ (median CD45R0+CD38+CD8+%: AHD 14, IQR 10–25—N-AHD 11, IQR 7–19; P = 0.008) percentages in comparison to N-AHD ().
3.5. AIDS Presenters
An AIDS defining condition was reported for 49/275 (18%) subjects with a new HIV diagnosis during the study period. The most common diseases were Kaposi's Sarcoma (12/49, 24%), Pneumocystis jiroveci pneumonia (8/49, 16%), and tuberculosis (7/49, 14%). Other AIDS-related illnesses were CMV infection (sepsis, chorioretinitis, and colitis, 4/49, 8%), neurological diseases (HIV-associated dementia, “HAD,” progressive multifocal leukoencephalitis, “PML,” and neurotoxoplasmosis, 7/49, 14%), lymphomas (4/49, 8%), esophageal candidiasis (3/49, 7%), Wasting syndrome (3/49, 7%), and cervical cancer (1/49, 2%).
AIDS presenters were more frequently older (median age: AIDS presenters: 42, IQR 35–52—N-AIDS presenters 37, IQR 31–44; P = 0.0001), male (AIDS presenters: male 45, 92%—female 4, 8%; N-AIDS presenters: male 180, 80%—female 46, 20%; P = 0.045), and heterosexuals (heterosexual transmission: AIDS presenters 29, 59%—N-AIDS presenters 82, 36%; homosexual transmission: AIDS presenters 17, 35%—N-AIDS presenters 135, 60%; intravenous drug users: AIDS presenters 3, 6%—N-AIDS presenters 7, 3%; P = 0.044), compared to N-AIDS presenters (226 subjects).
Comparing immune phenotypes between AIDS presenters and N-AIDS presenters, we observed that AIDS presenters were associated with lower CD4+ T-cell count (median CD4+ cells/μL: AIDS presenters 132, IQR 60–286—N-AIDS presenters 438, IQR 286–583; P = 0.0001), and higher CD8+ T cells (median CD8+%: AIDS presenters 59, IQR 50–66—N-AIDS presenters 49, IQR 42–59; P = 0.0001). AIDS presenters featured lower CD127+CD4+% (median CD127+CD4+%: AIDS presenters 6, IQR 4–11—N-AIDS presenters 14, IQR 8–21; P = 0.0001), higher CD95+CD8+% (median CD95+CD8+%: AIDS presenters 3, IQR 2–6—N-AIDS presenters 1, IQR 2–4; P = 0.003), CD38+CD8+% (median CD38+CD8+%: AIDS presenters 12, IQR 5–23—N-AIDS presenters 6, IQR 2–11; P = 0.0001), and CD45R0+CD38+CD8+% (median CD45R0+CD38+CD8+%: AIDS presenters 16, IQR 10–25—N-AIDS presenters 11, IQR 7–19; P = 0.02).
3.6. Factors Independently Associated with Late Presentation
Given that LPs were distinguished by a peculiar peripheral immune phenotype, we investigated the association between T lymphocyte patterns and late presentation, controlling for potentially confounding factors. We performed a logistic regression model () including the peripheral immune phenotypes that resulted significantly associated with LP in the univariate analysis (CD8+%, CD4+CD127+%, CD8+CD95+%, CD8+CD38+%, and CD8+CD38+CD45R0+%) (), mutually adjusting for demographic factors (age, exposure category for HIV, ethnicity). Higher CD8+ T-cell percentages (AOR 1.051 for each unit more, 95%CI 1.022–1.080, P = 0.0001) and lower CD127+ expression on CD4+ cells (AOR 0.887 for each unite more, 95%CI 0.857–0.919, P = 0.0001) resulted significantly associated with late presentation, independently of demographic factors.
Multivariate logistic regression analysis of the association of demographic and HIV-related characteristics with late presentation.
As expected, also demographic factors were significantly and independently associated with late presentation; in fact, older age (AOR 1.052 for each year more, 95%CI 1.020–1.086, P = 0.001), heterosexual acquisition of infection (AOR 2.435 versus other risk groups, 95%CI 1.251–4.741, P = 0.009), and non-White race (AOR 2.543 versus white ethnicity, 95%CI 1.178–5.486, P = 0.017) were associated with higher risk of delayed HIV testing.
3.7. Factors Independently Associated with Advanced HIV Disease
To identify possible factors associated with AHD, significant T-cells immune phenotypes in the univariate analysis (CD8+%, CD4+CD127+%, CD8+CD95+%, CD8+CD38+%, and CD8+CD38+CD45R0+%) () were entered in a logistic regression model, mutually adjusted for age and risk group ().
Multivariate logistic regression analysis of the association of demographic and HIV-related characteristic with advanced HIV disease at presentation.
The immune phenotypes independently associated with AHD, after controlling for age and risk groups, were higher CD8+% (AOR 1.051 for each unit more, 95%CI 1.022–1.081, P = 0.001), lower CD127+CD4+% (AOR 0.909 for each unit more, 95%CI 0.878–0.942, P = 0.0001), and, in this case, also higher-activated CD38+CD8+% (AOR 1.065 for each unit more, 95%CI 1.020–1.112, P = 0.004) and lower terminal-differentiated CD45R0+CD38+CD8+% (AOR 0.955 for each unit more, 95%CI 0.916–0.996, P = 0.032). AHD patients were confirmed again significantly characterized by older age than N-AHD subjects (AOR 1.040 for each year more, 95%CI 1.010–1.071, P = 0.008).
3.8. Factors Independently Associated with AIDS Presentation
To explore eventual immune phenotypes specifically characterizing patients with an AIDS-defining pathology at new diagnosis of HIV, we also conducted a multivariate logistic regression analysis considering AIDS presentation (). Also, in this case, the parameters with a P value ≤0.05 in the univariate analysis entered the logistic regression model: the covariates were CD4+%, CD8+%, CD4+CD127+%, CD8+CD95+%, CD8+CD38+%, and CD8+CD38+CD45R0+%, and the model was adjusted for age, gender, and risk group.
Multivariate logistic regression analysis of the association of demographic and HIV-related characteristic with AIDS presentation.
The immunological patterns associated with AIDS presentation independently of demographic factors were of course lower CD4+% T cells (AOR 0.996 for each unit more, 95%CI 0.993–0.998, P = 0.008) but also higher CD38+CD8+% (AOR 1.049 for each unit more, 95%CI 1.004–1.096, P = 0.033). In addition, AIDS presenters were confirmed significantly associated with heterosexual risk group (AOR 4.555 versus other risk categories, 95%CI 1.937–10.711, P = 0.001) and male gender (AOR 9.369 versus female, 95%CI 2.401–36.551, P = 0.001).
3.9. Comparison between AHD Subjects/AIDS Presenters and N-LP
We further compared the 79 AHD subjects and 49 AIDS presenters each with the 145 N-LP (comparison group).
AHD patients and AIDS presenters resulted older (median age: N-LP 36, IQR 30–43 versus AHD 42, IQR 34–52, P = 0.0001; versus AIDS presenters 42, IQR 35–52, P = 0.0001) and more frequently heterosexually infected (heterosexuals: N-LP 47, 32% versus AHD 41, 52%, P = 0.016; versus AIDS presenters 29, 59%, P = 0.003) in comparison to N-LP (see Supplementary Material Table 1 available online at doi: 10.1155/2012/314849).
As concern peripheral T lymphocyte immune phenotypes, compared to N-LP, AHD patients and AIDS presenters were characterized by higher CD8+% (NLP: 45, 38–45 versus AHD: 59, 51–66, P = 0.0001; versus AIDS presenters: 59, 50–66, P = 0.0001), lower CD127+CD4+% (NLP: 19, 12–24 versus AHD: 6, 3–11, P = 0.0001; versus AIDS presenters: 6, 4–11, P = 0.0001), higher CD95+CD8+% (NLP: 2, 1–3 versus AHD: 3, 2–6, P = 0.0001; versus AIDS presenters: 3, 2–6, P = 0.0001), CD38+CD8+% (NLP: 5, 2–9 versus AHD: 11, 3–25, P = 0.0001; versus AIDS presenters: 12, 5–23, P = 0.0001), and CD45R0+CD38+CD8+% (NLP: 9, 5–16 versus AHD: 14, 10–25, P = 0.0001; versus AIDS presenters: 16, 10–25, P = 0.0001) (Supplementary Table 1).
Finally, we performed two different logistic regression models to assess eventual independent markers of AHD and AIDS presentation, respectively, always using N-LP as the unique comparison group.
Interestingly, CD8+% (AOR 1.061 for each unit more, 95%CI 1.031–1.093, P = 0.0001), CD8+CD38+% (AOR 1.066 for each unit more, 95%CI 1.009–1.126, P = 0.022), CD8+CD38+CD45R0+% (AOR 0.955 for each unit more, 95%CI 0.993–0.997, P = 0.0001), and CD4+CD127+% (AOR 0.837 for each unit more, 95%CI 0.792–0.884, P = 0.0001) were significantly associated with AHD, also after controlling for age and risk groups for HIV infection (Supplementary Table 2).
Indeed, AHD subjects were confirmed older than N-LP (AOR 1.051 for each year more, 95%CI 1.012–0.976, P = 0.010) also in the multivariate analysis (Supplementary Table 2).
Similarly, we observed an independent association between AIDS presentation and CD8+CD38+% (AOR 1.078 for each unit more, 95%CI 1.015–1.146, P = 0.015), CD8+CD38+CD45R0+% (AOR 0.996 for each unit more, 95%CI 0.994–0.999, P = 0.004), and CD4+CD127+% (AOR 0.827 for each unit more, 95%CI 0.759–0.902, P = 0.0001). Also, this model was adjusted for age and exposure category for HIV transmission, and, as expected, for each year more of age (AOR 1.065 for each year more, 95%CI 1.019–1.113, P = 0.005) and for heterosexual transmission (AOR 3.176 versus other risk categories, 95%CI 1.182–8.531, P = 0.022), we reported a significant increase of risk of AIDS presentation.