Function In HIV-positive Patients Research Articles

Disturbances of lung function in HIV positive patients

The presence of disturbances in the respiratory function on HIV positive patients, derive from multiple causes. The principal mechanism of injury is the inflammation that triggers a flood of biomarkers, which leads to a respiratory function decline. Within the causes, we find modifiable factors such as tobacco and drugs use, and non-modifiable factors like gender, age, CD4 recount, viral burden, HIV itself, ART, co-infections such us HCV and the presence of breathing infections like Pneumocystis Jiroveci pneumonia and Tuberculosis. Facing a chronic pathology requires to control obstructive alterations so, it results convenient to request spirometry and diffusion tests

Endothelial dysfunction in HIV-positive patients with acute coronary syndromes

This study investigated endothelial function in HIV-positive patients with acute coronary syndrome (ACS). Flow-mediated dilatation, pulse-wave velocity, carotid intima-media thickness and endothelial biomarkers were used to non-invasively investigate endothelial dysfunction. Twenty HIV-positive patients with ACS (HIV+/ACS) were compared to 20 HIV-negative patients with ACS (HIV-/ACS) and 20 HIV-positive patients without ACS (HIV+/no ACS). Endothelial function measured by flow-mediated dilatation (FMD) was similar in both the HIV+/ACS (5.2; IQR 1.4-13.4%) and HIV-/ACS groups (3.7; IQR 2.3-4.4%) (p = 0.78). Arterial stiffness, measured by pulse-wave velocity (PWV) was low in all three cohorts. Carotid intima-media thickness (CIMT) was also low in all three cohorts. The vascular cellular adhesion molecule-1 (VCAM-1) levels in HIV-positive patients with and without ACS were significantly higher than in the HIV-/ACS cohort (p = 0.033 and 0.024, respectively). Non-invasive investigations such as FMD, CIMT and PWV did not identify patients with HIV who were at high risk of ACS. Endothelial biomarkers may be more useful markers to identify HIV-positive patients who have endothelial dysfunction and increased risk of ACS.

SAT-140 PREVALENCE AND ASSOCIATED FACTORS OF KIDNEY FAILURE IN HIV INFECTED PATIENTS ADMITTED FOR NON-RENAL CONDITIONS IN GENERAL MEDICAL WARDS OF SECONDARY HOSPITALS IN CAMEROON

The prevalence of renal failure or renal dysfunction among HIV positive patients varies from 6% to 48.5% in most sub-Saharan African countries. However, most of those studies were conducted in tertiary health facilities with nephrology services. The burden among HIV positive patients admitted into general medical ward in district hospitals without nephrology services is unknown. Objective: Evaluate renal function in HIV positive patients admitted for non-renal conditions in a general medical ward of district hospitals in Yaounde, Cameroon. We conducted a cross sectional study over 3 months (January to April 2018) in the general medical wards of the five main secondary hospitals of Yaounde (political Capital of Cameroon). We excluded patients receiving high doses of cotrimoxazole (≥ 2880g/day), major limb amputees and patients with transurethral catheter. HIV infection was classified according to the OMS classification. Glomerular filtration rate was estimated using the MDRD equation. Kidney failure (KF) was defined as an eGFR < 60 ml/min/1.73m2 and classified as mild (60 < eGFR ≤ 30), severe (30 < eGFR ≤ 15) and very severe (eGFR < 15). We included 102 patients with 53% (n=52%) females. Mean age was 44.1 ± 12.2 years and 70 (67%) reported complimentary and alternate medicine (CAM) use. Hypertension (9%), diabetes (8%) and hepatitis B (10%) or Hepatitis C (4%) were infrequent. In all 84.5% (n=86) of patients were in OMS stage 3 and 4, and 71.5% (n=73) were on combined antiretroviral therapy (c-ART) with about two-thirds receiving tenofovir (n=61). Main reasons for admission were tuberculosis (31.5%), gastro-enteritis (18.6%) and malaria (17%). In all 26.5% (n=27) had proteinuria and the median eGFR was 88 [25th-75th IQ 45-122] ml/min/1.73m2 A total of 37.2% (n= 38) had kidney failure with mild KF in 53% (n=20), severe KF in 29% (n=11) and very severe KF in 18% (n=7). CAM use (82.5% Vs 62.5%, p=0.02) and proteinuria (55% Vs 9%, p<0.001) were more common in KF patients. Only proteinuria was associated with KF [adjusted OR =9.14 CI (3.16-28.13); p<0.001]. Kidney failure is very frequent among HIV positive patients admitted for non-renal condition in general medical ward. Evaluation of renal function needs to be systematic especially in patients using CAM and with proteinuria.

Circulating levels of PRO-C3 reflect liver fibrosis and liver function in HIV positive patients receiving modern cART

Background and aimsAlthough combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.Methods116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.ResultsFifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.ConclusionThe formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.

Confirmed marijuana use and lymphocyte count in black people living with HIV

BackgroundMarijuana is a commonly used recreational substance with purported analgesic and mood enhancing properties. Many people living with HIV identify marijuana as a palliative substance. However, through its main psychoactive component, tetrahydrocannabinol (THC), is known to influence the immune system. The effects of marijuana use in people with HIV are still controversial, with very scant literature in Black adults. MethodsThe current study determined the differences in the lymphocyte count, specifically the number cluster differentiation 4 and 8 (CD4+ and CD8+), among patients who urine drug tested negative for THC (n = 70) and those who tested positive for THC (n = 25). The sample included 95 Black people living with HIV, 51% female, with a mean age of 46 ± 11 years. Participants provided a urine sample for substance use testing and a trained researcher extracted clinical data from clinical charts on the day of appointment. ResultsAfter adjusting for demographic and HIV-related covariates, THC-positive patients had significantly higher CD4+ and CD8+ counts than their THC-negative counterparts. ConclusionThese results extend previous HIV-related immunity findings in an underrepresented group, and suggest that THC use does not reduce immune function as measured by CD count. Further research is warranted on the overall effects of THC on immune function in HIV positive patients.

Deciphering Endothelial Dysfunction in the HIV-Infected Population.

Cardiovascular disease (CVD), as a possible consequence of endothelial dysfunction, is prevalent among HIV-infected patients despite successful administration of antiretroviral drugs. This warrants the routine clinical assessment of endothelial function in HIV-positive patients to circumvent potential CVD events. Several different non-invasive strategies have been employed to assess endothelial function in clinical research studies yielding inconsistencies among these reports. This review summarises the different techniques used for assessing endothelial function, with a focus on proposed blood-based biomarkers, such as endothelial leukocyte adhesion molecule-1 (E-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), TNF-α, interleukin 6 (IL6) and soluble thrombomodulin (sTM). The identification of suitable blood-based biomarkers, especially those that can be measured using a point-of-care device, would be more applicable in under-resourced countries where the prevalence of HIV is high.

RETRACTED: Confirmed marijuana use and lymphocyte count in black people living with HIV

Marijuana is a commonly used recreational substance with purported analgesic and mood enhancing properties. Many people living with HIV identify marijuana as a palliative substance. However, through its main psychoactive component, tetrahydrocannabinol (THC), is known to influence the immune system. The effects of marijuana use in people with HIV are still controversial, with very scant literature in Black adults. The current study determined the differences in the lymphocyte count, specifically the number cluster differentiation 4 and 8 (CD4+ and CD8+), among patients who urine drug tested negative for THC (n=70) and those who tested positive for THC (n=25). The sample included 95 Black people living with HIV, 51% female, with a mean age of 46±11years. Participants provided a urine sample for substance use testing and a trained researcher extracted clinical data from clinical charts on the day of appointment. After adjusting for demographic and HIV-related covariates, THC-positive patients had significantly higher CD4+ and CD8+ counts than their THC-negative counterparts. These results extend previous HIV-related immunity findings in an underrepresented group, and suggest that THC use does not reduce immune function as measured by CD count. Further research is warranted on the overall effects of THC on immune function in HIV positive patients.

Evaluation of salivary flow rate and gustatory function in HIV-positive patients with or without highly active antiretroviral therapy.

Objectives:The aim of this study is to evaluate the salivary flow rate and gustatory changes in HIV-positive patients on highly active anti-retroviral therapy (HAART) and without HAART. We also correlated CD4 count and salivary flow rate and gustatory function in both groups.Methods:Sample size for each group was thirty. After obtaining informed consent, we measured salivary flow rate using Schimer's method and gustatory function using four tastants (sweet, sour, bitter, and salty) of different concentrations. The readings were recorded at 0 month, 2nd, 4th, and 6th month interval. The data obtained was statistically analyzed.Results:The mean salivary flow rate was decreased more in Group I as compared to Group II. The mean identification score for sweet, salty, sour, and bitter was significantly higher in Group II than Group I. The mean detection threshold score for sweet, salty, sour and bitter taste was comparatively higher in Group I than Group II. The Pearson's correlation analysis showed inverse relation between age and salivary flow rate in Group II. No significant correlation was observed in CD4 count and salivary flow rate.Conclusion:Along with routine oral health appraisal in seropositive patients, evaluation of salivary flow rate, and taste abnormalities should also be considered an integral part of patient assessment.

Circulating levels of Pro-C3 reflect liver fibrosis and function in HIV positive patients receiving cART

Background and aims: Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen type III accumulates in the liver during fibrogenesis. Recent studies could show that circulating levels of fragments of extracellular matrix (ECM) might reflect fibrosis stage and degree of portal hypertension in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation marker of collagen type III in HIV positive patients receiving cART.

Monitoring of kidney function in HIV-positive patients.

HIV-positive patients are at increased risk of developing chronic kidney disease. Although guidelines recommend regular monitoring of renal function in individuals living with HIV, the optimal frequency remains to be defined. In this review, we discuss the renal syndromes that may be identified at an earlier stage via routine assessment of kidney function, and provide guidance in terms of the frequency of monitoring, the most useful tests to perform, and their clinical significance. Specifically, we address whether annual monitoring of kidney function is appropriate for the majority of HIV-positive patients.

Antiretrovirals and the kidney in current clinical practice: renal pharmacokinetics, alterations of renal function and renal toxicity.

Assessment of renal function in HIV-positive patients is of increasing importance in the context of ageing and associated comorbidities. Exposure to nephrotoxic medications is widespread, and several commonly used antiretroviral drugs have nephrotoxic potential. Moreover, specific antiretrovirals inhibit renal tubular transporters resulting in the potential for drug-drug interactions as well as increases in serum creatinine concentrations, which affect estimates of glomerular filtration rate in the absence of changes in actual glomerular filtration rate. This review explores the effects of antiretroviral therapy on the kidney and offers an understanding of mechanisms that lead to apparent and real changes in renal function.

Assessment of the usefulness of β2-microglobulin and retinol binding protein for the purpose of testing kidney function in HIV-positive patients

AimThe aim of the study was to assess the importance and usefulness in everyday clinical practice of the urinary concentrations of β-microglobulin (β2M) and retinol binding protein (RBP) in evaluation of the renal function in HIV-positive patients. BackgroundKidney proximal tubule cells are the most prone to the damage and for low molecular-weight proteins as β-microglobulin (β2M) and retinol binding protein (RBP) are sensible markers of the pathology of this part of the nephron. Materials and methodsUrine collected from 86 HIV-positive patients consulted in HIV/AIDS Outpatients Clinic in Wroclaw. ResultsIn the group with decreased base-line GFR on tenofovir β2M level was statistically significant higher than in group on tenofovir with normal base-line GFR (p≤0.05), in group on other antiretroviral treatment (p≤0.001) and in cART-naïve patients (p≤0.001). Mean RBP levels in groups on tenofovir both with decreased and normal baseline GFR were statistically significant higher (p≤0.01; p≤0.01) than in controls. There is statistically significant (p≤0.05) negative linear correlations between the urinary concentrations of β2M and RBP and GFR as well as between urinary β2M and serum creatinine level (p≤0.05) in a group of patients receiving cART with tenofovir. Conclusionβ2M and RBP concentrations in urine may become useful in diagnosis of renal failure and are more sensitive than the standard determination of creatinine in plasma and eGFR in patients treated with tenofovir.The determination of the excretion of β2M seems a better measurement of tenofovir nephrotoxicity than RBP.

Neurocognitive function in HIV infected patients on antiretroviral therapy.

ObjectiveTo describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy.DesignWe undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial.Main outcome measureNC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression.ResultsOf the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was −0.5 (−1.2/−0) overall, and −0.3 (−0.7/0.1) and −1.4 (−2/−0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001).ConclusionsIn this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised.Trial registryClinicalTrials.gov, NCT01230580

Comparison of CKD-EPI and MDRD to estimate baseline renal function in HIV-positive patients

Renal dysfunction is common in HIV-positive patients, and guidelines suggest regular monitoring of renal function with estimated glomerular filtration rate (eGFR) and urinalysis. It is unknown whether Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) or Modification of Diet in Renal Disease (MDRD) provide better estimates of glomerular filtration rate (GFR) in this population. We compared the CKD-EPI and MDRD equations to estimate GFR at baseline in 20,132 HIV-positive individuals in the UK CHIC cohort. Kappa statistics and Bland-Altman plots were used to assess agreement between the two estimates and Kaplan-Meier plots and Cox regression analysis to describe mortality patterns. At baseline, median eGFR was 100 (87, 112) (CKD-EPI) and 94 (83, 108) (MDRD) (mL/min/1.73 m(2)). Good overall agreement between CKD-EPI- and MDRD-defined eGFR bands was observed (Kappa = 0.71, 95% confidence interval: 0.70-0.72). Of the 367 patients with eGFR MDRD 30-59, 57 (15.5%) were categorized as eGFR 60-89 by CKD-EPI. After adjustment for covariates, eGFR <60 (CKD-EPI), eGFR <30 (MDRD) and eGFR ≥105 (both formulae) were significantly associated with an increased risk of death. Mortality in patients classified as having eGFR 60-89 by CKD-EPI and eGFR 30-59 by MDRD more closely resembled mortality of patients who had eGFR 60-89 by both formulae. MDRD and CKD-EPI equations showed a high degree of agreement in stratifying patients by baseline eGFR. CKD-EPI estimates of GFR <60 at baseline are more strongly associated with mortality than MDRD estimates of GFR <60, supporting the concept that MDRD may have overestimated the severity of renal impairment in these patients. Our findings support the use of CKD-EPI in HIV-positive individuals.

Renal dysfunction among HIV-infected patients starting antiretroviral therapy

HIV-related renal dysfunction is associated with high mortality. Data on the prevalence of renal dysfunction among HIV-infected outpatients starting antiretroviral therapy (ART) in sub-Saharan Africa are limited. Recent recommendations to include the nephrotoxic drug tenofovir in first-line ART regimens make clarification of this issue urgent. We screened for renal dysfunction by measuring serum creatinine, proteinuria, and microalbuminuria in HIV-positive outpatients initiating ART in Mwanza, Tanzania. We excluded patients with pre-existing renal disease, hypertension, diabetes, or hepatitis C virus co-infection. Estimated glomerular filtration rates (eGFRs) were calculated by Cockroft-Gault and Modification of Diet in Renal Disease equations. Only 129 (36%) of 355 enrolled patients had normal eGFRs (grade 0 or 1) above 90 ml/min per 1.73 m. Grade 2 renal dysfunction (eGFR between 60 and 89 ml/min per 1.73 m) was present in 137 patients (38.6%), and 87 patients (25%) had grade 3 dysfunction (eGFR between 30 and 59 ml/min per 1.73 m). Microalbuminuria and proteinuria were detected in 72 and 36% of patients, respectively. Factors predictive of renal dysfunction in multivariate analysis included female sex [odds ratio (OR) 3.0, 95% confidence interval (1.8-5.1), P < 0.0001], BMI less than 18.5 [OR 2.3 (1.3-4.1), P = 0.004], CD4 T-cell count below 200 cells/μl [OR 2.3 (1.1-4.8), P = 0.04], and WHO clinical stage II or above [OR 1.6 (1.2-2.3), P = 0.001]. Renal dysfunction was highly prevalent in this population of HIV-positive outpatients initiating first ART in Tanzania. This highlights the critical and underappreciated need to monitor renal function in HIV-positive patients in sub-Saharan Africa, particularly given the increasing use of tenofovir in first-line ART.

The assessment of renal function in HIV-positive patients before the introduction of antiretroviral therapy

A wide clinical spectrum of kidney diseases has been recognized in individuals with HIV (human immunodeficiency virus). The aim of this retrospective study was to assess renal function in HIV patients before the introduction of combined antiretroviral therapy (cART). The study group consisted of 106 HIV-positive patients (72 males, 34 females). The level of serum creatinine and creatinine clearance using the Cockcroft-Gault formula were assessed. Urine analysis for proteinuria was performed. The relationship between HIV infection including CD4 cells count, CD4 nadir and renal function was determined. The correlation between the creatinine clearance and CD4 nadir and CD4 cells count before the introduction of cART was found (p = 0.037, p = 0.036). Conclusion: The kidney dysfunction measured with the creatinine clearance before the introduction of cART was associated with the immunodeficiency.

Autologous stem cell transplant (ASCT) for AIDS-related lymphoma (ARL)

High-dose therapy with ASCT is an established therapy for relapsed Non-Hodgkins (NHL) and Hodgkin's lymphoma (HL). Randomized trials have shown a benefit for this approach when compared to standard dose salvage therapy for HIV-negative NHL. Since these first trials, transplant-related mortality (TRM) has decreased due to the use of peripheral stem cells and improved supportive care. Concomitantly, the treatment of HIV infection has also improved. Highly active antiretroviral therapy (HAART) has improved hematologic and immune function in HIV positive patients. In addition, with the use of HAART and prophylactic antibiotics, the incidence of opportunistic infections has greatly decreased. This improvement in control of OIs and immunologic function in HIV infected patients due to HAART set the platform for the use of ASCT in patients with high-risk ARL. Herein we report the long-term follow-up of 32 patients with ARL who underwent ASCT at the City of Hope Cancer Center between 1998 and 2007. Median age at ASCT was 42 years. Histologies included Diffuse large cell n = 16, Burkitts n = 9, Anaplastic large cell n = 2, HL n = 5. The conditioning regimen consisted of CBV (carmustine 450 mg/m2, cyclophosphamide (CY) 100 mg/kg, VP16 60 mg/kg) in 28 patients and FTBI 1200 cGY/CY 100 mg/kg/VP16 60 mg/kg in 4 patients, All patients engrafted at a median of 10 days to an ANC >500 (range 5–19 days). One patient died of regimen-related cardiac toxicity. Other regimen-related toxicities included grade 3–4 hepatic toxicity n = 3, interstitial pneumonitis n = 2. OI's included PCP pneumonia in 2 patients who were not compliant with prophylaxis, CMV infection n = 3, VZV n = 2. One case of treatment related myelodysplasia was seen and the patient ultimately died of myelodysplasia while in remission from his ARL. Median HIV viral load at ASCT was 5726 copies/ml, with 25 patients having an undetectable viral load. Median CD4 count at ASCT was 156 (range 25–1064), which rose to 420 (range 95–1164) at 2-year follow-up. Only 10 patients had an undetectable VL at 2 years. Three patients who were in remission were lost to follow-up after 4 years. Median f/u for the entire group is 47 (range 0.7–104) months. Two-year overall survival is 80 percent (95% CI 66–89) and progression-free survival (PFS) is 81 percent (95% CI 67–90). In conclusion, this large single institution series of ASCT in ARL demonstrates that the procedure has low transplant-related mortality and can lead to long-term remission without deleterious effects on the underlying HIV infection.

Current Update on HIV‐associated Vascular Disease and Endothelial Dysfunction

Highly active antiretroviral therapy (HAART) has greatly reduced the risk of early death from opportunistic infections and extended the lifespan of people infected with the human immunodeficiency virus (HIV). Thus, many complications and organic damage in the HIV-infected population emerge. Cardiovascular disease as coronary artery disease has become a matter of particular concern. Its incidence is greatly increased in the HIV-infected population over that of people of the same age in the absence of general cardiovascular risk factors. Despite several clinical and laboratory studies in the association between HIV infection and cardiovascular disease, the pathogenic mechanisms of this significant clinical problem are largely unknown and are now under active investigation. Endothelial dysfunction is possibly the most plausible link between HIV infection and atherosclerosis. Increased expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and endothelial adhesion molecule (E-selectin) and inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL-6 has been reported in HIV-positive patients. The effect of HAART on endothelial function in HIV-positive patients is also demonstrated. In this review, we focus on the recent research update of HIV-associated vascular disease and vascular injury. We analyze and discuss the recent clinical and laboratory investigations on the effect of HIV, viral protein, and HAART therapy on endothelial injury and vascular disease; identify the areas of controversy and clinical relevance; and suggest some directions for future research.

Antidepressants May Bolster Immune Function in HIV-Positive Patients

Antidepressants May Bolster Immune Function in HIV-Positive Patients

Changes in thymic function in HIV-positive patients treated with highly active antiretroviral therapy and interleukin-2.

Despite its potent antiviral activity, highly active antiretroviral therapy (HAART) only exerts a marginal effect on CD4+ T-cell regeneration in HIV-infected subjects. Combination therapies aimed at boosting T-cell activity and maturation may provide an important contribution to the restoration of immune function. Here, we report the results obtained by a two-year follow-up of a cohort of HIV-infected patients treated with a combination of HAART and interleukin-2 (IL-2). In these patients, in addition to a series of quantitative virological and immunological parameters, we investigated T-cell regeneration by an immunophenotypic assay monitoring CD4+ naïve T cells, and by analysis of thymic function, through the quantification of the excision DNA products of T-cell receptor rearrangement (TRECs) in lymphocytes. Compared with HAART alone, we found that the IL-2 combination therapy was equally effective in reducing the levels of viremia and marginally more effective in decreasing proviral DNA load. Strikingly, the IL-2 combination produced a marked increase in the number of CD4+ T cells bearing a naïve phenotype (CD45RA+, CD62L+), which was apparent for over 96 weeks after therapy. To assess whether these cells were the product of improved T-cell generation, we exploited a competitive quantitative molecular assay to quantify TRECs in peripheral blood lymphocytes. Surprisingly, we found that the levels of these molecules were unchanged in these patients. These findings indicate that improved thymic function does not account for the early rise of CD4 naïve cells in HIV-positive patients treated with IL-2, and suggest that alternative mechanisms of T-cell maturation and differentiation are responsible for this event.