Long-term clinical, virological and immunological outcomes following planned treatment interruption in HIV-infected children.

OBJECTIVES: Planned treatment interruption (PTI) of antiretroviral therapy (ART) in adults is associated with adverse outcomes. The PENTA 11 trial randomized HIV-infected children to continuous ART (CT) vs. CD4-driven PTIs. We report 5 years' follow-up after the end of main trial. METHODS: Post-trial, all children resumed ART. Clinical, immunological, virological and treatment data were collected annually. A sub-study investigated more detailed immunophenotype. CT and PTI arms were compared using intention-to-treat. Laboratory parameters were compared using linear regression, adjusting for baseline values; mixed models were used to include all data over time. RESULTS: In all, 101 children (51 CT, 50 PTI) contributed a median of 7.6 years, including 5.1 years of post-trial follow-up. Post-trial, there were no deaths, one pulmonary tuberculosis and no other CDC stage B/C events. At 5 years post-trial, 90% of children in the CT vs. 82% in the PTI arm had HIV RNA < 50 copies/mL (P = 0.26). A persistent increase in CD8 cells was observed in the PTI arm. The sub-study (54 children) suggested that both naïve and memory populations contributed to higher CD8 cells following PTI. Mean CD4/CD8 ratios at 5 years post-trial were 1.22 and 1.08 in CT and PTI arms, respectively [difference (CT - PTI) = -0.15; 95% CI: -0.34-0.05), P = 0.14]. The sub-study also suggested that during the trial and at early timepoints after the end of the trial, reduction in CD4 in the PTI arm was mainly from loss of CD4 memory cells. CONCLUSIONS: Children tolerated PTI with few long-term clinical, virological or immunological consequences.

IgG4-positive plasma cells are more often detected in chronic periapical lesions arising from permanent rather than primary teeth.

AIM: To characterize plasma cell subsets in chronic periapical lesions affecting permanent and primary teeth. METHODOLOGY: Only chronic periapical lesions without root canal treatment were selected. Twenty-one radicular cysts and 7 periapical granulomas affecting permanent teeth and 19 radicular cysts and 4 periapical granulomas affecting primary teeth were assessed for immunoglobulin (Ig) light chain (kappa and lambda), Ig heavy chain (IgG, IgG4, IgA, IgM and IgD) and plasma cell immunohistochemical markers (MUM1/IRF4, EMA and CD138). The data acquired were analysed by Student's t test, Mann-Whitney U, Friedman test followed by Dunn's multiple comparison test and Spearman's rank correlation. RESULTS: All cases were polyclonal (having similar kappa/lambda light chain ratios). IgG was most abundant compared to other Ig heavy chains (all, P < 0.001); like Ig light chains, but unlike IgA, there was greater expression of IgG in the primary compared to the permanent dentition, for both radicular cysts (P < 0.001) and periapical granulomas (P = 0.53). Notably, IgG4 expression was greater in the permanent than the primary dentition, for both radicular cyst (P < 0.05) and periapical granuloma (P = 0.65). IgM and IgD expression was scarce and variable, whereas plasma cell populations were detected efficiently through EMA, CD138 and MUM1/IRF4 markers, the latter being more sensitive in both dentitions. CONCLUSIONS: There were slight variations in the Ig light and heavy chain profiles in chronic periapical lesions when comparing the permanent and primary dentitions. The ability of IgG4+ plasma cell infiltration to modulate inflammatory responses in chronic periapical lesions arising from permanent as opposed to primary teeth should be considered in future studies.

Effect of intercellular adhesion molecule 1 deficiency on the development of apical periodontitis.

AIM: To evaluate the specific role of ICAM-1 in host responses against endodontic infection. METHODS: Apical periodontitis was experimentally induced in the mandibular first molars of ICAM-1 knockout and wild-type (WT) mice by pulp exposure to the oral environment. At 7, 21 and 42 days following pulp infection, the animals were euthanized and the jaws were prepared for analysis under conventional and fluorescence microscopy (histopathologic and morphometric analysis), immunohistochemistry (polymorphonuclear leucocytes), enzyme histochemistry (osteoclasts and cementoclasts) and RT-PCR (IL-1 α, TNF-α, INF-γ, IL-10, RANK, RANKL and OPG). A generalized linear model with GLIMMIX procedure with Satterthwaite approximation method of degrees of freedom, Tukey-Kramer, pseudo-ranking nonparametric, Bonferroni-Holm multiple testing adjustment, analysis of variance (ANOVA) and the Tukey's multiple comparisons tests were used to evaluate the statistical differences between the groups using SAS 9.4 and the GraphPad Prism 5.0 software (α = 0.05). RESULTS: Compared to WT mice, ICAM-1 knockout mice had significantly greater bone resorption (P < 0.05), reduced recruitment of neutrophils to periapical inflammatory tissues (P < 0.05) and an increased number of fibroblasts (P < 0.05) at all experimental periods. The osteoclast number was significantly higher in ICAM-1 KO than that of WT animals at all times (P < 0.05), while there was no significant difference between the groups regarding cementoclasts. At day 21, the level of IL-1α, RANK, RANKL and IL-10 had increased significantly in tissues from ICAM-1 KO versus WT mice (P < 0.05), while no significant difference was observed in TNF-α and OPG levels (P > 0.05). Tissue levels of INF-γ were significantly lower in ICAM-1 KO than those in WT mice (P < 0.05). CONCLUSION: ICAM-1 deficiency impaired the host response against endodontic infection, resulting in increased tissue destruction.

Fibroblast growth factor receptor 2 expression in apical periodontitis in mice.

AIM: To investigate the presence, localization and the possible correlation of the fibroblast growth factor receptor-2 (FGFR2) with inflammatory resorption of cementum, periodontal ligament and alveolar bone during development of apical periodontitis in mice. METHODOLOGY: Apical periodontitis was experimentally induced in mandibular first molars of mice by pulp exposure to the oral environment. Healthy teeth without pulp exposure were used as controls. At 7, 21 and 42 days following pulp exposure, the animals were euthanized and the jaws were prepared for analysis under conventional and fluorescence microscopy, immunohistochemistry (FGFR2), RT-PCR (RNAm levels of RANK, RANKL, OPG, Runx2 and cathepsin K) and enzyme histochemistry (cementoclasts and osteoclasts). Statistical analysis was performed by Kruskal-Wallis tests and Dunn's post hoc tests for multiple comparisons (α = 0.05) using SAS 9.4 software. RESULTS: FGFR2-positive cells were not observed in the tissues surrounding healthy teeth but were observed in teeth with periapical lesions from seven days after root canal contamination. At days 21 and 42 after endodontic infection, the increase in periapical lesion size was accompanied by significantly enhanced expression of FGFR2 (P < 0.0001), significantly increased intensity of inflammatory cells, number of osteoclasts (P < 0.0001) and cementoclasts (P < 0.0001), and significantly enhanced RNAm levels of RANK/RANKL/OPG, Runx2 and cathepsin K compared to day 0 (P < 0.0001). At 21 and 42 days, FGFR2 was also expressed on osteoblasts, fibroblasts and inside enlarged lacunae of cementocytes along with acute and chronic inflammatory cells (macrophages, plasma cells and neutrophils). At all periods and cells, FGFR2 expression was observed in the cell membrane and cytoplasm, but not in the nucleus. CONCLUSION: In mice, FGFR2 was not expressed in tissues surrounding healthy teeth but was expressed in apical periodontitis, specifically in the membrane and cytoplasm of osteoblasts, fibroblasts, lacunae of cementocytes, and acute and chronic inflammatory cells (macrophages, plasma cells and neutrophils). Its expression was correlated with the size of the periapical lesions.

Differences in telomere length between sporadic and familial cutaneous melanoma.

BACKGROUND: Several pieces of evidence indicate that a complex relationship exists between constitutional telomere length (TL) and the risk of cutaneous melanoma. Although the general perception is that longer telomeres increase melanoma risk, some studies do not support this association. We hypothesize that discordant data are due to the characteristics of the studied populations. OBJECTIVES: To evaluate the association of TL with familial and sporadic melanoma. MATERIALS AND METHODS: TL was measured by multiplex quantitative polymerase chain reaction in leukocytes from 310 patients with melanoma according to familial/sporadic and single/multiple cancers and 216 age-matched controls. RESULTS: Patients with sporadic melanoma were found to have shorter telomeres compared with those with familial melanoma. In addition, shorter telomeres, while tending to reduce the risk of familial melanoma regardless of single or multiple tumours, nearly trebled the risk of single sporadic melanoma. CONCLUSIONS: This is the first time that TL has been correlated to opposite effects on melanoma risk according to the presence or absence of familial predisposition. Individual susceptibility to melanoma should be taken into account when assessing the role of TL as a risk factor.

Narrowband optical parametric amplification measurements in Ga0.5In0.5P photonic crystal waveguides.

We report the first demonstration of narrowband parametric amplification in a chip scale semiconductor waveguide. A dispersion engineered, Ga0.5In0.5P photonic crystal waveguide with a dispersion function that exhibits two zero crossings was used with a pulsed pump placed in the normal dispersion regime while a tunable probe was scanned on either side of the pump. A peak conversion efficiency of -10 dB was obtained with a peak pump power of only 650 mW. The narrowband nature of the gain spectrum was clearly demonstrated.

Absence of interleukin 22 affects the oral microbiota and the progression of induced periapical lesions in murine teeth.

AIM: To evaluate the absence of IL-22 on the progression of periapical lesions in wild-type (WT) and IL-22 knockout (IL-22 KO) mice. METHODOLOGY: The evaluation of the oral microbial profile of mice was performed by Checkerboard DNA-DNA hybridization from saliva samples. Periapical lesions were induced in manbibular first molars by pulpal exposure and evaluated after 7, 21 and 42 days (n = 15). Haematoxylin-eosin-stained sections were analysed under conventional and fluorescence microscopy to evaluate the tissue features and size of periapical lesions and tartrate-resistant acid phosphatase histoenzymology (TRAP), Brown & Brenn staining and immunohistochemistry. The scores of the number of bacterial cells present in the oral cavity were analysed by the Mann-Whitney test, and the results and comparisons for periapical lesion size and number of osteoclasts were subjected to one-way anova and Bonferroni's post-test (α = 0.05). RESULTS: Significant differences were observed for bacterial load between the groups of animals for 6 bacterial species (P < 0.05), with five species found in higher levels in the WT group, and one in the IL-22 KO group. WT mice had significantly larger periapical lesions (P < 0.05) between 7 and 42 days and between 21 and 42 days, with an increase in the mean size and number of osteoclasts. IL-22 KO mice had an increase in periapical lesion size and number of osteoclasts between 7 and 21 days (P < 0.05). No differences were found between bacteria localization in the root canal system between the experimental groups. Small variations related to the location of immunostaining were found between the groups. CONCLUSION: This study revealed differences in the composition of oral microbiota between mice that may be taken into account in the susceptibility to infections and development of periapical lesions. The absence of IL-22 in mice resulted in smaller periapical lesions with fewer osteoclasts at the final experimental period, suggesting the participation of IL-22 in the host immune and inflammatory response to a periradicular infection.

MyD88 knockout mice develop initial enlarged periapical lesions with increased numbers of neutrophils.

AIM: To characterize the formation and progression of experimentally induced periapical lesions in teeth of MyD88 knockout (MyD88 KO) mice compared with wild-type (WT) mice. METHODOLOGY: Periapical lesions were induced in the mandibular first molars of 30 WT and 30 MyD88 KO mice. After 7, 21 and 42 days, the animals were euthanized and the mandibles were subjected to histotechnical processing. Histological sections were stained with haematoxylin and eosin (HE), TRAP histoenzymology, Brown and Brenn staining and immunohistochemistry (RANK, RANKL, OPG). Data were subjected to statistical analysis by the nonparametric Mann-Whitney and Kruskal-Wallis tests and the Dunn post-test, using the SPSS software, version 17.0 (α = 0.05). RESULTS: Regarding the periapical lesion size, the MyD88 KO group had significantly higher values than the WT group in the periods of 7 (P = 0.001) and 21 days (P = 0.05). A larger number of neutrophils in the MyD88 KO group were observed (P = 0.01 at 7 days, P = 0.004 at 21 days and P < 0.001 at 42 days). Regarding the number of osteoclasts, no statistically significant difference was observed between the groups at any of the experimental periods (P = 0.884 at 7 days, P = 0.506 at 21 days and P = 0.211 at 42 days). CONCLUSIONS: In the absence of MyD88, the animals had larger periapical lesions, with a severe inflammatory infiltrate and a significantly larger number of neutrophils.

Telomerase is an independent prognostic marker of overall survival in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is an important cause of cancer-related death. Prediction of recurrence is an important issue in the treatment of disease, particularly for stage II patients. The level of telomere-specific reverse transcriptase (hTERT), the catalytic component of the telomerase complex, increases along with CRC progression, but its prognostic value is still unclear. METHODS: One hundred and thirty-seven CRC patients were studied for hTERT expression in tumour cells by real-time PCR. hTERT level was evaluated as a prognostic factor of overall survival (OS) in all patients and of disease recurrence in a subgroup of 50 stage II patients. RESULTS: The median hTERT level was 93.8 copies (interquartile range 48-254). Patients with high hTERT levels (above the median) showed a significantly worse survival than those with low hTERT levels (below the median; log-rank test P<0.0001; hazard ratio (HR)=3.30 (95% confidence interval (CI) 1.98-5.52); P<0.0001). The negative prognostic value of high hTERT level is independent of the pathological stage and microsatellite instability (HR=2.09 (95% CI 1.20-3.64), P=0.009). Moreover, in stage II CRC, high hTERT levels identified patients with a higher risk of disease recurrence (HR=3.06 (95% CI 1.03-9.04), P=0.043) and death (HR=3.24 (95% CI 1.37-7.71), P=0.008). CONCLUSION: hTERT level is an independent prognostic marker of OS in CRC patients. In addition, assessment of hTERT level could improve stratification of stage II CRC patients for the risk of disease recurrence.

Dual-pump parametric amplification in dispersion engineered photonic crystal waveguides.

This paper describes a numerical simulation of narrow band parametric amplification in dispersion engineered photonic crystal waveguides. The waveguides we analyze exhibit group velocity dispersion functions which cross zero twice thereby enabling many interesting pumping schemes. We analyze the case of two pulsed pumps each placed near one of the zero dispersion wavelengths. These configurations are compared to conventional single pump schemes. The two pumps may induce phase matching conditions in the same spectral location enabling to control the gain spectrum. This is used to study the gain and fidelity of 40 G bps NRZ data signals.

Parametric gain in dispersion engineered photonic crystal waveguides.

We present a numerical simulation of parametric gain properties in GaInP PhC dispersion engineered waveguides in which the group velocity dispersion crosses zero twice and where the pump and the signal are 100 ps pulses. The simulations use the M-SSFT algorithm which incorporates dispersive nonlinear coefficients and losses. We concentrate on narrow band parametric gain which occurs for pump wavelengths in the normal group velocity dispersion regime. The effects of structural details, of pump wavelength and of losses are carefully analyzed.

In young men sperm telomere length is related to sperm number and parental age.

STUDY QUESTION: What are the relationships between telomere lengths in leukocytes and sperm, sperm count and parents' age at conception in a group of apparently healthy subjects of the same age? SUMMARY ANSWER: Sperm telomere length (STL) is related to sperm count, it is lower in oligozoospermic than in normozoospermic men and it is directly related to parents' age at conception. WHAT IS KNOWN ALREADY: Leukocyte telomere length (LTL) decreases with age but STL increases and offspring of older fathers tend to have longer leukocyte telomeres. Only one study analyzed STL in relation to male fertility, and reported shorter telomeres in infertile versus fertile men. No data have been reported on STL in relation to parents' age at conception. STUDY DESIGN, SIZE, DURATION: Prospective study conducted from January to December 2012 of 18-19-year-old high school students. PARTICIPANTS/MATERIALS, SETTING AND METHODS: The volunteers were 81 apparently healthy subjects, including 61 with normozoospermia and 20 with idiopathic oligozoospermia. Leukocyte and sperm telomere length were measured by real-time PCR. Data were analyzed for determining the relationships between LTL, STL, sperm count and parents' age at conception. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm and leukocyte telomere length were strongly correlated, but STL was significantly longer. A significant positive correlation between STL and total sperm number was found. STL was significantly lower in oligozoospermic than in normozoospermic men. Finally, we found a significant positive relationship between maternal age and both leukocyte and sperm telomere length and a significant positive relation between paternal age and STL in the offspring. The relative contributions of mothers' and fathers' ages to their offspring's telomere length could not be determined because of the high correlation between paternal and maternal ages. LIMITATIONS AND REASONS FOR CAUTION: Although consistent with previous findings, this is the first study on telomere length in oligo- and normozoospermic men and included a relatively low number of subjects. Our study was also restricted to young (18-19 year old) men, so future studies should determine whether our findings can be generalized to men at ages typically encountered at fertility centers. Future studies should also try to determine the possible effect of abstinence time and frequency of ejaculation with STL. WIDER IMPLICATIONS OF THE FINDINGS: Our study sheds new light on the association between STL and sperm count and on the inheritance of telomere length (in leukocytes and sperm) in relation to the parents' age at conception. Additional studies are needed to confirm these observations, to clarify if the association between shorter STL and damaged spermatogenesis represents a pathophysiological link, and to determine the effect on offspring telomere length of assisted reproduction techniques performed on couples of advanced age or where the man is oligozoospermic. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Italian Ministry of University and Research (grant no. 2009AMPA9C to C.F.) and Padova University (grant 2010 to A.D.R.). The authors have no competing interests to declare.

The treatment of a maxillary lateral incisor with unusual morphology with long-term follow-up.

AIM: To report the treatment of an unusual combination of one dens evaginatus and two dens invaginatus in a single tooth and its healing outcome after 10 years. SUMMARY: The long-term outcome of a maxillary lateral incisor with dens evaginatus combined with two Oehlers type II dens invaginatus and a large periradicular lesion in an 11-year-old female treated endodontically and restoratively is described. The endodontic treatment included intracanal medication with calcium hydroxide and canal filling using a thermoplastic root canal filling technique. The crown was restored with conventional composite resin. During periodic clinical and radiographic follow-up, the patient remained symptom free, and the periradicular region was completely healed, meeting both aesthetic and functional expectations after 10 years. KEY LEARNING POINTS: The co-occurrence of dens evaginatus and two dens invaginatus in the same tooth is an unusual finding that compromises aesthetics and predisposes the patient to dental pulp infection. The complex morphology observed in this case represented both endodontic and restorative challenges.

Prognostic role and interaction of TERT promoter status, telomere length and MGMT promoter methylation in newly diagnosed IDH wild-type glioblastoma patients.

BACKGROUND: The clinical relevance of promoter mutations and single nucleotide polymorphism rs2853669 of telomerase reverse transcriptase (TERT) and telomere length in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients remains unclear. Moreover, some studies speculated that TERT promoter status might influence the prognostic role of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in newly diagnosed GBM. We carried out a large study to investigate their clinical impact and their interaction in newly diagnosed GBM patients. PATIENTS AND METHODS: We included 273 newly diagnosed IDH wild-type GBM patients who started treatment at Veneto Institute of Oncology IOV - IRCCS (Padua, Italy) from December 2016 to January 2020. TERT promoter mutations (-124 C>T and -146 C>T) and SNP rs2853669 (-245 T>C), relative telomere length (RTL) and MGMT methylation status were retrospectively assessed in this prospective cohort of patients. RESULTS: Median overall survival (OS) of 273 newly diagnosed IDH wild-type GBM patients was 15 months. TERT promoter was mutated in 80.2% of patients, and most had the rs2853669 single nucleotide polymorphism as T/T genotype (46.2%). Median RTL was 1.57 (interquartile range 1.13-2.32). MGMT promoter was methylated in 53.4% of cases. At multivariable analysis, RTL and TERT promoter mutations were not associated with OS or progression-free survival (PFS). Notably, patients C carrier of rs2853669 (C/C+C/T genotypes) showed a better PFS compared with those with the T/T genotype (hazard ratio 0.69, P = 0.007). In terms of OS and PFS, all interactions between MGMT, TERT and RTL and between TERT and rs2853669 genotype were not statistically significant. CONCLUSIONS: Our findings suggest the presence of the C variant allele at the rs2853669 of the TERT promoter as an attractive independent prognostic biomarker of disease progression in IDH wild-type GBM patients. RTL and TERT promoter mutational status were not correlated to survival regardless of MGMT methylation status.

Kerr-induced all-optical switching in a GaInP photonic crystal Fabry-Perot resonator.

We describe nonlinear properties of a GaInP photonic crystal Fabry-Perot resonator containing integrated reflectors. The device exhibits an extremely large static nonlinearity due to a thermal effect. Dynamical measurements were used to discriminate between the thermal and Kerr contributions to the nonlinearity. The high frequency nonlinear response is strictly due to the Kerr effect and the efficiency is similar to that obtained in self-phase modulation and four wave mixing experiments. The waveguide dispersion and the wavelength dependent integrated reflectors yield a series of transmission peaks with varying widths which determine the maximum speed at which the device can operate. Switching and wavelength conversion experiments with 92ps and 30ps wide pulses were demonstrated using pulse energies of a few pJ. The switching process is Kerr dominated with the fundamental response being essentially instantaneous so that the obtainable switching speed is strictly determined by the resonator structure.

Narrowband optical parametric gain in slow mode engineered GaInP photonic crystal waveguides.

We predict narrowband parametric amplification in dispersion-tailored photonic crystal waveguides made of gallium indium phosphide. We use a full-vectorial model including the dispersive nature both of the nonlinear response and of the propagation losses. An analytical formula for the gain is also derived.

Temporal gap solitons and all-optical control of group delay in line-defect waveguides.

We show that a model based on anticrossing between highly group velocity-mismatched gap-guided and index-guided modes describes gap soliton propagation in photonic crystal waveguides. Such nonlinear solutions can be exploited for exploring new regimes such as all-optical control of group velocity (dispersionless slow light) over a submillimeter length scale, and propagation beyond the linear modal cutoff. The results are validated by means of finite-difference time domain simulations.

Blue self-frequency shift of slow solitons and radiation locking in a line-defect waveguide.

We investigate experimentally resonant radiation processes driven by slow solitons in a dispersion-engineered photonic crystal waveguide in a regime virtually free of dissipative nonlinear processes (two-photon absorption and Raman scattering). Strong (30% energy conversion) Cherenkov-like radiation accompanied by the blue self-frequency shift of the soliton is observed close to the zero dispersion point, and is explained in terms of the soliton-radiation locking of the velocity.

Repair of Dental Restorations: A 10-year Retrospective Analysis of Clinical Data.

OBJECTIVES: This study collected and analyzed clinical data regarding the repair of dental restorations in patients treated in the clinics of a dental school over 10 years. METHODS AND MATERIALS: Data related to repair procedures for permanent tooth restorations were extracted from the digital dental records system and filtered according to year (January 1, 2008, to December 31, 2017), age (<30, 30-60, >60), tooth group, and dental surfaces. Data were analyzed with descriptive statistics in terms of the absolute and relative frequency, and chi-square tests (95% confidence) were used to compare the frequency of repairs between years, age, tooth, and dental surfaces. RESULTS: A total of 48,915 dental records were accessed by searching for general restorative procedures, of which 1,408 were repairs of dental restorations on permanent teeth. The number of repairs per year increased over the period assessed, and there was a significant increase in the years 2016 and 2017. Individuals aged between 30 and 60 years received the largest number of repairs, with significantly more repairs than the other groups. Regarding the tooth group and surface, the canines and the incisal and lingual surfaces received the least number of repairs. CONCLUSIONS: The number of repairs increased over the study period. When comparing frequencies between groups, those belonging to the 30- to 60-years of age group received more repairs; the least repaired surfaces were the lingual and the incisal.

Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children.

The function of CD4(+) T cells with regulatory activity (T(regs)) is the down-regulation of immune responses. This suppressive activity may limit the magnitude of effector responses, resulting in failure to control human immunodeficiency virus 1 (HIV-1) infection, but may also suppress chronic immune activation, a characteristic feature of HIV-1 disease. We evaluated the correlation between viral load, immune activation and T(regs) in HIV-1-infected children. Eighty-nine HIV-1-infected children (aged 6-14 years) were included in the study and analysed for HIV-1 plasmaviraemia, HIV-1 DNA load, CD4 and CD8 cell subsets. T(reg) cells [CD4(+)CD25(high)CD127(low) forkhead box P3 (FoxP3(high))] and CD8-activated T cells (CD8(+)CD38(+)) were determined by flow cytometry. Results showed that the number of activated CD8(+)CD38(+)T cells increased in relation to HIV-1 RNA plasmaviraemia (r = 0·403, P < 0·0001). The proportion of T(regs) also correlated positively with HIV-1 plasmaviraemia (r = 0·323, P = 0·002), but correlated inversely with CD4(+) cells (r = -0·312, P = 0·004), thus suggesting a selective expansion along with increased viraemia and CD4(+) depletion. Interestingly, a positive correlation was found between the levels of T(regs) and CD8(+)CD38(+)T cells (r = 0·305, P = 0·005), and the percentage of T(regs) tended to correlate with HIV-1 DNA load (r = 0·224, P = 0·062). Overall, these findings suggest that immune activation contributes to the expansion of T(reg) cells. In turn, the suppressive activity of T(regs) may impair effector responses against HIV-1, but appears to be ineffective in limiting immune activation.