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Biomedical subjects

B Clotet

Publications and source records attributed to B Clotet.

At least 19 recordsLinked to original sources

Influence of the type of pegylated interferon on the onset of depressive and neuropsychiatric symptoms in HIV-HCV coinfected patients.

This is a prospective observational comparative 48-week study to assess the impact of the different types of Peg-IFN on depressive and neuropsychiatric symptoms during treatment in HIV-HCV coinfected patients. Thirty-one patients treated with Peg-IFN alpha-2b 1.5 microg/kg/w plus ribavirine (RBV) (Peg-IFN alpha-2b Group) and 32 patients receiving Peg-IFN alpha-2a 180 microg/w plus RBV (Peg-IFN alpha-2a Group) were included. Depressive and neuropsychiatric symptoms, quality of life and adherence were assessed. Fifteen subjects (23%) discontinued therapy (p = 0.3, between groups). Overall, 37 patients presented mild to moderate depressive symptoms, 9 moderate to severe and 3 severe, without differences between groups. Patients in Peg-IFN alpha-2b reported higher fatigue and dizziness at weeks 12 (p < 0.05) and 24 (p < 0.05), and irritability and memory loss at week 24 (p < 0.05) with respect to Peg-IFN alpha-2a Group. At week 12, role functioning, general health perception, vitality, emotional role, mental health and the summary areas of physical health and mental health were lower in Peg-IFN alpha-2b Group (p < 0.05). The same was observed in physical functioning (p = 0.05) and role functioning, general health perception, emotional role and mental health (p < 0.001) at week 24. Three months after finishing treatment, no patient had depressive or neuropsychiatric symptoms, and quality of life improved. Antiretroviral adherence was low but adherence to anti-HCV therapy remained high in both groups. According to our data, Peg-IFN alpha-2a and Peg-IFN alpha-2b exert a similar impact on the overall rate of depressive symptoms, although patients treated with Peg-IFN alpha-2a experience less fatigue and fewer neuropsychiatric symptoms and a lower impairment in their physical and mental quality of life.

Adult↗

Induction of interleukins IL-6 and IL-8 by siRNA.

The HIV-1 co-receptor CCR5 has been thought a relevant target for small interfering RNA (siRNA)-based therapeutics. However, recent findings suggest that siRNA can stimulate innate cytokine responses in mammals. All siRNA agents tested were able to down-regulate the expression of CCR5, albeit with different efficiency (51-74% down-regulation), block HIV-induced syncytia formation between HIV-1 BaL-infected and uninfected CD4(+) cells or block single-round HIV-1 infection as measured by a luciferase reporter assay (46-83% inhibition). Conversely, siRNA directed against CCR5 did not affect replication of a vesicular stomatitis virus (VSV) pseudotyped virus, suggesting that inhibition of HIV replication was specific to CCR5 down-regulation. However, two of four siRNA tested were able to induce the production of interleukin (IL) IL-6 (sixfold induction) and IL-8 (ninefold induction) but no interferon (IFN)-alpha, IFN-beta, IFN-gamma, tumour necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES, IL-1beta, IL-10 or IL-12p70 cytokine induction was noted. In the absence of detectable IFN-alpha, IL-6 or IL-8 may represent markers of non-specific effects triggered by siRNA.

Base Sequence↗

Treatment of monocytes with interleukin (IL)-12 plus IL-18 stimulates survival, differentiation and the production of CXC chemokine ligands (CXCL)8, CXCL9 and CXCL10.

During inflammation, interleukin (IL)-12 and IL-18 are produced by macrophages and other cell types such as neutrophils (IL-12), keratinocytes and damaged endothelial cells (IL-18). To explore the role of IL-12 and IL-18 in inflammatory innate immune responses we investigated their impact on human peripheral blood monocytes and mature bronchoalveolar lavage (BAL) macrophages. IL-12 and IL-18 together, but not alone, prevented spontaneous apoptosis of cultured monocytes, promoted monocyte clustering and subsequent differentiation into macrophages. These morphological changes were accompanied by increased secretion of CXC chemokine ligands (CXCL)9, CXCL10 (up to 100-fold, P < 0.001) and CXCL8 (up to 10-fold, P < 0.001) but not CCL3, CCL4 or CCL5. Mature macrophages (from BALs) expressed high basal levels of CXCL8, that were no modified upon stimulation with IL-12 and IL-18. In contrast, the basal production of CXCL9 and CXCL10 by BALs was increased by 10-fold (P < 0.001) in the presence of either IL-12 or IL-18 alone and by 50-fold in the presence of both cytokines. In conclusion, our results indicate a relevant role for IL-12 and IL-18 in the activation and resolution of inflammatory immune responses, by increasing the survival of monocytes and by inducing the production of chemokines. In particular, those that may regulate angiogenesis and promote the recruitment of monocytes, activated T cells (CXCL9 and CXCL10) and granulocytes (CXCL8).

Analysis of Variance↗

Analysis of genotypic and phenotypic clinical cut-off levels for ritonavir-boosted saquinavir.

There is a need for new, clinically relevant interpretation algorithms for genotypic and phenotypic resistance for ritonavir-boosted saquinavir (SQV/r) at the current approved dosage [1000/100 mg twice a day (bid)]. Clinical cut-off levels, which correlate baseline measures of resistance with HIV RNA responses in large cohorts or clinical trials, are the ideal reference for developing such algorithms. Cut-off levels previously developed for unboosted saquinavir may no longer apply, as the plasma drug levels with SQV/r are significantly higher and may be able partially to overcome protease inhibitor-resistant HIV. Clinical cut-off levels for SQV/r, assessed in several cohort studies and clinical trials, also suggest that multiple genotypic mutations are required for complete loss of virological response. For phenotypic analysis of resistance, saquinavir cut-off levels 10-11-fold higher than the wild-type IC50 have best distinguished responders from non-responders in cohort studies. Using Virtual Phenotype, a 12.3-fold upper cut-off level was determined from analysis of large cohort databases. These genotypic and phenotypic algorithms need to be validated in larger prospective studies.

Algorithms↗

Comparison of gastrointestinal tolerability and patient preference for treatment with the 625 mg and 250 mg nelfinavir tablet formulations.

OBJECTIVES: To compare gastrointestinal (GI) tolerability and patient preference for the new 625 mg formulation of nelfinavir (NFV) and the marketed 250 mg tablets (Viracept) in HIV-1-infected patients. METHODS: Virologically controlled patients (n=126) treated with a nelfinavir (NFV) 250 mg-containing regimen for > or =8 weeks completed a stool diary for 14 days to assess baseline bowel function. After switching to the NFV 625 mg formulation [1250 mg twice a day (bid)] for 28 days, patients continued their stool diaries and at study completion answered a questionnaire regarding formulation preferences. RESULTS: The incidence and mean weekly duration of GI upset over a 2-week period were lower with NFV 625 mg than with NFV 250 mg (79.8% vs. 84.9% of patients and 2.1 vs. 3.0 days, respectively). Fewer patients experienced moderate or severe diarrhoea with NFV 625 mg (6.5% vs. 11.1%), and the incidence of investigator-assessed diarrhoea also decreased with NFV 625 mg. Importantly, there was a significant improvement overall in the incidence of diarrhoea (any grade) when patients switched to NFV 625 mg [38 of 124 (31%) improving, 69 of 124 (56%) stable and 17 of 124 (14%) worsening on NFV 625 mg; P<0.01]. At study completion, most patients expressed a preference to continue treatment with NFV 625 mg [112 of 122 (91.8%); P<0.0001], with only one patient (0.8%) preferring to resume treatment with NFV 250 mg. The new formulation was well tolerated with no new safety concerns. CONCLUSIONS: The new NFV 625 mg formulation is better tolerated and preferred by patients switching from NFV 250 mg tablets. By reducing the daily pill count and improving GI tolerability, the NFV 625 mg formulation may enhance patient adherence to NFV-containing antiretroviral regimens and thus potentially improve virological outcomes.

CD4 Lymphocyte Count↗

Therapeutic immunization with an inactivated HIV-1 Immunogen plus antiretrovirals versus antiretroviral therapy alone in asymptomatic HIV-infected subjects.

To determine whether the addition of an inactivated-gp120-depleted HIV-1 Immunogen to antiretrovirals (ARTs) conferred a beneficial effect on delaying time to virologic failure relative to that obtained by ARTs alone, a phase II clinical trial was performed in 243 asymptomatic, ART naïve, HIV-1 seropositive adults. The Cox model showed that HIV-1 Immunogen treatment was associated with a 34% decrease in the risk of virologic failure (P = 0.056). When the analysis incorporated baseline HIV-RNA stratification the risk of virologic failure in the HIV-1 Immunogen Arm was significantly reduced a 37% compared to the IFA placebo Arm (P = 0.034). The data suggest that therapeutic immunization plus ARTs could influence virologic control.

AIDS Vaccines↗

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Anti-HIV Agents↗

Differential expression of the cytokine receptors for human interleukin (IL)-12 and IL-18 on lymphocytes of both CD45RA and CD45RO phenotype from tonsils, cord and adult peripheral blood.

The objective of this study was to demonstrate the variable expression of cytokine receptors on naive versus memory human CD4+ T cell subpopulations in tonsillar tissue, cord blood and adult blood. We prove that the receptors for both interleukin (IL)-12 and IL-18 are expressed exclusively on memory T cells. This observation was seen not only on the CD45RO+ memory T cells but also on a significant percentage of the CD45RA+, CD62L-, CD27- and CCR7- populations. Furthermore, CD45RA+ CD62L+, CD27+ or CCR7+ CD4+ T cells that expressed IL-12Rbeta1 and IL-18Ralpha did not express CD31, a marker for recent thymic emigrants. We reveal that cord blood lymphocytes do not express IL-12Rbeta1 whereas IL-18Ralpha expression was detected at low levels. Importantly, the IL-12Rbeta2 signalling chain, which is absent in all resting T cells, was up-regulated in both CD45RA+ and CD45RO+ T cells as a result of stimulation with anti-CD3 and anti-CD28 in vitro. This observed up-regulation was, however, restricted to 80% of the total CD4+ population. Finally, a very small proportion of the CD4+ CD45RO+ tonsillar T cells expressed the IL-12 and IL-18 receptors, thereby establishing the differential expression of these receptors between peripheral and tonsillar memory T cell subpopulations.

Adolescent↗

CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease.

The pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL) has been linked to an overexpression of the chemokine receptor CXCR4 and increased in vitro functional response to its natural ligand CXCL12 (SDF-1). The CXCR4/SDF-1 system appears to be important for tissue localization and increased survival of B-CLL cells. The aim of our study was to examine if CXCR4 expression and SDF-1 blood levels were correlated to clinical and pathological stage of B-CLL. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to determine CXCR4 expression and SDF-1 plasma levels, respectively, in a cohort of 51 patients diagnosed with B-CLL to correlate these measurements with several parameters that define the clinical stage of the disease. We confirmed that CXCR4 was consistently expressed on circulating B-CLL cells with a fluorescence intensity that was five-fold greater than in cells from healthy volunteers. There was a correlation between CXCR4 expression and leukocyte count ( r: 0.55, p<0.01), and CD19(+)/CD5(+ )cells ( r: 0.63, p<0.01). Interestingly, the group of B-CLL patients showed lower SDF-1 plasma levels compared to the control group. However, there was no correlation between CXCR4 or SDF-1 expression and the clinical stage of disease or the pattern of bone marrow infiltration. The results obtained suggest that other factors, and not only alteration in the SDF-1/CXCR4 chemokine system, must account for marrow infiltration of neoplastic cells observed in B-CLL and that CXCR4 could be involved in other features that exhibit malignant B cells, such as increased survival, rather than in their homing or migration to the bone marrow.

Adult↗

Time on antiretroviral therapy is a protective factor for liver fibrosis in HIV and hepatitis C virus (HCV) co-infected patients.

To assess the factors associated with liver fibrosis in human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients eligible for anti-HCV therapy, we performed an observational, single-centred, cross-sectional study of 180 HIV/HCV co-infected patients who underwent liver biopsy between May 1998 and November 2001. A total of 126 patients with a known date of HCV infection were evaluated. Liver fibrosis was defined as a Knodell stage of fibrosis 1-4. The mean age was 36.7 (3.8) years, 81% were male and had a mean age of 20.5 (3.8) years at HCV infection. Mean CD4 cell count and plasma HIV-1 RNA load at the time of biopsy were 552 cell/mm3 (239) and 2.5 log10 (0.9), respectively; 118 patients had been on antiretroviral therapy (ART) for a median of 45 months (Q1-Q3: 21-75) and 84 on protease inhibitor for a median of 12.0 months (Q1-Q3: 0-29.5); 55 had an AIDS event or a CD4 cell count nadir < 200 cells/mm3 prior to biopsy. Median histological activity index was 6 and 27% had a Knodell stage of fibrosis 0. On the multivariate analysis time on ART (OR for 6 months extra: 0.954, 95% CI: 0.859-0.994), CD4 cell count at the time of liver biopsy (OR for 100 cells/mL increase: 0.740, 95% CI: 0.670-0.905), age at HCV infection acquisition (OR for 5 years extra: 2.594, 95% CI: 1.326-5.133) and alcohol intake (> 50 g/day) (OR: 2.73, 95% CI: 1.108-6.731) were associated with liver fibrosis. Hence ART should be a priority in HIV/HCV co-infected patients eligible for anti-HCV treatment as it is a protective factor for liver fibrosis.

Adult↗

Changes in bloodstream infections in HIV-positive patients in a university hospital in Spain (1995-1997).

OBJECTIVES: The Hospital Universitario Germans Trias i Pujol is a 600-bed center serving 700,000 inhabitants including 1800 patients with HIV infection in Catalonia (Spain). Highly active antiretroviral therapy (HAART) became available at the end of 1996. Thus, the period 1995 1997 was considered appropriate for evaluating possible epidemiological changes in bloodstream infections (BSI) in HIV-infected patients. METHODS: All significant bloodstream infections, including mycobacteremia and fungemia, observed in HIV-positive patients from January, 1995 to December, 1997 have been included in the study. RESULTS: One hundred and eighty six cases were evaluated, in whom a decrease in BSI was observed (68 in 1995, 86 in 1996, 32 in 1997). Over time, we observed an improvement in the immunologic situation of the patients (1995: CD4 <50/mm3 73.8% vs 1997: CD4 <50/mm3 45.5% (P=0.05)). The source of BSI was known in 80.7% of the episodes. BSI secondary to catheter and respiratory infections prevailed in 1995, whereas an increase in bacteremias related to intravenous drug use, with or without endocarditis, was seen in 1997. The most frequent isolates were Mycobacterium avium intracellulare (23) (MAI), M. tuberculosis (20), Staphylococcus aureus (20), coagulase-negative staphylococci (16), Salmonella spp. (16) and Streptococcus pneumoniae (15). In 1997, a decrease was observed in the isolation of Gram-negatives and Mycobacterium spp. with S. aureus and enterococci prevailing. CONCLUSIONS: The prevalence of bloodstream infections in HIV-positive patients has decreased since the introduction of HAART and the immunologic state has improved. Furthermore there is a trend to a decrease or disappearance of microorganisms, such as Pseudomonas spp., Mycobacterium tuberculosis, MAI or fungi related to severe immunosuppression. Lastly, bacteremia caused by the active use of intravenous drugs remains stable with the highest percentage in Spain.

AIDS-Related Opportunistic Infections↗

Initiation, changes in use and effectiveness of highly active anti-retroviral therapy in a cohort of injecting drug users.

The prevalence of anti-retroviral therapy (ART) use over time and the incidence of AIDS in a cohort of HIV-seroconverting injecting drug users (IDUs) were assessed by means of a hospital-based study of IDUs with a well documented date of HIV infection. Use of ART and clinical endpoints were assessed by hospital records. Three calendar periods (before 1992, 1992-6 and 1997-2000) were defined as corresponding to modalities of ART available. Prevalence of ART usage in each calendar period, changes in medication and, hazard of AIDS in patients reaching the same duration of HIV infection at different calendar periods were analysed. In total, 132 IDUs with a median age of 23 years at seroconversion were followed up for 6.8 years (median) (range 0.2-15.7). At the end of the study, 58 patients (44%) had developed AIDS. Before the introduction of highly active anti-retroviral therapy (HAART) 12% of patients were on ART. Starting in 1997, an increasing proportion were receiving HAART with a prevalence of 39.5% by January 2000. Taking 1992-6 as the reference category the relative hazard of AIDS during 1997-2000 was 0.42 (95% CI, 0.1-1.1) (P = 0.09). A 40% penetration of HAART in a cohort of IDUs with known dates of seroconversion resulted in a 58 % reduction of the hazard of AIDS.

Acquired Immunodeficiency Syndrome↗

Response to antiretroviral therapy among patients exposed to three classes of antiretrovirals: results from the EuroSIDA study.

There is an increasing proportion of HIV-positive patients exposed to all licensed classes of antiretrovirals, and the response to salvage regimens may be poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four-hundred-and-thirteen patients, who had failed virologically two highly active antiretroviral therapy (HAART) regimens and experienced all three main drug classes, started a salvage regimen of at least three drugs, in which at least one new PI or NNRTI was included. Median viral load was 4.7 log copies/ml [Interquartile range (IQR) 4.2-5.2], CD4 lymphocyte count 150/mm3 (IQR 60-274/mm3) and follow-up 14 months. Of these patients, 283 (69%) subsequently experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral load < 500 copies/ml. Conversely, the CD4 count halved from the baseline value in 88 (21%), and 45 (11%) experienced a new AIDS-defining disease. In multivariable analyses, a 1 log viral load reduction was related to baseline viral load [relative hazard (RH) 1.27 per 1 log higher; P = 0.008], a previous viral load of less than 500 copies/ml (RH 1.69; P = 0.002), more recent initiation of the regimen (RH 1.36 per year more recent; P = 0.02), number of new drugs in the regimen (RH 1.20 per drug; P = 0.02), time since start of antiretroviral therapy (RH 0.94 per extra year; P = 0.035) and time spent on HAART with viral load > 1000 copies/ml (RH 0.96 per extra month; P = 0.0001). Analysis of factors associated with CD4 count decline and new AIDS disease also indicated improved outcomes in more recent times and a tendency for a better response in those starting more new drugs, but no relationship with the total number of drugs. Outcomes in people starting salvage regimens appear to depend on the number of new drugs started but not on the total number of drugs being used.

Acquired Immunodeficiency Syndrome↗

Viral load outcome of non-nucleoside reverse transcriptase inhibitor regimens for 2203 mainly antiretroviral-experienced patients.

OBJECTIVE: To assess the factors associated with virologic response to non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimens in a large clinic cohort. DESIGN: Inception cohort. SETTING: HIV clinics in Europe PATIENTS: We identified all patients in EuroSIDA who began a regimen including either nevirapine or efavirenz (not both) after July 1997 and for whom pre-therapy viral load and CD4 cell count were known. MAIN OUTCOME MEASURES: Virological failure. RESULTS: A total of 1325 patients initiated nevirapine and 878 efavirenz. Respectively, median start dates were October 1998 and May 1999. Other factors at baseline, including CD4 cell count, viral load, previous AIDS, previous antiretroviral drug use and make-up of the NNRTI-containing regimen were all approximately similar between the nevirapine and efavirenz groups. A total of 669 patients experienced virological failure during follow-up. In a Cox model, less protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs) previously used, higher CD4 nadir, lower viral load at baseline, a previous AIDS diagnosis and less NRTIs in the regimen were associated with lower risk of virological failure. The relative hazard of virological failure comparing those on efavirenz with those on nevirapine was 0.57 (95% confidence interval, 0.47-0.69; P < 0.0001). CONCLUSIONS: The difference in virologic outcome between those using nevirapine and efavirenz in this almost entirely drug-experienced population could reflect differences in effectiveness of the drugs in this setting but, despite the similarity between groups at baseline, bias cannot be excluded as an explanation. Replication of these findings in randomized trials and other cohort studies is required.

Adult↗

Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile.

BACKGROUND: Protease inhibitor-containing antiretroviral therapy for the treatment of HIV-1 infection is associated with elevated triglyceride and low-density lipoprotein (LDL)-cholesterol levels which may expose patients to an increased risk of coronary artery disease (CAD). We report the lipid and lipoprotein profiles of a representative subset of treatment-naive patients included in the Atlantic Study. This study compares patients treated with stavudine and didanosine plus the random addition of either the non-nucleoside reverse transcriptase inhibitor nevirapine (NVP), the protease inhibitor indinavir or the nucleoside reverse transcriptase inhibitor lamivudine. METHODS: Lipids and lipoproteins were quantified from prospectively collected and cryopreserved plasma samples obtained at weeks 0, 6 and 24. RESULTS: We observed a striking increase in high-density lipoprotein (HDL)-cholesterol (49%), apolipoprotein AI (19%), lipoprotein AI (38%) and HDL particle size (3%) in the NVP-treated patients (n = 34) at week 24. Much less pronounced changes in these parameters were seen to a similar extent both in patients receiving lamivudine (n = 39) and indinavir (n = 41). LDL-cholesterol also increased significantly both in the NVP and indinavir arms, but only in the NVP arm was this offset by a significant reduction (14%) in total over HDL-cholesterol ratio. Using a multivariate linear regression model, adjusting for CD4 cell count and plasma HIV RNA both at baseline and during treatment, randomization to the NVP-containing arm remained significant in explaining the observed changes in HDL-cholesterol and other HDL-related parameters. CONCLUSIONS: In HIV-1 infected patients treated with a regimen of stavudine, didanosine and NVP we found changes in lipids and lipoproteins which are associated with a sharp decrease in risk for CAD in other settings. If confirmed in larger studies, these findings both may influence the initial choice of therapy for HIV-1 infection, and might lead to novel approaches targeted at raising HDL-cholesterol for CAD prevention.

Adult↗

Stromal-cell-derived factor 1 prevents the emergence of the syncytium-inducing phenotype of HIV-1 in vivo.

In a correlative study, the mean plasma level of the chemokine stromal-cell-derived factor 1 (SDF-1) was lower in subjects with syncytium-inducing (SI) than in subjects with non-syncytium-inducing (NSI) HIV isolates, regardless of the CD4 cell count or when compared with HIV-negative individuals. Individuals with high SDF-1 had an 81% probability of having an NSI virus phenotype compared with individuals with lower SDF-1. Increased expression of SDF-1 may help explain why the more pathogenic SI HIV-1 variants do not appear in some individuals.

Chemokine CXCL12↗

Changes in the rate of genotypic resistance to antiretroviral drugs in Spain.

Genotypic resistance to antiretroviral drugs was examined in 684 individuals attending 18 outpatient clinics distributed across Spain in June 2000. Compared with similar surveys conducted before 1998, the prevalence of resistance to nucleosides has declined significantly among naive chronic HIV carriers. In contrast, resistance among pre-treated patients has increased; resistance to all three drug families having been recognized in nearly a quarter of patients.

Anti-HIV Agents↗

Psychological impact of structured treatment interruptions in patients with prolonged undetectable HIV-1 viral loads.

Structured treatment interruption strategies may help overcome problems of highly active antiretroviral therapy, but might also represent a cause of stress. We present data that indicate a psychological benefit from structured treatment interruption. Although some disturbances appear at the resumption of therapy, no definitive problems are found that preclude such therapeutic approaches from a psychological perspective. However, a close follow-up of patients during interruption periods is advisable to avoid difficulties reported at treatment resumption presenting a risk to patients' health.

Antiretroviral Therapy, Highly Active↗