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Introduction Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). Methods All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan-Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. Results Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. Conclusion In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs. Plain Language Summary People living with HIV (PLHIV) need lifelong treatment to prevent progression to AIDS. Standard HIV treatments use three different drugs in combination, but these can potentially cause unwanted side effects. Treatments using just two drugs have been developed. These aim to reduce side effects and treat HIV effectively. This study included 5664 participants in Spain who were split into two groups: 5047 participants switched from their old treatment to a three-drug regimen (3DR), and 617 participants switched to a two-drug regimen (2DR). The researchers measured how long it took for the participants to stop taking their treatment because it was not working, or it caused too many side effects. At the end of the study, more than 70% of participants in either group were still taking the same treatment. Of the 30% of participants who stopped treatment because it stopped working, those taking a 2DR stopped sooner than those taking a 3DR. This difference started to appear at about 18 months and got bigger until the study ended, which was 3 years after starting treatment. Participants taking a 2DR were twice as likely to stop treatment because it was not working than those taking a 3DR. There was no difference between the groups for how long it took for participants to stop their treatment because of side effects. These results show that for some PLHIV, the 2DR stopped working sooner than 3DR, without the benefit of fewer side effects.

Resumen Objetivo Determinar la proporcion de personas con infeccion por VIH o sida que se encontraban en seguimiento en la cohorte VACH en 2012 y que resultaron perdidas del mismo en 2013 y 2014, asi como establecer las caracteristicas sociodemograficas relacionadas con dicha perdida. Metodos Consideramos perdidos del seguimiento a los sujetos con menos de un registro de consulta por ano analizado. Construimos modelos de regresion logistica para la estimacion de las razones de ventajas (odds ratio [OR]) y sus intervalos de confianza del 95% (IC del 95%) de las variables relacionadas con la perdida de seguimiento. Resultados El porcentaje global de perdidas en seguimiento fue del 15,5% (IC del 95%: 14,9-16,1). Las variables asociadas con la perdida de seguimiento fueron no recibir tratamiento antirretroviral (TAR) (OR: 1,948; IC del 95: 1,651-2,298), ser inmigrante (OR: 1,746; IC del 95: 1,494-2,040), el consumo de farmacos por via intravenosa como mecanismo de transmision del VIH (OR: 1,498; IC del 95: 1,312-1,711), encontrarse en situacion de desempleo (OR: 1,331; IC del 95: 1,179-1,503), no tener pareja (OR: 1,948, IC del 95: 1,651-1,298), pertenecer a un estrato socioeconomico bajo (OR: 1,279; IC del 95: 1,143-1,431) y ser atendido en un hospital con menos de 1.000 pacientes en seguimiento (OR: 1,257; IC del 95%: 1,121-1,457), ademas de menor edad y menos tiempo de seguimiento en la cohorte. Conclusiones El 15,5% de los pacientes fueron perdidos del seguimiento en un periodo de 2 anos en la cohorte VACH. Ello se asocio a una serie de variables sociodemograficas y epidemiologicas, cuya identificacion puede ser util para disenar iniciativas focalizadas sobre las poblaciones mas susceptibles de abandonar los circuitos asistenciales y a orientar estrategias disenadas a la consecucion del objetivo 90-90-90.

Teràpia antiretroviral; Diagnòstic i gestió del VIH; Teràpia amb inhibidors de la proteasa Terapia antirretroviral; Diagnóstico y gestión del VIH; Terapia con inhibidores de la proteasa Antiretroviral therapy; HIV diagnosis and management; Protease inhibitor therapy Background Since 1996, the standard of care (SOC) therapy for HIV treatment has consisted of a backbone of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug combinations (2DC) has been considered for selected patients to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase strand transfer inhibitor (INSTI)-containing triple therapy (TT) to dolutegravir- (DTG) and/or boosted protease inhibitor (bPI)-based 2DC in a large Spanish cohort of HIV patients. Methods A retrospective analysis was performed using data from the VACH cohort, a prospective multicentre Spanish cohort of adult HIV patients. All treatment experienced patients initiating a TT of an INSTI combined with two NRTIs or a 2DC-containing DTG and/or a bPI between 01/01/2012 and 01/06/2017 were included. The unit of analysis was patient-regimens. The overall sample analysis was complemented with two sub-analyses. The first sub-analysis focused on patients treated with a backbone plus DTG compared to those treated with DTG+ one other antiretroviral. The second sub-analysis focused on patients with HIV RNA

Objectives The aim of the study was to investigate whether very low level viraemia (VLLV) (20-50 HIV-1 RNA copies/mL) was associated with increased risk of virological failure (VF) as compared with persistent full suppression (< 20 copies/mL). Methods From the VACH Cohort database, we selected those patients who started antiretroviral therapy (ART) after January 1997 and who achieved effective viral suppression [two consecutive viral loads (VLs) < 50 copies/mL] followed by full suppression (at least one VL < 20 copies/mL). We carried out survival analyses to investigate whether the occurrence of VLLV rather than maintaining full suppression at < 20 copies/mL was associated with virological failure (two consecutive VLs > 200 copies/mL or one VL > 200 copies/mL followed by a change of ART regimen, administrative censoring or loss to follow-up), adjusted for nadir CD4 cell count, sex, age, ethnicity, transmission group, type of ART and time on effective suppression at < 50 copies/mL. Results Of 21 480 patients who started ART, 13 674 (63.7%) achieved effective suppression at < 50 copies/mL, of whom 4289 (31.4%) further achieved full suppression at < 20 copies/mL after May 2009. A total of 2623 patients (61.1%) remained fully suppressed thereafter, while 1666 had one or more episodes of VL detection > 20 copies/mL (excluding virological failure). A total of 824 patients had VLLV after suppression at < 20 copies/mL. VLLV was not associated with virological failure as compared with persistent full suppression [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.44-1.00], independently of the number of blips recorded (from one to 18). Conclusions In our population of HIV-infected patients on ART who achieved viral suppression at < 20 copies/mL, the risk of virological failure was no different for patients who remained fully suppressed compared with those who experienced subsequent episodes of VLLV.

Introduction: Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC + pegylated interferon-alpha 2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. Methods: This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. Results: From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). Conclusions: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC + PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferonfree therapies are not available yet., Funded by Merck: BOC-HIV Study.Maria Martinez-Rebollar is funded by a grant Sara Borrell, CM13-00123, from Instituto de Salud Carlos III, Ministerio Economia y Competitividad. - Other authors declare no other conflict of interest.

Background and Objectives: The influence of the polymorphisms of the CX3CR1 chemokine receptor gene on the natural history of HIV-1 infection is controversial. This study aimed to determine whether functionally active CX3CR1 genetic variants are associated with long-term nonprogressive infection of > 15 years in HIV-1-infected Spanish patients. Patients and Methods: Two single-nucleotide polymorphisms, V249I (G > A) and T280M (C > T), of the CX3CR1 gene were assessed in 271 Spaniards. These included 60 HIV-1-infected patients who were long-term nonprogressors (LTNPs) of > 15 years, 109 HIV-1-infected patients who were usual progressors (UPs), and 102 control subjects. The CCR5Δ32 was also assessed. Genotyping was performed using polymerase chain reaction and automatic sequencing analysis methods on white cell DNA. Genotype and allele frequencies were compared by the χ 2 test and the Fisher exact test. Results: The frequencies of the 249I variant allele were 42% for LTNPs, 24.5% for UPs, and 35% for healthy controls; the differences between LTNPs and UPs were significant (odds ratio 0.46; 95% CI: 0.27 to 0.75; P = 0.0017). For 280M the distribution was 16% for LTNPs, 14% for UPs, and 17% for healthy controls (P = NS). The haplotype 249I280T was significantly more common in LTNPs than in UPs (P = 0.0007). These results persisted after excluding from the analysis the individuals carrying the CCR5Δ32. Conclusions: CX3CR1 249I variant allele is more frequent in Spanish HIV-1-infected LTNPs of > 15 years. This effect is independent of the presence of the CCR5Δ32 allele.

Objective Investigate the metabolic and mitochondrial effects of switching a highly active antiretroviral therapy (HAART) regimen with a high mitochondrial toxicity profile to a HAART with a theoretically low mitochondrial toxicity. Patients and Methods Six consecutive HAART-experienced patients receiving at least one dideoxy-nucleoside reverse transcriptase inhibitor (NRTI) switched to enfuvirtide plus tenofovir plus saquinavir/ritonavir (T20+TDF+SQV/r). Blood samples were collected at baseline, 12 and 24 weeks after the switch, and viral load (VL) and lymphocyte CD4+ T-cell count were determined. Metabolic parameters consisted of fasting serum triglycerides, cholesterol (total and fractions), glucose, insulin, C-peptide and lactate. Mitochondrial assessment consisted on mitochondrial DNA (mtDNA) quantification, COX-II mitochondrial protein expression rate, mitochondrial respiratory chain complex III and IV activities, and oxygen consumption in peripheral blood mononuclear cells. For baseline mitochondrial comparisons, we included six HIV-infected patients naive for ART. Results Switched patients exhibited a mean increase of 26 CD4+ T-cells/mm3 and a mean decrease of 1.1 log in VL ( P=NS for both). Lactate, lipids and glycaemia remained stable during the study; only insulin levels increased significantly ( PConclusion Switching a HAART-containing dideoxy-NRTI to T20+TDF+SQV/r minimally alters metabolic parameters and exerts beneficial effects on mitochondrial function at 24 weeks. Mitochondrial improvement should be considered as an additional advantage of this rescue therapy.

To investigate the effects of HIV infection on mitochondrial DNA (mtDNA) content and other mitochondrial parameters, we used peripheral blood mononuclear cells (PBMCs) from 25 asymptomatic antiretroviral-naive human immunodeficiency virus (HIV)-infected patients and from 25 healthy control subjects. HIV-infected patients had significant decreases in mtDNA content (decrease, 23%; P

Introduction : Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients’ well-being, assessed by several validated measures. Methods : Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. Results : Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load

Survey in 349 HIV infected subjects in 19 Spanish Hospitals in 2010-2011, to assess the reasons for antiretroviral treatment change. Simplification was the most frequent reason for change (37%), followed by toxicity (30%) and treatment failure (21%). There were statistically significant differences according to treatment line and transmission category. In conclusion, in many patients treatment is changed in order to obtain the benefits of a regimen easier to follow.

Objectives: Primary - evaluate the improvement in psychiatric symptoms attributable to changing the antiretroviral drug responsible for such symptoms to nevirapine (NVP). The tools used were a sleep test (the Pittsburgh Sleep Quality Index [PSQI]) and the Hospital Anxiety and Depression Scale (HADS). Secondary - determine the neuropsychiatric disorders and evaluate adherence to treatment and quality of life. Methods : Prospective, observational post-authorisation study that included HIV-1 patients from 36 Spanish hospitals who satisfied the following criteria: age over 18 years; change of antiretroviral treatment to NVP due to CNS side-effects; a PSQI score >5 (significant sleep disturbance); a HADS score ≥10 on the day of starting NVP treatment; and no psychoactive drug treatment initiated during the 6 weeks prior to starting treatment with NVP. Other data gathered from the patients included clinical and demographic details and administration of the Epworth somnolence scale, the Medical Outcomes Study-short form 30 items (MOS-SF-30) quality of life scale and the Simplified Medication Adherence Questionnaire (SMAQ). Evaluations were performed at baseline, 1 and 3 months after the change. Results : 129 patients were included (73.6% men; mean age, 43.2 ± 9.8 years; 36.5% homosexual, 30.2% heterosexual; 28.7% drug users; 38% AIDS; 33.3% co-infection). The drug changed was efavirenz in 89.9% of cases. The reason for the change was sleep disturbances in 75.2%, anxiety in 65.1%, other psychiatric disturbances in 38.7%, attention disturbances in 31%, and other reasons in 31%; a mean of 2.4 neuropsychiatric disturbances were detected in each patient. CD4 rose from 582 ± 261 to 619 ± 299 (non-significant difference). Only three patients had developed an HIV viral load at the end of the study. The differences produced by the change are shown in Table 1. 29 patients withdrew from the study, for the following reasons: 9 for NVP-related toxicity (7 cases of rash and 2 of hepatitis); 7 for loss to follow-up; 4 for voluntary withdrawal; 9 for other reasons. Discussion : The study shows that the change to NVP from a drug that is causing neuropsychiatric disturbances (principally, efavirenz) is effective in resolving those disturbances, with an improvement in all the parameters studied (quality of sleep, anxiety/depression and somnolence). This leads to better adherence and a better quality of life with no detriment to their immunological and virological control. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Pedrol E et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18347 http://www.jiasociety.org/index.php/jias/article/view/18347 | http://dx.doi.org/10.7448/IAS.15.6.18347

Background : Until the past decade, immune/viral failure was the main reason for antiretroviral treatment changes. After HAART generalization the management of antiretroviral treatment toxicities was the most prevalent reason for treatment modification. Today, with the advent of new more potent and less toxic drugs as well as more convenient combinations may have changed the situation. We aim to describe the main reasons that today leads to ART changes in HIV+ patients in Spain in the current clinical practice. Methods : Multicentre, national, cross-sectional epidemiological study. Eligible patients had to be HIV+, >18 years old and under current ART that was going to be changed by any reason. Patients did sign inform consent. The study consisted in a single visit (change of treatment) in which data on social and demographic characteristics, HIV disease and ARV treatment were collected. Results : 349 patients were included; mean age: 43.7±8.9 y, 70.5% male and 89.1% Caucasian. Main transmission categories were IVDU (36.4%) and heterosexual (36.4%). Mean time from HIV diagnosis was 11.3±7.6 y. 59.5% were CDC C category. Median CD4 nadir was: 155 cells/mm 3 and median CD4 at the time of switching was 467 cells/mm 3 . 64.1% had undetectable viral load (

Investigate the metabolic and mitochondrial effects of switching a highly active antiretroviral therapy (HAART) regimen with a high mitochondrial toxicity profile to a HAART with a theoretically low mitochondrial toxicity.Six consecutive HAART-experienced patients receiving at least one dideoxy-nucleoside reverse transcriptase inhibitor (NRTI) switched to enfuvirtide plus tenofovir plus saquinavir/ritonavir (T20+TDF+SQV/r). Blood samples were collected at baseline, 12 and 24 weeks after the switch, and viral load (VL) and lymphocyte CD4+ T-cell count were determined. Metabolic parameters consisted of fasting serum triglycerides, cholesterol (total and fractions), glucose, insulin, C-peptide and lactate. Mitochondrial assessment consisted on mitochondrial DNA (mtDNA) quantification, COX-II mitochondrial protein expression rate, mitochondrial respiratory chain complex III and IV activities, and oxygen consumption in peripheral blood mononuclear cells. For baseline mitochondrial comparisons, we included six HIV-infected patients naive for ART.Switched patients exhibited a mean increase of 26 CD4+ T-cells/mm3 and a mean decrease of 1.1 log in VL (P = NS for both). Lactate, lipids and glycaemia remained stable during the study; only insulin levels increased significantly (P0.05). Switched patients exhibited, at baseline, low mitochondrial measurements, being significant only for complex III and IV activities with respect to naive patients (P0.05 for both). MtDNA content did not rise significantly during the study. However, we observed increases in COX-II mitochondrial protein synthesis (124%, P0.05), complex III activity (127%, P0.05), complex IV activity (86%, P = 0.37) and oxygen consumption (194%, P0.05).Switching a HAART-containing dideoxy-NRTI to T20+TDF+SQV/r minimally alters metabolic parameters and exerts beneficial effects on mitochondrial function at 24 weeks. Mitochondrial improvement should be considered as an additional advantage of this rescue therapy.

To examine whether polymorphisms of the RANTES chemokine gene promoter are associated with long-term nonprogressive HIV-1 infection in white Spanish subjects, we performed a cross-sectional genetic association case-control study. Two-hundred sixty-seven white Spaniards were studied: 58 were HIV-1-infected long-term nonprogressors (LTNPs) of more than 16 years, 109 were HIV-1-infected usual progressors (UPs), and 100 were control subjects. Three RANTES single nucleotide polymorphisms (SNPs) at positions -28C>G, -109T>C, and -403G>A were assessed. The prevalence of the CCR5Delta 32 allele was also examined. Genotyping was performed using polymerase chain reaction and automatic sequencing analysis methods. Genotype and allele frequencies between the 3 groups were compared by the chi2 test and the Fisher exact test. The distribution of allelic variants of RANTES in controls, UPs, and LTNPs, respectively, was 3%, 2%, and 5% for -28G; 4%, 2%, and 2% for -109C; and 18%, 18%, and 18% for -403A (P = not significant). The differences were still nonsignificant when we exclusively analyzed individuals not carrying the CCR5Delta32 allele. We conclude that LTNP of more than 16 years is not associated with SNPs in the RANTES gene promoter in white Spanish HIV-1-infected subjects.

Background Information concerning lipid disturbances in HIV-infected women on antiretroviral therapy (ART) is scarce. The objective of the study is to describe the lipid profile in a large cohort of HIV-infected women on contemporary ART and analyse differences between regimes and patient's characteristics. Methods Observational, multicentre, cross-sectional study from the Spanish VACH Cohort. 922 women on stable ART without lipid-lowering treatment were included. Results Median age was 42 years, median CD4 lymphocyte count was 544 cells/mm3, and 85.6% presented undetectable HIV-1 viral load. Median total cholesterol (TC) was 189 mg/dL (interquartile range, IQR, 165-221), HDL cholesterol 53 mg/dL (IQR, 44-64), LDL cholesterol 108 mg/dL (IQR, 86-134), and triglycerides 116 mg/dL (IQR, 85-163). Mean accumulated time on ART was 116 months; 47.4% were on NNRTI-based regimes, 44.7% on PI, and 6.7% on only-NRTI therapy. 43.8% were also hepatitis C (HCV) coinfected. Patients on PI treatment presented higher TC/HDL ratio than those on NNRTI (p < 0.001). Significantly higher HDL values were observed in NNRTI-treated patients. HCV-coinfected patients presented lower TC/HDL ratio than the non HCV-coinfected. In multivariate analysis, factors independently associated with TC/HDL ratio were age, triglyceride levels and HCV co-infection. PI treatment presented a non-significant association with higher TC/HDL ratio. Conclusions In HIV-infected women, the NNRTI-based ART is associated with a better lipid profile than the PI-based. Factors unrelated to ART selection may also exert an independent, significant influence on lipids; in particular, age, and triglyceride levels are associated with an increased TC/HDL ratio while HCV co-infection is associated with a reduced TC/HDL ratio.

A strong inverse relationship between the plasma concentration of HDL-C and the incidence of coronary heart disease is widely accepted. Few interventions have succeeded to increase plasma HDL levels in HIV-infected pts. NVP has a favorable lipid profile, and clinical trials have suggested that it could have a differential effect on plasma HDL-C levels. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P79 Cite this article as: Rodriguez et al.: Switching to nevirapine (NVP) significantly increases high-density lipoprotein cholesterol (HDL-C) in treatment-experienced patients (NEVICOR study). Journal of the International AIDS Society 2010 13(Suppl 4):P79. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113085/

The most prevalent adverse event was diarrhoea in the SQV cohort (11%) and hypertrigliceridaemia in the FPV cohort (4%). Only four patients (2%) withdrew their treatment due to an adverse event. One patient (0.5%) with baseline mild renal impairment (GFR: 63 mL/min) withdrew his treatment due to a grade 1 GFR decrease. Conclusion In this cohort, concomitant use of TDF with SQV or FPV was associated with good tolerability and an adequate rate of viral effectiveness, suggesting these combinations are suitable as rescue therapy in highly treatment-experienced patients. from Ninth International Congress on Drug Therapy in HIV Infection Glasgow, UK. 9–13 November 2008

Purpose of the study Antiretroviral (ARV) toxicity, especially of nucleoside-analogues, together with HIV-infection have both been demonstrated to induce mitochondrial DNA (mtDNA) depletion and mitochondrial dysfunction. The contribution of each mechanism (either HIV or ARV) to the observed mitochondrial damage present in HIV-infected patients on highly active ARV treatment (HAART) is difficult to elucidate. HIV-induced mitochondrial lesion has been studied in HIV-infected but non-HAART-treated individuals, but ARV-related mitochondrial damage has been poorly explored in non-infected subjects. The aim of the present study is to assess in vivo mitochondrial toxicity of HAART without HIV-infection effects.

BackgroundSimplified antiretroviral regimens are needed to improve patient adherence and quality of life. The purpose of this study was to evaluate the efficacy and safety of a once-daily regimen consisting of didanosine (ddI), lamivudine (3TC) and nevirapine (NVP) for adult antiretroviral-naive patients with HIV-1 infection.MethodsThis was a prospective, one-arm, multicentre pilot study. Daily drug dosage was 250 or 400 mg didanosine, 300 mg lamivudine and 400 mg nevirapine. The primary outcome measure was the percentage of patients with a plasma HIV-RNA level ResultsSeventy patients were enrolled in the study. At baseline, mean plasma HIV-1 RNA was 5.10 log10copies/ml, and mean CD4 cell count was 262 cells/μl. At month 12, 67% (95% CI: 56–78) of patients maintained a viral load of 100 cells/μl than in those with a poorer immunological status at baseline, although the number of patients with CD4 counts ConclusionA once-daily combination of ddI, 3TC and NVP seems to be an effective, safe and easy-to-take regimen in antiretroviral-naive patients, at least in those who do not have severe immunodepression at baseline.