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Background Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. Objectives We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). Methods We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. Results After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78–1.04] or hospitalization (aOR 0.93; 95% CI, 0.60–1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or hospitalization (aOR 0.51; 95% CI, 0.15–1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10–1.07) compared with TAF/FTC. Conclusions TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.

Background Switching from boosted PIs to dolutegravir in virologically suppressed HIV-infected patients with high cardiovascular risk significantly decreased total cholesterol and other proatherogenic lipid fractions at 48 weeks. The impact of this strategy on subclinical cardiovascular disease is unknown. Methods NEAT022 is a European, multicentre, open-label, randomized, non-inferiority trial. HIV-infected adults aged >50 years or with a Framingham score >10% were eligible if plasma HIV RNA was 24 weeks on a boosted PI-based regimen. Patients were randomized 1:1 to switch from boosted PIs to dolutegravir or to continue on boosted PIs. Common carotid arteries intima–media thickness (CIMT) and pulse wave velocity (PWV) were measured following a standardized protocol in a subgroup of NEAT022 study participants at baseline and at Week 48. Results One hundred and fifty-six patients participated in the ultrasonography and arterial stiffness substudies, respectively. In each substudy, population characteristics did not differ between arms and matched those of the main study. At 48 weeks, patients who switched to dolutegravir had lower mean progression of both right (+4 versus +14.6 μm) and left (−6.1 versus +1.6 μm) CIMT and also a smaller increase in mean PWV (+0.18 versus +0.39 m/s) than patients continuing on boosted PIs, although differences were not statistically significant. CIMT trends were consistent across Framingham score, age and country. Inconsistent effects were seen in arterial stiffness. Conclusions Relative to continuing on boosted PIs, switching to dolutegravir in virologically suppressed patients with high cardiovascular risk showed consistent favourable although non-significant trends on CIMT progression at 48 weeks.

Objectives To describe the effectiveness and safety of an abacavir/lamivudine + rilpivirine regimen in naive HIV-1-infected patients, as there is a lack of data with this combination. Methods This was an observational, retrospective, multicentre study in eight Spanish hospitals. All antiretroviral-naive patients ≥18 years old and starting abacavir/lamivudine + rilpivirine were included. Effectiveness (ITT and on-treatment) and safety (adverse events and laboratory parameters) were assessed during follow-up. Values are expressed as n (%) or median (IQR). The Wilcoxon signed-rank test was used to compare baseline and 6 and 12 month values. Results Eighty-four patients were included [93% males, age = 36 (30-45) years]. Time since HIV diagnosis was 12 (4-35) months. Fifty-one per cent of patients had comorbidities. Baseline CD4+ was 425 (340-519) cells/mm3 and baseline HIV-RNA was 19 000 (9500-42 000) copies/mL. Median follow-up was 18 (9-22) months; 100% and 68% patients with at least 6 and 12 months, respectively. At 6 and 12 months effectiveness was 94% and 86% by ITT analysis and 96% and 97% by on-treatment analysis. At 12 months, there were significant increases in CD4+ (+262 cell/mm3) and HDL cholesterol (+4 mg/dL) and a significant decrease in the total cholesterol/HDL cholesterol ratio (-0.2). There were two (2.4%) virological failures (HIV-RNA 50-100 copies/mL); one patient later achieving virological suppression without changing the treatment. Six patients (7.1%) changed treatment due to reasons other than virological failure or side effects. One patient discontinued treatment due to gastrointestinal complaints attributed to abacavir/lamivudine. Conclusions Abacavir/lamivudine + rilpivirine was an effective and safe option in a selected group of HIV-1-infected treatment-naive patients.

Objectives To assess LDL subfraction phenotype and lipoprotein-associated phospholipase A2 (Lp-PLA2) in naive HIV-infected patients starting atazanavir/ritonavir or darunavir/ritonavir plus tenofovir/emtricitabine. Methods This was a substudy of a multicentre randomized study. Standard lipid parameters, LDL subfraction phenotype (by gradient gel electrophoresis) and Lp-PLA2 activity (by 2-thio-PAF) were measured at baseline and weeks 24 and 48. Multivariate regression analysis was performed. Results are expressed as the median (IQR). Results Eighty-six (atazanavir/ritonavir, n = 45; darunavir/ritonavir, n = 41) patients were included: age 36 (31–41) years; 89% men; CD4 319 (183–425) cells/mm3; and Framingham score 1% (0%–2%). No differences in demographics or lipid measurements were found at baseline. At week 48, a mild but significant increase in total cholesterol and HDL-cholesterol was observed in both arms, whereas LDL cholesterol increased only in the darunavir/ritonavir arm and triglycerides only in the atazanavir/ritonavir arm. The apolipoprotein A-I/apolipoprotein B ratio increased only in the atazanavir/ritonavir arm. At week 48, the LDL subfraction phenotype improved in the darunavir/ritonavir arm (increase in LDL particle size and in large LDL particles), whereas it worsened in the atazanavir/ritonavir arm (increase in small and dense LDL particles, shift to a greater prevalence of phenotype B); the worsening was related to the greater increase in triglycerides in the atazanavir/ritonavir arm. No changes in total Lp-PLA2 activity or relative distribution in LDL or HDL particles were found at week 48 in either arm. Conclusions In contrast with what occurred in the atazanavir/ritonavir arm, the LDL subfraction phenotype improved with darunavir/ritonavir at week 48. This difference was associated with a lower impact on plasma triglycerides with darunavir/ritonavir.

ObjectivesEx vivo analysis of mitochondrial function may reveal HIV progression and the impact of ART. We propose a mitochondrial and apoptotic in vitro model using Jurkat T cells incubated with plasma. The objectives of this study were to evaluate mitochondrial and apoptotic lesions in this model in relation to HIV progression, and to assess the effect of >1 year of standard non-thymidine-containing therapy.MethodsThis was a cross-sectional comparison among three age- and gender-matched groups (n = 19 × 3): healthy non-HIV-infected participants, HIV-infected long-term non-progressors (LTNPs) and standard antiretroviral-naive chronically infected patients [standard progressors (Sps)], longitudinally evaluated before (Sp1) and after (Sp2) >1 year of efavirenz + tenofovir + emtricitabine therapy. We analysed mitochondrial DNA content by RT–PCR, mitochondrial function by spectrophotometry, mitochondrial protein synthesis by western blot analysis, mitochondrial dynamics by western blot analysis (MFN2), apoptotic transition pore formation by western blot analysis (VDAC-1) and mitochondrial membrane potential and annexin V/propidium iodide fluorescence by flow cytometry.ResultsThere was a decreasing non-significant trend towards lower mitochondrial parameters for HIV-infected values with respect to uninfected control reference values. HIV progression (LTNP versus Sp1) was associated with decreased mitochondrial genetic, functional and translational parameters, which partially recovered after treatment intervention (Sp2). Mitochondrial fusion showed a trend to decrease non-significantly in Sp patients compared with LTNP patients, especially after therapy. All apoptotic parameters showed a trend to increase in Sp1 with respect to LTNP, followed by recovery in Sp2.ConclusionsWe proposed an in vitro model for mitochondrial and apoptotic assessment to test the effects of HIV infection and its therapy, resembling in vivo conditions. This model could be useful for clinical research purposes.

To evaluate the association of host genetics with changes in limb or trunk fat in a group of antiretroviral therapy (ART)-naive HIV-infected patients prospectively followed up according to the initiation and the type of ART. Fifty single nucleotide polymorphisms (SNPs) in 26 genes, associated with obesity, insulin resistance, lipid metabolism or lipodystrophy in previously published genetic studies, were assessed in ART-naive HIV-infected Caucasian patients divided into three groups: 24 (27%) did not start ART, 29 (32.6%) received zidovudine or stavudine and 36 (40.4%) received neither zidovudine nor stavudine in their initial regimen. Patients underwent body fat measurements (using dual-energy X-ray absorptiometry) at baseline and Month 12. A multivariate model using backward stepwise elimination was used to assess the influence of SNPs and baseline levels of non-genetic covariates on changes in limb or trunk fat. The baseline characteristics were: 73% men, 17% coinfected with hepatitis C virus and/or hepatitis B virus, median age 37 years, median CD4+ T cell count 228/mm(3), median HIV-RNA 5.2 log copies/mL, median plasma glucose 85 mg/dL, median plasma insulin 9.1 IU/mL, median limb fat 5.6 kg and median trunk fat 7.0 kg. There were no baseline differences among the three groups except for the CD4+ T cell count. The decrease in limb fat was greater in the no-ART group relative to the other two groups (PaEuroS < aEuroS0.05). The multivariate model showed associations of rs1801278 in IRS1 (PaEuroS=aEuroS0.029, ORaEuroS=aEuroS0.13), baseline viral load (PaEuroS=aEuroS0.006; ORaEuroS=aEuroS4.453) and baseline glucose levels (PaEuroS=aEuroS0.008, ORaEuroS=aEuroS0.926) with loss of limb fat, and rs2228671 in LDLR (PaEuroS=aEuroS0.012, ORaEuroS=aEuroS0.108), rs405509 in APOE (PaEuroS=aEuroS0.048, ORaEuroS=aEuroS0.205), baseline viral load (PaEuroS=aEuroS0.005, ORaEuroS=aEuroS0.186) and baseline CD4+ T cell count (PaEuroS=aEuroS0.01, ORaEuroS=aEuroS1.008) with gain of trunk fat. Specific polymorphisms in IRS1 (limb fat loss) and LDLR and APOE (trunk fat gain) were identified as independent markers of fat changes irrespective of the initiation of ART and the type of ART and deserve further validation.

BACKGROUND: Tenofovir has been associated with a decrease in bone mineral density (BMD). However, data on changes in BMD after discontinuing tenofovir are lacking. METHODS: We performed a two-centre randomized pilot study in virologically suppressed HIV-infected patients receiving tenofovir with osteopenia/osteoporosis (OsteoTDF study, ClinicalTrials.gov number NCT 01153217). Fifty-four patients were randomly assigned to switch from tenofovir to abacavir (n = 26) or to continue with tenofovir (n = 28). Changes in lumbar and total hip BMD were evaluated at Week 48 from baseline. RESULTS: Five patients discontinued the study (three from the tenofovir group and two from the abacavir group). No significant differences were detected between the groups at Week 48 (P = 0.229 for total hip and P = 0.312 for lumbar spine). However, hip BMD improved by 2.1% (95% CI -0.6 to 4.7) (P = 0.043) in the abacavir group and 0.7% (95% CI -0.9 to 2.4) (P = 0.372) in the tenofovir group. Lumbar spine BMD varied by -0.7% (95% CI -3.8 to 3.3) (P ≤ 0.001) in the abacavir group and -1.2% (95% CI -3.8 to 0.4) (P < 0.001) in the tenofovir group. CONCLUSIONS: Switching from tenofovir to abacavir led to a slight improvement in femoral BMD although no differences were detected between groups. Larger studies are necessary before firm recommendations can be made on the discontinuation of tenofovir in patients with a low BMD.

A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS.This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis.LBP rs2232582 T→C polymorphism was significantly associated with HALS (P = 0.01 and P = 0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (P = 0.009) and LBP (P 0.001) were significantly higher and sCD14 significantly lower (P 0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (P 0.001) and hepatitis C virus (P = 0.038), LBP levels by HALS (P 0.001) and sCD14 levels by age (P = 0.008), current HIV-1 viral load (P = 0.001) and protease inhibitor use (P = 0.018).HALS is associated with LBP polymorphism and with higher bacterial translocation.

OBJECTIVES Ritonavir-boosted protease inhibitor monotherapy (PIMT) is a maintenance strategy that prevents nucleoside reverse transcriptase inhibitor toxicity and reduces costs. Some trials compare PIMT with combined antiretroviral therapy, but restricted selection criteria and low sample size hamper data extrapolation to routine practice. Here, we analyse the effectiveness and safety of PIMT in clinical practice. METHODS This was a retrospective, observational, multicentre study. Adult HIV-1 patients receiving PIMT with darunavir or lopinavir were included. A Cox regression model identified independent predictors for virological failure (VF). RESULTS A total of 664 patients (435 on darunavir/ritonavir and 229 on lopinavir/ritonavir) [74% male, median age of 54 years, one-third with previous protease inhibitor VF, CD4 nadir 189 cells/mm(3) and 42% coinfected with hepatitis C virus (HCV)] were analysed. After a median follow-up of 16 months, 78% of patients (95% CI 74%-81%) remained free from therapeutic failure (TF) (change between ritonavir-boosted PIs not considered failure). At 12 months, by intention-to-treat analysis (change between ritonavir-boosted PIs equals failure), 83% of patients were free from TF (87% darunavir/ritonavir versus 77% lopinavir/ritonavir, P = 0.001). Regarding VF, 88% of patients maintained viral suppression at 12 months (93% darunavir/ritonavir versus 88% lopinavir/ritonavir, P = not significant). CD4 nadir

This study investigated strategies that may increase the yield of drug resistance testing prior to starting antiretroviral therapy (ART), and whether transmitted and polymorphic resistance-associated mutations (RAMs) correlated with virological outcomes.We carried out retrospective testing of baseline samples from patients entering the SENSE trial of first-line ART in Europe, Russia and Israel. Prior to randomization to etravirine or efavirenz plus two nucleos(t)ide reverse transcriptase inhibitors (NRTIs), plasma samples underwent routine Sanger sequencing of HIV-1 RT and protease ((plasma)SS) in order to exclude patients with transmitted RAMs. Retrospectively, Sanger sequencing was repeated with HIV-1 DNA from baseline peripheral blood mononuclear cells (PBMCSS); baseline plasma samples were retested by allele-specific PCR targeting seven RT RAMs (AS-PCR) and ultra-deep RT sequencing (UDS).By (plasma)SS, 16/193 (8.3%) patients showed ≥ 1 transmitted RAM affecting the NRTIs (10/193, 5.2%), non-nucleoside reverse transcriptase inhibitors (4/193, 2.1%) or protease inhibitors (2/193, 1.0%). No additional RAMs were detected by AS-PCR (n = 152) and UDS (n = 24); PBMCSS (n = 91) yielded two additional samples with one RAM each. Over 48 weeks, 4/79 (5.1%) patients on etravirine and 7/78 (9.0%) on efavirenz experienced virological failure; none had baseline RAMs. Conversely, 11/79 (13.9%) patients randomized to etravirine had one polymorphic RAM from the etravirine score in baseline plasma (V90I, V106I or E138A), without any impact on virological outcomes.The detection of resistance increased marginally with PBMC testing but did not increase with sensitive plasma testing. A careful consideration is required of the cost-effectiveness of different strategies for baseline HIV drug resistance testing.

OBJECTIVES To assess the most frequent resistance-associated mutations (RAMs) to lopinavir/ritonavir in a cohort of patients attended in daily practice. METHODS We retrospectively identified 195 multitreated subjects with virological failure. Patients were classified as follows: (i) 71 (36.4%) never received lopinavir/ritonavir (lopinavir/ritonavir naive); (ii) 75 (38.5%) had previously failed on lopinavir/ritonavir; and (iii) 49 (25.1%) were on lopinavir/ritonavir at failure. RAM patterns were assessed. Medians, IQRs, percentages, Kruskal-Wallis, χ(2) or Fisher's exact test, and multinomial logistic regression were used whenever appropriate. RESULTS L10I/F, K20R, L24I, L33F, M36I, M46I/L, I47V, G48V, F53L, I54V, A71V, G73S, V82A, I84V and L90M (all with P ≤ 0.037) were protease RAMs overexpressed in patients with lopinavir/ritonavir failure. L10I, M36I, M46I, I54V, L63P, A71V, V82A, I84V and L90M were the most common in lopinavir/ritonavir-naive patients. Other IAS-USA RAMs for lopinavir/ritonavir (L10R/V, K20M, V32I, I47A, I50V, I54L/A/M/T/S, A71T, L76V and V82F/T/S) were not associated with previous or current failure to lopinavir/ritonavir. Lopinavir/ritonavir failure was associated with the number of protease RAMs (OR = 1.146, 95% CI = 1.287, 1.626), higher exposure to protease inhibitors, and the presence of E44D, L33F, I54V and I84V. CONCLUSIONS In multitreated patients with previous or current lopinavir/ritonavir failure, some protease mutations are selected at significantly greater rates. L10I, M36I, I54V, L63P, A71V, V82A and L90M were found in >50% of cases. Thus, their presence should be expected when genotypic testing results are not available. The number of protease RAMs and higher prior exposures to protease inhibitors were significantly associated with lopinavir/ritonavir failure.

Background: Etravirine is approved for use in treatment-experienced patients at a dose of 200 mg twice daily. Efavirenz has been associated with greater increases in serum lipids compared with other non-nucleosides in randomized trials of first-line treatment. Methods:In this double-blind, placebo-controlled trial, 157 treatment-naive patients with HIV RNA 5000 copies/mL were randomized 1:1 to either 400 mg of etravirine once daily (n79) or 600 mg of efavirenz once daily (n78) plus two nucleoside analogues (either abacavir/lamivudine, zidovudine/lamivudine or tenofovir/emtricitabine) for 48 weeks. Lipids were measured under fasting conditions at baseline and all visits to Week 48. Clinicaltrials.gov identifier: NCT00903682. Results:Overall, the patients had a median baseline CD4 count of 302 cells/mm(3) (range 74722) and a median HIV RNA of 4.8 log(10) copies/mL (range 3.56.6). Both the non-nucleosides and the nucleoside analogues used caused changes in serum lipids. In the efavirenz arm, patients showed significantly larger increases in high-density lipoprotein (HDL) (0.15 mmol/L, P0.004), low-density lipoprotein (LDL) (0.35 mmol/L, P0.005), total cholesterol (0.61 mmol/L, P0.0001) and triglycerides (0.33 mmol/L, P0.03) at Week 48 compared with the etravirine arm. Across the two arms, patients taking abacavir/lamivudine showed greater increases in total cholesterol (0.47 mmol/L, P0.005) compared with patients taking tenofovir/emtricitabine. There were fewer grade 3/4 elevations in total cholesterol, LDL and triglycerides in the etravirine arm (2 patients, 1 patient and 0 patients, respectively) versus the efavirenz arm (8 patients, 6 patients and 2 patients, respectively). Conclusions:In the SENSE trial, first-line treatment with 400 mg of etravirine once daily plus two nucleoside analogues led to fewer grade 3 or 4 lipid elevations compared with efavirenz plus two nucleoside analogues.

Objectives: The effects of antiretroviral drugs on the response to pegylated interferon plus ribavirin remain uncertain. We evaluated whether antiretroviral drugs affected the response to pegylated interferon plus ribavirin in patients co-infected with HIV and hepatitis C virus (HCV). Methods: We conducted a retrospective analysis of two cohorts of HIV/HCV-co-infected patients treated with pegylated interferon plus ribavirin between 2001 and 2007 in Spain. The outcome measure was sustained virological response (SVR). Logistic regression models were used to test possible associations between non-response and pre-treatment characteristics, including accompanying antiretroviral drugs. Results: The study sample comprised 1701 patients: 63% were infected with HCV genotype (G) 1 or 4 and 88% were taking highly active antiretroviral therapy (HAART). Factors independently associated with increased odds of SVR were G2 or 3, HVC RNA,500000 IU/mL and CDC clinical category A or B. When we adjusted for these prognostic factors and dose of ribavirin/kg, the adjusted odds ratio (AOR) of SVR for patients without HAART was 1.31 [95% confidence interval (CI) 0.91-1.88; P=0.144]. Taking the backbone of tenofovir and lamivudine/emtricitabine as a reference, we found that, with the exception of regimens including zidovudine, the effect of other nucleoside reverse transcriptase inhibitor backbones had little effect on SVR. The AOR of SVR for zidovudine and lamivudine was 0.65 (95% CI 0.46-0.93, P=0.017). We carried out several sensitivity analyses, the results of which were consistent with the findings of the primary analysis. Conclusions: Our results suggest that, with the exception of regimens including zidovudine, accompanying antiretroviral drugs have little effect on the virological response to pegylated interferon plus ribavirin in HIV/HCV-co-infected patients. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Highly active antiretroviral therapy plays a central role in the development of lipodystrophy syndrome, which may affect up to 50% of patients depending on the diagnostic criteria used. Most protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs) are involved in body fat changes and associated metabolic disturbances. In contrast, non-NRTIs have not been directly related to the onset of this syndrome. One of the most widely used methods to evaluate body fat changes is dual-energy X-ray absorptiometry (DEXA), which can detect differences in the distribution of body fat in patients with and without lipodystrophy. New information from a randomized open-label clinical trial suggests that efavirenz could have greater potential for causing lipoatrophy than lopinavir+ritonavir. This paper examines the impact of efavirenz on adipose tissue and body fat composition in order to evaluate whether this drug plays a role in the development of lipodystrophy. We have focused on the evidence obtained from comparative randomized clinical trials that use an objective measurement of fat distribution, such as DEXA. We analysed available in vitro data and evidence from non-comparative clinical trials.

OBJECTIVES To determine the feasibility and outcomes of long-distance interactive expert advice for treatment-experienced patients. METHODS HIV-1-infected patients on failing highly active antiretroviral therapy (HAART) were prospectively submitted for consultation by treating physicians to an expert panel using a standard e-mail form including: resistance tests, antiretroviral history, adherence, CD4 counts, HIV-1-RNA levels and HCV/HBV co-infection. Conference calls (CCs) were scheduled monthly to discuss 10 new patients. RESULTS One hundred and fifteen patients were discussed (86% male; 45% intravenous drug users). The median length of HIV infection was 10 years and subjects were treated for a median of 8 years with a median of 5.25 previous HAART regimens. Ninety per cent were triple-class experienced [nucleoside reverse transcriptase inhibitors (NRTIs)/non-NRTIs (NNRTIs)/protease inhibitors (PIs)]. Median CD4 cell count was 298 cells/mm(3) and median viral load was 19 700 copies/mL. Overall, 60% had >or=5 reverse transcriptase mutations and 67% had >or=5 protease mutations, and most patients were NNRTI-resistant. Drugs more frequently recommended by experts were: lamivudine/emtricitabine > tenofovir > abacavir > zidovudine > didanosine > stavudine (NRTIs) and tipranavir > lopinavir > atazanavir > saquinavir (PIs). Enfuvirtide was recommended in 65% of cases. Concordance between recommended and prescribed regimens was 74.7%. Virtually all discordances were due to patient refusal of complex regimens. Outcomes at 24 weeks: HIV-1-RNA

Objectives To assess plasma steady-state pharmacokinetics (PK) of rifampicin, isoniazid, saquinavir and ritonavir in HIV and tuberculosis (TB) co-infected patients, and investigate potential interactions between TB drugs and protease inhibitors (PIs). Methods Open-label, single-arm, sequential PK study including 22 patients with HIV infection and TB. During the first 2 months, patients received rifampicin, isoniazid and pyrazinamide, with or without ethambutol (first PK study, n = 22). Then patients stopped pyrazinamide and ethambutol and started once-daily antiretroviral therapy (ART) with didanosine, lamivudine, ritonavir (200 mg) and saquinavir (1600 mg) (second PK study, n = 18). Patients stopped all TB drugs after 9 months continuing the same ART (third PK study, n = 15). Differences between TB drug parameters in the first and second PK studies, and between PI parameters in the second and third PK studies were used to assess interactions. Results Rifampicin and isoniazid pharmacokinetics did not change substantially with saquinavir and ritonavir. A significant 39.5%, 34.9% and 48.7% reduction in median saquinavir AUC(0-24), C(max) and C(trough), respectively, was seen with rifampicin and isoniazid. Ritonavir AUC(0-24), C(max) and C(trough) decreased 42.5%, 49.6% and 64.3%, respectively, with rifampicin and isoniazid. Conclusions There was a significant interaction between saquinavir, ritonavir and rifampicin, with reduction in median plasma concentrations of saquinavir and ritonavir. Saquinavir should be given with caution in patients receiving rifampicin. Twice-daily dosing or higher saquinavir doses in once-daily administration should be tested to obtain more appropriate plasma levels.