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The risk of drug-drug interactions (DDIs) is elevated in aging people living with HIV (PLWH) because of highly prevalent age-related comorbidities leading to more comedications. To investigate the impact of aging on DDI magnitudes between comedications (amlodipine, atorvastatin, rosuvastatin) and boosted darunavir, we conducted a clinical trial in aging PLWH aged at least 55 years. DDI magnitudes were comparable with those reported in young individuals supporting that the clinical management of DDIs in aging PLWH can be similar.

Causes of morbidity and mortality of people living with HIV are changing with access to antiretroviral therapy and increased life expectancy. Age-related data on comorbidities and their impact on mortality in sub-Saharan Africa are scarce.This prospective analysis evaluated comorbidities, assessed by means of International Classification of Diseases and Related Health problems 10th revision codes and clinical variables, derived from data collected from the KilomberoUlanga antiretroviral cohort of people living with HIV in rural Tanzania.We calculated prevalences and incidences of comorbidities in patients enrolled from 2013 to 2017 and evaluated their association with a combined endpoint of death and loss to follow-up (LTFU) in various age groups (15-29, 30-49 and ≥50 years) using Cox regression analysis.Of 1622 patients [65% females, median age 38 years (interquartile range 31-46)], 11% were at least 50 years. During a median follow-up of 22.1 months (interquartile range 10.6-37.3), 48 (2.9%) patients died and 306 (18.9%) were LTFU. Anaemia was the most prevalent comorbidity (66.3%) irrespective of age and was associated with increased mortality/LTFU [hazard ratios 2.02 (95% confidence interval (CI) 1.57-2.60); P 0.001]. In patients aged at least 50 years, arterial hypertension was highly prevalent (43.8%), but not associated with mortality/LTFU [hazard ratios 1.04 (95% CI 0.56-1.93), P = 0.9]. Undernutrition ranged from 25.5% in the youngest to 29.1% in the oldest age group and contributed to mortality/LTFU [hazard ratios 2.24 (95% CI 1.65-3.04); P 0.001]. Prevalence of tuberculosis was 21.4% with hazard ratios of 2.54 (95% CI 1.72-3.75, P 0.001) for mortality/LTFU.We show that anaemia, arterial hypertension and undernutrition are the most relevant comorbidities with different age-associated frequencies and impact on death/LTFU in this population.

Background: Tenofovir is associated with reduced renal function, but it is not clear whether there is a greater decline in renal function when tenofovir is co-administered with a boosted protease inhibitor rather than with a nonnucleoside reverse transcriptase inhibitor (NNRTI). Methods: We calculated the estimated glomerular filtration rate (eGFR) for patients in the Swiss HIV Cohort Study. We estimated the difference in eGFR over time between first therapies containing tenofovir and either the NNRTI efavirenz or the protease inhibitors lopinavir (LPV/r) or atazanavir (ATV/r), both boosted with ritonavir. Results: Patients on a first therapy of tenofovir co-administered with efavirenz (n ¼484), LPV/r (n ¼269) and ATV/r (n ¼187) were followed for a median of 1.7, 1.2 and 1.3 years, respectively. Relative to tenofovir and efavirenz, the estimated difference in eGFR for tenofovir and LPV/r was � 2.6ml/min per 1.73m 2 [95% confidence interval (CI) � 7.3 to 2.2) during the first 6 months of therapy, then followed by a difference of 0.0ml/min per 1.73m 2 (95% CI � 1.1 to 1.1) for each additional 6 months of therapy. Relative to tenofovir and efavirenz, the estimated difference in eGFR fortenofovirandATV/r was � 7.6ml/min per 1.73m 2 (95% CI � 11.8to � 3.4) duringthe first 6 months of therapy, then followed by a difference of � 0.5ml/min per 1.73m 2 (95% CI � 1.6 to 0.7) for each additional 6 months of therapy. Conclusion: Tenofovir with either boosted protease inhibitor leads to a greater initial decline in eGFR than tenofovir with efavirenz; this decline may be worse with ATV/r than with LPV/r. 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2012, 26:567‐575

Objective: To determine the effects of cognitive–behavioral stress management (CBSM) training on clinical and psychosocial markers in HIV-infected persons. Methods: A randomized controlled trial in four HIV outpatient clinics of 104 HIVinfected persons taking combination antiretroviral therapy (cART), measuring HIV-1 surrogate markers, adherence to therapy and well-being 12 months after 12 group sessions of 2 h CBSM training. Results: Intent-to-treat analyses showed no effects on HIV-1 surrogate markers in the CBSM group compared with the control group: HIV-1 RNA < 50 copies/ml in 81.1% [95% confidence interval (CI), 68.0–90.6] and 74.5% (95% CI, 60.4–85.7), respectively (P ¼ 0.34), and mean CD4 cell change from baseline of 53.0 cells/ml (95% CI, 4.1– 101.8) and 15.5 cells/ml (95% CI, � 34.3 to 65.4), respectively (P ¼ 0.29). Self-reported adherence to therapy did not differ between groups at baseline (P ¼ 0.53) or at 12 month’s post-intervention (P ¼ 0.47). Significant benefits of CBSM over no intervention were observed in mean change of quality of life scores: physical health 2.9 (95% CI, 0.7–5.1) and � 0.2 (95% CI, � 2.1 to 1.8), respectively (P ¼ 0.05); mental health 4.8 (95% CI, 1.8–7.3) and � 0.5 (95% CI, � 3.3 to 2.2) (P ¼ 0.02); anxiety � 2.1 (95% CI, � 3.6 to � 1.0) and 0.3 (95% CI, � 0.7 to 1.4), respectively (P ¼ 0.002); and depression � 2.1 (95% CI, � 3.2 to � 0.9) and 0.02 (95% CI, � 1.0 to 1.1), respectively (P ¼ 0.001). Alleviation of depression and anxiety symptoms were most pronounced among participants with high psychological distress at baseline. Conclusion: CBSM training of HIV-infected persons taking on cART does not improve clinical outcome but has lasting effects on quality of life and psychological well-being. 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2008, 22:767–775

OBJECTIVE Zidovudine-containing antiretroviral therapy has been associated with a lower rise in absolute CD4 cell counts in several randomized trials. We examined the predictive factors for this phenomenon and assessed its impact on clinical progression during treatment in a large patient cohort. DESIGN An analysis of data from the Swiss HIV Cohort Study. METHODS All 2177 treatment-naive adults who began potent antiretroviral therapy (ART) between September 1995 and September 2004 were included. Exclusion criteria were previous ART and treatment duration of less than 3 months. Follow-up was censored in the case of a treatment switch or stop. RESULTS A total of 1312 patients initiated zidovudine-containing ART and 865 started ART without zidovudine. Except for slightly higher absolute CD4 cell counts in the zidovudine group, prognostic characteristics at baseline and viral suppression during treatment did not differ. During an observation time of 2343 and 1486 patient-years, the CD4 cell count increased by a median of 221 versus 286 cells/microl at 2 years and 290 versus 379 cells/microl at 4 years in the zidovudine versus no zidovudine group; however, the rise in the percentage of CD4 cells was similar in both groups. The zidovudine group had a significantly slower rise in total lymphocytes and haemoglobin. In multivariable Cox models, the hazard for new HIV-associated clinical events was not affected by zidovudine-containing ART. CONCLUSION Over 4 years, zidovudine led to a smaller increase in absolute, but not percentage, CD4 cell counts. The effect can be explained as a slower rise in total lymphocytes and has no impact on clinical efficacy.

Design: Mortality within the Swiss HIV Cohort Study for the years 1990-2001 was compared with the mortality of the general Swiss population. Methods: Standardized mortality ratios (SMR) and life tables were calculated for strata defined by combinations of gender and HIV transmission group. The effect of dropouts was investigated with a sensitivity analysis and by analysing CD4 cell counts before dropout. Results: During the study period 10 977 individuals had at least one cohort visit with a median observation time of 46 months. A total of 3630 patients died and 2290 dropped out. SMR decreased from 79.3 [95% confidence interval (CI), 77.2-81.51 before the introduction of highly active antiretroviral treatment (HAART) in 1996 to 15.3 (95% Cl, 14.2-16.4) thereafter. For persons who acquired HIV infection by injecting drug use (IDUs), the SMR decreased from 98.2 (95% Cl, 94.9-103.5) to 40.9 (95% Cl, 37.0-44.8) after 1996; for all other HIV transmission groups the SMR decreased from 69.2 (95% Cl, 66.9-71.6) to 9.4 (95% Cl, 8.5-10.4). Thus, IDUs had significantly lower survival in comparison with other patient groups after 1996. Patients who had started HAART during the time period in which this treatment was available, had even lower SMRs. Conclusions: Although overall survival has improved considerably since the introduction of HAART, cohort life expectancy remains below that of the Swiss population. We noted, however, substantial differences in mortality among subgroups, and the results indicate that the additional risk related to injection drug use before 19911 had been masked by HIV-associated mortality.

OBJECTIVE: Pancreatic disorders in HIV-positive patients are frequent. CFTR and SPINK-1 mutations have been reported to increase the risk of pancreatitis, but no data are available in HIV-positive patients. This study will evaluate the frequency of CFTR mutations and SPINK-1 polymorphisms in HIV-positive patients with clinical pancreatitis or asymptomatic elevation of serum pancreatic enzymes. METHOD: Cases (patients with hyperamylasemia) were identified during a toxicity study conducted in August 1999 among 1152 participants of the Swiss HIV Cohort Study. We designed a case-control study in which each case was matched one to one to an HIV-infected control according to sex, age, CD4 cell count, viraemia and medication use. CFTR mutations and SPINK-1 polymorphisms were studied using polymerase chain reaction techniques. RESULTS: Fifty-one HIV-positive patients with hyperamylasemia were detected among 1152 participants in the toxicity study (4.4%). There were 13 carriers of CFTR and SPINK-1 mutations (12.7%). Amylase levels were 316 +/- 130 U/l for the group with mutations, and 135 +/- 18 U/l for non-carriers (P = 0.79). However, among patients with hyperamylasemia, those with CFTR or SPINK-1 mutations had 648 +/- 216 U/l amylase levels compared with 232 +/- 28 U/l for those without (P = 0.025). Ten patients had acute pancreatitis, four of whom had CFTR mutations or SPINK-1 polymorphisms (40%) compared with seven of the control patients (14%) (P = 0.01). CONCLUSION: CFTR mutations and SPINK-1 polymorphisms are frequent among HIV-positive patients suffering from acute pancreatitis. These mutations may increase the susceptibility to pancreatitis when exposed to environmental risk factors.

Low-level viral rebound (LLVR) was identified in 704 of 2055 patients on effective antiretroviral treatment. It was followed by a value of 50 copies/ml, a 'blip', in 490 patients, whereas two consecutive values between 51 and 500 copies/ml, a 'bump', were observed in 155. Hazard ratios of viral failure were 2.01 for blips and 5.80 for bumps. LLVR is frequent and generally resolves spontaneously, but is associated with an increased risk of viral failure.

A single-nucleotide polymorphism (3'322C/G) was identified in the gene encoding a key cholesterol/triglyceride regulator, sterol-regulatory element-binding protein 1c (SREBP-1c). Although it did not alter the amino acid sequence, SREBP-1c-3'322C/G was predictive of highly active antiretroviral therapy-related hyperlipoproteinaemia. Increases in cholesterol were less frequently associated with homozygous SREBP-1c-3'322G (genotype 22) than with heterozygous/homozygous SREBP-1c-3'322C (genotypes 11/12) and correlated with leptin and insulin increases, particularly in genotype 11/12 carriers. A functional mutation linked to SREBP-1c-3'322C/G or messenger RNA conformation differences may explain our findings.

To evaluate the efficacy of isoniazid for the prevention of tuberculosis in tuberculin skin test-positive and negative individuals with HIV infection.Meta-analysis of randomized controlled trials.Seven trials from Mexico, Haiti, the United States, Zambia, Uganda and Kenya.Individuals free from tuberculosis, 2367 persons in the intervention and 2162 in the control groups.Comparison of isoniazid with placebo or no prophylaxis.A systematic search of the literature was carried out from 1985 to October 1997 for randomized controlled trials of isoniazid prophylaxis in HIV-infected persons. Two reviewers evaluated the relevance of each candidate study and the validity of eligible trials. Studies were pooled using a random effect model, conducting secondary analyses for tuberculin skin test-positive and negative persons.Mean follow-up in trials varied between 0.4 and 3.2 years. Pooling all seven trials, a risk ratio was found for persons treated with isoniazid for developing tuberculosis of 0.58 [95% confidence interval (CI), 0.43-0.80] and 0.94 (95% CI, 0.83-1.07) for death. In groups of tuberculin skin test-positive and negative persons, the risk ratio of tuberculosis was 0.40 (95% CI, 0.24-0.65) and 0.84 (95% CI, 0.54-1.30), respectively, and the difference in the effectiveness of isoniazid versus placebo between these groups was statistically significant (P = 0.03, for the difference of summary estimates). Consistency of results was found across trials (P0.10, heterogeneity value) for all comparisons.Prophylaxis with isoniazid reduces the risk of tuberculosis in persons with HIV infection. The effect is restricted to tuberculin skin test-positive persons.