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Current international targets aim for 90% of people diagnosed with HIV to be on antiretroviral treatment (ART). This paper aims to identify sociodemographic and attitudinal factors associated with ART non-use over time in three sa...
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Current international targets aim for 90% of people diagnosed with HIV to be on antiretroviral treatment (ART). This paper aims to identify sociodemographic and attitudinal factors associated with ART non-use over time in three samples of Australian people living with HIV (PLHIV). Data for this paper were derived from an Australian cross-sectional survey of PLHIV that was repeated at three different time points: 1997, 2003, and 2012. There were approximately 1000 respondents to each survey (n = 3042 in total). The survey included approximately 250 items related broadly to health and well-being, ART use, and attitudes towards ART use. Univariate and multivariate logistic regression analyses were used. While the proportion of participants using ART increased between 1997 and 2012 (78.8-87.6%, p<.001), there was a decrease between 1997 and 2003 to 70.6% (p<.001). Factors linked to ART non-use remained steady over those 15 years. In all cohorts, people less likely to be using ART were younger and had a more recent diagnosis of HIV. In 2003 and 2012, people in full-time employment were less likely to be using ART, while those whose main source of income was a pension or social security were more likely to be using ART. Multivariate models showed that, at each time point, a belief in the health benefits of delayed ART uptake was associated with non-use. These findings suggest that there may be barriers to ART uptake that have persisted over time despite changes to clinical guidelines that now encourage early uptake.
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Alternative modes of antiretroviral administration are sought for people with impaired intestinal passage and/or absorption. We present a case of late HIV diagnosis (CD4+ count 160 cells/mu L) with gastric outlet obstruction due t...
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Alternative modes of antiretroviral administration are sought for people with impaired intestinal passage and/or absorption. We present a case of late HIV diagnosis (CD4+ count 160 cells/mu L) with gastric outlet obstruction due to stomach adenocarcinoma. Co-morbidities included oesophageal candidiasis, Helicobacter pylori-positive duodenal ulcers and cytomegalovirus duodenitis. The gastric outlet obstruction required total parenteral nutrition and parenteral medication during four weeks of diagnostic work-up leading to pyloric resection. Crushed dolutegravir, abacavir and lamivudine were administered during this time in the evening via nasogastric tube, which was kept clamped overnight. The tube was unclamped in the morning and stomach content was drained during the daytime. This mode of administration resulted in rapid and sustained viral load suppression (from 300,000 to 115 copies per mL in 28 days, 81 copies/mL after 42 days of treatment and less than 40 copies/mL thereafter). Therapeutic drug monitoring confirmed sufficient antiretroviral plasma levels during this mode of administration. The absorption of crushed dolutegravir, abacavir and lamivudine in the stomach may be considered in people with questionable gastrointestinal passage or impaired gastric emptying to achieve viral load suppression.
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Objectives: We investigated the vitamin D status of patients receiving frequently used types of combination antiretroviral therapy (cART), including boosted protease inhibitor (PI) monotherapy. Methods: For this cross-sectional st...
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Objectives: We investigated the vitamin D status of patients receiving frequently used types of combination antiretroviral therapy (cART), including boosted protease inhibitor (PI) monotherapy. Methods: For this cross-sectional study, out of 450 HIV-infected patients followed in the Hospital Severo Ochoa (Madrid, Spain), we selected 352 patients for whom vitamin D levels had been measured (January 2009 to December 2010). We collected the following data: demographics, cART duration, main cART regimen, viral load (VL), CD4 cell count, and concentrations of 25(OH)-vitamin D [25(OH)-D], parathyroid hormone (PTH), albumin and calcium. Vitamin D status cut-off points were: (1) deficiency (vitDd): 25(OH)-D <20ng/mL; (2) insufficiency (vitDi): 25(OH)-D from 20 to 29.99ng/mL; and (3) optimal (vitDo): 25(OH)-D ≥30ng/mL. Results: The percentages of patients with vitDd, vitDi and vitDo were 44, 27.6 and 28.5%, respectively. Twenty-nine out of 30 (96.7%) Black patients had vitDd or vitDi, vs. 71.6% in the global sample (P<0.001). Former injecting drug users (IDUs) had a higher prevalence of vitDo (P<0.001) than patients in other transmission categories. Among patients with vitDd, vitDi and vitDo, the proportions of patients with a VL ≤ 50 HIV-1 RNA copies/mL were 77.4, 68 and 91%, respectively (P<0.0001). Of the cART regimens, only boosted PI monotherapy was associated with significant differences in vitamin D levels (P=0.039). Multivariate logistic regression analysis showed an increased risk of vitDi or vitDd associated with the following variables: Black vs. Caucasian ethnicity [odds ratio (OR) 10.6; 95% confidence interval (CI) 1.2-94; P=0.033]; heterosexual (OR 2.37; 95% CI 1.13-4.93; P=0.022) or men who have sex with men (MSM) (OR 3.25; 95% CI 1.25-8.50; P=0.016) transmission category vs. former IDU; and VL >50 copies/mL (OR 2.56; 95% CI 1.10-7.25; P=0.040). A lower risk of vitamin D insufficiency or deficiency was found in patients on boosted PI monotherapy vs. no treatment (OR 0.08; 95% CI 0.01-0.6; P=0.018). Conclusions: Our data show an increased risk of vitamin D deficiency or insufficiency in patients with detectable VL and a Black ethnic background. Among cART regimens, boosted PI monotherapy was associated with a lower risk of vitamin D deficiency or insufficiency. The more favourable vitamin D status in former IDUs was probably attributable to a higher frequency of outdoor jobs in this group of patients.
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Decisions regarding whether to start combination antiretroviral therapy (cART) during primary infection and when to initiate treatment during chronic infection continue to evolve. Although current data suggest that there may be a ...
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Decisions regarding whether to start combination antiretroviral therapy (cART) during primary infection and when to initiate treatment during chronic infection continue to evolve. Although current data suggest that there may be a benefit to therapy during primary infection, results are inconclusive. Once begun, treatment probably should be continued indefinitely, since its potential advantages disappear over time if treatment is stopped. Recent studies suggest that cART may be useful at higher CD4 cell count thresholds than are currently recommended in several guidelines. Several regimens are acceptable as initial therapy, with tenofovir/emtricitabine/efavirenz favored by many because of potency and ease of administration. Other favored regimens include combinations of 2 nucleoside (or nucleotide) reverse-transcriptase inhibitors and a ritonavir-boosted protease inhibitor. Some new antiretroviral drugs under study, particularly integrase inhibitors, may prove useful in treatment-naive patients.
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Background. Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). Methods. Sixteen cohorts from Europe a...
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Background. Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). Methods. Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART. Results. A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0-1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2-52.7] during the first year of ART and 9.1 [95% CI, 5.8-14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. Conclusions. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management.
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There is limited information regarding the outcome of infants treated with highly active antiretroviral therapy (HAART) in middle- and low-income countries. The mean/median age of children enrolled on HAART in these countries is g...
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There is limited information regarding the outcome of infants treated with highly active antiretroviral therapy (HAART) in middle- and low-income countries. The mean/median age of children enrolled on HAART in these countries is generally high; however, it is acknowledged that untreated HIV-infected children under 2 years of age, including infected infants, are an extremely vulnerable group. This article assessed the findings of a recently published paper describing the outcome of 63 infants randomized to commence immediate or deferred HAART in a resource-poor setting and documented favorable short-term outcome in both groups, with correspondingly high adherence rates. The recent change in global treatment guidelines, recommending that all HIV-infected infants should be commenced on HAART soon after diagnosis, irrespective of their clinical status and/or immunological severity, is discussed in relation to the key findings of the article.
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A 42-year-old Thai man was administered the combination drugs liponavir/ritonavir and abacavir/lamivudine. On day 3 he was admitted and his electrocardiogram demonstrated sinus arrest with junctional escape rhythm with a rate of 4...
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A 42-year-old Thai man was administered the combination drugs liponavir/ritonavir and abacavir/lamivudine. On day 3 he was admitted and his electrocardiogram demonstrated sinus arrest with junctional escape rhythm with a rate of 42 min-1. Three days after stopping the medication he reverted to normal sinus rhythm. A 55-year-old Caucasian man was admitted to hospital with triple vessel disease. He had a permanent pace maker inserted 4 years previously for Mobitz type II AV block detected on stress electrocardiogram, which developed 1 month after initiation of lopinavir/ritonavir. These two cases highlight the importance of considering lopinavir/ritonavir induced arrhythmias when dealing with HIV-positive individuals.
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Objectives Integrase resistance has not been reported with co-formulated dolutegravir/lamivudine in clinical trials or real-life cohorts. We aim to report, to the best of our knowledge, the first case of selection of the key integ...
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Objectives Integrase resistance has not been reported with co-formulated dolutegravir/lamivudine in clinical trials or real-life cohorts. We aim to report, to the best of our knowledge, the first case of selection of the key integrase mutation R263K in a subject treated with this regimen started as a switch strategy with undetectable plasma HIV-1 viraemia. Methods Clinical case report. Results A patient with long-term suppressed HIV-1 viraemia (<50 copies/mL) with no known risk factors for virological failure and never exposed previously to an integrase inhibitor developed virological failure (consecutive plasma HIV-1 RNA 149 and 272 copies/mL) with 322 CD4 cells/mm(3) despite good treatment adherence. He was receiving the anticonvulsant clobazam, considered to have a potential weak interaction with dolutegravir, unlikely to require a dose adjustment. Plasma HIV-1 genotypic deep sequencing (Vela System) revealed the emergence of R263K (79.6%) and S230N (99.4%) mutations in the integrase region (intermediate resistance to dolutegravir, score = 30 Stanford HIVDB 9.0). The reverse transcriptase and protease regions could not be amplified due to low viral loads. PBMC DNA deep sequencing performed some months later revealed mutations M184I (14.29%) and M230I (6.25%) in the reverse transcriptase and G163R (9.77%) and S230N (98.8%) in the integrase. R263K was only found at extremely low levels (0.07%). Conclusions This case illustrates that integrase resistance can emerge in patients treated with co-formulated dolutegravir/lamivudine and raises awareness of the need to carefully consider and monitor drug-drug interactions, even when regarded as having a low potential, in subjects treated with dolutegravir/lamivudine.
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Purpose of review As the evidence for two-drug regimens (2DR) for HIV treatment accumulates and 2DR start to enter consensus guidelines, this review covers the history, rationale and current evidence for 2DR in first-line and swit...
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Purpose of review As the evidence for two-drug regimens (2DR) for HIV treatment accumulates and 2DR start to enter consensus guidelines, this review covers the history, rationale and current evidence for 2DR in first-line and switch settings. Recent findings Until recently, most evidence for 2DR was for boosted protease inhibitor-based therapies but now we have large, randomized trials to support the use of dolutegravir (DTG)-based 2DR, both for initial therapy and suppressed switch, with high efficacy and no emergent resistance at failure. Summary 2DR will increasingly form part of the choice we are able to offer people with HIV but we must consider some of the limitations to ensure these regimens are used in the most clinically appropriate manner.
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