Background Overseas-born people who are ineligible for government-subsidised health care experience barriers to accessing HIV pre-exposure prophylaxis (PrEP) in Australia. This study aimed to assess ...a program providing free PrEP to overseas-born adults at risk of acquiring HIV. Methods Medicare-Ineligible Expanded Implementation in Communities (MI-EPIC) was a single-arm, open-label trial of daily tenofovir disoproxil fumarate/emtricitabine as PrEP. Six clinics recruited Medicare-ineligible adults who met HIV risk criteria in New South Wales, Australia. We recorded data on HIV and sexually transmitted infection (STI) diagnoses, and PrEP dispensing from July 2019 to June 2020. PrEP adherence as a medication possession ratio (MPR) was calculated as pills dispensed divided by days. We administered an optional survey on behaviours and attitudes to PrEP and sexual health. Results The 221 participants (206 men; 93.2%) had a median age of 29years (IQR 26-34). Participants were mostly born in Asia (53.4%), Latin America or the Caribbean (25.3%), or Europe (10.9%). Adherence was high; 190 participants (86.0%) had an MPR of >60%. Of 121 survey participants, 42 (34.7%) completed the survey in a language other than English. Of participants who had not used PrEP in the 6months before enrolment (n=45, 37.2%), the most common reasons were cost (n=22, 48.9%), and lack of knowledge about accessing PrEP (n=20, 44.4%). Conclusions Medicare-ineligible people at risk of HIV demonstrate high adherence when given access to free PrEP and translated information. Increasing PrEP awareness and reducing barriers to accessing PrEP in this high-risk population should be priorities in HIV prevention.
Tolerability of HIV integrase inhibitors Lee, Frederick J; Carr, Andrew
Current opinion in HIV & AIDS,
2012-September, 2012-Sep, 2012-09-00, Letnik:
7, Številka:
5
Journal Article
PURPOSE OF REVIEWThis review discusses the available safety data for three integrase strand transfer inhibitors (INSTIs) – raltegravir, elvitegravir and dolutegravir – derived from studies in both ...HIV-infected and HIV-uninfected cohorts.
RECENT FINDINGSPhase 2 and 3 clinical trials show that all three INSTIs are well tolerated in treatment-naive and treatment-experienced patients with headache and gastrointestinal effects being the most commonly reported adverse events. Other nervous system (including neuropsychiatric) effects are often reported with INSTIs but are milder and less frequent than with efavirenz. Limited data suggest that effects upon lipid metabolism with raltegravir and dolutegravir are favourable compared with efavirenz and protease inhibitors, with more variable findings for elvitegravir because of coadministration with the boosting agent cobicistat. Cobicistat and dolutegravir have effects upon proximal renal tubular function causing mild-to-moderate creatinine elevation. Rare and severe events possibly related to INSTIs include systemic hypersensitivity reactions and rhabdomyolysis.
SUMMARYINSTIs are an important recent addition to the antiretroviral armamentarium, with good short-term and medium-term safety. Long-term data from ongoing clinical studies are needed for a definitive assessment of their safety profile.
Little prospective data are published on the natural history of HIV-associated lipodystrophy (HIVLD) in individuals beginning their first antiretroviral regimen. To investigate this a study was ...designed to explore changes in body composition occurring with antiretroviral therapy.
A non-randomized, prospective, exploratory study of 40, HIV-infected men, naive to treatment, beginning antiretroviral therapy. Regular assessments of body composition, and metabolic and immunological parameters were performed.
Mean follow-up was 96 (SD 45) weeks of therapy. There were increases in limb fat, central abdominal fat and lean mass over the initial 24 weeks of therapy followed by a selective, progressive loss of limb fat from week 24. There was a median 13.6% interquartile range (IQR), 0.9-26.3 loss of limb fat per year from week 24 onwards. Treatment with stavudine, higher baseline HIV RNA, higher baseline 'T' score and lower week 24 lean mass were associated with higher rate of limb fat loss from week 24. In multivariate analysis, treatment with stavudine was the strongest independent factor associated with rate of limb fat loss (P = 0.05). Hypercholesterolaemia developed early in treatment, whereas hypertriglyceridaemia, hyperinsulinaemia and decreased bone mineral density developed later. The largest changes in CD4 cell counts and HIV viral load, seen early into treatment, were associated with gain rather than loss of fat.
This is the first prospective study demonstrating that treatment with antiretrovirals results in progressive, selective loss of limb fat. Loss of limb fat occurred after the period of most intense immune restoration, making an immune aetiology unlikely.
Research assessing whether major depressive disorders (MDD) impacts neurocognitive functions in HIV+ persons has yielded inconsistent results. However, none have considered the role of MDD remission, ...chronicity, and stability on treatment. Ninety-five HIV+ adults clinically stable on combined antiretroviral treatment completed a psychiatric interview, a depression scale, a neuropsychological, daily living, and cognitive complaints assessments at baseline and 18 months. Participants were screened for current (within 12 months of study entry) alcohol and/or substance use disorder. History of alcohol and/or substance abuse disorder prior to the 12 months entry screen and MDD treatments were recorded. Participants were grouped into two psychiatric nomenclatures: (1) lifetime: no MD episode (MDE), single MDE life-event treated and fully remitted, chronic MDD treated and stable, chronic MDD treated and unstable, and baseline untreated MDE; (2) recent: last 2 years MDE (yes or no). We found that lifetime and recent psychiatric history were more strongly associated with decreased in independence in daily living and cognitive complaints than with baseline neuropsychological performance. However, lack of full remission, instability on treatment in chronic MDD, and severity of symptoms in current MDE were factors in whether MDD impacted baseline neuropsychological performance. Depressive symptoms improved at follow-up in those with baseline moderate-severe symptoms, and MDD was not associated with neurocognitive change at 18 months. A history of alcohol and/or substance abuse disorder was significantly more frequent in those with treated and unstable chronic MDD but it was not associated with neuropsychological performance. MDD recurrence, chronicity profiles, and associated comorbidities are keys factors to understand any potential impact on neurocognitive abilities in HIV infection. More comprehensive consideration of these complex effects could serve at constructively updating the HAND diagnostic criteria.
Purpose To assess the responsiveness and minimal change for the Oxford Elbow Score (OES) using anchorand distribution-based approaches. Methods A prospective observational study of 104 patients ...undergoing elbow surgery at a specialist orthopaedic hospital was carried out. Patients completed the OES and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaires (both scored on a 0 to 100 scale) pre-and 6 months post-surgery. Transition items (used as anchors) assessed perceived changes following surgery. Indicators of responsiveness were the effect size; the anchor-based minimal clinically important difference (MCID) and best cut-point on the receiver operator characteristic (ROC) curve; and the distribution-based minimal detectable change (MDC). Results The three elbow-specific OES scales (Function, Pain, Social-Psychological) produced generally larger effect sizes (0.79, 1.14 and 1.18, respectively) than the upper-limb-specific DASH scale (0.76). Clear associations were observed between transition items and all OES and DASH scores (all r > 10.351). The MCIDs for the OES Function scale and the DASH were similar (≈10), but were larger for the OES Pain and Social-Psychological scales (≈18), reflecting their lower (i.e. poorer) baseline scores and larger effect sizes. The MCIDs were, however, only consistently larger than the MDCs for the OES Pain domain. The OES Function scale and the DASH performed similarly on ROC analysis, but with the OES Pain and Social-Psychological scales demonstrating superior efficiency. Conclusions For elbow surgery, the 12-item three-scale OES is highly responsive to 6-month post-operative outcomes, with its performance being generally better than that of the 30-item one-scale DASH. Study estimates of minimal change for the OES may be useful for informing sample size calculations and interpreting outcomes in future clinical trials.
Background. Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently ...regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression. Methods. In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4⁺ antigen-specific T cells and intracellular cytokine staining for CD4⁺ and CD8⁺ antigen-specific T cells. Results. Of 134 participants (mean SD age, 51 9.3 years; 31 23.1% infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6-and E7-specific CD4⁺ T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6-and E7-specific CD8⁺ T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8⁺ T-cell responses (odds ratio, 4.09 95% confidence interval, 1.55-10.77, P = .004), but not with any CD4⁺ T-cell response (P ≥ .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4⁺ T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065). Conclusions. Systemic HPV-16 E6-and E7-specific T-cell responses were common in men who have sex with men. E6-specific CD4⁺ T-cell responses may be associated with recent HSIL regression. Clinical Trials Registration. NCT02007421.
Objectives
HIV infection is associated with a higher prevalence of low bone mineral density (BMD) and fractures than that found in the general population. There are limited data in HIV‐positive ...adults, naïve to antiretroviral therapy (ART), with which to estimate the relative contribution of untreated HIV infection to bone loss.
Methods
The primary objective of the Strategic Timing of AntiRetroviral Treatment (START) Bone Mineral Density Substudy is to compare the effect of immediate versus deferred initial ART on bone. We evaluated traditional, demographic, HIV‐related and immunological factors for their associations with baseline hip and lumbar spine BMD, measured by dual‐energy X‐ray absorptiometry, using multiple regression.
Results
A total of 424 ART‐naïve participants were enrolled at 33 sites on six continents; the mean age was 34 years standard deviation (SD) 10.1 years, 79.0% were nonwhite, 26.0% were women, and 12.5% had a body mass index (BMI) < 20 kg/m2. Mean (SD) Z‐scores were −0.41 (0.94) at the spine and −0.36 (0.88) for total hip; 1.9% had osteoporosis and 35.1% had low BMD (hip or spine T‐score < −1.0). Factors independently associated with lower BMD at the hip and spine were female sex, Latino/Hispanic ethnicity, lower BMI and higher estimated glomerular filtration rate. Longer time since HIV diagnosis was associated with lower hip BMD. Current or nadir CD4 cell count and HIV viral load were not associated with BMD.
Conclusions
In this geographically and racially diverse population of ART‐naïve adults with normal CD4 cell counts, low BMD was common, but osteoporosis was rare. Lower BMD was significantly associated with traditional risk factors but not with CD4 cell count or viral load.
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