Social determinants of quality of life among PLHIV in Australia: implications for health promotion.

A cascade of care model is central to contemporary approaches to HIV prevention. The model prioritizes strategies to increase rates of HIV testing and promote early and sustained uptake of antiretroviral treatment (ART) among people living with HIV (PLHIV). The model aims to prevent new HIV transmissions by increasing the number of PLHIV who have achieved HIV viral suppression. However, good quality of life (QoL) among PLHIV has been proposed as an additional goal. This prioritizes the basic right of PLHIV to lead meaningful lives and acknowledges the relationship between better QoL and consistent ART use. A better understanding of factors associated with the QoL can thus inform health promotion programmes for PLHIV. In this study, N=465 Australian participants, recruited through social media and various HIV community organizations, completed an online survey that included a measure of QoL and a range of demographic, health-related and social variables. Overall, social factors accounted uniquely for the most variance in QoL (18%), followed by health-related (11%) and demographic factors (2%). Social support, HIV-related discrimination and treatment convenience were among the strongest determinants of QoL. These findings reinforce the importance of a more holistic approach to health promotion among PLHIV. Specifically, our results indicate that to improve the QoL of PLHIV and to boost related public health benefits, community advocates and healthcare professionals must be responsive to the broader psychological, social and functional needs of PLHIV.

Development and validation of PozQoL: a scale to assess quality of life of PLHIV.

BACKGROUND: Advances in medical treatment for HIV are driving major changes in HIV policy and practice, including the encouragement of intake and adherence to HIV antiretroviral treatment (ART) by people living with HIV (PLHIV) for both personal and public health benefits. However, there is increasing recognition that achieving these goals will require a concurrent focus on the broader psychological and social wellbeing of PLHIV. Increasingly calls are being been made to incorporate a stronger focus on quality of life (QoL) of PLHIV into HIV prevention policy. In order to achieve this goal, HIV community, support and healthcare services need a valid, short and practical way to evaluate QoL of PLHIV accessing their programs. Current QoL measures are either long, complex, restricted in their use, or expensive. To address these shortcomings, the PozQoL study aimed to develop, test and validate a short and freely available scale assessing QoL among PLHIV. METHODS: Drawing on a literature review, the prioritisation of domains and development of the initial pool of items was conducted in consultation with PLHIV community organisations in Australia. The items covered health concerns, psychological, social, and functional wellbeing. Testing involved a baseline and a follow-up survey of 465 adult Australians living with HIV. Participants were recruited through social media and various community organizations nationwide. The survey included the pilot PozQoL scale and other validated measures of health and wellbeing. RESULTS: Guided by an Exploratory Factor Analysis and conceptual considerations, a 13-item scale was developed. The PozQoL scale demonstrated high levels of fit in a Confirmatory Factor Analysis, very good internal consistency, test-retest reliability, and concurrent validity with other measures that approximated different aspects of QoL. CONCLUSION: The PozQoL scale has been tested in a diverse sample of adult PLHIV living in Australia, demonstrating very good reliability and validity. The insights from PLHIV and other stakeholders supported the balancing of statistical rigour and conceptual accuracy. The scale is now ready to be implemented and field-tested across a range of community, support and healthcare programs for PLHIV. This will make a significant contribution to the evaluation and enhancement of programs for PLHIV.

Understanding Treatment Preferences Among People Living with HIV in Australia: A Discrete Choice Experiment.

Purpose: To better understand what is most important to people living with human immunodeficiency virus (PLWH) when choosing their treatment. We assessed how PLWH trade off the potential risks and benefits of oral and long acting injectable (LAI) treatments. Participants and Methods: Firstly, in-depth interviews were conducted with 11 PLWH to develop a holistic understanding of experiences and determine attributes that contribute to treatment decision-making. Secondly, a discrete choice experiment (DCE) was used to understand the treatment preferences for PLWH with n = 99 PLWH aged 18 years or over with a diagnosis of human immunodeficiency virus (HIV) and who were currently using anti-retroviral therapy (ART). Study participants were presented with 12 scenarios and asked to select their preferred treatment among two hypothetical injectable treatment alternatives, "injection 1" and "injection 2" and their current oral ART treatment. The DCE data were modelled using a latent class model (LCM). Results: The model revealed significant heterogeneity in preferences for treatment attributes among study participants. Two segments/classes of PLWH were identified. The first segment expressed a strong preference for their current oral treatment; the second segment showed strong preference for the injection treatment and for it to be administered in a GP clinic. Overall, out-of-pocket cost was the most important attribute for participants. One-third of PLWH were willing to switch to an LAI. Conclusion: Not all PLWH valued the same treatment attributes equally. Overall, out-of-pocket costs for treatments were considered by respondents as the most determining factor in making treatment choices. Results have important implications for healthcare policy and will serve to better inform patients and stakeholders involved in the treatment decision-making process about the treatment preferences of PLWH. Clinicians are encouraged to consider shared decision-making to establish the treatment course that best aligns with PLWH's treatment goals.

High annual syphilis testing rates among gay men in Australia, but insufficient retesting.

INTRODUCTION: Since 2000, infectious syphilis notifications have increased substantially among Australian gay men. We describe testing at a frequency lower than guidelines recommend. METHODS: We examined data from a cross-sectional survey of gay men in 5 Australian cities in 2010. We used logistic regression to identify correlates of no lifetime syphilis test among HIV-uninfected men and <2 tests per year in HIV-infected men and higher-risk HIV-uninfected men. RESULTS: Of 6329 HIV-uninfected men, 65% reported a syphilis test in the past year, and 86% in their lifetime, and factors associated with no lifetime syphilis test were lower social engagement with gay men, older age, fewer sexual partners, no anal sex with casual partners, and not being aware syphilis could be asymptomatic. Among higher-risk HIV-uninfected men (>10 partners in the past 6 months), factors associated with <2 syphilis tests in the past year were nonmetropolitan residence, older age, no anal sex or unprotected anal intercourse with casual partners, not aware syphilis could be acquired through oral sex, and testing at a nonregular general practitioner. Of the 580 HIV-infected, 87% reported a syphilis test in the past year, and 96% in their lifetime, and factors associated with <2 syphilis tests in the past year were unprotected anal intercourse with HIV-uninfected casual partner and recruitment from social or sex-on-premises venues. CONCLUSIONS: Our analysis showed high lifetime and annual syphilis testing rates in Australian gay men, but low retesting rates. We identified factors associated with less frequent syphilis testing rates among Australian gay men to assist in developing targeted screening strategies.

Chemoprophylaxis is likely to be acceptable and could mitigate syphilis epidemics among populations of gay men.

BACKGROUND: Over the last decade, syphilis epidemics have resurged around the world, particularly among gay men. An innovative public health response could be the use of chemoprophylaxis. We sought out to determine the acceptability of syphilis chemoprophylaxis and its likely population effectiveness if it were adopted. METHODS: We conducted a mixed-methods study. An online survey (n = 2095 participants) and focus groups (n = 23 participants) were conducted to determine whether syphilis chemoprophylaxis is likely to be acceptable to gay men in Australia. We also developed an individual-based mathematical model that simulated a population of gay men, to explore the potential impact of introducing chemoprophylaxis. RESULTS: Of the 2095 gay men surveyed, 52.7% (95% confidence interval, 50.6%-54.8%) indicated that they would be very likely or slightly likely to use chemoprophylaxis to reduce their chance of acquiring syphilis, increasing to 75.8% (95% confidence interval, 74.0%-77.6%) if chemoprophylaxis would help reduce infections in the gay community. In this model, 70% use-effectiveness of chemoprophylaxis used by 50% of gay men is expected to reduce the number of syphilis cases by ∼50% after 12 months and 85% after 10 years. The majority of the prevention efforts can be gained by targeting subpopulations of men with higher sexual activity. CONCLUSIONS: Chemoprophylaxis offers promise as an acceptable and effective intervention for mitigating syphilis epidemics. The outcomes of a planned placebo-controlled syphilis chemoprophylaxis trial are eagerly anticipated.

Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.

BACKGROUND: In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]).We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis. METHODS AND FINDINGS: Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1+2. Two studies were conducted: (1) a nested case-control study for studying biomarker associations with mortality, and (2) a study to compare DC and VS participants for biomarker changes. For (1), markers were determined at study entry and before death (latest level) for 85 deaths and for two controls (n = 170) matched on country, age, sex, and date of randomization. Odds ratios (ORs) were estimated with logistic regression. For each biomarker, each of the three upper quartiles was compared to the lowest quartile. For (2), the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following randomization. Higher levels of hsCRP, IL-6, and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality. Unadjusted ORs (highest versus lowest quartile) were 2.0 (95% confidence interval [CI], 1.0-4.1; p = 0.05), 8.3 (95% CI, 3.3-20.8; p < 0.0001), and 12.4 (95% CI, 4.2-37.0; p < 0.0001), respectively. Associations were significant after adjustment, when the DC and VS groups were analyzed separately, and when latest levels were assessed. IL-6 and D-dimer increased at 1 mo by 30% and 16% in the DC group and by 0% and 5% in the VS group (p < 0.0001 for treatment difference for both biomarkers); increases in the DC group were related to HIV-RNA levels at 1 mo (p < 0.0001). In an expanded case-control analysis (four controls per case), the OR (DC/VS) for mortality was reduced from 1.8 (95% CI, 1.1-3.1; p = 0.02) to 1.5 (95% CI, 0.8-2.8) and 1.4 (95% CI, 0.8-2.5) after adjustment for latest levels of IL-6 and D-dimer, respectively. CONCLUSIONS: IL-6 and D-dimer were strongly related to all-cause mortality. Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels. Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation.

Interruption of antiretroviral therapy and risk of cardiovascular disease in persons with HIV-1 infection: exploratory analyses from the SMART trial.

BACKGROUND: The SMART trial found a raised risk of cardiovascular disease (CVD) events in patients undergoing CD4+ T cell-count guided intermittent antiretroviral therapy (ART) compared with patients on continuous ART. Exploratory analyses were performed to better understand the reasons for this observation. METHODS: A total of 5,472 patients with CD4+ T-cell counts >350 cells/mm3 were recruited and randomized to either continuous ART (the viral suppression arm; VS) or CD4+ T-cell count-guided use of ART (the drug conservation arm; DC). RESULTS: Major CVD events developed in 79 patients. The hazard ratio (HR) for risk of CVD events for DC versus VS was 1.57 (95% confidence interval 1.00-2.46; P=0.05). There was no evidence that being off ART or a higher current HIV viral load were associated with increased CVD risk. Total cholesterol and low-density lipoprotein cholesterol were reduced as a result of ART interruption in DC patients but so was high-density lipoprotein (HDL) cholesterol, leading to a net unfavourable change in the total/HDL cholesterol ratio. CONCLUSIONS: Reasons for the higher risk of CVD for DC compared with VS patients remain unclear. There was no clear evidence to suggest that ART interruption per se or a higher HIV viral load were associated with an increased CVD risk in the DC group. Lipid changes were less favourable among DC compared with VS patients, which could offer a partial explanation.

A retrospective clinical audit of general practices in Australia to determine the motivation for switch to dolutegravir/abacavir/lamivudine and clinical outcomes.

The most common reasons for switching HIV-1 therapy in patients with virologic suppression are treatment regimen simplification and resolving tolerability issues. Single-pill regimens that include an integrase inhibitor are recommended options. A retrospective clinical audit was performed to determine the motivations for switching to dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC) at high HIV-caseload general practice clinics in Australia. The most common reasons for switching from a prior suppressive therapy to DTG/ABC/3TC were simplification of regimen, resolving toxicity/intolerance and patient preference (73%, 13% and 12%, respectively). Kaplan-Meier analysis showed that the probability of patients remaining on DTG/ABC/3TC therapy at 12 months was 95.1%. Switching to DTG/ABC/3TC from a range of other regimens was associated with a discontinuation rate of 3.2%, with 2.5% of patients discontinuing due to adverse events and no patients discontinuing due to virologic failure. Switching to DTG/ABC/3TC was a viable treatment strategy in this cohort of Australian patients.

Funding antiretroviral treatment for HIV-positive temporary residents in Australia prevents transmission and is inexpensive.

Background The aim of this study is to estimate the reduction in new HIV infections and resultant cost outcomes of providing antiretroviral treatment (ART) through Australia's 'universal access' health scheme to all temporary residents with HIV infection living legally in Australia, but currently deemed ineligible to access subsidised ART via this scheme. METHODS: A mathematical model to estimate the number of new HIV infections averted and the associated lifetime costs over 5 years if all HIV-positive temporary residents in Australia had access to ART and subsidised medical care was developed. Input data came from a cohort of 180 HIV-positive temporary residents living in Australia who are receiving free ART donated by pharmaceutical companies for up to 4 years. RESULTS: Expanding ART access to an estimated total 450 HIV+ temporary residents in Australia for 5 years could avert 80 new infections. The model estimated the total median discounted (5%) cost for ART and associated care to be A$36million, while the total savings in lifetime-discounted costs for the new infections averted was A$22million. CONCLUSIONS: It is estimated that expanded access to ART for all HIV-positive temporary residents in Australia will substantially reduce HIV transmission to their sexual partners at little additional cost. In the context of Australia's National HIV strategy and Australia's endorsement of global goals to provide universal access to ART for all people with HIV, this is an important measure to remove inequities in the provision of HIV-related treatment and care.

Reliable genotypic tropism tests for the major HIV-1 subtypes.

Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic "tropism tests" to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic.

Randomized, open-label, comparative trial to evaluate the efficacy and safety of three antiretroviral drug combinations including two nucleoside analogues and nevirapine for previously untreated HIV-1 Infection: the OzCombo 2 study.

PURPOSE: To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients. METHOD: Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts >50/microL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP), stavudine + didanosine + nevirapine (d4T+ddI+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity. RESULTS: The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 1.29, 2.13, and 1.78 log(10) copies/mL, respectively (p =.389). The proportions of patients with HIV RNA <50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 73%, 68%, and 80%, respectively (p =.71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 139, 113, and 174 cells/microL, respectively (p =.30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddI+NVP arm) ceased assigned treatment due to neuropathy. CONCLUSION: All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone.

Inflammation, coagulation and cardiovascular disease in HIV-infected individuals.

BACKGROUND: The SMART study was a trial of intermittent use of antiretroviral therapy (ART) (drug conservation [DC]) versus continuous use of ART (viral suppression [VS]) as a strategy to reduce toxicities, including cardiovascular disease (CVD) risk. We studied the predictive value of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer with CVD morbidity and mortality in HIV-infected patients who were enrolled in SMART beyond other measured CVD risk factors. METHODS: A blood sample was available in 5098 participants who were enrolled in the SMART study for the measurement of IL-6, hsCRP and D-dimer. Hazard ratios (HR) with 95% CI for CVD events were estimated for each quartile (Q) for each biomarker vs the 1(st) quartile and for 1 SD higher levels. For both treatment groups combined, unadjusted and adjusted HRs were determined using Cox regression models. RESULTS: There were 252 participants who had a CVD event over a median follow-up of 29 months. Adjusted HRs (95% CI) for CVD for Q4 vs Q1 were 4.65 (2.61, 8.29), 2.10 (1.40, 3.16), and 2.14 (1.38, 3.33) for IL-6, hsCRP and D-dimer, respectively. Associations were similar for the DC and VS treatment groups (interaction p-values were >0.30). The addition of the three biomarkers to a model that included baseline covariates significantly improved model fit (p<0.001). Area under the curve (AUC) estimates improved with inclusion of the three biomarkers in a model that included baseline covariates corresponding to other CVD risk factors and HIV factors (0.741 to 0.771; p<0.001 for difference). CONCLUSIONS: In HIV-infected individuals, IL-6, hsCRP and D-dimer are associated with an increased risk of CVD independent of other CVD risk factors. Further research is needed to determine whether these biomarkers can be used to improve CVD risk prediction among HIV positive individuals.

Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection.

OBJECTIVES: Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compared with those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART. METHODS: Stored specimens for 254 participants (126 drug conservation [DC] and 128 viral suppression [VS]) who were naïve to ART or off ART (6 months or longer) were analyzed for interleukin-6, high sensitivity C-reactive protein, and D-dimer at baseline and Months 2 and 6. RESULTS: At Month 6, 62% of the VS group had HIV RNA less than 400 copies/mL and median CD4 count was 190 cells/mm3 higher than for the DC group (590 versus 400 cells/mm3). Compared with DC, the VS group had 32% (95% confidence interval, 19%-43%) lower D-dimer levels at Month 6 (P < 0.001); differences were not significant for high sensitivity C-reactive protein or interleukin-6 levels. CONCLUSIONS: In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not interleukin-6 and high sensitivity C-reactive protein, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection.

The effects of intermittent, CD4-guided antiretroviral therapy on body composition and metabolic parameters.

OBJECTIVE: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. DESIGN: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or to continuous [Viral Suppression (VS) group] antiretroviral therapy. METHODS: Participants at 33 sites were coenrolled in the Strategies for Management of Anti-Retroviral Therapy Body Composition substudy. Regional fat was assessed annually by whole-body dual-energy X-ray absorptiometry and abdominal computed tomography. Fasting metabolic parameters were assessed at months 4, 8, and annually. Treatment groups were compared for changes in fat and metabolic markers using longitudinal mixed models. RESULTS: Two hundred and seventy-five patients were randomized to the DC (n = 142) or VS (n = 133) group and followed for a median of 2.0 years. By month 12, limb fat (DC-VS difference 9.8%, 95% confidence interval 3.5-16.1; P = 0.003) and subcutaneous abdominal fat (DC-VS difference 14.3 cm, 95% confidence interval -0.1 to 28.7; P = 0.05) increased in the DC group. There was no treatment difference in visceral abdominal fat (DC-VS difference -2.1%, 95% confidence interval -13.5 to 9.4; P = 0.72). Lipids significantly decreased in the DC group by month 4 and treatment differences persisted throughout follow-up (P < or = 0.001). By 12 months, hemoglobin A1C increased in the DC (+0.3%) and remained stable in the VS group (P = 0.003); the treatment difference remained significant throughout follow-up (P = 0.02). CONCLUSION: After 12 months, intermittent antiretroviral therapy increased subcutaneous fat, had no effect on visceral abdominal fat, decreased plasma lipids, and increased hemoglobin A1C compared with continuous antiretroviral therapy.