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Background Human immunodeficiency virus (HIV) infection leads to chronic immune activation/inflammation that can persist in virally suppressed persons on fully active antiretroviral therapy (ART) and increase risk of malignancies. The prognostic role of low CD4:CD8 ratio and elevated CD8 cell counts on the risk of cancer remains unclear. Methods We investigated the association of CD4:CD8 ratio on the hazard of non-AIDS defining malignancy (NADM), AIDS-defining malignancy (ADM) and most frequent group of cancers in ART-treated people with HIV (PWH) with a CD4 and CD8 cell counts and viral load measurements at baseline. We developed Cox proportional hazard models with adjustment for known confounders of cancer risk and time-dependent cumulative and lagged exposures of CD4:CD8 ratio to account for time-evolving risk factors and avoid reverse causality. Results CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI }1.10–6.19] and 2.03 [95% CI 1.24–3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. Conclusions In ART-treated PWH low CD4:CD8 ratios were associated with ADM and infection-related cancers independently from CD4 and CD8 cell counts and may alert clinicians for cancer screening and prevention of NADM. [ABSTRACT FROM AUTHOR]

Despite the mental health and substance use burden among people living with HIV (PLHIV) in the Asia–Pacific, data on their associations with HIV clinical outcomes are limited. This cross-sectional study of PLHIV at five sites assessed depression and substance use using PHQ-9 and ASSIST. Among 864 participants, 88% were male, median age was 39 years, 97% were on ART, 67% had an HIV viral load available and < 1000 copies/mL, 19% had moderate-to-severe depressive symptoms, and 80% had ever used at least one substance. Younger age, lower income, and suboptimal ART adherence were associated with moderate-to-severe depressive symptoms. Moderate-to-high risk substance use, found in 62% of users, was associated with younger age, being male, previous stressors, and suboptimal adherence. Our findings highlight the need for improved access to mental health and substance use services in HIV clinical settings. [ABSTRACT FROM AUTHOR]

Objectives: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all‐cause mortality among Asian adults living with HIV. Methods: Participants enrolled in a regional Asian HIV‐infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing‐risk regression models were used to investigate the association of MetS with all‐cause mortality. Results: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29–41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48–63) kg and 20.5 (18.4–22.9) kg/m2, respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9–2.5 kg] and baseline HIV RNA ≥ 100 000 HIV‐1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2–1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)‐based ART (diff = 2.1 kg; 95% CI 0.7–3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05–1.32)/100 person‐years (PY)]. The mortality rate was 0.7 (95% CI 0.6–0.8)/100 PY. MetS was not significantly associated with all‐cause mortality in the adjusted model (P = 0.236). Conclusions: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI‐based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed. [ABSTRACT FROM AUTHOR]

Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear.Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy.Design: Multinational prospective cohort study.Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States.Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts <350 and <500 × 109 cells/L) ART initiation strategies.Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer.Limitation: Potential residual confounding due to observational study design.Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer.Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee. [ABSTRACT FROM AUTHOR]

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Introduction: People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV‐negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. Methods: We developed a discrete‐state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid‐lowering therapy. The model simulated each individual's probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles over a 20‐year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. Results: Pravastatin was estimated to be less effective and less cost‐effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost‐effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy, pill burden, and targeting of PLHIV based on CVD risk. At a willingness‐to‐pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost‐effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost‐effective at an annual cost of 600 Baht ($US19.30)/year. Conclusions: Neither pravastatin nor pitavastatin were projected to be cost‐effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction. [ABSTRACT FROM AUTHOR]

Objectives: We extend the method of Significant Zero Crossings of Derivatives (SiZer) to address within-subject correlations of repeatedly collected longitudinal biomarker data and the computational aspects of the methodology when analyzing massive biomarker databases. SiZer is a powerful visualization tool for exploring structures in curves by mapping areas where the first derivative is increasing, decreasing or does not change (plateau) thus exploring changes and normalization of biomarkers in the presence of therapy. Methods: We propose a penalized spline SiZer (PS-SiZer) which can be expressed as a linear mixed model of the longitudinal biomarker process to account for irregularly collected data and within-subject correlations. Through simulations we show how sensitive PS-SiZer is in detecting existing features in longitudinal data versus existing versions of SiZer. In a real-world data analysis PS-SiZer maps are used to map areas where the first derivative of weight change after antiretroviral therapy (ART) start is significantly increasing, decreasing or does not change, thus exploring the durability of weight increase after the start of therapy. We use weight data repeatedly collected from persons living with HIV initiating ART in five regions in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) worldwide collaboration and compare the durability of weight gain between ART regimens containing and not containing the drug stavudine (d4T), which has been associated with shorter durability of weight gain. Results: Through simulations we show that the PS-SiZer is more accurate in detecting relevant features in longitudinal data than existing SiZer variants such as the local linear smoother (LL) SiZer and the SiZer with smoothing splines (SS-SiZer). In the illustration we include data from 185,010 persons living with HIV who started ART with a d4T (53.1%) versus non-d4T (46.9%) containing regimen. The largest difference in durability of weight gain identified by the SiZer maps was observed in Southern Africa where weight gain in patients treated with d4T-containing regimens lasted 59.9 weeks compared to 133.8 weeks for those with non-d4T-containing regimens. In the other regions, persons receiving d4T-containing regimens experienced weight gains lasting 38–62 weeks versus 55–93 weeks in those receiving non-d4T-based regimens. Discussion: PS-SiZer, a SiZer variant, can handle irregularly collected longitudinal data and within-subject correlations and is sensitive in detecting even subtle features in biomarker curves. [ABSTRACT FROM AUTHOR]

Background Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART). Methods We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death. Results A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015–2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09–1.28]), lower height-for-age z score (OR, 1.15 for less than −3 vs greater than −2 [95% CI, 1.08–1.22]), anemia (OR, 1.08 [95% CI, 1.02–1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18–1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17–9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77–1.34]). Conclusions Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency. [ABSTRACT FROM AUTHOR]

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: In 2015, the World Health Organization recommended that all HIV‐infected individuals consider ART initiation as soon as possible after diagnosis. Sex differences in choice of initial ART regimen, indications for switching, time to switching and choice of second‐line regimens have not been well described. The aims of this study were to describe first‐line ART and CD4 count at ART initiation by sex, calendar year and region, and to analyse time to change or interruption in first‐line ART, according to sex in each region. Methods: Participating cohorts included: Southern, East and West Africa (IeDEA‐Africa), North America (NA‐ACCORD), Caribbean, Central/South America (CCASAnet) and Asia‐Pacific including Australia (IeDEA Asia‐Pacific). The primary outcomes analysed for each region and according to sex were choice of initial ART, time to switching and time to discontinuation of the first‐line regimen. Results and Discussion: The combined cohort data set comprised of 715,252 participants across seven regions from low‐ to high‐income settings. The median CD4 count at treatment initiation was lower in men compared with women in nearly all regions and time periods. Women from North America and Southern Africa were more likely to switch ART compared to men (p < 0.001) with approximately 90% of women reporting a major change after 10 years in North America. Overall, after 8 years on ART, >50% of HIV‐ positive men and women from Southern Africa, East Africa, South and Central America remained on their original regimen. Men were more likely to have a treatment interruption compared with women in low‐ and middle‐income countries from the Asia/Pacific region (p < 0.001) as were men from Southern Africa (p < 0.001). Greater than 75% of men and women did not report a treatment interruption after 10 years on ART from all regions except North America and Southern Africa. Conclusions: There are regional variations in the ART regimen commenced at baseline and rates of major change and treatment interruption according to sex. Some of this is likely to reflect changes in local and international antiretroviral guideline recommendations but other sex‐specific factors such as pregnancy may contribute to these differences. [ABSTRACT FROM AUTHOR]

Introduction: Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries. Methods: The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring =0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements =400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed. Results: Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution. Conclusions: The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries. [ABSTRACT FROM AUTHOR]

Antiretroviral treatment (ART) guidelines have changed over the past decade, recommending earlier initiation and more tolerable regimens. The study objective was to examine the CD4 response to ART, depending on the year of ART initiation, in HIV-positive patients in the Asia-Pacific. We included HIV-positive adult patients who initiated ART between 2003 and 2013 in our regional cohort from eight urban referral centres in seven countries within Asia. We used mixed-effects linear regression models to evaluate differences in CD4 response by year of ART initiation during 36 months of follow-up, adjusted a priori for other covariates. Overall, 16,962 patients were included. Patients initiating in 2006-9 and 2010-13 had an estimated mean CD4 cell count increase of 8 and 15 cells/µl, respectively, at any given time during the 36-month follow-up, compared to those in 2003-5. The median CD4 cell count at ART initiation also increased from 96 cells/µl in 2003-5 to 173 cells/µl in 2010-13. Our results suggest that the CD4 response to ART is modestly higher for those initiating ART in more recent years. Moreover, fewer patients are presenting with lower absolute CD4 cell counts over time. This is likely to reduce their risk of opportunistic infections and future non-AIDS defining cancers. [ABSTRACT FROM AUTHOR]

The scale-up of antiretroviral therapy (ART) has led to a substantial change in the clinical population of HIV-positive patients receiving care. We describe the temporal trends in the demographic and clinical characteristics of HIV-positive patients initiating ART in 2003–13 within an Asian regional cohort. All HIV-positive adult patients that initiated ART between 2003 and 2013 were included. We summarized ART regimen use, age, CD4 cell count, HIV viral load, and HIV-related laboratory monitoring rates during follow-up by calendar year. A total of 16 962 patients were included in the analysis. Patients in active follow-up increased from 695 patients at four sites in 2003 to 11,137 patients at eight sites in 2013. The proportion of patients receiving their second or third ART regimen increased over time (5% in 2003 to 29% in 2013) along with patients aged ≥50 years (8% in 2003 to 18% in 2013). Concurrently, CD4 monitoring has remained stable in recent years, whereas HIV viral load monitoring, although varied among the sites, is increasing. There have been substantial changes in the clinical and demographic characteristics of HIV-positive patients receiving ART in Asia. HIV programmes will need to anticipate the clinical care needs for their aging populations, expanded viral load monitoring, and, the eventual increase in second and third ART regimens that will lead to higher costs and more complex drug procurement needs. [ABSTRACT FROM PUBLISHER]

Introduction: An important determinant of the effectiveness of HIV treatment programs is the capacity of sites to implement recommended services and identify systematic changes needed to ensure that invested resources translate into improved patient outcomes. We conducted a survey in 2014 of HIV care and treatment sites in the seven regions of the International epidemiologic Database to Evaluate AIDS (IeDEA) Consortium to evaluate facility characteristics, HIV prevention, care and treatment services provided, laboratory capacity, and trends in the comprehensiveness of care compared to data obtained in the 2009 baseline survey. Methods: Clinical staff from 262 treatment sites in 45 countries in IeDEA completed a site survey from September 2014 to January 2015, including Asia-Pacific with Australia (n = 50), Latin America and the Caribbean (n = 11), North America (n = 45), Central Africa (n = 17), East Africa (n = 36), Southern Africa (n = 87), and West Africa (n = 16). For the 55 sites with complete data from both the 2009 and 2014 survey, we evaluated change in comprehensiveness of care. Results: The majority of the 262 sites (61%) offered seven essential services (ART adherence, nutritional support, PMTCT, CD4+ cell count testing, tuberculosis screening, HIV prevention, and outreach). Sites that were publicly funded (64%), cared for adults and children (68%), low or middle Human Development Index (HDI) rank (68%, 68%), and received PEPFAR support (71%) were most often fully comprehensive. CD4+ cell count testing was universally available (98%) but only 62% of clinics offered it onsite. Approximately two-thirds (69%) of sites reported routine viral load testing (44-100%), with 39% having it onsite. Laboratory capacity to monitor antiretroviral-related toxicity and diagnose opportunistic infections varied widely by testing modality and region. In the subgroup of 55 sites with two surveys, comprehensiveness of services provided significantly increased across all regions from 2009 to 2014 (5.7 to 6.5, p < 0.001). Conclusions: The availability of viral load monitoring remains suboptimal and should be a focus for site capacity, particularly in East and Southern Africa, where the majority of those initiating on ART reside. However, the comprehensiveness of care provided increased over the past 5 years and was related to type of funding received (publicly funded and PEPFAR supported). [ABSTRACT FROM AUTHOR]

Background: Integrase inhibitors (INSTI) are a newer class of antiretroviral (ARV) drugs that offer additional treatment options for experienced patients. Our aim is to describe treatment durability and virological outcomes in treatment-experienced HIV-positive patients using INSTI-based regimens. Methods: All patients in the Australian HIV Observational Database who had received an INSTI-based regimen ≥ 14 days as well as previous therapy were included in the study. We defined two groups of treatment-experienced patients: (1) those starting a second-line regimen with INSTI; and (2) highly experienced patients, defined as having prior exposure to all three main ARV classes, nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitors and protease inhibitors, before commencing INSTI. Survival methods were used to determine time to viral suppression and treatment switch, stratified by patient treatment experience. Covariates of interest included age, gender, hepatitis B and C co-infection, previous antiretroviral treatment time, patient treatment experience and baseline viral load. Results: Time to viral suppression and regimen switching from INSTI initiation was similar for second-line and highly experienced patients. The probability of achieving viral suppression at 6 months was 77.7% for second-line patients and 68.4% for highly experienced patients. There were 60 occurrences of regimen switching away from INSTI observed over 1274.0 person-years, a crude rate of 4.71 (95% CI: 3.66-6.07) per 100 person-years. Patient treatment experience was not a significant factor for regimen switch according to multivariate analysis, adjusting for relevant covariates. Conclusions: We found that INSTI-based regimens were potent and durable in experienced HIV-positive patients receiving treatment outside clinical trials. These results confirm that INSTI-based regimens are a robust treatment option. [ABSTRACT FROM AUTHOR]

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection. [ABSTRACT FROM AUTHOR]

Introduction: HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. Methods: We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time tofirst major ART modification. Results: Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural-regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Conclusions: Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods. [ABSTRACT FROM AUTHOR]

Background: In the Asia-Pacific region many countries have adopted the WHO’s public health approach to HIV care and treatment. We performed exploratory analyses of the factors associated with first major modification to first-line combination antiretroviral therapy (ART) in resource-rich and resource-limited countries in the region. Methods: We selected treatment naive HIV-positive adults from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD). We dichotomised each country’s per capita income into high/upper-middle (T-H) and lower-middle/low (T-L). Survival methods stratified by income were used to explore time to first major modification of first-line ART and associated factors. We defined a treatment modification as either initiation of a new class of antiretroviral (ARV) or a substitution of two or more ARV agents from within the same ARV class. Results: A total of 4250 patients had 961 major modifications to first-line ART in the first five years of therapy. The cumulative incidence (95% CI) of treatment modification was 0.48 (0.44–0.52), 0.33 (0.30–0.36) and 0.21 (0.18–0.23) for AHOD, T-H and T-L respectively. We found no strong associations between typical patient characteristic factors and rates of treatment modification. In AHOD, relative to sites that monitor twice-yearly (both CD4 and HIV RNA-VL), quarterly monitoring corresponded with a doubling of the rate of treatment modifications. In T-H, relative to sites that monitor once-yearly (both CD4 and HIV RNA-VL), monitoring twice-yearly corresponded to a 1.8 factor increase in treatment modifications. In T-L, no sites on average monitored both CD4 & HIV RNA-VL concurrently once-yearly. We found no differences in rates of modifications for once- or twice-yearly CD4 count monitoring. Conclusions: Low-income countries tended to have lower rates of major modifications made to first-line ART compared to higher-income countries. In higher-income countries, an increased rate of RNA-VL monitoring was associated with increased modifications to first-line ART. [ABSTRACT FROM AUTHOR]

Introduction HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. Methods All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. Results Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of<200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m2. Conclusions The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham. [ABSTRACT FROM AUTHOR]

Of 682 antiretroviral-na_ve patients initiating antiretroviral therapy in a prospective, multicenter HIV-1 drug resistance monitoring study involving eight sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation(s) was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy in Asia.(See editorial commentary by Jordan on pages 1058–1060.)Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia. [ABSTRACT FROM AUTHOR]

Background: Recent papers have suggested that expanded combination antiretroviral treatment (cART) through lower viral load may be a strategy to reduce HIV transmission at a population level. We assessed calendar trends in detectable viral load in patients recruited to the Australian HIV Observational Database who were receiving cART. Methods: Patients were included in analyses if they had started cART (defined as three or more antiretrovirals) and had at least one viral load assessment after 1 January 1997. We analyzed detectable viral load (>400 copies/ml) in the first and second six months of each calendar year while receiving cART. Repeated measures logistic regression methods were used to account for within and between patient variability. Rates of detectable viral load were predicted allowing for patients lost to follow up. Results: Analyses were based on 2439 patients and 31,339 viral load assessments between 1 January 1997 and 31 March 2009. Observed detectable viral load in patients receiving cART declined to 5.3% in the first half of 2009. Predicted detectable viral load based on multivariate models, allowing for patient loss to follow up, also declined over time, but at higher levels, to 13.8% in 2009. Conclusions: Predicted detectable viral load in Australian HIV Observational Database patients receiving cART declined over calendar time, albeit at higher levels than observed. However, over this period, HIV diagnoses and estimated HIV incidence increased in Australia. [ABSTRACT FROM AUTHOR]

Several clinical studies have shown that, relative to disease progression, HIV-1 isolates that are less fit are also less pathogenic. The aim of the present study was to investigate the relationship between viral fitness and control of viral load (VL) in acute and early HIV-1 infection. Samples were obtained from subjects participating in two clinical studies. In the PULSE study, antiretroviral therapy (ART) was initiated before, or no later than six months following seroconversion. Subjects then underwent multiple structured treatment interruptions (STIs). The PHAEDRA study enrolled and monitored a cohort of individuals with documented evidence of primary infection. The subset chosen were individuals identified no later than 12 months following seroconversion to HIV-1, who were not receiving ART. The relative fitness of primary isolates obtained from study participants was investigated ex vivo. Viral DNA production was quantified using a novel real time PCR assay. Following intermittent ART, the fitness of isolates obtained from 5 of 6 PULSE subjects decreased over time. In contrast, in the absence of ART the fitness of paired isolates obtained from 7 of 9 PHAEDRA subjects increased over time. However, viral fitness did not correlate with plasma VL. Most unexpected was the high relative fitness of isolates obtained at Baseline from PULSE subjects, before initiating ART. It is widely thought that the fitness of strains present during the acute phase is low relative to strains present during chronic HIV-1 infection, due to the bottleneck imposed upon transmission. The results of this study provide evidence that the relative fitness of strains present during acute HIV-1 infection may be higher than previously thought. Furthermore, that viral fitness may represent an important clinical parameter to be considered when deciding whether to initiate ART during early HIV-1 infection. [ABSTRACT FROM AUTHOR]

Background. The risk of myocardial infarction (MI) in patients with human immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Methods. Poisson regression models were adjusted for cardiovascular risk factors, cohort, calendar year, and use of other antiretroviral drugs and assessed the association between MI risk and cumulative (per year) or recent (current or in the past 6 months) use of antiretroviral drugs, with 130,000 person-years of exposure. Results. Over 178,835 person-years, 580 patients developed MI. There were no associations between use of tenofovir, zalcitabine, zidovudine, stavudine, or lamivudine and MI risk. Recent exposure to abacavir or didanosine was associated with an increased risk of MI. No association was found between MI risk and cumulative exposure to nevirapine, efavirenz, nelfinavir, or saquinavir. Cumulative exposure to indinavir and lopinavir-ritonavir was associated with an increased risk of MI (relative rate [RR] per year, 1.12 and 1.13, respectively). These increased risks were attenuated slightly (RR per year, 1.08 [95% confidence interval {CI}, 1.02-1.14] and 1.09 [95% CI, 1.01-1.17], respectively) after adjustment for lipids but were not altered further after adjustment for other metabolic parameters. Conclusions. Of the drugs considered, only indinavir, lopinavir-ritonavir, didanosine, and abacavir were associated with a significantly increased risk of MI. As with any observational study, our findings must be interpreted with caution (given the potential for confounding) and in the context of the benefits that these drugs provide. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated changes in mortality following HIV and AIDS in Australia. HIV/AIDS was revolutionized with the introduction of highly active antiretroviral therapy (HAART) in the 1990s. The Standardised Mortality Ratios (SMRs) for deaths were calculated before antiretroviral therapy, pre- and early-HAART and HAART. Findings revealed that there 1,789 deaths following HIV without AIDS and 6,730 deaths after AIDS. The SMRs for deaths after AIDS were 2.99, 1.22 and 1.6 during the periods before 1990, 1990-1996 and 1997-2003. In addition, the crude death rate following HIV without AIDS rose to 19.6 in 2003.

The article presents an analysis of the statement that individuals who have received effective antiretroviral therapy are sexually non-infectious. The authors found that the risk in heterosexual couples is low but non-zero, and that the risk of transmission in male homosexual couples is high over repeated exposures. The authors also note that if condoms are rejected because an individual believes him or herself sexually non-infectious, then there is potential for marked increases in HIV transmission. The authors provide charts and graphs to support their analysis.

OBJECTIVE--The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated with the onset of diabetes, and to identify possible mechanisms for any relationships found. RESEARCH DESIGN AND METHODS--D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes and exposure to cART after adjusting for known risk factors for diabetes, CD4 count, lipids, and lipodystrophy. RESULTS--Over 130,151 person-years of follow-up (PYFU), diabetes was diagnosed in 744 patients (incidence rate of 5.72 per 1,000 PYFU [95% CI 5.31-6.13]). The incidence of diabetes increased with cumulative exposure to cART, an association that remained significant after adjustment for potential risk factors for diabetes. The strongest relationship with diabetes was exposure to stavudine; exposures to zidovudine and didanosine were also associated with an increased risk of diabetes. Time-updated measurements of total cholesterol, HDL cholesterol, and triglycerides were all associated with diabetes. Adjusting for each of these variables separately reduced the relationship between cART and diabetes slightly. Although lipodystrophy was significantly associated with diabetes, adjustment for this did not modify the relationship between cART and diabetes. CONCLUSION--Stavudine and zidovudine are significantly associated with diabetes after adjustment for risk factors for diabetes and lipids. Adjustment for lipodystrophy did not modify the relationship, suggesting that the two thymidine analogs probably directly contribute to insulin resistance, potentially through mitochondrial toxicity. [ABSTRACT FROM AUTHOR]

Background. Toxicities observed with current combination antiretroviral therapy (CART) warrant a search for novel options, such as class-sparing regimens. Ritonavir-boosted double-protease inhibitor (PI)-only regimens are such an option but are prone to pharmacokinetic interactions. Methods. This 48-week randomized study examined the safety and efficacy of a switch in CART to a oncedaily regimen of saquinavir (SQV), ritonavir (RTV), and atazanavir (ATV) that did not include nucleoside reversetranscriptase inhibitors (NRTIs). The study also assessed the pharmacokinetic profile of a change in the SQV formulation, from 200 mg to 500 mg, in 2 regimens (SQV-RTV twice per day plus NRTIs [arm 1] and SQV-RTVATVo nce per day without NRTIs [arm 2]) in human immunodeficiency virus type 1-infected subjects (plasma human immunodeficiency virus RNA level, <50 copies/mL). [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes. Definitions exist to identify those "at risk." Treatment of HIV infection with highly active antiretroviral therapy can induce severe metabolic complications including lipodystrophy, dyslipidemia, and insulin resistance. The purpose of this study was to report the prevalence of metabolic syndrome in HIV-infected patients and compare insulin resistance and total body, limb, and visceral fat and adipokines in those with and without metabolic syndrome. RESEARCH DESIGN AND METHODS -- This was an international cross-sectional study of a well-characterized cohort of 788 HIV-infected adults recruited at 32 centers. Metabolic syndrome prevalence was examined using International Diabetes Federation (IDF) and U.S. National Cholesterol Education Program Adult Treatment Panel III (ATPIII) criteria, relative to body composition (whole-body dual-energy X-ray absorptiometry and abdominal computed tomography), lipids, glycemic parameters, insulin resistance, leptin, adiponectin, and C-reactive protein (CRP). RESULTS -- The prevalence of metabolic syndrome was 14% (n = 114; 83 men) by IDF criteria and 18% (n = 139; 118 men) by ATPIII criteria; the concordance was significant but only moderate (κ = 0.46, P < 0.0001). Many patients (49%) had at least two features of metabolic syndrome but were not classified as having metabolic syndrome as their waist circumferences or waist-to-hip ratios were in the non-metabolic syndrome range. Metabolic syndrome was more common in those currently receiving protease inhibitors (P = 0.04). Type 2 diabetes prevalence was five- to ninefold higher in those with metabolic syndrome. With IDF criteria, subjects with metabolic syndrome showed disturbances in inflammation and adipokines: they had higher CRP (5.5 ± 7.0 vs. 3.9 ± 6.0 mg/l, P < 0.003) and leptin (9 ± 9 vs. 4 ± 6 ng/ml, P < 0.0001) and lower adiponectin (12 ± 8 vs. 15 ± 10 µg/ml, P < 0.0001) levels. By ATPIII criteria, those with metabolic syndrome had higher leptin (6 ± 8 ng/ml, P = 0.006) and lower adiponectin (15 ± 10 vs. 18 ± 8 µg/ml, P < 0.0001) levels. CONCLUSIONS -- Metabolic syndrome prevalence in HIV-positive adults was lower than that reported for the general population. Metabolic syndrome was associated with a substantially increased prevalence of type 2 diabetes in this specific cohort. Many subjects without metabolic syndrome had at least two metabolic syndrome components (particularly elevated lipid levels) but did not meet waist circumference or waist-to-hip ratio cutoff metabolic syndrome criteria in this group with high rates of body fat partitioning disturbances. [ABSTRACT FROM AUTHOR]

Background: It is critical to understand the pattern of antiretroviral treatment (ART) prescription in different regions of the world as ART procurement needs to be anticipated. We aimed at exploring rates and predictors of ART combination changes in clinical practice in Treat Asia HIV Observational Database (TAHOD). Methods: Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen. Results: A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year. In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 - 1.96), p < 0.001, RR 3.39 (2.76 - 4.16) p < 0.001, RR 6.37 (4.51 - 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 - 0.99), p = 0.035, RR 0.77 (0.61 - 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 - 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 - 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse events were 31, 27 and 32 in 1st, 2nd and 3rd treatment combinations, respectively. Conclusion: Our study suggests that drug availability impacts on ART prescription patterns. Our data, reflecting real clinic use in Asia, suggest that around half of all patients require second combination ART by 3 years after treatment initiation. [ABSTRACT FROM AUTHOR]

Background. Body composition changes complicate antiretroviral therapy. Improvements in lipoatrophy after a switch in nucleoside reverse-transcriptase inhibitors (NRTIs) have been demonstrated.We investigated 60 patients switching from failed NRTIs to ritonavir-boosted indinavir and efavirenz. Methods. Body composition (assessed by dual-energy x-ray absorptiometry scan and by single-slice computed tomography of the abdomen through the level of the fourth lumbar vertebra [L4] and the mid-right thigh) and fasted metabolics were measured at the baseline time-point at switch and at weeks 48 and 96 thereafter. Mitochondrial DNA and RNA were extracted from right-thigh subcutaneous fat and peripheral-blood mono nuclear cells (PBMCs) at weeks 0 and 48. The primary end point was the change in mean limb fat over 48 weeks. Results. At week 96, we observed increases in mean (standard deviation [SD]) limb fat (+620 [974] g; P = .003), L4 subcutaneous adipose tissue (+20 [35] cm² P<.001), mid-thigh subcutaneous adipose tissue (+5 [10] cm² and L4 visceral adipose tissue (+11 [34] cm² P = .01), but we also observed reduced lean limb mass (-831 [1100] g; P = .3). Mean (SD) mtDNA content in subcutaneous fat and in PBMCs increased (+109 [274] and +45 [100] copies/cell, respectively). Improved virological control or immune recovery did not explain the results. Triglyceride, total cholesterol, estimated low-density lipoprotein cholesterol, ratio of total cholesterol to high-density lipoprotein cholesterol, and blood glucose levels deteriorated (i.e., had increased by 206%, 67%, 58%, 19%, and 6%, respectively, at week 96). Conclusions. This regimen was associated with statistically significant but clinically modest increases in peripheral fat, visceral fat, and mitochondrial nucleic acid content. A predominantly adverse metabolic profile developed. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to compare the efficacy of different HIV drug resistance test reports (genotype and virtual phenotype) in patients who were changing their antiretroviral therapy (ART). Design: Randomised, open-label trial with 48-week followup. Setting: The study was conducted in a network of primary healthcare sites in Australia and New Zealand. Participants: Patients failing current ART with plasma HIV RNA > 2000 copies/mL who wished to change their current ART were eligible. Subjects were required to be > 18 years of age, previously treated with ART, have no intercurrent illnesses requiring active therapy, and to have provided written informed consent. Interventions: Eligible subjects were randomly assigned to receive a genotype (group A) or genotype plus virtual phenotype (group B) prior to selection of their new antiretroviral regimen. Outcome Measures: Patient groups were compared for patterns of ART selection and surrogate outcomes (plasma viral load and CD4 counts) on an intention-to-treat basis over a 48-week period. Results: Three hundred and twenty seven patients completing > one month of followup were included in these analyses. Resistance tests were the primary means by which ART regimens were selected (group A: 64%, group B: 62%; p 1/4 0.32). At 48 weeks, there were no significant differences between the groups for mean change from baseline plasma HIV RNA (group A: 0.68 log copies/mL, group B: 0.58 log copies/mL; p = 0.23) and mean change from baseline CD4+ cell count (group A: 37 cells/mm³, group B: 50 cells/mm³; p = 0.28). Conclusions: In the absence of clear demonstrated benefits arising from the use of the virtual phenotype interpretation, this study suggests resistance testing using genotyping linked to a reliable interpretive algorithm is adequate for the management of HIV infection. [ABSTRACT FROM AUTHOR]

Describes an objective lipodystrophy severity grading scale derived from the lipodystrophy case definition score (LCDS). LDCD score as the best objective measure of lipodystrophy severity; Data showing that the LDCD score and its derived lipodystrophy grading scale merit prospective evaluation.

The article discusses various topics published within the issue including the importance of tailoring antiretroviral therapy (ART) to an aging population of people living with HIV (PLHIV), the issues affecting the kidneys in aging PLHIV and the liver-associated issues among the population of aging PLHIV.

Introduction Development of a simple, widely applicable risk score for chronic kidney disease (CKD) allows comparisons of risks or benefits of starting potentially nephrotoxic antiretrovirals (ARVs) as part of a treatment regimen. Materials and Methods A total of 18,055 HIV-positive persons from the Data on Adverse Drugs (D:A:D) study with >3 estimated glomerular filtration rates (eGFRs) >1/1/2004 were included. Persons with use of tenofovir (TDF), atazanavir (ritonavir boosted (ATV/r) and unboosted (ATV)), lopinavir (LPV/r) and other boosted protease inhibitors (bPIs) before baseline (first eGFR >60 ml/min/1.73 m2 after 1/1/2004) were excluded. CKD was defined as confirmed (>3 months apart) eGFR <60. Poisson regression was used to develop a score predicting low (<0 points), medium (1-4 points) and high (>5 points) risk of developing CKD. Increased incidence of CKD associated with starting ARVs was modelled by including ARVs as time-updated variables. The risk score was externally validated on two independent cohorts. Results A total of 641 persons developed CKD during 103,278.5 PYFU (incidence 6.2/1000 PYFU, 95% CI 5.7-6.7). Older age, intravenous drug use, HCV+ antibody status, lower baseline eGFR, female gender, lower CD4 nadir, hypertension, diabetes and cardiovascular disease predicted CKD and were included in the risk score (Figure 1). The incidence of CKD in those at low, medium and high risk was 0.8/1000 PYFU (95% CI 0.6-1.0), 5.6 (95% CI 4.5-6.7) and 37.4 (95% CI 34.0-40.7) (Figure 1). The risk score showed good discrimination (Harrell's c statistic 0.92, 95% CI 0.90-0.93). The number needed to harm (NNTH) in patients starting ATV or LPV/r was 1395, 142 or 20, respectively, among those with low, medium or high risk. NNTH were 603, 61 and 9 for those with a low, medium or high risk starting TDF, ATV/r or bPIs. The risk score was externally validated on 2603 persons from the Royal Free Hospital clinic cohort (94 events, incidence 5.1/1000 PYFU; 95% CI 4.1-6.1) and 2013 persons from the control arms of SMART/ESPRIT (32 events, incidence 3.8/1000 PYFU; 95% CI 2.5-5.1). External validation showed consistent CKD rates across risk groups (Figure 2). Interpretation Traditional and HIV-related risk factors were predictive of CKD; all are routinely available, making the risk score easy to incorporate into clinical practise and of direct relevance for clinical decision making. NNTH in persons starting potentially nephrotoxic ARVs at high risk of CKD were low, and alternative ARVs may be more appropriate. [ABSTRACT FROM AUTHOR]

Background & objectives: Although the World Health Organization recommends same day or rapid (< seven days) antiretroviral therapy (ART) initiation, delays in ART initiation remain common due to waiting for laboratory test results. This study employed a simplified clinical algorithm the HATI [HIV Awal (Early) Test & Treat Indonesia]-SAI (Simple ART Initiation) aimed to increase the proportion of ART uptake and decrease the time to ART initiation that can be used in various care settings. Methods: This study compared the percentage of ART uptake and retention, viral load (VL) suppression and time to ART initiation between the observation and intervention phases among newly diagnosed HIV patients from key populations. As part of the intervention, the newly diagnosed patients underwent screening using a simple form [consisting of data on age, height and weight (for body mass index calculation), questions on the presence of symptoms of HIV stages 1 and 2, tuberculosis, history of diabetes, hypertension and kidney disease], to determine eligibility for immediate ART initiation. Those who met the pre-defined criteria immediately received a combination of tenofovir lamivudine and efavirenz for two weeks. The baseline laboratory examination due to this was moved up to two weeks post ART. Factors significantly associated with ART uptake were also determined and their odds ratios were measured using logistic regression analysis. Results: A total of 2173 people newly diagnosed with HIV were recruited, with 1579 and 594 in the observation and intervention phases, respectively. In both phases, the majority were men who have sex with men, who were young (<30 yr old) and employed, with high levels of education. The intervention phase significantly increased the proportion of ART initiation [91%, 95% confidence interval (CI): 89-93% vs. 78%, 95% CI: 76-80%] but did not have any impact on the proportion of six months retention and VL suppression. The intervention also significantly decreased the time to ART initiation from median ± interquartile range: 9±20 days to 2±10 days. Interpretation & conclusions: The findings of this study suggest that the HATI-SAI intervention increased the uptake and decreased the time for immediate ART initiation. The HATI-SAI provides a simple and safe clinical approach that can readily be adopted in different settings without a costly investment in technology. [ABSTRACT FROM AUTHOR]

This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger (P = 0.002), had HIV viral load ⩾500 copies/mL or missing (P = 0.021), had shorter history of HIV infection (P = 0.048), and received no, single- or double antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P < 0.001). 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin (P < 0.001), missing recent HIV viral load (P < 0.001), negative hepatitis C test (P = 0.025), and previous temporary LTFU episodes (P < 0.001). Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced. [ABSTRACT FROM AUTHOR]

The article discusses the study focusing on the random effects models used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART). Data for the study was gathered from patients in Asia Pacific Human Immunodeficiency Virus (HIV) Observational Database. It suggests that the long-term shape of post-cART CD4 cell count changes depend only on a 3-way interaction between baseline CD4 cell count, viral load response and time.

The article determines whether the addition of hydroxyurea in combination with antiretroviral (ARV) therapy including didanosine results in improved virologic control in the setting of structured treatment interruptions (STI) in patients with primary HIV infection (PHI). Success of the treatment was defined as maintaining viral loads at less than 5000 copies/ml for six months after ARV interruption. The study reveals that hydroxyurea was not found to be beneficial when used in association with STI in patients during PHI.