Has COVID-19 changed the approach to HIV diagnosis?: A multicentric Italian experience.

ABSTRACT: The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.

Variation in HIV care and treatment outcomes by facility in South Africa, 2011-2015: A cohort study.

BACKGROUND: Despite widespread availability of HIV treatment, patient outcomes differ across facilities. We propose and evaluate an approach to measure quality of HIV care at health facilities in South Africa's national HIV program using routine laboratory data. METHODS AND FINDINGS: Data were extracted from South Africa's National Health Laboratory Service (NHLS) Corporate Data Warehouse. All CD4 counts, viral loads (VLs), and other laboratory tests used in HIV monitoring were linked, creating a validated patient identifier. We constructed longitudinal HIV care cascades for all patients in the national HIV program, excluding data from the Western Cape and very small facilities. We then estimated for each facility in each year (2011 to 2015) the following cascade measures identified a priori as reflecting quality of HIV care: median CD4 count among new patients; retention 12 months after presentation; 12-month retention among patients established in care; viral suppression; CD4 recovery; monitoring after an elevated VL. We used factor analysis to identify an underlying measure of quality of care, and we assessed the persistence of this quality measure over time. We then assessed spatiotemporal variation and facility and population predictors in a multivariable regression context. We analyzed data on 3,265 facilities with a median (IQR) annual size of 441 (189 to 988) lab-monitored HIV patients. Retention 12 months after presentation increased from 42% to 47% during the study period, and viral suppression increased from 66% to 79%, although there was substantial variability across facilities. We identified an underlying measure of quality of HIV care that correlated with all cascade measures except median CD4 count at presentation. Averaging across the 5 years of data, this quality score attained a reliability of 0.84. Quality was higher for clinics (versus hospitals), in rural (versus urban) areas, and for larger facilities. Quality was lower in high-poverty areas but was not independently associated with percent Black. Quality increased by 0.49 (95% CI 0.46 to 0.53) standard deviations from 2011 to 2015, and there was evidence of geospatial autocorrelation (p < 0.001). The study's limitations include an inability to fully adjust for underlying patient risk, reliance on laboratory data which do not capture all relevant domains of quality, potential for errors in record linkage, and the omission of Western Cape. CONCLUSIONS: We observed persistent differences in HIV care and treatment outcomes across South African facilities. Targeting low-performing facilities for additional support could reduce overall burden of disease.

Assessment of Tp-e interval and Tp-e/QT ratio in patients with human immunodeficiency virus.

OBJECTIVE: Sudden cardiac death (SCD) plays an important part in all-cause mortality in patients infected with human immunodeficiency virus (HIV). The T-peak to T-end (Tp-e) interval, corrected Tp-e (Tp-ec) interval, and Tp-e/QT ratio on the ECG are parameters used to stratify risk for SCD. The objective of this study was to investigate the differences between HIV-infected patients and healthy individuals in terms of Tp-e interval, Tp-ec interval, and Tp-e/QT ratio, as well as other influencing factors. METHODS: Ninety-eight HIV-infected patients and 62 healthy controls were included in this prospective case-control study. Tp-e interval, Tp-ec interval, and Tp-e/QT ratio were measured in all participants. Echocardiographic examination and routine laboratory analysis were performed. In addition, CD4 T-cell count and HIV RNA levels were assessed in HIV-infected patients. RESULTS: All baseline characteristics were comparable in both groups. The median survival of those living with HIV was 20.63 months; 53% of them had controlled viral load, and 74% were receiving antiretroviral therapy. Mean baseline CD4 T-cell count was 409. In HIV-infected patients, the Tp-e interval and Tp-ec interval were prolonged, and the Tp-e/QT ratio was higher (p<0.001, p<0.001 and p=0.021, respectively). In bivariate and partial correlation analyses, there was a negative correlation between CD4 T-cell level and Tp-e interval, Tp-ec interval, and Tp-e/QT ratio. CONCLUSION: Tp-e interval, Tp-ec interval, and Tp-e/QT ratio were greater in HIV-infected patients compared with healthy individuals. HIV-infected patients, particularly those with low baseline CD4 T-cell counts, should be closely monitored due to risk of SCD.

Modelling immune deterioration, immune recovery and state-specific duration of HIV-infected women with viral load adjustment: using parametric multistate model.

BACKGROUND: CD4 cell and viral load count are highly correlated surrogate markers of human immunodeficiency virus (HIV) disease progression. In modelling the progression of HIV, previous studies mostly dealt with either CD4 cell counts or viral load alone. In this work, both biomarkers are in included one model, in order to study possible factors that affect the intensities of immune deterioration, immune recovery and state-specific duration of HIV-infected women. METHODS: The data is from an ongoing prospective cohort study conducted among antiretroviral treatment (ART) naïve HIV-infected women in the province of KwaZulu-Natal, South Africa. Participants were enrolled in the acute HIV infection phase, then followed-up during chronic infection up to ART initiation. Full-parametric and semi-parametric Markov models were applied. Furthermore, the effect of the inclusion and exclusion viral load in the model was assessed. RESULTS: Inclusion of a viral load component improves the efficiency of the model. The analysis results showed that patients who reported a stable sexual partner, having a higher educational level, higher physical health score and having a high mononuclear component score are more likely to spend more time in a good HIV state (particularly normal disease state). Patients with TB co-infection, with anemia, having a high liver abnormality score and patients who reported many sexual partners, had a significant increase in the intensities of immunological deterioration transitions. On the other hand, having high weight, higher education level, higher quality of life score, having high RBC parameters, high granulocyte component scores and high mononuclear component scores, significantly increased the intensities of immunological recovery transitions. CONCLUSION: Inclusion of both CD4 cell count based disease progression states and viral load, in the time-homogeneous Markov model, assisted in modeling the complete disease progression of HIV/AIDS. Higher quality of life (QoL) domain scores, good clinical characteristics, stable sexual partner and higher educational level were found to be predictive factors for transition and length of stay in sequential adversity of HIV/AIDS.

Assessing the Quality of Human Immunodeficiency Virus Care in Nursing Homes.

BACKGROUND: Quality of human immunodeficiency virus (HIV) care in nursing homes (NHs) has never been measured. DESIGN: A cross-sectional study. SETTING: NHs. PARTICIPANTS: A total of 203 NHs and 1375 persons living with HIV. MEASUREMENTS: Medicare claims from 2011 to 2013 were linked to assessments of resident health, prescription dispensing data, and national reports of NH characteristics. Five nationally validated HIV care quality measures (prescription of antiretroviral therapy; CD4/viral load monitoring; frequency of medical visits; gaps in medical visits; and Pneumocystis pneumonia prophylaxis) were adapted and applied to NHs. Logistic regression predicted compliance by organizational factors. Random intercept logistic regression predicted if persons living with HIV received care by person and organizational factors. RESULTS: Compliance ranged from 43.3% (SD = 31.1%) for CD4/viral load monitoring to 92.4% (SD = 13.6%) for gaps in medical visits. More substantiated complaints against an NH decreased the likelihood of high compliance with CD4/viral load monitoring (odds ratio [OR] = 0.846; 95% confidence interval [CI] = 0.726-0.986), while NH-reported incidents increased the likelihood of high compliance with pneumocystis pneumonia prophylaxis (OR = 1.173; 95% CI = 1.044-1.317). Differences between NHs explained 21.2% or less of variability in receipt of care. CONCLUSIONS: Since 2013, the population with HIV and NH HIV care quality has inevitably evolved; however, this study provides previously unknown baseline metrics on NH HIV care quality and highlights significant challenges when measuring HIV care in NHs. J Am Geriatr Soc 68:1226-1234, 2020.

A More Efficient Causal Mediator Model Without the No-Unmeasured-Confounder Assumption.

Mediator models have been developed primarily under the assumption of no-unmeasured-confounding. In many situations, this assumption is violated and may lead to the identification of mediator variables that actually are statistical artifacts. The rank preserving model (RPM) is an alternative approach to estimate controlled direct and mediator effects. It is based on the structural mean models framework and a no-effect-modifier assumption. The RPM assumes that unobserved confounders do not interact with treatment or mediators. This assumption is often more plausible to hold than the no-unmeasured-confounder assumption. So far, models using the no-effect-modifier assumption have been rarely used, which might be due to its low power and inefficiency in many scenarios. Here, a semi-parametric nonlinear extension, the nRPM, is proposed that overcomes this inefficiency using thin plate regression splines that both increase the predictive power of the model and decrease the misspecification present in many situations. In a simulation study, it is shown that the nRPM provides estimates that are robust against the violation of the no-effect-modifier assumption and that are substantively more efficient than those of the RPM. The model is illustrated using a data set on CD4 cell counts in a context of the human immunodeficiency virus (HIV).

Clinical determinants associated with quality of life for people who live with HIV/AIDS: a Meta-analysis.

BACKGROUND: During recent years, Quality of Life (QoL) is a significant assessment factor in clinical trials and epidemiological researches due to the advent of Antiretroviral Therapy (ART), Human Immunodeficiency Virus (HIV) has become a manageable,chronic disease. With regards, more attention must be paid to the QoL of infected patients. Limited evidence exists on the impact of ART on QoL among HIV infected patients. Due to lacking of a systematic approach to summarizing the available evidence on the clinical determinants of People Who Live with HIV/AIDS (PWLHs') QoL, this study aimed to analyze the impact of clinical determinants (ART experience, CD4 count < 200, co-morbidities, time diagnosis and accessibility to cares) on QoL among PWLHs'. METHODS: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Science Direct, Web of Science, and Cochrane electronic databases were searched in February 2017 to identify all past studies that discussed social and behavioral characteristics of QoL in PLWHA. To recognize effective factors on social and behavioral QoL, a meta-analysis was conducted. Polled Odds Ratios (ORs) were utilized at a 95% confidence level. Since sampling methods differed between articles in the systematic review, we evaluated pooled estimates using a random effect model. Metan, metareg, metacum, and metabias commands in STATA version 13.0 were applied to analyze the data. RESULTS: Our findings indicated that ART has a positive impact on QoL, with a pooled effect size at approximately 1.04 with a confidence interval between 0.42 to 1.66 which indicates this impact is not very considerable and may be relatively neutral. The pooled effect size for CD4 count on QoL was .29 (95%CI = .22-.35), indicating that there is a negative associate between CD4 count and QoL. The co-morbidity as a negative determinant for QoL among HIV/AIDS infected people. The pooled effect size implies on a relative neutral association, although the confidence interval is wide and ranges between 0.32 to 1.58. The pooled effect size is about 1.82 with confidence interval 1.27 to 2.37 which indicates a considerable positive association with lowest level of heterogeneity. CONCLUSIONS: The results illustrated that time diagnosing and availability to hospital services had significant relationship with a higher QoL and CD4 < 200 was associated with a lower QoL. In conclusion, policy makers should set an agenda setting to provide a suitable diagnostic and therapeutic facilities to early detecting and continues monitoring the health status of People Who Live with HIV/AIDS (PWLHs').

External Quality Assessment on CD4+ T-Cell Count Using in-House Proficiency Testing Panels for CD4 Count Laboratories in Addis Ababa, Ethiopia.

BACKGROUND: CD4+ T-cell count External Quality Assessment program is important for the evaluation of performance of CD4 count laboratories. The aim of this study was to assess the quality of CD4count laboratory performance using in-house Proficiency testing panels that perform routine CD4 counts in Addis Ababa, Ethiopia, 2013/14. METHODS: Participating laboratories were 20, 23 and 25 in trials 1, 2 and 3, respectively. In-house prepared fresh whole blood samples both with "normal" and "low" CD4 values were sent to participating laboratories. Percentage and absolute counts of CD4+ T-lymphocytes were done using their routine procedures. Data were analyzed for each trial including trimmed mean, standard deviation (SD), percent coefficient of variation (%CV), residual, and standard deviation index (SDI) values for both absolute counts and percentages of CD4+ lymphocytes (%CD4). RESULTS: Most participating laboratories produced results that were within 2SD of the mean. Average inter-laboratory precision (trimmed %CV) was 10.87% and 5.14% for CD4 absolute counts and %CD4, respectively. For normal material, the trimmed mean %CV was 9.59% and3.23% for CD4 absolute counts and %CD4, respectively. For low material, the trimmed mean % CV was 12.15% and 7.05% for CD4 absolute counts and %CD4 respectively. BDFACSCount™ users showed the best accuracy and precision as evidenced by longitudinal analysis. CONCLUSION: This study was found to help facilities in early identifying their gaps with regard to their CD4 count performance and in avoiding the challenges encountered during participation in external EQA providers like the high cost, transportation problem, feedback delay and CD4laboratory coverage.

Improving Laboratory Efficiency in the Caribbean to Attain the World Health Organization HIV Treat All Recommendations.

Scientific evidence showing the benefits of early initiation of antiretroviral therapy (ART) prompted World Health organization (WHO) to recommend that all persons diagnosed as HIV positive should commence ART irrespective of CD4 count and disease progression. Based on this recommendation, countries should adopt and implement the HIV "Treat All" policy to achieve the UNAIDS 90-90-90 targets and ultimately reach epidemic control. Attaining this goal along the HIV treatment cascade depends on the laboratory to monitor progress and measure impact. The laboratory plays an important role in HIV diagnosis to attain the first 90 and in viral load (VL) and HIV drug resistance testing to reinforce adherence, improve viral suppression, and measure the third 90. Countries in the Caribbean region have endorsed the WHO HIV "Treat all" recommendation; however, they are faced with diminishing financial resources to support laboratory testing, seen as a rate-limiting factor to achieving this goal. To improve laboratory coverage with fewer resources in the Caribbean there is the need to optimize laboratory operations to ensure the implementation of high quality, less expensive evidence-based approaches that will result in more efficient and effective service delivery. Suggested practical and innovative approaches to achieve this include: (1) targeted testing within HIV hotspots; (2) strengthening sample referral systems for VL; (3) better laboratory data collection systems; and (4) use of treatment cascade data for programmatic decision-making. Furthermore, strengthening quality improvement and procurement systems will minimize diagnostic errors and guarantee a continuum of uninterrupted testing which is critical for routine monitoring of patients to meet the stated goal.

Highly active antiretroviral therapy and cervical cytologic abnormalities among women with HIV infection in a limited-resource setting.

OBJECTIVE: To examine the relationship between highly active antiretroviral therapy (HAART) and cervical cytologic abnormalities among women with HIV infection. METHODS: A cross-sectional prospective study was undertaken of 110 women attending an HIV clinic in Nnewi, Nigeria, between January 2016 and January 2017. A cervical smear was obtained. A bivariate analysis was undertaken, and multiple logistic regression models were used to identify factors independently associated with cervical cytologic analysis. RESULTS: Cervical cytologic abnormalities were identified in 31 (28.2%) participants. On bivariate analysis, use of HAART for 2-5 years was associated with a reduction in the risk of cervical cytologic abnormalities (P=0.033), and this risk was further reduced when HAART was taken for more than 5 years (P<0.001). Other factors that significantly reduced risk of cervical cytologic abnormalities included a CD4 count of 300 cells per mL or more (P<0.001), age 30 years or older (P<0.001), and time since HIV diagnosis of more than 5 years (P=0.021). On multivariate analysis, risk of cervical cytologic abnormalities among the women were significantly reduced by use of HAART for more than 5 years (P=0.032) and CD4 count of 300 cells per mL or more (P<0.001). CONCLUSION: Long-term use of HAART and CD4 count of 300 cells per mL or more were associated with a reduced risk of cervical cytologic abnormalities.

Mixed hidden Markov quantile regression models for longitudinal data with possibly incomplete sequences.

Quantile regression provides a detailed and robust picture of the distribution of a response variable, conditional on a set of observed covariates. Recently, it has be been extended to the analysis of longitudinal continuous outcomes using either time-constant or time-varying random parameters. However, in real-life data, we frequently observe both temporal shocks in the overall trend and individual-specific heterogeneity in model parameters. A benchmark dataset on HIV progression gives a clear example. Here, the evolution of the CD4 log counts exhibits both sudden temporal changes in the overall trend and heterogeneity in the effect of the time since seroconversion on the response dynamics. To accommodate such situations, we propose a quantile regression model, where time-varying and time-constant random coefficients are jointly considered. Since observed data may be incomplete due to early drop-out, we also extend the proposed model in a pattern mixture perspective. We assess the performance of the proposals via a large-scale simulation study and the analysis of the CD4 count data.

The evolving role of CD4 cell counts in HIV care.

PURPOSE OF REVIEW: The role of the CD4 cell count in the management of people living with HIV is once again changing, most notably with a shift away from using CD4 assays to decide when to start antiretroviral therapy (ART). This article reflects on the past, current and future role of CD4 cell count testing in HIV programmes, and the implications for clinicians, programme managers and diagnostics manufacturers. RECENT FINDINGS: Following the results of recent randomized trials demonstrating the clinical and public health benefits of starting ART as soon as possible after HIV diagnosis is confirmed, CD4 cell count is no longer recommended as a way to decide when to initiate ART. For patients stable on ART, CD4 cell counts are no longer needed to monitor the response to treatment where HIV viral load testing is available. Nevertheless CD4 remains the best measurement of a patient's immune and clinical status, the risk of opportunistic infections, and supports diagnostic decision-making, particularly for patients with advanced HIV disease. SUMMARY: As countries revise guidelines to provide ART to all people living with HIV and continue to scale up access to viral load, strategic choices will need to be made regarding future investments in CD4 cell count and the appropriate use for clinical disease management.

Evaluating strategies to improve HIV care outcomes in Kenya: a modelling study.

BACKGROUND: With expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health. METHODS: We created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya. We calibrated the model to a longitudinal dataset from the Academic Model Providing Access To Healthcare (known as AMPATH) programme describing the routes into care, losses from care, and clinical outcomes. We simulated the cost and effect of interventions at different stages of HIV care, including improvements to diagnosis, linkage to care, retention and adherence of ART, immediate ART eligibility, and a universal test-and-treat strategy. FINDINGS: We estimate that, of people dying from AIDS between 2010 and 2030, most will have initiated treatment (61%), but many will never have been diagnosed (25%) or will have been diagnosed but never started ART (14%). Many interventions targeting a single stage of the health-care cascade were likely to be cost-effective, but any individual intervention averted only a small percentage of deaths because the effect is attenuated by other weaknesses in care. However, a combination of five interventions (including improved linkage, point-of-care CD4 testing, voluntary counselling and testing with point-of-care CD4, and outreach to improve retention in pre-ART care and on-ART) would have a much larger impact, averting 1·10 million disability-adjusted life-years (DALYs) and 25% of expected new infections and would probably be cost-effective (US$571 per DALY averted). This strategy would improve health more efficiently than a universal test-and-treat intervention if there were no accompanying improvements to care ($1760 per DALY averted). INTERPRETATION: When resources are limited, combinations of interventions to improve care should be prioritised over high-cost strategies such as universal test-and-treat strategy, especially if this is not accompanied by improvements to the care cascade. International guidance on ART should reflect alternative routes to programme strengthening and encourage country programmes to evaluate the costs and population-health impact in addition to the clinical benefits of immediate initiation. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, National Institutes of Health.

Cost-effectiveness of implementing the chronic care model for HIV care in Uganda.

OBJECTIVE: The chronic care model (CCM) is an integrated, population-based approach for treating those with chronic diseases that involves patient self-management, delivery system design and decision support for clinicians to ensure evidence-based care. We sought to determine effectiveness and cost-effectiveness of implementing the CCM for HIV care in Uganda. DESIGN: This controlled, pre/post-intervention study used difference-in-differences analysis to evaluate effectiveness of the CCM to improve patient adherence to antiretroviral therapy (ART) and CD4 counts. SETTING: One district hospital and two smaller facilities each in one intervention and one control district in Uganda. PARTICIPANTS: About 46 randomly sampled patients receiving HIV services at three control sites and 56 patients from three intervention sites. INTERVENTION: Two group training sessions and monthly coaching visits from improvement experts over 1 year, implementing the CCM. MAIN OUTCOME MEASURE(S): Patient adherence to ART prescriptions (pill counts) and CD4 counts were measured at baseline and en dline. RESULTS: The odds of increased CD4 in the intervention group was 3.2 times higher than controls (P = 0.022). Clinician-reported ART adherence was 60% (P = 0.001) higher in the intervention group. The intervention cost $11 740 and served 7016 patients ($1.67 per patient). Incremental cost-effectiveness ratios of the intervention compared to business-as-usual was $6.90 per additional patient with improved CD4 and $3.40 per additional ART patient with stable or improved adherence. CONCLUSION: For modest expenditure, it is possible to improve indicators of HIV care quality using the CCM. We recommended implementing the CCM in Uganda; it may be applicable in similar settings in other countries.

HIV outcomes at a Canadian remand centre.

Purpose The purpose of this paper is to assess the impact of short-term incarceration on antiretroviral therapy (ART) adherence, virologic suppression, and engagement and retention in community care post-release. Design/methodology/approach A retrospective chart review of patients who attended the human immunodeficiency virus (HIV) Outreach Clinic at a Canadian remand center between September 2007 and December 2011 was carried out. Data extraction included CD4 lymphocyte count, HIV viral load, ART prescription refills, and community engagement and retention during and one-year pre- and post-incarceration. Findings Outpatient engagement increased by 23 percent ( p=0.01), as did ART adherence (55.2-70.7 percent, p=0.01), following incarceration. Retention into community care did not significantly improve following incarceration (22.4 percent pre-incarceration to 25.9 percent post-release, p=0.8). There was a trend toward improved virologic suppression (less than 40 copies/ml; 50-77.8 percent ( p=0.08)) during incarceration and 70. 4 percent sustained this one-year post-incarceration ( p=0.70). Originality/value The impact of short-term incarceration in a Canadian context of universal health coverage has not been previously reported and could have significant implications in optimizing HIV patient outcomes given the large number of HIV-positive patients cycling through short-term remand centers.

Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015: the Global Burden of Disease Study 2015.

BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015. METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification. FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections. INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. FUNDING: Bill & Melinda Gates Foundation, and National Institute of Mental Health and National Institute on Aging, National Institutes of Health.

How Will New Guidelines Affect CD4 Testing in Veterans With HIV?

BACKGROUND: Guidelines now recommend limited use of routine CD4 cell count testing in human immunodeficiency virus (HIV)-infected patients with successful viral control who are not immunocompromised. METHODS: CD4 and viral load tests for patients receiving HIV care from the US Department of Veterans Affairs during 2009-2013 were evaluated to determine trends in CD4 testing frequency and the number, cost, and results of CD4 tests considered optional under the guidelines. RESULTS: There were 28 530 individuals with sufficient testing to be included. At the time of the last CD4 test, 19.8% of the cohort was eligible for optional monitoring and 15.6% for minimal monitoring. CD4 testing frequency declined by 10.8% over 4 years, reducing the direct cost of testing by US$196 000 per year. Full implementation of new treatment guidelines could reduce CD4 testing a further 28.9%, an additional annual savings of US$600 000. CD4 tests conducted during periods of potentially reduced monitoring were rarely <200 cells/µL: 1.1% of the tests conducted when minimal monitoring was recommended and just 0.3% of tests conducted when optional monitoring was recommended were less than this value. CONCLUSIONS: Reduced CD4 monitoring of HIV-infected patients would result in modest cost savings and likely reduce patient anxiety, with little or no impact on the quality of care. Veterans Affairs has made substantial progress in reducing the frequency of optional CD4 testing, but further reductions may still be warranted.

The Immunology Quality Assessment Proficiency Testing Program for CD3⁺4⁺ and CD3⁺8⁺ lymphocyte subsets: a ten year review via longitudinal mixed effects modeling.

Since 1999, the National Institute of Allergy and Infectious Diseases Division of AIDS (NIAID DAIDS) has funded the Immunology Quality Assessment (IQA) Program with the goal of assessing proficiency in basic lymphocyte subset immunophenotyping for each North American laboratory supporting the NIAID DAIDS HIV clinical trial networks. Further, the purpose of this program is to facilitate an increase in the consistency of interlaboratory T-cell subset measurement (CD3(+)4(+)/CD3(+)8(+) percentages and absolute counts) and likewise, a decrease in intralaboratory variability. IQA T-cell subset measurement proficiency testing was performed over a ten-year period (January 2003-July 2012), and the results were analyzed via longitudinal analysis using mixed effects models. The goal of this analysis was to describe how a typical laboratory (a statistical modeling construct) participating in the IQA Program performed over time. Specifically, these models were utilized to examine trends in interlaboratory agreement, as well as successful passing of proficiency testing. Intralaboratory variability (i.e., precision) was determined by the repeated measures variance, while fixed and random effects were taken into account for changes in interlaboratory agreement (i.e., accuracy) over time. A flow cytometer (single-platform technology, SPT) or a flow cytometer/hematology analyzer (dual-platform technology, DPT) was also examined as a factor for accuracy and precision. The principal finding of this analysis was a significant (p<0.001) increase in accuracy of T-cell subset measurements over time, regardless of technology type (SPT or DPT). Greater precision was found in SPT measurements of all T-cell subset measurements (p<0.001), as well as greater accuracy of SPT on CD3(+)4(+)% and CD3(+)8(+)% assessments (p<0.05 and p<0.001, respectively). However, the interlaboratory random effects variance in DPT results indicates that for some cases DPT can have increased accuracy compared to SPT. Overall, these findings demonstrate that proficiency in and among IQA laboratories have, in general, improved over time and that platform type differences in performance do exist.

Association of Supplemental Nutrition Assistance Program (SNAP) with health related quality of life and disease state of HIV infected patients.

The literature on the potential clinical and non-clinical benefits of participation in food assistance programs for people living with HIV in developed countries is scarce. We conducted a cross-sectional study of 165 HIV infected adults to determine the impact of the Supplemental Nutrition Assistance Program (SNAP) on HIV disease status and health related quality of life (HQROL). There was no significant association between SNAP participation and disease status; CD4 cell count (ß = 0.02, P = 0.837) and viral load (ß = 0.02, P = 0.836). The mean scores for all the HRQOL domains were lower compared to the US population, but none were associated with SNAP participation. Higher scores on the general health domain, were marginally associated with SNAP participation (ß = 0.16, P = 0.071). In this study, SNAP participation was not significantly associated with less disease progression, and only marginally associated with quality of life among this population of HIV infected individuals.

Gender differences in HIV disease progression and treatment outcomes among HIV patients one year after starting antiretroviral treatment (ART) in Dar es Salaam, Tanzania.

BACKGROUND: We investigated gender differences in treatment outcome during first line antiretroviral treatment (ART) in a hospital setting in Tanzania, assessing clinical, social demographic, virological and immunological factors. METHODS: We conducted a cohort study involving HIV infected patients scheduled to start ART and followed up to 1 year on ART. Structured questionnaires and patients file review were used to collect information and blood was collected for CD4 and viral load testing. Gender differences were assessed using Kruskal-Wallis test and chi-square test for continuous and categorical data respectively. Survival distributions for male and female patients were estimated using the Kaplan-Meier method and compared using Cox proportional hazards models. RESULTS: Of 234 patients recruited in this study, 70% were females. At baseline, women had significantly lower education level; lower monthly income, lower knowledge on ARV, less advanced HIV disease (33% women; 47% men started ART at WHO stage IV, p = 0.04), higher CD4 cell count (median 149 for women, 102 for men, p = 0.02) and higher BMI (p = 0.002). After 1 year of standard ART, a higher proportion of females survived although this was not significant, a significantly higher proportion of females had undetectable plasma viral load (69% women, 45% men, p = 0.003), however females ended at a comparable CD4 cell count (median CD4, 312 women; 321 men) signifying a worse CD4 cell increase (p = 0.05), even though they still had a higher BMI (p = 0.02). The unadjusted relative hazard for death for men compared to women was 1.94. After correcting for confounding factors, the Cox proportional hazards showed no significant difference in the survival rate (relative hazard 1.02). CONCLUSION: We observed women were starting treatment at a less advanced disease stage, but they had a lower socioeconomical status. After one year, both men and women had similar clinical and immunological conditions. It is not clear why women lose their immunological advantage over men despite a better virological treatment response. We recommend continuous follow up of this and more cohorts of patients to better understand the underlying causes for these differences and whether this will translate also in longer term differences.