Addressing an HIV cure in LMIC.

HIV-1 persists in infected individuals despite years of antiretroviral therapy (ART), due to the formation of a stable and long-lived latent viral reservoir. Early ART can reduce the latent reservoir and is associated with post-treatment control in people living with HIV (PLWH). However, even in post-treatment controllers, ART cessation after a period of time inevitably results in rebound of plasma viraemia, thus lifelong treatment for viral suppression is indicated. Due to the difficulties of sustained life-long treatment in the millions of PLWH worldwide, a cure is undeniably necessary. This requires an in-depth understanding of reservoir formation and dynamics. Differences exist in treatment guidelines and accessibility to treatment as well as social stigma between low- and-middle income countries (LMICs) and high-income countries. In addition, demographic differences exist in PLWH from different geographical regions such as infecting viral subtype and host genetics, which can contribute to differences in the viral reservoir between different populations. Here, we review topics relevant to HIV-1 cure research in LMICs, with a focus on sub-Saharan Africa, the region of the world bearing the greatest burden of HIV-1. We present a summary of ART in LMICs, highlighting challenges that may be experienced in implementing a HIV-1 cure therapeutic. Furthermore, we discuss current research on the HIV-1 latent reservoir in different populations, highlighting research in LMIC and gaps in the research that may facilitate a global cure. Finally, we discuss current experimental cure strategies in the context of their potential application in LMICs.

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.

Performance indicator as the main and the only goal: a "dark side" of the intervention aims to accelerate HIV treatment entry among people who inject drugs in Kyiv, Ukraine.

BACKGROUND: To improve healthcare entry and antiretroviral therapy (ART) initiation for HIV-positive people who inject drugs (PWID) in Ukraine, an intervention built upon a successful community-based harm reduction project and the existing best practices was developed. In this article, we present the results of the study conducted in collaboration with one of the recipient organizations of the intervention in Kyiv. The research question was formulated as follows: how does the interaction between different actors work to lead it to a positive outcome (initiation PWIDs into ART) within the limited period of the intervention implementation? METHODS: The central focus of the study was on the work activities of case managers. Their daily routines as well as their interactions with their clients and medical workers were observed and analyzed. Using the institutional ethnography approach, we explore the institutional orders, power imbalances, and social factors that play different roles in coordinating the process of PWIDs entry into healthcare and HIV treatment. RESULTS: The most intriguing result of the study is that the performance indicator that must be completed in order to receive a full salary-as a way to manage the activities of case managers-produces conditions for them to develop their cooperation with medical workers but leaves the clients and their needs out of this "boat" because interaction with them, in fact, does not help to meet case managers' goals. CONCLUSIONS: Accountability of case managers' work assumes the primacy of the result over the process, which makes the process itself less important and the need to achieve the goal becomes the main and the only goal. This can be identified as an unintended consequence of the intervention implementation on the ground, or wider-an unintended consequence of the payment by results practice as a part of the general number-based policy.

Epidemiology and clinical management of HIV-HBV coinfected patients in a large AIDS Reference Center in Belgium.

Objectives: Human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are both worldwide health concerns with similar routes of transmission and no curative treatment to date. Coinfection is associated with increased morbidity and mortality. We aim to provide epidemiological data about HIV-HBV coinfected patients and asses if management of patients following European recommendation (EACS) was achieved in a large AIDS Reference Center in Belgium. Methods: Retrospective review of the HIV database of Saint-Pierre University Hospital in Brussels (Belgium) focusing on HIV-HBV coinfected patients in active follow-up. We classified patients in six serological profiles: (A) patients with active chronic HBV infection (HBsAg positive and HBeAg positive), (B) patients with persistent chronic HBV infection (HBsAg positive and HBeAg negative), (C) patients with isolated core antibody (isolated anti-HBc positive), (D) patients with resolved HBV infection (anti-HBc positive and anti-HBs positive), (E) vaccinated patients (anti-HBs positive), and (F) patients with all above markers negative. Chronic HBV infection (cHBV) was defined by two positive hepatitis B surface antigens (AgHBs positive) with at least 6-month intervals and chronic HBeAg positive group by a positive AgHBe (Ag HBe positive). We reviewed individual files of HIV-HBV chronically coinfected patients to assess if European recommendations in terms of HBV coinfection management were adequately followed in our center. Results: Among 2601 HIV-infected patients in active follow-up, 98 (3.8%) were chronically infected with HBV. Median age of chronically coinfected patients was 46 years with male predominance and heterosexual Africans representing the majority. Among the chronically coinfected patients, 33.7% were HBeAg positive carriers. Mean HBV DNA and ALT/AST were significantly higher in the chronic HBeAg positive (cHBeAg positive) patients compared to chronic HBeAg negative patients (cHBeAg negative). Nearly 95% of the cHBV patients were treated with two anti-HBV drugs (99% for the cHBeAg positive group), with 79% having Tenofovir (TDF) in their antiretroviral treatment history. 8% were screened for hepatitis D virus (HDV) antibodies. Liver fibrosis, upper endoscopy and alpha-foetoprotein were assessed at least once in the last 5 years in 32%, 31% and 32% of cHBV patients respectively. cHBeAg positive patients were not significantly monitored closer except for liver fibrosis assessment in 52% (p < 0.0017). Conclusion: The prevalence of cHBV coinfection in the Saint-Pierre HIV cohort is lower than in neighboring European countries. Hepatic monitoring should be reinforced in our cHBV and cHBeAg positive patients because of higher risk of progression to cirrhosis progression and hepatocellular carcinoma.

Inequalities in HAART uptake and differential survival according to exposure category in Rio de Janeiro, Brazil.

Despite substantial improvement in prognosis and quality of life among people living with HIV/AIDS (PLWHA) in Brazil, inequalities in access to treatment remain. We assessed the impact of these inequalities on survival in Rio de Janeiro over a 12-year period (2000/11). Data were merged from four databases that comprise the national AIDS monitoring system: SINAN-AIDS (Brazilian Information System for Notificable Diseases; AIDS cases), SISCEL (laboratory tests), SICLOM (electronic dispensing system), and SIM (Brazilian Mortality Information System), using probabilistic linkage. Cox regressions were fitted to assess the impact of HAART (highly active antiretroviral therapy) on AIDS-related mortality among men who have sex with men (MSM), people who inject drugs (PWID), and heterosexuals diagnosed with AIDS, between 2000 and 2011, in the city of Rio de Janeiro, RJ, Brazil. Among 15,420 cases, 60.7% were heterosexuals, 36.1% MSM and 3.2% PWID. There were 2,807 (18.2%) deaths and the median survival time was 6.29. HAART and CD4+ > 200 at baseline were associated with important protective effects. Non-whites had a 33% higher risk of dying in consequence of AIDS than whites. PWID had a 56% higher risk and MSM a 11% lower risk of dying of AIDS than heterosexuals. Non-white individuals, those with less than eight years of formal education, and PWID, were more likely to die of AIDS and less likely to receive HAART. Important inequalities persist in access to treatment, resulting in disparate impacts on mortality among exposure categories. Despite these persistent disparities, mortality decreased significantly during the period for all categories under analysis, and the overall positive impact of HAART on survival has been dramatic.

Predicting death and lost to follow-up among adults initiating antiretroviral therapy in resource-limited settings: Derivation and external validation of a risk score in Haiti.

BACKGROUND: Over 18 million adults have initiated life-saving antiretroviral therapy (ART) in resource-poor settings; however, mortality and lost-to-follow-up rates continue to be high among patients in their first year after treatment start. Clinical decision tools are needed to identify patients at high risk for poor outcomes in order to provide individualized risk assessment and intervention. This study aimed to develop and externally validate risk prediction tools that estimate the probability of dying or of being lost to follow-up (LTF) during the year after starting ART. METHODS: We used a derivation cohort of 7,031 adults age 15-70 years initiating ART from 2007 to 2013 at 6 clinics in Haiti; 242 (3.5%) had documented death and 1,521 (21.6%) were LTF at 1 year after starting ART. The following routinely collected data were used as predictors in two logistic regression models (one to predict death and another to predict LTF): age, gender, weight, CD4 count, WHO Stage, and diagnosis of tuberculosis (TB). The validation cohort consisted of 1,835 adults initiating ART at a different HIV clinic in Haiti during 2012. We assessed model discrimination by measuring the C-statistic, and measured model calibration by how closely the predicted probabilities approximated actual probabilities of the two outcomes. We derived a nomogram and a point-based risk score from the predictive models. FINDINGS: The model predicting death within the year after starting ART had a C-statistic of 0.75 (95% CI 0.74 to 0.81). There was no evidence for significant overfitting and the predictions were well calibrated. The strongest predictors of 1-year mortality were male gender, low weight, low CD4 count, advanced WHO stage, and the absence of TB. In the validation cohort, the C-statistic was 0.69 (95% CI 0.59 to 0.77). A point-based risk score for death had a C-statistic 0.73 (95% CI 0.69 to 0.76) and categorizes patients as low risk (<2% risk of death), average risk (3-4%), and high-risk (8-10%) and very high-risk (14-19%) with likelihood ratios to be used in settings where the baseline risk is different from our study population. The model predicting LTF did not discriminate well (C-statistic 0.59). CONCLUSIONS: A simple risk-score using routinely collected data can predict 1-year mortality after ART initiation for HIV-positive adults in Haiti. However, predicting lost to follow-up using routinely collected data was not as successful. The next step is to assess whether use of this risk score can identify patients who need tailored services to reduce mortality in resource-poor settings such as Haiti.

The Continuing Burden of Advanced HIV Disease Over 10 Years of Increasing Antiretroviral Therapy Coverage in South Africa.

Background: Antiretroviral treatment (ART) has been massively scaled up to decrease human immunodeficiency virus (HIV)-related morbidity, mortality, and HIV transmission. However, despite documented increases in ART coverage, morbidity and mortality have remained substantial. This study describes trends in the numbers and characteristics of patients with very advanced HIV disease in the Western Cape, South Africa. Methods: Annual cross-sectional snapshots of CD4 distributions were described over 10 years, derived from a province-wide cohort of all HIV patients receiving CD4 cell count testing in the public sector. Patients with a first CD4 count <50 cells/µL in each year were characterized with respect to prior CD4 and viral load testing, ART access, and retention in ART care. Results: Patients attending HIV care for the first time initially constituted the largest group of those with CD4 count <50 cells/µL, dropping proportionally over the decade from 60.9% to 26.7%. By contrast, the proportion who were ART experienced increased from 14.3% to 56.7%. In patients with CD4 counts <50 cells/µL in 2016, 51.8% were ART experienced, of whom 76% could be confirmed to be off ART or had recent viremia. More than half who were ART experienced with a CD4 count <50 cells/µL in 2016 were men, compared to approximately one-third of all patients on ART in the same year. Conclusions: Ongoing HIV-associated morbidity now results largely from treatment-experienced patients not being in continuous care or not being fully virologically suppressed. Innovative interventions to retain ART patients in effective care are an essential priority for the ongoing HIV response.

Generic antiretroviral drug use in HIV-infected patients: A cohort study from the French health insurance database.

OBJECTIVE: This study aimed to estimate the rate of generic users among HIV-infected patients treated by antiretroviral (ARV) drugs potentially substitutable and to determine factors associated with switch from brand to generic ARV in real-life settings in a French region. METHODS: Cohort of HIV-infected patients aged of ≥18 years, exposed to at least one of the generic of lamivudine (3TC-150mg/300mg), zidovudine/lamivudine (AZT-200mg/3TC-150mg), nevirapine (NVP-200mg), efavirenz (EFV-600mg) and those exposed to brand 3TC, AZT/3TC, NVP, EFV, the fixed-dose combination abacavir/lamivudine (ABC/3TC) or the single-tablet regimen efavirenz/emtricitabine/tenofovir (EFV/FTC/TDF) as recorded in the French health insurance database between January 2012 and May 2015 were included. Factors associated with switch (for each generic versus its brand drug; and for situation requiring breaking the combination) were investigated through a logistic regression. RESULTS: Among the 1539 patients likely to switch from brand ARV drugs, only 165 (11%) were exposed to generics. For EFV users, switch from brand to generic was associated with age (aOR=1.04 [CI: 1.00-1.08]). For ABC/3TC users, switch was significantly more frequent in patients receiving a monthly average of more than two non-ARV drugs (3.08 [1.42-6.68]) and whose regimen contained a non-nucleoside reverse transcriptase inhibitor (NNRTI) as index medication (3rd agent) (5.68 [2.68-11.39]). By contrast, switch was less frequent in AZT/3TC users exposed to drugs used in digestive disorders (0.39 [0.18-0.88]) or analgesics (0.42 [0.20-0.90]). CONCLUSION: Treatment-experienced HIV patients whose disease has been stabilized (less comorbidities) are more likely to switch to generic antiretroviral drugs.

Inequalities in HAART uptake and differential survival according to exposure category in Rio de Janeiro, Brazil / Desigualdades no acesso à HAART e diferenças de sobrevida de acordo com a categoria de exposição ao HIV no Rio de Janeiro, Brasil / Desigualdades en el consumo de la TARGA y supervivencia diferencial según la categoría de exposición en Río de Janeiro, Brasil

Abstract: Despite substantial improvement in prognosis and quality of life among people living with HIV/AIDS (PLWHA) in Brazil, inequalities in access to treatment remain. We assessed the impact of these inequalities on survival in Rio de Janeiro over a 12-year period (2000/11). Data were merged from four databases that comprise the national AIDS monitoring system: SINAN-AIDS (Brazilian Information System for Notificable Diseases; AIDS cases), SISCEL (laboratory tests), SICLOM (electronic dispensing system), and SIM (Brazilian Mortality Information System), using probabilistic linkage. Cox regressions were fitted to assess the impact of HAART (highly active antiretroviral therapy) on AIDS-related mortality among men who have sex with men (MSM), people who inject drugs (PWID), and heterosexuals diagnosed with AIDS, between 2000 and 2011, in the city of Rio de Janeiro, RJ, Brazil. Among 15,420 cases, 60.7% were heterosexuals, 36.1% MSM and 3.2% PWID. There were 2,807 (18.2%) deaths and the median survival time was 6.29. HAART and CD4+ > 200 at baseline were associated with important protective effects. Non-whites had a 33% higher risk of dying in consequence of AIDS than whites. PWID had a 56% higher risk and MSM a 11% lower risk of dying of AIDS than heterosexuals. Non-white individuals, those with less than eight years of formal education, and PWID, were more likely to die of AIDS and less likely to receive HAART. Important inequalities persist in access to treatment, resulting in disparate impacts on mortality among exposure categories. Despite these persistent disparities, mortality decreased significantly during the period for all categories under analysis, and the overall positive impact of HAART on survival has been dramatic.

Resumo: Apesar de uma melhora substancial no prognóstico e na qualidade de vida de pessoas vivendo com HIV/aids (PVHA) no Brasil, permanecem desigualdades no acesso ao tratamento. Avaliamos o impacto dessas desigualdades na sobrevida na cidade do Rio de Janeiro ao longo de 12 anos (2000/11). Os dados foram consolidados a partir de quatro bases que constituem o sistema nacional de monitoramento da aids: SINAN-aids (Sistema de Informação de Agravos de Notificação; casos de aids), SISCEL (exames laboratoriais), SICLOM (controle logístico de medicamentos) e SIM (Sistema de Informações sobre Mortalidade), usando relacionamento probabilístico. As regressões de Cox foram ajustadas para avaliar o impacto da HAART (terapia antirretroviral altivamente ativa) na mortalidade relacionada à aids entre homens que fazem sexo com homens (HSH), usuários de drogas injetáveis (UDI) e heterossexuais diagnosticados com aids entre 2000 e 2011 na cidade do Rio de Janeiro. Dos 15.420 casos, 60,7% eram heterossexuais, 36,1% HSH e 3,2% UDI. Houve 2.807 óbitos (18,2%) e a sobrevida mediana foi 6,29 anos. Houve associação significativa entre HAART e contagem de CD4+ > 200 na linha de base e importantes efeitos protetores. Comparados aos brancos, os não-brancos tiveram um risco 33% maior de morrer de aids. Os UDI tiveram um risco 56% maior, enquanto HSH tiveram um risco 11% menor de morrer de aids, comparados aos heterossexuais. Os indivíduos não-brancos, aqueles com menos de oito anos de escolaridade e UDI mostraram probabilidade mais alta de não receber HAART e de morrer de aids. No Rio de Janeiro, persistem desigualdades importantes no acesso ao tratamento, que resultam em impactos diferenciados na mortalidade de acordo com as categorias de exposição. Apesar da persistência dessas disparidades, a mortalidade diminuiu significativamente ao longo do período em todas as categorias analisadas, e o acesso à HAART teve impacto dramático no tempo de sobrevida.

Resumen: Pese a la mejora sustancial en el pronóstico y calidad de vida entre las personas que viven con VIH/SIDA (PLWHA) en Brasil, persisten las desigualdades en el acceso al tratamiento. Evaluamos el impacto de estas desigualdades en la supervivencia en Río de Janeiro, durante un período de 12 años (2000/11). Los datos fueron recabados de cuatros bases de datos que comprenden el sistema nacional de monitoreo del SIDA: SINAN-SIDA (Sistema de Información de Agravios de Notificación; casos de SIDA), SISCEL (pruebas de laboratorio), SICLOM (sistema dispensador electrónico), y SIM (Sistema de Información sobre la Mortalidad), usando una vinculación probabilística. Las regresiones de Cox fueron usadas para evaluar el impacto de la TARGA (terapia antirretroviral de gran actividad) en la mortalidad relacionada con el SIDA, entre hombres que tienen sexo con hombres (HSH), individuos que se inyectan drogas por vía intravenosa (PWID por sus siglas en inglés), y heterosexuales diagnosticados con SIDA, entre 2000 y 2011, en la ciudad de Río de Janeiro, RJ, Brasil. Entre 15.420 casos, un 60,7% eran heterosexuales, un 36,1% HSH y un 3,2% PWID. Hubo 2.807 (18.2%) muertes y el tiempo medio de supervivencia fue 6,29. TARGA y CD4+ > 200 en la base de referencia estuvieron asociados con efectos importantes de protección. Los no-blancos tuvieron un riesgo un 33% mayor de morir a consecuencia de SIDA que los blancos. Los PWID tuvieron un riesgo un 56% mayor, y los HSH un riesgo un 11% menor, de morir de SIDA que los heterosexuales. Los no-blancos, con menos de ocho años de educación formal, y los PWID, eran más propensos a morir de SIDA y menos a recibir TARGA. Existen importantes inequidades en el acceso al tratamiento, resultando en efectos dispares en la mortalidad entre las diferentes categorías exposición. A pesar de estas persistentes disparidades, la mortalidad decreció significativamente durante el periodo para todas las categorías bajo análisis, y el impacto general positivo del TARGA en la supervivencia había sido importantísimo.

Universal test, treat, and keep: improving ART retention is key in cost-effective HIV control in Uganda.

BACKGROUND: With ambitious new UNAIDS targets to end AIDS by 2030, and new WHO treatment guidelines, there is increased interest in the best way to scale-up ART coverage. We investigate the cost-effectiveness of various ART scale-up options in Uganda. METHODS: Individual-based HIV/ART model of Uganda, calibrated using history matching. 22 ART scale-up strategies were simulated from 2016 to 2030, comprising different combinations of six single interventions (1. increased HIV testing rates, 2. no CD4 threshold for ART initiation, 3. improved ART retention, 4. increased ART restart rates, 5. improved linkage to care, 6. improved pre-ART care). The incremental net monetary benefit (NMB) of each intervention was calculated, for a wide range of different willingness/ability to pay (WTP) per DALY averted (health-service perspective, 3% discount rate). RESULTS: For all WTP thresholds above $210, interventions including removing the CD4 threshold were likely to be most cost-effective. At a WTP of $715 (1 × per-capita-GDP) interventions to improve linkage to and retention/re-enrolment in HIV care were highly likely to be more cost-effective than interventions to increase rates of HIV testing. At higher WTP (> ~ $1690), the most cost-effective option was 'Universal Test, Treat, and Keep' (UTTK), which combines interventions 1-5 detailed above. CONCLUSIONS: Our results support new WHO guidelines to remove the CD4 threshold for ART initiation in Uganda. With additional resources, this could be supplemented with interventions aimed at improving linkage to and/or retention in HIV care. To achieve the greatest reductions in HIV incidence, a UTTK policy should be implemented.

Differentiated Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings: An Economic Analysis.

BACKGROUND.: Viral load (VL) monitoring for patients receiving antiretroviral therapy (ART) is recommended worldwide. However, the costs of frequent monitoring are a barrier to implementation in resource-limited settings. The extent to which personalized monitoring frequencies may be cost-effective is unknown. METHODS.: We created a simulation model parameterized using person-level longitudinal data to assess the benefits of flexible monitoring frequencies. Our data-driven model tracked human immunodeficiency virus (HIV)-infected individuals for 10 years following ART initiation. We optimized the interval between viral load tests as a function of patients' age, gender, education, duration since ART initiation, adherence behavior, and the cost-effectiveness threshold. We compared the cost-effectiveness of the personalized monitoring strategies to fixed monitoring intervals every 1, 3, 6, 12, and 24 months. RESULTS.: Shorter fixed VL monitoring intervals yielded increasing benefits (6.034 to 6.221 discounted quality-adjusted life-years [QALYs] per patient with monitoring every 24 to 1 month over 10 years, respectively, standard error = 0.005 QALY), at increasing average costs: US$3445 (annual monitoring) to US$5393 (monthly monitoring) per patient, respectively (standard error = US$3.7). The adaptive policy optimized for low-income contexts achieved 6.142 average QALYs at a cost of US$3524, similar to the fixed 12-month policy (6.135 QALYs, US$3518). The adaptive policy optimized for middle-income resource settings yields 0.008 fewer QALYs per person, but saves US$204 compared to monitoring every 3 months. CONCLUSIONS.: The benefits from implementing adaptive vs fixed VL monitoring policies increase with the availability of resources. In low- and middle-income countries, adaptive policies achieve similar outcomes to simpler, fixed-interval policies.

Stigma, discrimination and HIV outcomes among people living with HIV in Rio de Janeiro, Brazil: The intersection of multiple social inequalities.

Limited research has examined the social context surrounding stigma and discrimination and HIV outcomes among people living with HIV (PLHIV). We surveyed 900 PLHIV in Brazil and examined the relationship between stigma, discrimination and HIV outcomes utilising multivariable logistic regression. HIV stigma and discrimination were inversely associated with age (AOR Stigma 0.65, 95% CI 0.49-0.88; AOR Discrimination 0.72, 95% CI 0.54-0.95) and income (AOR Stigma 0.74, 95% CI 0.55-0.99; AOR Discrimination 0.62, 95% CI 0.46-0.82). Stigma was inversely associated with education (AOR 0.71, 95% CI 0.52-0.96) and no history of sex work (AOR 0.56, 95% CI 0.35-0.90), and positively associated with having children (AOR 1.71, 95% CI 1.18-2.48). Discrimination was inversely associated with no history of drug use (AOR 0.63, 95% CI 0.42-0.95). Stigma and discrimination were found to be inversely associated with overall health (AOR Stigma 0.54, 95% CI 0.40-0.74; AOR Discrimination 0.71, 95% CI 0.52-0.97). Discrimination was associated with having a sexually transmitted infection since HIV diagnosis (AOR 1.63, 95% CI 1.14-2.32). Findings suggest that future interventions should address multiple social inequalities faced by PLHIV to reduce HIV stigma and discrimination and improve health and HIV outcomes.

Survival functions for defining a clinical management Lost To Follow-Up (LTFU) cut-off in Antiretroviral Therapy (ART) program in Zomba, Malawi.

BACKGROUND: While, lost to follow-up (LTFU) from antiretroviral therapy (ART) can be considered a catch-all category for patients who miss scheduled visits or medication pick-ups, operational definitions and methods for defining LTFU vary making comparisons across programs challenging. Using weekly cut-offs, we sought to determine the probability that an individual would return to clinic given that they had not yet returned in order to identify the LTFU cut-off that could be used to inform clinical management and tracing procedures. METHODS: Individuals who initiated ART with Dignitas International supported sites (n = 22) in Zomba, Malawi between January 1 2007-June 30 2010 and were ≥ 1 week late for a follow-up visit were included. Lateness was categorized using weekly cut-offs from ≥1 to ≥26 weeks late. At each weekly cut-off, the proportion of patients who returned for a subsequent follow-up visit were identified. Cumulative Distribution Functions (CDFs) were plotted to determine the probability of returning as a function of lateness. Hazard functions were plotted to demonstrate the proportion of patients who returned each weekly interval relative to those who had yet to return. RESULTS: In total, n = 4484 patients with n = 7316 follow-up visits were included. The number of included follow-up visits per patient ranged from 1-10 (median: 1). Both the CDF and hazard function demonstrated that after being ≥9 weeks late, the proportion of new patients who returned relative to those who had yet to return decreased substantially. CONCLUSIONS: We identified a LTFU definition useful for clinical management. The simple functions plotted here did not require advanced statistical expertise and were created using Microsoft Excel, making it a particularly practical method for HIV programs in resource-constrained settings.

The indirect impact of antiretroviral therapy: Mortality risk, mental health, and HIV-negative labor supply.

To reduce the burden of the HIV/AIDS epidemic, international donors recently began providing free antiretroviral therapy (ART) in parts of Sub-Saharan Africa. ART dramatically prolongs life and reduces infectiousness for people with HIV. This paper shows that ART availability increases work time for HIV-negative people without caretaker obligations, who do not directly benefit from the medicine. A difference-in-difference design compares people living near and far from ART, before and after treatment becomes available. Next we explore the possible reasons for this pattern. Although we cannot pinpoint the mechanism, we find that ART availability substantially reduces subjective mortality risk and improves mental health. These results show an undocumented economic consequence of the HIV/AIDS epidemic and an important externality of medical innovation. They also provide the first evidence of a link between the disease environment and mental health.

Potential impact on HIV incidence of higher HIV testing rates and earlier antiretroviral therapy initiation in MSM.

BACKGROUND: Increased rates of testing, with early antiretroviral therapy (ART) initiation, represent a key potential HIV-prevention approach. Currently, in MSM in the United Kingdom, it is estimated that 36% are diagnosed by 1 year from infection, and the ART initiation threshold is at CD4 cell count 350/µl. We investigated what would be required to reduce HIV incidence in MSM to below 1 per 1000 person-years (i.e. <535 new infections per year) by 2030, and whether this is likely to be cost-effective. METHODS: A dynamic, individual-based simulation model was calibrated to multiple data sources on HIV in MSM in the United Kingdom. Outcomes were projected according to future alternative HIV testing and ART initiation scenarios to 2030, considering also potential changes in levels of condomless sex. RESULTS: For ART use to result in an incidence of close to 1/1000 person-years requires the proportion of all HIV-positive MSM with viral suppression to increase from below 60% currently to 90%, assuming no rise in levels of condomless sex. Substantial increases in HIV testing, such that over 90% of men are diagnosed within a year of infection, would increase the proportion of HIV-positive men with viral suppression to 80%, and it would be 90%, if ART is initiated at diagnosis. The scenarios required for such a policy to be cost-effective are presented. CONCLUSION: This analysis provides targets for the proportion of all HIV-positive MSM with viral suppression required to achieve substantial reductions in HIV incidence.

Patients Accessing Ambulatory Care for HIV-infection: Epidemiology and Prevalence Assessment.

This study describes the demographics and treatment status of HIV-infected adults accessing ambulatory care in the Republic of Ireland and estimates diagnosed HIV prevalence rates. 3254 HIV-infected adults attended 1 of the 6 specialist HIV centres in the 12- month period 1st July 2009 to 30th June 2010. 2023/3254 (62%) were male, 1761/3133 (56%) Irish and 1048/3133 (34%) African. 1924/3098 (62%) resided in the Dublin area. The mean age was 39.8 years (SD 9.3); probable route of acquisition was available for 2898/3254 (89%); heterosexual acquisition accounted for 1442 (50%), MSM 777 (27%) and IDU 598 (21%). 2574/3202 (80%) were on highly active antiretroviral therapy (HAART). Of these 87% had HIV-RNA levels < 50cpm and 94% < 500cpm. The HIV diagnosed prevalence rate is estimated at 1.09/1000 nationally and at 2.25/1000 in the Dublin area for 15-59 year olds.

Health & Demographic Surveillance System Profile: The Magu Health and Demographic Surveillance System (Magu HDSS).

The Magu Health and Demographic Surveillance System (Magu HDSS) is part of Kisesa OpenCohort HIV Study located in a rural area of North-Western Tanzania. Since its establishment in 1994, information on pregnancies, births, marriages, migrations and deaths have been monitored and updated between one and three times a year by trained fieldworkers. Other research activities implemented in the cohort include: sero surveys which have been conducted every 2-3 years to collect socioeconomic data, HIV sero status and health knowledge attitude and behaviour in adults aged 15 years or more living in the area; verbal autopsy (VA) interviews conducted to establish cause of death in all deaths encountered in the area; Llnking data collected at health facilities to community-based data; monitoring voluntary counselling and testing (VCT); and assessing uptake of antiretroviral treatment (ART). In addition, within the community, qualitative studies have been conducted to address issues linked to HIV stigma, the perception of ART access and adherence.In 2014, the population was over 35 000 individuals. Magu HDSS has contributed to Tanzanian estimates of fertility and mortality, and is a member of the INDEPTH network. Demographic data for Magu HDSS are available via the INDEPTH Network's Sharing and Accessing Repository (iSHARE) and applications to access HDSS data for collaborative analysis are encouraged.

Trends and Differences Among Three New Indicators of HIV Infection Progression.

OBJECTIVE: This study proposes three indicators of, and assesses the disparities and trends in, the risk of HIV infection progression among people living with diagnosed HIV infection in the United States. METHODS: Using data reported to national HIV surveillance through June 2012, we calculated the AIDS diagnosis hazard, HIV (including AIDS) death hazard, and AIDS death hazard for people living with diagnosed HIV infection for each calendar year from 1997 to 2010. We also calculated a stratified hazard in 2010 by age, race/ethnicity, mode of transmission, region of residence at diagnosis, and year of diagnosis. RESULTS: The risk of HIV infection progression among people living with diagnosed HIV infection decreased significantly from 1997 to 2010. The risks of progression to AIDS and death in 2010 were higher among African Americans and people of multiple races, males exposed through injection drug use (IDU) or heterosexual contact, females exposed through IDU, people residing in the South at diagnosis, and people diagnosed in 2009 compared with white individuals, men who have sex with men, females with infection attributed to heterosexual contact, those residing in the Northeast, and those diagnosed in previous years, respectively. People aged 15-29 years had the highest AIDS diagnosis hazard in 2010. CONCLUSION: Continued efforts are needed to ensure early HIV diagnosis as well as initial linkage to and continued engagement in HIV medical care among all people living with HIV. Targeted interventions are needed to improve health-care and supportive services for those with worse health outcomes.

Sex and Racial/Ethnic Differences in Premature Mortality Due to HIV: Florida, 2000-2009.

OBJECTIVE: This study aimed to characterize premature mortality among people diagnosed with HIV infection from 2000 to 2009 in Florida, by sex and race/ethnicity, to estimate differences in premature mortality that could be prevented by linkage to HIV care and treatment. METHODS: Florida surveillance data for HIV diagnoses (excluding concurrent AIDS diagnoses) were linked with vital records data to ascertain deaths through 2011. Years of potential life lost (YPLL) were obtained from the expected number of remaining years of life at a given age from the U.S. sex-specific period life tables. RESULTS: Among 41,565 people diagnosed with HIV infection during the study period, 5,249 died, and 2,563 (48.8%) deaths were due to HIV/AIDS. Age-standardized YPLL (aYPLL) due to HIV/AIDS per 1,000 person-years was significantly higher for females than males (372.6, 95% confidence interval [CI] 349.8, 396.2 vs. 295.2, 95% CI 278.4, 312.5); for non-Hispanic black (NHB) females than non-Hispanic white (NHW) and Hispanic females (388.2, 95% CI 360.7, 416.9; 294.3, 95% CI 239.8, 354.9; and 295.0, 95% CI 242.9, 352.5, respectively); and for NHB males compared with NHW and Hispanic males (378.7, 95% CI 353.7, 404.7; 210.6, 95% CI 174.3, 250.8; and 240.9, 95% CI 204.8, 280.2, respectively). In multilevel modeling controlling for individual factors, NHB race was associated with YPLL due to HIV/AIDS for women (p=0.04) and men (p<0.001). CONCLUSION: Among people diagnosed with HIV infection, females and NHB people had a disproportionately high premature mortality from HIV/AIDS, suggesting the need for enhanced efforts to improve linkage to and retention in care and medication adherence for these groups.