Do people living with HIV face more secondary cancers than general population: From the French CANCERVIH network.

INTRODUCTION: People living with HIV (PLWHIV) are at a higher risk of cancer compared to the general population. With improved cancer treatments and the increased life expectancy of PLWHIV, the incidence of second cancers is also expected to increase. METHODS: We reviewed the cases of PLWHIV with cancer that have been presented to the CANCERVIH national multidisciplinary board since 2014. We included all cases with a history of cancer, and studied the incidence and types of second cancers. RESULTS: In total, 719 cases were reviewed, out of which 94 (13%) had a history of at least one cancer. For the first primary cancers, 46 (49%) were AIDS-defining cancers (ADCs) and 48 (51%) were non-AIDS-defining cancers (NADCs). Kaposi sarcoma (33%) and NHL (15%) occurred most frequently as first cancers. Among the first cancers that were ADCs, 15% of the second cancers were NHL, 11% anal canal cancers, 9% bladder and 9% Hodgkin lymphomas. Among the first cancers that were NADCs, 38% of the second cancers were lung cancers, 8% bladder, 8% head and neck and 8% NHL. DISCUSSION: With the aging of PLWHIV, the incidence of second and subsequent cancers is expected to increase in this population. Immuno-virological control should be maintained. Increased surveillance, early prevention and screening programs should be offered to all PLWHIV, including those with an undetectable HIV viral load and/or immune restoration.

Impact of the COVID-19 pandemic situation on HIV care in Liège, Belgium.

BACKGROUND: Background: The COVID-19 pandemic and associated containment measures dramatically affected the health care systems including the screening of human immunodeficiency virus and the management people living with HIV around the world by making the access to preventive care services and specific medical monitoring more difficult. OBJECTIVE: Objective: To study the impact of the COVID-19 pandemic on the holistic care of people living with HIV in Liège (Belgium). METHODS: Methods: In this retrospective observational study conducted in Liège University Hospital, we compared the out-patient follow-up of HIV-infected individuals as well as the number of new HIV diagnoses between 2019 and 2020 and between the different waves of the COVID-19 pandemic in 2020. RESULTS: Results: In 2020, when compared to 2019, we observed a significant decrease in the number of new HIV diagnoses, especially during the first wave of the pandemic, and in the number of consultations undertaken by sexual health services, psychologists and specialists in infectious diseases at our HIV clinic. We also observed a decrease in the number of viral load assays and blood CD4 + T-cells count analyses performed, although we found less patients with HIV plasma viral load above 400 copies per mL in 2020. Finally, we noted a significant reduction in terms of screening of our HIV-infected patients for hepatitis C, syphilis, colorectal and anal cancers and hypercholesterolemia. CONCLUSIONS: Conclusions: Our experience exhibits the deleterious impact of the COVID-19 pandemic on the HIV care and the need to implement new strategies to guarantee its continuum.

Persistent HIV-controllers are more prone to spontaneously clear HCV: a retrospective cohort study.

INTRODUCTION: HIV-controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV-controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV-controllers. Some of these subjects eventually lose HIV-controller status (transient controllers), whereas some HIV-controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers. METHODS: We recruited HIV-controllers from January 1981 up to October 2016 with available antibodies to HCV (anti-HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV-controllers with anti-HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV-controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV-controller status were explored (n = 744) using Log rank test and Kaplan-Meier curves, in this case the multivariate analysis consisted in a Cox regression model. RESULTS: A higher frequency of HCV spontaneous clearance was found in persistent HIV-controllers (25.5%) compared to non-controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, CD4+ T-cell nadir and time of follow-up, HCV clearance was independently associated with persistent HIV spontaneous control (p = 0.002; OR (95% CI) = 2.573 (1.428 to 4.633)), but not with transient spontaneous control (p = 0.119; 1.589 (0.888 to 2.845)). Furthermore, persistent HIV-controllers were more likely to spontaneously clear the HCV in comparison with transient controllers (p = 0.027; 0.377 (0.159 to 0.893). Finally, not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance (p = 0.010; 0.503 (0.297 to 0.850). CONCLUSIONS: This study shows an association between spontaneous persistent HIV-control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV-controllers but not transient controllers as a good model of functional HIV cure.

Brief Report: CYP27B1 rs10877012 T Allele Was Linked to Non-AIDS Progression in ART-Naïve HIV-Infected Patients: A Retrospective Study.

BACKGROUND: HIV/AIDS progression is linked to vitamin D, which is regulated by several key cytochromes P450 (CYP). Single nucleotide polymorphisms (SNPs) in CYP genes influence vitamin D metabolism and serum levels. The objective of this study was to evaluate the association between CYP SNPs and the clinical AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients. METHODS: We performed a retrospective study in 661 ART-naïve HIV-infected patients who were stratified by their AIDS progression pattern [181 long-term nonprogressors (LTNPs), 332 moderate progressors, and 148 rapid progressors (RPs)]. Four CYP SNPs (CYP2R1 rs10500804, CYP2R1 rs1993116, CYP27B1 rs10877012, and CYP24A1 rs6013897) were genotyped using Agena Bioscience's MassARRAY platform. Correction for multiple testing was performed using the false discovery rate (Benjamini-Hochberg procedure). RESULTS: The adjusted regression showed a significant association only for CYP27B1 rs10877012 SNP. When analyzing all HIV patients, the rs10877012 T allele was protective against AIDS progression (ordinal outcome) under the dominant [adjusted odds ratio (aOR) = 0.69; P = 0.021) and additive (aOR) = 0.75; P = 0.025] inheritance models. When analyzing LTNPs versus RPs, the rs10877012 T allele also showed a significant protective association under the dominant (aOR = 0.45; P = 0.004) and additive (aOR = 0.54; P = 0.008) inheritance models. P values remained significant after correcting by multiple comparisons only for the comparison of LTNPs versus RPs (extreme phenotypes). CONCLUSIONS: The CYP27B1 rs10877012 T allele was linked to non-AIDS progression in ART-naïve HIV-infected patients. The rs10877012 SNP seems to have an impact on the clinical AIDS progression, possibly modifying vitamin D levels, which could be relevant for the pathogenesis of HIV infection.

Differences in social and mental well-being of long-term survivors among people who inject drugs and other participants in the Swiss HIV Cohort Study: 1980-2018.

BACKGROUND: People living with HIV who were diagnosed before highly active antiretroviral therapy became available in 1996 and who survived at least 15 years after HIV diagnosis, termed long-term survivors (LTS), form a particularly vulnerable population. We study social, clinical and mental factors of LTS in the Swiss HIV Cohort Study, with a particular focus on people who inject drugs (PWID). METHODS: We quantified differences between PWID LTS, and men who have sex with men (MSM) and heterosexual (HET) LTS. Using phylogenetic methods, we distinguished between heterosexual LTS who most likely shared a social network with PWID at the time of infection, termed clusteredHET, and those who did not, termed HET not clustered (HETnc). The analysis was performed using data collected at least 15 years post diagnosis. RESULTS: Overall, 1,663 of 5,686 (29.2%) PWID were LTS. We found significant differences between PWID LTS and MSM/HETnc LTS regarding self-reported depression (59.4% versus 43.3%; odds ratio [OR]=1.8; P<0.001), incarceration (30.6% versus 7.0%; OR=6.9; P<0.001) and full work ability (25.4% versus 59.0%; OR=0.27; P<0.001). ClusteredHET were less vulnerable with respect to these variables than PWID LTS but more at risk compared with MSM/HETnc LTS, indicating that clusteredHET are closer to PWID with regard to social and mental aspects compared with all MSM/HETnc. CONCLUSIONS: Even more than 15 years post HIV diagnosis, special care for HIV-positive PWID is needed, with emphasis on mental health and social integration of PWID LTS.

Pregnancies Among the First Generation of Survivors of Perinatal HIV Infection.

OBJECTIVE: Little is known about pregnancy outcomes among women who have acquired human immunodeficiency virus (HIV) through perinatal infection and survived into adulthood. The objectives of this study were to describe pregnancy outcomes among women with perinatal HIV infection (PHIV) in Canada and to identify potential challenges in the prevention of perinatal HIV transmission in this population. METHODS: A retrospective review of all pregnancies among women with PHIV who were previously followed as children at two tertiary care centres in Montréal, Québec, was conducted. Data were extracted from pediatric and obstetrical records. RESULTS: There were 21 pregnancies among 11 women, and 18 of these pregnancies were unintentional. Mean age at first pregnancy was 19.5 years (range 15-29 years). At the first prenatal visit, 79% had a detectable viral load, 36% were immunosuppressed (CD4 T cell count <200 mm3), and only 36% were receiving antiretroviral therapy (ART). At the time of delivery, although all were prescribed ART, 50% of these women still had a detectable viral load, and 36% remained immunosuppressed. All of the women harboured mutations conferring drug resistance to zidovudine and lamivudine, and the majority (73%) were also resistant to nevirapine. None of the infants were HIV infected, although all received prophylaxis with agents to which their mother's virus was resistant. CONCLUSION: Unplanned pregnancies, difficulties with adherence to ART, and drug resistance were identified challenges in the management of pregnancies among women with PHIV. This study highlights a gap in the reproductive counselling of adolescents with PHIV and the need for close follow-up and adherence support during pregnancy in this population.

Subclinical cardiovascular disease in HIV controller and long-term nonprogressor populations.

OBJECTIVES: Elite controllers (ECs), viraemic controllers (VCs), and long-term nonprogressors (LTNPs) control HIV viral replication or maintain CD4 T-cell counts without antiretroviral therapy, but may have increased cardiovascular disease (CVD) risk compared to HIV-uninfected persons. We evaluated subclinical carotid and coronary atherosclerosis and inflammatory biomarker levels among HIV controllers, LTNPs and noncontrollers and HIV-uninfected individuals in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS). METHODS: We measured carotid plaque presence and common carotid artery intima-media thickness (IMT) in 1729 women and 1308 men, and the presence of coronary artery calcium and plaque in a subgroup of men. Associations between HIV control category and carotid and coronary plaque prevalences were assessed by multivariable regression analyses adjusting for demographics and CVD risk factors. Serum inflammatory biomarker concentrations [soluble CD163 (sCD163), soluble CD14 (sCD14), galectin-3 (Gal-3), galectin-3 binding protein (Gal-3BP) and interleukin (IL)-6] were measured and associations with HIV control category assessed. RESULTS: We included 135 HIV controllers (30 ECs) and 135 LTNPs in the study. Carotid plaque prevalence and carotid IMT were similar in HIV controllers, LTNPs and HIV-uninfected individuals. HIV controllers and LTNPs had lower prevalences of carotid plaque compared to viraemic HIV-infected individuals. The prevalence of coronary atherosclerosis was similar in HIV controllers/LTNPs compared to HIV-uninfected and viraemic HIV-infected men. Controllers and LTNPs had higher concentrations of sCD163 and sCD14 compared to HIV-uninfected persons. CONCLUSIONS: Subclinical CVD was similar in HIV controllers, LTNPs and HIV-uninfected individuals despite elevated levels of some inflammatory biomarkers. Future studies of HIV controllers and LTNPs are needed to characterize the risk of CVD among HIV-infected persons.

Understanding health-related behavior among adolescents living with HIV in Lima, Peru.

BACKGROUND: The global HIV burden among adolescents ages 10-19 is growing. This population concurrently confronts the multifaceted challenges of adolescence and living with HIV. With the goal of informing future interventions tailored to this group, we assessed sexual activity, HIV diagnosis disclosure, combination antiretroviral therapy (cART) adherence, and drug use among adolescents living with HIV (ALHIV) in Lima, Peru. METHODS: Adolescents at risk or with a history of suboptimal cART adherence completed a self-administered, health behaviors survey and participated in support group sessions, which were audio recorded and used as a qualitative data source. Additionally, we conducted in-depth interviews with caregivers and care providers of ALHIV. Thematic content analysis was performed on the group transcripts and in-depth interviews and integrated with data from the survey to describe adolescents' health related behaviors. RESULTS: We enrolled 34 ALHIV, of which 32 (14 male, 18 female, median age 14.5 years) completed the health behavior survey. Nine (28%) adolescents reported prior sexual intercourse, a minority of whom (44%) reported using a condom. cART adherence was highest in the 10-12 age group with 89% reporting ≤2 missed doses in the last month, compared to 36% in adolescents 13 years or older. Over 80% of adolescents had never disclosed their HIV status to a friend or romantic partner. Adolescents, caregivers, and health service providers described sexual health misinformation and difficulty having conversations about sexual health and HIV. CONCLUSIONS: In this group of ALHIV, adherence to cART declined with age and condom use among sexually active adolescents was low. Multifactorial interventions addressing sexual health, gaps in HIV-related knowledge, and management of disclosure and romantic relationships are urgently needed for this population.

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients.

AIM: Ageing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities. METHODS: Included were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997-1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, ß2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses. RESULTS: At the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45-56); BMI was 23.0 kg/m2 (21.1-25.4), CD4+ lymphocytes were 620 cells/mm3 (453-790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events. CONCLUSION: In long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.

Long-term survival outcomes of HIV infected children receiving antiretroviral therapy: an observational study from Zambia (2003-2015).

BACKGROUND: In 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART. METHODS: Using a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods. RESULTS: Overall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3-8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4-1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6-16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3-6.4), compared to those aged 6-15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3-10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit. CONCLUSION: We observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.

Reduced Natural Killer Cell Subsets in Perinatally Acquired Long-Term Non-Progressor Human Immunodeficiency Virus-Infected Children.

Lymphocyte subsets of long-term non-progressor (LPNT) HIV-infected children is a less studied aspect of HIV infection. Evaluation of different lymphocyte subsets was done in HIV-infected children ≥8 years of age. Subjects were divided in two groups-group 1 (LTNP), treatment-naive with CD4 ≥ 500 cells/µL (n = 20); group 2, non-long-term non-progressor (nLTNPs) receiving antiretroviral therapy (ART) with CD4 count ≤500 on at least one occasion (n = 21). Group 3 comprised age-, sex-matched healthy controls (HCs, n = 20). Lymphocyte subsets were acquired with a flow cytometer (Navios; Beckman Coulter), and data were analyzed using Kaluza flow analysis software. The mean ages were 12.1 (±2.4 SD) and 12.5 (±2.7) years with mean duration of follow-up of 6.8 (±3.4) and 5.6 (±1.95) years in LTNP and nLTNP subjects, respectively. The mean duration of ART was 5.17 years for group 2. Absolute count and percentage of CD4+ T cells was lower in nLTNPs than in LTNPs. Cytotoxic T cells were high in both HIV-infected groups compared with HCs. Natural killer (NK) cells were found to be significantly lower in LTNP and nLTNP groups compared with HCs (p ≤ .000003 and p ≤ .00003, respectively). Naïve B cells were more in HIV-infected individuals than in HCs. NK cells were significantly lower in LTNP and nLTNP groups. Immune reconstitution was comparable in children initiated with ART early versus long-term HIV-infected children receiving no ART.

People Living With HIV in U.S. Nursing Homes in the Fourth Decade of the Epidemic.

As the number of persons living with HIV (PLWH) will continue to increase in the coming years, it is critical to understand factors influencing appropriate nursing home (NH) care planning. This study described the sociodemographic characteristics as well as the antiretroviral therapy treatment and physical and mental health among Medicare-eligible PLWH in NHs. Persons living with HIV were identified and summarized using a 2011-2013 nationwide data set of Medicare claims linked to NH resident health assessments and a prescription dispensing database, comparing new admissions in 2011-2013 with those from 1998 to 2000. We identified 7,188 PLWH from 2011 to 2013 in NHs of whom 4,031 were newly admitted. Of the total, 79% were prescribed antiretroviral therapy. Most were male (73%), Black/African American (51.1%), and a plurality resided in southern NHs (47%). Comparing the data sets, new admissions were older (60 vs. 44), had higher prevalence of viral hepatitis (16.2% vs. 7.5%), and anemia (31.1% vs. 25.1%) but had less pneumonia (11.0% vs. 13.6%) and dementia (8.7% vs. 21.0%). NH nurses can better anticipate health care needs of PLWH using these health profiles, understanding that there have been changes in the health of PLWH at admission over time.

Brief Report: Prevalence of Posttreatment Controller Phenotype Is Rare in HIV-Infected Persons After Stopping Antiretroviral Therapy.

BACKGROUND: Posttreatment control of HIV infection is a rare phenomenon primarily described among those initiating treatment with antiretroviral therapy (ART) during early/acute HIV infection. METHODS: We examined a large, well-characterized cohort of HIV-infected Department of Defense beneficiaries for the presence of posttreatment controllers (PTCs) whom we defined as individuals with sustained viral suppression for ≥6 months after discontinuation of ART. We defined those who became viremic within 6 months of discontinuing ART as rapid viremics (RVs) and compared demographic and clinical characteristics, CD4 counts, and viral loads prior, during, and after ART discontinuation between the 2 groups. RESULTS: From a cohort of 6070 patients, we identified 95 who had been treated with ART for 2 years or more who subsequently discontinued ART and had viral load assessments available after discontinuation. Four (4.2%) of these 95 met our definition of PTC. The duration of viral suppression off of ART ranged from 267 to 1058 days with 1 of the 4 restarting ART without having redeveloped a significant viremia. All 4 patients initiated ART during chronic HIV infection. Demographic and clinical characteristics of PTCs were similar to RVs. CONCLUSIONS: While posttreatment control has predominantly been described among individuals who initiated ART in early/acute HIV infection, we identified 4 PTCs who started ART during chronic infection suggesting that posttreatment control also occurs among such patients. The rarity of PTCs identified in our cohort is consistent with reports from previous studies.

[Characteristics of long-term non-progressors and HIV controllers among HIV-infections in Henan, China].

OBJECTIVE: To study the prevalence and characteristics of long-term non-progressors (LTNPs) and HIV controllers (HCs) among HIV-infections in Henan, China. METHODS: Data in two databases (Information management system of HIV/AIDS prevention and control; HIV/AIDS testing application platform of Henan) were used to identify the LTNPs and HCs, investigation and verification, sample collection and correlation testing were carried out thereafter. RESULTS: A total of 148 LTNPs/HCs were identified. Among them, 71 were followed up, including 58 LTNPs and 22 HCs, 12 cases were both LTNP and HC, 46 cases were LTNP but non-HC(LTNP+ HC-), 10 cases of HC but non-LTNP. Of the 71 individuals, 50 (70.4%) were males, 55 (77.5%) were older than 40 years of age, all belonged to Han nationality, 61 (85.9%) were farmers, 52 (73.2%) were infected through former plasma donation, 56 (78.9%) were-HCV positive. Median (interquartile range) of the CD4 counts was 538 (445-654) cell/µl and with virus load as 3.14 (2.03-3.82) log(10) copies/ml. The median viral load of HC was lower than that of LTNP + HC-(P=0.001). CONCLUSION: The characteristic of LTNPs and HCs in Henan HIV-infections were remarkable, more accurate classification of these cases was helpful to further research.

Long-term outcomes of antiretroviral therapy in an adult HIV program: a 10-year retrospective cohort study in Kano, Nigeria.

BACKGROUND: Treatment outcomes from HIV/AIDS programs in resource-limited settings mostly describe short-term follow-up. We report 10-year treatment outcomes in an HIV clinic in Kano, Nigeria. METHODS: Using paper medical charts, the authors conducted a retrospective cohort study of patients that initiated ART from June 1, 2004 to December 31, 2007, and were followed up until June 30, 2014. The authors abstracted data from patient case files and did a time-to-event analysis on ART failure and loss to follow-up, and determined immunologic trends. RESULTS: The authors studied 345 patient records (29,860 person months of follow-up); 82 records (23.7%) indicated that patients failed their first-line ART regimen at the rate of 2.75 failures per 1000 person-months. The estimates of durability on first-line ART regimen were 99.1% at 1 year and 59.0% at 10 years. Of the studied patients, 83.0% were still in care at the end of the 10-year period. Only being on abacavir (hazard ratio: 8.0) was a positive predictor of ART failure. CD4 increment at 4 years (hazard ratio: 0.9) and 5 years (hazard ratio: 0.9) were negative predictors. CONCLUSION: A high rate of long-term ART durability and modest long-term retention in care were achieved among our cohort. Improved availability of low-cost virologic and immunologic monitoring tools and provision of resistance testing technology will go a long way in improving early detection of treatment failure in the developing world.

A Copula Approach to Joint Modeling of Longitudinal Measurements and Survival Times Using Monte Carlo Expectation-Maximization with Application to AIDS Studies.

Joint modeling of longitudinal measurements and time to event data is often performed by fitting a shared parameter model. Another method for joint modeling that may be used is a marginal model. As a marginal model, we use a Gaussian model for joint modeling of longitudinal measurements and time to event data. We consider a regression model for longitudinal data modeling and a Weibull proportional hazard model for event time data modeling. A Gaussian copula is used to consider the association between these two models. A Monte Carlo expectation-maximization approach is used for parameter estimation. Some simulation studies are conducted in order to illustrate the proposed method. Also, the proposed method is used for analyzing a clinical trial dataset.

To count or not to count deaths: reranking effects in health distribution evaluation.

Populations' structures and sizes can be a result of healthcare policy decisions. We use a two-period theoretical framework and a dynamic microsimulation model to examine the consequences of this assertion on the appraisal of alternative health policy options. Results show that standard welfare-in-health measures are sensitive to changes in populations' sizes, in that taking into account the (virtual) existence of the dead can alter the ranking of policy options. Disregarding differences in the survivals induced by alternative policies can bias programmes' ranking in favour of less live-saving policies. The paper alerts on the risk of policy misranking by the use of ex-post cross-sectional analyses, neglecting deaths occurring in the past as well as counterfactual deaths in alternative policy scenarios.

[A follow-up study of HIV long-term non-progress populations in Henan province].

OBJECTIVE: To explore the related testing indicators variation of HIV long-term non-progress populations. METHODS: The long-term non-progress populations in some areas of Henan were recruited, and the study was carried out according to different CD4(+)T lymphocytes counts for two groups. The dynamic characteristics of immune status and viral load between LTNP-1group (CD4(+)T lymphocytes ≥ 500/µl, 42 cases) and LTNP-2 group(350/µl ≤ CD4(+)T lymphocytes < 500/µl, 49 cases) from July 2010 to August 2013 were observed. The characteristics of HIV elite controllers during the follow-up were also described. RESULTS: LTNP were recruited, 56% (51 cases) were men, and 44% (40 cases) were women. The study population were aged from 38 to 65 years old. A total of 320 individuals were followed-up, 14 cases were lost, 2 deaths, and 16 cases had received antiretroviral therapy during four years. To analyze the annual changes of CD4(+)T lymphocytes and VL of the group from 2010 to 2013, LTNP-1 group CD4(+)T lymphocytes from 654.0(545.2-809.5) decreased to 494.0(341.0-574.7), and LTNP-2 group decreased from 493.0 (429.5-770.0) to 343.5(253.0-500.8), CD4(+)T lymphocytes decline of over times of two groups in longitudinal analysis (χ(2) = 50.32, P < 0.01; χ(2) = 31.03, P < 0.01). lg (VL) of LTNP-1 group were 3.52 (3.15-4.27), 3.71 (2.70-4.55), 3.86 (3.59-4.55), 3.96 (3.25-4.36), and lg (VL) of TNP-2 group were 4.35 (3.72-4.83), 4.35 (3.97-4.94), 4.71 (3.96-4.95), 5.04(4.78-5.26), respectively (P > 0.05). The same year inter-group comparison found CD4(+)T lymphocytes of LTNP-1 group were higher than LTNP-2 group (Z = 5.23, P < 0.01; Z = 3.06, P < 0.01; Z = 2.51, P < 0.05; Z = 2.47, P < 0.05). VL of LTNP-2 group increased from 4.35(3.97-4.94) to 5.04 (4.78-5.26) during 2011 to 2013, were higher than LTNP-1 group in the same year (Z = 2.28, P < 0.05; Z = 2.58, P < 0.05; Z = 2.76, P < 0.05). 65 cases HCV antibody were positive in 91 individuals, and the HCV antibody positive rate was 76% (32/42), 67% (33/49) between LTNP-1 group and LTNP-2 group. Six elite controllers maintained CD4(+)T lymphocytes ≥ 500/µl, VL<1 000 copies/ml during four years follow-up. CONCLUSION: The long-term non-progress populations in Henan were overall healthy, and VL were relatively stable, there was a decreased trend of CD4 year by year, and HCV co-infection rate was high.