Early HAART Initiation May Not Reduce Actual Reproduction Number and Prevalence of MSM Infection: Perspectives from Coupled within- and between-Host Modelling Studies of Chinese MSM Populations

Having a thorough understanding of the infectivity of HIV, time of initiating treatment and emergence of drug resistant virus variants is crucial in mitigating HIV infection. There are many challenges to evaluating the long-term effect of the Highly Active Antiretroviral Therapy (HAART) on disease transmission at the population level. We proposed an individual based model by coupling within-host dynamics and between-host dynamics and conduct stochastic simulation in the group of men who have sex with men (MSM). The mean actual reproduction number is estimated to be 3.6320 (95% confidence interval: [3.46, 3.80]) for MSM group without treatment. Stochastic simulations show that given relatively high (low) level of drug efficacy after emergence of drug resistant variants, early initiation of treatment leads to a less (greater) actual reproduction number, lower (higher) prevalence and less (more) incidences, compared to late initiation of treatment. This implies early initiation of HAART may not always lower the actual reproduction number and prevalence of infection, depending on the level of treatment efficacy after emergence of drug resistant virus variants, frequency of high-risk behaviors and etc. This finding strongly suggests early initiation of HAART should be implemented with great care especially in the settings where the effective drugs are limited. Coupling within-host dynamics with between-host dynamics can provide critical information about impact of HAART on disease transmission and thus help to assist treatment strategy design and HIV/AIDS prevention and control.

Below:  Time series of susceptible and infected individuals

Below:  Histogram of the number of secondary cases induced by a single infected individual in a simulation

Full article at:   http://goo.gl/MHsHUH

By:  Xiaodan Sun,¹ Yanni Xiao,^1,* Sanyi Tang,² Zhihang Peng,³ Jianhong Wu,⁴ and Ning Wang^5,*

Gui-Quan Sun, Editor

¹Department of Applied Mathematics, Xi’an Jiaotong University, Xi’an, Shaanxi, China

²College of Mathematics and Information Science, Shaanxi Normal University, Xi’an, Shaanxi, China

³School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China

⁴Laboratory for Industrial and Applied Mathematics, Centre for Disease Modelling, York Institute for Health Research, York University, Toronto, ON, Canada

⁵National Center for AIDS/STD Prevention and Control, Chinese Center for Disease Control and Prevention, Beijing, China

Shanxi University, CHINA

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Missed Opportunities of Inclusion of HIV-Infected Children to Initiate Antiretroviral Treatment Before the Age of Two in West Africa, 2011 to 2013

INTRODUCTION:

The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso.

METHODS:

All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion.

RESULTS:

Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father's refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency.

CONCLUSIONS:

Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.

Below:  Cohort profile ofthe ANRS 12206 MONOD study, Abidjan, Ouagadougou, May 2011 to February 2013

Full article at:   http://goo.gl/ILmMTv

By:  Dahourou DL1,2,3, Amorissani-Folquet M4,5, Coulibaly M1,2, Avit-Edi D4, Meda N1,6,7, Timite-Konan M8, Arendt V9, Ye D7,10, Amani-Bosse C4, Salamon R2,Lepage P11, Leroy V12; Monod Anrs 12206 Study Group.

• 1MONOD Project, ANRS 12206, Centre de Recherche Internationale pour la Santé, Ouagadougou, Burkina Faso.
• 2Inserm, U1219, Institut de Santé Publique, Epidémiologie et Développement, University of Bordeaux, Bordeaux, France.
• 3Centre Muraz, Bobo-Dioulasso, Burkina Faso; ddahourou@gmail.com; ddahourou@gmail.com.
• 4PACCI Programme, Site ANRS, Projet Monod, Abidjan, Côte d'Ivoire.
• 5Pediatric Department, CHU of Cocody, Abidjan, Côte d'Ivoire.
• 6Centre Muraz, Bobo-Dioulasso, Burkina Faso.
• 7University of Ouagadougou, Ouagadougou, Burkina Faso.
• 8Pediatric Department, Centre Hospitalier Universitaire (CHU) de Yopougon, Abidjan, Côte d'Ivoire.
• 9Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg.
• 10Pediatric Department, CHU Charles de Gaulle, Ouagadougou, Burkina Faso.
• 11Pediatric Department, Hôpital Universitaire des Enfants de la Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium.
• 12Inserm, U1027, Université Toulouse, Toulouse, France. 
• J Int AIDS Soc. 2016 Mar 23;19(1):20601. doi: 10.7448/IAS.19.1.20601.

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Reported Church Attendance at the Time of Entry into HIV Care is Associated with Viral Load Suppression at 12 Months

The Southeast has high rates of church attendance and HIV infection rates. We evaluated the relationship between church attendance and HIV viremia in a Southeastern US, HIV-infected cohort. 

Viremia (viral load ≥200 copies/ml) was analyzed 12 months after initiation of care. Univariate and multivariable logistic regression models were fit for variables potentially related to viremia. Of 382 patients, 74 % were virally suppressed at 12 months. 

Protective variables included church attendance, being on antiretroviral therapy, CD4⁺ T lymphocyte count 200-350 cells/mm³ at care entry, and education. Variables predicting viremia included black race and selective disclosure of HIV status. 

Church attendance may provide needed support for patients entering HIV care for the first time.

Purchase full article at:   http://goo.gl/OszJIU

By:  Van Wagoner N1, Elopre L2, Westfall AO1, Mugavero MJ1, Turan J3, Hook EW1.

• 1Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, ZRB 206, 1720 2nd Ave South, Birmingham, AL, 35294, USA.
• 2Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, ZRB 206, 1720 2nd Ave South, Birmingham, AL, 35294, USA. lelopre@uabmc.edu.
• 3Department of Health Care Organization and Policy, University of Alabama at Birmingham, Birmingham, AL, USA. 

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Prevalence Of & Factors Associated with Prediabetes & Diabetes among HIV-Infected Adults in Cameroon

BACKGROUND:

HIV and certain antiretrovirals (ARVs) are associated with diabetes. Few studies have examined the prevalence of and factors associated with diabetes amongst HIV-infected individuals on combination antiretroviral therapy (cART) in sub-Saharan Africa; some report prevalence estimates between 3.5-26.5% for diabetes in Cameroon and 20.2-43.5% for prediabetes in sub-Saharan Africa.

METHODS:

In a cross-sectional study, HIV-infected individuals (16-65 years old) were screened for diabetes using haemoglobin A_1C (HbA_1C ). We further categorized HbA_1C as normoglycemia (HbA_1C <5.7%), prediabetes (HbA_1C 5.7-6.4%), or diabetes (HbA_1C  ≥6.5%). Dysglycemia was defined as HbA_1C ≥5.7%. Logistic regression modeling was used to assess factors associated with having dysglycemia. .

RESULTS:

Of 500 participants, 363 (72.6%) were female. Median age was 42.5 years [Interquartile Range (IQR):36.5-49.5]. Nineteen (3.8%) were diabetic, and 170 (34%) were prediabetic. One hundred nine (22%) had a CD4+ count <200 cells/mm³ , and 464 (93%) had received >28 days of antiretroviral therapy (ART) at time of screening. Median abdominal circumference for women was 79.5 cm (IQR: 75.5-85.3) and for men, 86.5 cm (IQR: 81.7-90.5). Adjusting for age, sex, socio-economic status, CD4 cell count, being on cART >28 days, BMI, hypertension, history of hypertension, abdominal circumference, and duration of HIV infection, larger abdominal circumference was associated with higher prevalence of prediabetes or diabetes [adjusted Odds Ratio (aOR)=1.07, 95% Confidence Interval (CI):1.03-1.11], while being on cART (aOR=0.46, CI:0.22-0.99) was associated with lower prevalence.

CONCLUSIONS:

There was a high prevalence of Cameroonian HIV-infected adults with dysglycemia. Larger abdominal circumference was associated with higher prevalence, while cART was associated with lower prevalence.

Purchase full article at:   http://goo.gl/V3OmKe

By:  Rhee JY1, Bahtila TD2, Palmer D2, Tih PM2, Aberg JA3, LeRoith D4, Jao J5.

• 1Department of Medical Education, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• 2Cameroon Baptist Convention Health Services, Bamenda, Cameroon.
• 3Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• 4Department of Medicine, Division of Endocrinology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
• 5Department of Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 
• Diabetes Metab Res Rev. 2016 Feb 17. doi: 10.1002/dmrr.2792

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High Prevalence of Being Overweight and Obese HIV-Infected Persons, Before and After 24 Months on Early ART in the ANRS 12136 Temprano Trial

BACKGROUND:

HIV is usually associated with weight loss. World health Organization (WHO) recommends early antiretroviral (ART) initiation, but data on the progression of body mass index (BMI) in participants initiating early ART in Africa are scarce.

METHODS:

The Temprano randomized trial was conducted in Abidjan to assess the effectiveness of early ART and Isoniazid (INH) prophylaxis for tuberculosis in HIV-infected persons with high CD4 counts below 800 cells/mm(3) without any indication for starting ART. Patients initiating earlyART before December 2010 were included in this sub-study. BMI was categorized as: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)). At baseline and after 24 months of ART, prevalence of being overweight orobese and factors associated with being overweight or obese were estimated using univariate and multivariate logistic regression.

RESULTS:

At baseline, 755 participants (78 % women; median CD4 count 442/mm(3), median baseline BMI 22 kg/m(2)) initiated ART. Among them, 19.7 % were overweight, and 7.2 % were obese at baseline. Factors associated with being overweight or obese were: female sex aOR 2.3 (95 % CI 1.4-3.7), age, aOR for 5 years 1.01 (95 % CI 1.0-1.2), high living conditions aOR 2.6 (95 % CI 1.5-4.4), High blood pressure aOR 4.3 (95 % CI 2.0-9.2), WHO stage 2vs1 aOR 0.7 (95 % CI 0.4-1.0) and Hemoglobin ≥95 g/dl aOR 3.0 (95 % CI 1.6-5.8). Among the 597 patients who attended the M24 visit, being overweight or obese increased from 20.4 to 24.8 % (p = 0.01) and 7.2 to 9.2 % (p = 0.03) respectively and factor associated with being overweight or obese was immunological response measured as an increase of CD4 cell count between M0-M24 (for +50 cells/mm(3): aOR 1.01; 95 % CI 1.05-1.13, p = 0.01).

CONCLUSION:

The weight categories overweight and obese are highly prevalent in HIV-infected persons with high CD4 cell counts at baseline, and increased over 24 months on ART in this Sub-Saharan African population.

Below:  Changes of BMI vs baseline (Mean and 95 % confidence intervals) according to initial BMI category, among 597 patients who attended the 24-month visit in the Temprano trial. N number, % percentage, BMI body mass index, underweight BMI <18.5 kg/m², normal BMI 18.5–24.9 kg/m², Overweight BMI 25–29.9 kg/m², Obese BMI >30 kg/m²

Full article at:   http://goo.gl/ZkLOjA

By:  Guehi C1, Badjé A2, Gabillard D3, Ouattara E4, Koulé SO1, Moh R5, Ekouevi D2, Ahibo H6, N'Takpé JB7, Menan GK7, Deschamps N7, Lecarrou J3, Eholié S5,Anglaret X4, Danel C2.

• 1Unité de Soins Ambulatoire et de Conseil (USAC), 18 BP, 1125 Abidjan 18, Côte d'Ivoire.
• 2Programme PACCI, ANRS research Site, Abidjan, Côte d'Ivoire ; Inserm U 1219, Bordeaux University, Bordeaux, France.
• 3Inserm U 1219, Bordeaux University, Bordeaux, France ; ISPED, Bordeaux University, Bordeaux, France.
• 4Programme PACCI, ANRS research Site, Abidjan, Côte d'Ivoire ; Inserm U 1219, Bordeaux University, Bordeaux, France ; ISPED, Bordeaux University, Bordeaux, France.
• 5Programme PACCI, ANRS research Site, Abidjan, Côte d'Ivoire ; Department of Infectious Diseases, Treichville Hospital, Abidjan, Côte d'Ivoire.
• 6Centre de Recherche et Diagnostic sur le SIDA, (Cedres) CHU de Treichville, Abidjan, Côte d'Ivoire.
• 7Programme PACCI, ANRS research Site, Abidjan, Côte d'Ivoire. 
• AIDS Res Ther. 2016 Feb 25;13:12. doi: 10.1186/s12981-016-0094-y. eCollection 2016.

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Correlates of Combination Antiretroviral Adherence among Recently Diagnosed Older HIV-Infected Adults Between 50 and 64 years

Optimal adherence to combination antiretroviral therapy is essential to the health of older people living with HIV (PLWH), however, the literature on adherence and aging is limited. 

Using Medicaid data from 29 states (N = 5177), we explored correlates of optimal adherence among older PLWH. 

• The prevalence of optimal adherence was low (32 %) in this study. 
• Males were more adherent than females; 
• Persons with three or more co-morbidities (APR = 0.67, 95 % CI 0.60-0.74, P < 0.001), two co-morbidities (APR = 0.86, 95 % CI 0.75-0.98, P = 0.0319) and one co-morbidity (APR = 0.82, 95 % CI 0.73-0.92, P = 0.0008) were less adherent than those without any co-morbidity; 
• And residents of rural areas and small metropolitan areas were less adherent than residents of large metropolitan areas. 
• There were no racial differences in optimal adherence. 

Targeted interventions that provide adherence support, case management, and peer navigation services may be of benefit in achieving optimal adherence in this population.

Purchase full article at:   http://goo.gl/YCUhHq

By:  Abara WE1, Adekeye OA2, Xu J3, Heiman HJ4, Rust G3.

• 1Department of Community Health and Preventive Medicine, Satcher Health Leadership Institute, Morehouse School of Medicine, 720 Westview Drive SW, NCPC 214, Atlanta, GA, USA. winston_abara@yahoo.com.
• 2Department of Community Health and Preventive Medicine, Satcher Health Leadership Institute, Morehouse School of Medicine, 720 Westview Drive SW, NCPC 214, Atlanta, GA, USA.
• 3National Center for Primary Care, Morehouse School of Medicine, 720 Westview Drive SW, NCPC 214, Atlanta, GA, USA.
• 4Satcher Health Leadership Institute, Morehouse School of Medicine, 720 Westview Drive SW, NCPC 214, Atlanta, GA, USA.
• AIDS Behav. 2016 Feb 17. 

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Factors Associated with the Failure of First & Second-Line Antiretroviral Therapies in Cambodian HIV-1 Infected Children

BACKGROUND:

Little is known about the efficacy of first and and second-line antiretroviral therapies (ART) for HIV-1 infected children in resource limited Southeast Asian settings. Previous studies have shown that orphans are at a higher risk for virological failure (VF) in Cambodia. Consequently most of them required transfer to second-line ART. We assessed the factors associated with VF among HIV-1 infected children who were either under first-line (mostly 3TC + D4T + NVP) or under second-line (mostly ABC + DDI + LPV) therapies at a referral hospital in Cambodia.

METHODS:

A case-control study was conducted from February to July 2013 at the National Pediatric Hospital among HIV-1 infected children (aged 1-15 years) under second-line ART (cases) or first-line (matched controls at a ratio of 1:3) regimens. Children were included if a HIV-1 RNA plasma viral load (VL) result was available for the preceding 12 months. A standardized questionnaire explored family sociodemographics, HIV history, and adherence to ART. Associations between VF (HIV-1 RNA levels ≥1000 copies/ml) and the children's characteristics were assessed using bivariate and multivariate analyses.

RESULTS:

A total of 232 children, 175 (75.4 %) under first-line and 57 (24.6 %) under second-line ART, for a median of 72.0 (IQR: 68.0-76.0) months, were enrolled. Of them, 94 (40.5 %) were double orphans and 51 (22.0 %) single orphans, and 77 (33.2 %) were living in orphanages. A total of 222 children (95.6 %) were deemed adherent to ART. Overall, 18 (7.7 %; 95 % CI 4.6-11.9) showed a VF, 14 (8.6 %; 95 % CI 4.8-14.0) under first-line and 4 (7.0 %; 95 % CI 1.9-17.0) under second-line ART (p = 0.5). Their median CD4 percentage was 8 % (IQR 2.9-12.9) at ART initiation. Children under second-line ART were older; more often double orphans, and had lower CD4 cell counts at the last control. In the multivariate analysis, having the last CD4 percentage below 15 % was the only factor associated with VF for ART regimen separately or when combined (OR 40.4; 95 % CI 11-134).

CONCLUSIONS:

The pattern of risk factors for VF in children is changing in Cambodia. Improved adherence evaluation and intensified monitoring of children with low CD4 counts is needed to decrease the risk of VF.

Below:  Flow chart of first and second-line ART children enrolled in National Pediatric Hospital, Cambodia

Full article at:   http://goo.gl/fiJ5b1

By:  Hubert Barennes, Kang Virak, François Rouet, Yves Buisson, Michel Strobel, and Ung Vibol

Agence Nationale de Recherche sur le VIH et les Hépatites, Preah Monyvong Blvd, Phnom Penh, Cambodia

Institut de la Francophonie pour la Médecine Tropicale, Vientiane, Lao People’s Democratic Republic

ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Univ. Bordeaux, 33000 Bordeaux, France

Epidemiology Unit, Pasteur Institute, Phnom Penh, Cambodia

Virological Unit, Pasteur Institute, Phnom Penh, Cambodia

University of Health Science, Phnom Penh, Cambodia

Hubert Barennes, Phone: + 85512983572, Email: rf.oohay@buhsennerab.

BMC Res Notes. 2016 Feb 5;9(1):69.

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No Evidence of an Association Between Efavirenz Exposure and Suicidality among HIV Patients Initiating Antiretroviral Therapy in a Retrospective Cohort Study of Real World Data

Recently, published studies have reported conflicting results regarding the association between efavirenz exposure and the risk of suicidality among patients with human immunodeficiency virus. 

The objective of this analysis was to compare the rate of suicidality among patients initiating efavirenz-containing versus efavirenz-free antiretroviral (ARV) regimens.This retrospective cohort study used US administrative claims data for commercially and Medicaid-insured individuals for the years 2006 to 2013. ARV-naive patients aged ≥12 years initiating an efavirenz-containing or efavirenz-free ARV regimen with ≥6 months of continuous insurance enrollment prior to ARV initiation were selected. The primary outcome was suicidality, defined as the occurrence of any medical claim with a diagnosis code for suicidal ideation or an inpatient or emergency department medical claim for suicide attempt. Unadjusted incidence rates were calculated and propensity score-adjusted hazard ratios were estimated to account for differences in patient characteristics.

There were 19,983 patients (efavirenz-containing, n = 11,187; efavirenz-free, n = 8796) in the commercial database and 5154 patients (efavirenz-containing, n = 2224; efavirenz-free, n = 2930) in the Medicaid database. Unadjusted incidence rates (95% confidence interval [CI]) of suicidality per 1000 person-years were: commercial, efavirenz-containing (3.3 [2.4-4.4]), efavirenz-free (4.0 [2.7-5.8]); Medicaid, efavirenz-containing (25.7 [18.8-34.4]), efavirenz-free (40.6 [31.9-50.9]). In propensity score-adjusted analyses, efavirenz use was not associated with suicidality: adjusted hazard ratio (95% CI) of suicidality compared with efavirenz-free regimen, commercial, 1.029 (0.636-1.665); Medicaid, 0.902 (0.617-1.319).

This analysis found no conclusive evidence of an increased risk of suicidality among patients initiating an efavirenz-containing ARV regimen. However, channeling bias may exist even after adjusting for measured patient characteristics.

Below:  Cumulative hazards of suicidality in the (A) commercial and (B) Medicaid databases. EFV = efavirenz.

Full article at:   http://goo.gl/Ml67m4

By:  Nkhoma ET1, Coumbis J, Farr AM, Johnston SS, Chu BC, Rosenblatt LC, Seekins D, Villasis-Keever A.

• 1From the Bristol-Myers Squibb, Global Pharmacovigilance and Epidemiology, Wallingford, Connecticut (ETN); Bristol-Myers Squibb, Global Pharmacovigilance and Epidemiology, Hopewell, New Jersey (JC, DS); Truven Health Analytics, Bethesda, Maryland (AMF, SSJ, BCC); Bristol-Myers Squibb, Health Economics and Outcomes Research (LCR); and Bristol-Myers Squibb, US Medical, Plainsboro, New Jersey (AV-K). 
• Medicine (Baltimore). 2016 Jan;95(3):e2480. doi: 10.1097/MD.0000000000002480.

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