Awareness and perceived fairness of option B+ in Malawi: a population‐level perspective

Introduction : Policies for rationing antiretroviral therapy (ART) have been subject to on‐going ethical debates. Introduced in Malawi in 2011, Option B+ prioritized HIV‐positive pregnant women for lifelong ART regardless of the underlying state of their immune system, shifting the logic of allocation away from medical eligibility. Despite the rapid expansion of this policy, we know little about how it has been understood and interpreted by the people it affects. Methods : We assessed awareness and perceived fairness of the prioritization system for ART among a population‐based sample of young women (n = 1440) and their partners (n = 574) in southern Malawi. We use a card‐sort technique to elicit understandings of who gets ART under Option B+ and who should be prioritized, and we compare perceptions to actual ART policy using sequence analysis and optimal matching. We then use ordered logistic regression to identify the factors associated with policy awareness. Results : In 2015, only 30.7% of women and 21.1% of male partners understood how ART was being distributed. There was widespread confusion around whether otherwise healthy HIV‐positive pregnant women could access ART under Option B + . Nonetheless, more young adults thought that the fairest policy should prioritize such women than believed the actual policy did. Women who were older, more educated or had recently engaged with the health system through antenatal care or ART had more accurate understandings of Option B + . Among men, policy awareness was lower, and was patterned only by education. Conclusions : Although most respondents were unaware that Option B+ afforded ART access to healthy‐pregnant women, Malawians support the prioritization of pregnant women. Countries adopting Option B+ or other new ART policies such as universal test‐and‐treat should communicate the policies and their rationales to the public – such transparency would be more consistent with a fair and ethical process and could additionally serve to clarify confusion and enhance retention.​​     

Same‐day antiretroviral therapy (ART) initiation in pregnancy is not associated with viral suppression or engagement in care: A cohort study

Introduction

Many prevention of mother‐to‐child HIV transmission programmes across Africa initiate HIV‐infected (HIV positive) pregnant women on lifelong antiretroviral therapy (ART) on the first day of antenatal care (“same‐day” initiation). However, there are concerns that same‐day initiation may limit patient preparation before starting ART and contribute to subsequent non‐adherence, disengagement from care and raised viral load. We examined if same‐day initiation was associated with viral suppression and engagement in care during pregnancy.

Methods

Consecutive ART‐eligible pregnant women making their first antenatal care (ANC) visit at a primary care facility in Cape Town, South Africa were enrolled into a prospective cohort between March 2013 and June 2014. Before July 2013, ART eligibility was based on CD4 cell count ≤350 cells/μL (“Option A”), with a 1 to 2 week delay from the first ANC visit to ART initiation for patient preparation; thereafter all women were eligible regardless of CD4 cell count (“Option B+”) and offered ART on the same day as first ANC visit. Women were followed with viral load testing conducted separately from routine ART services, and engagement in ART services was measured using routinely collected clinic, pharmacy and laboratory records through 12 months postpartum.

Results

Among 628 HIV‐positive women (median age, 28 years; median gestation at ART start, 21 weeks; 55% newly diagnosed with HIV), 73% initiated ART same‐day; this proportion was higher under Option B+ versus Option A (85% vs. 20%). Levels of viral suppression (viral load <50 copies/mL) at delivery (74% vs. 82%) and 12 months postpartum (74% vs. 71%) were similar under same‐day versus delayed initiation respectively. Findings were consistent when viral suppression was defined at <1000 copies/mL, after adjustment for demographic/clinical measures and across subgroups of age, CD4 and timing of HIV diagnosis. Time to first viral rebound following initial suppression did not differ by timing of ART initiation nor did engagement in care through 12 months postpartum (same‐day = 73%, delayed = 73%, p = 0.910).

Conclusions

These data suggest that same‐day ART initiation during pregnancy is not associated with lower levels of engagement in care or viral suppression through 12 months post‐delivery in this setting, providing reassurance to ART programmes implementing Option B+.

     

Adherence to antiretroviral therapy for HIV in sub‐Saharan Africa and Asia: a comparative analysis of two regional cohorts

Introduction : Our understanding of how to achieve optimal long‐term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV‐positive persons receiving ART who were enrolled in a bi‐regional cohort in sub‐Saharan Africa and Asia. Methods : This multicentre prospective study of adults starting first‐line ART assessed patient‐reported adherence at follow‐up clinic visits using a 30‐day visual analogue scale. Determinants of suboptimal adherence (<95%) were assessed for six‐month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier. Results : Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p < 0.001). In the African cohort, determinants of suboptimal adherence were male sex (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06–1.53; p = 0.009), younger age (OR 0.8 per 10 year increase; 0.8–0.9; p = 0.003), use of concomitant medication (OR 1.8, 1.0–3.2; p = 0.044) and attending a public facility (OR 1.3, 95% CI 1.1–1.7; p = 0.004). In the Asian cohort, adherence was higher in men who have sex with men (OR for suboptimal adherence 0.6, 95% CI 0.4–0.9; p = 0.029) and lower in injecting drug users (OR for suboptimal adherence 1.6, 95% CI 0.9–2.6; p = 0.075), compared to heterosexuals. Risk of suboptimal adherence decreased with longer ART duration in both regions. Participants in low‐ and lower‐middle‐income countries had a higher risk of suboptimal adherence (OR 1.6, 1.3–2.0; p < 0.001), compared to those in upper‐middle or high‐income countries. Suboptimal adherence was strongly associated with virological failure, in Africa (OR 5.8, 95% CI 4.3–7.7; p < 0.001) and Asia (OR 9.0, 95% CI 5.0–16.2; p < 0.001). Patient‐reported adherence barriers among African participants included scheduling demands, drug stockouts, forgetfulness, sickness or adverse events, stigma or depression, regimen complexity and pill burden. Conclusions : Psychosocial factors and health system resources may explain regional differences. Adherence‐enhancing interventions should address patient‐reported barriers tailored to local settings, prioritizing the first years of ART.     

HIV transmission and retention in care among HIV‐exposed children enrolled in Malawi's prevention of mother‐to‐child transmission programme

Introduction : In Malawi, HIV‐infected pregnant and breastfeeding women are offered lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage (Option B+). Their HIV‐exposed children are enrolled in the national prevention of mother‐to‐child transmission (PMTCT) programme, but many are lost to follow‐up. We estimated the cumulative incidence of vertical HIV transmission, taking loss to follow‐up into account. Methods : We abstracted data from HIV‐exposed children enrolled into care between September 2011 and June 2014 from patient records at 21 health facilities in central and southern Malawi. We used competing risk models to estimate the probability of loss to follow‐up, death, ART initiation and discharge, and used pooled logistic regression and inverse probability of censoring weighting to estimate the vertical HIV transmission risk. Results : A total of 11,285 children were included; 9285 (82%) were born to women who initiated ART during pregnancy. At age 30 months, an estimated 57.9% (95% CI 56.6–59.2) of children were lost to follow‐up, 0.8% (0.6–1.0) had died, 2.6% (2.3–3.0) initiated ART, 36.5% (35.2–37.9) were discharged HIV‐negative and 2.2% (1.5–2.8) continued follow‐up. We estimated that 5.3% (95% CI 4.7–5.9) of the children who enrolled were HIV‐infected by the age of 30 months, but only about half of these children (2.6%; 95% CI 2.3–2.9) were diagnosed. Conclusions : Confirmed mother‐to‐child transmission rates were low, but due to poor retention only about half of HIV‐infected children were diagnosed. Tracing of children lost to follow‐up and HIV testing in outpatient clinics should be scaled up to ensure that all HIV‐positive children have access to early ART.     

Alignment of adherence and risk for HIV acquisition in a demonstration project of pre‐exposure prophylaxis among HIV serodiscordant couples in Kenya and Uganda: a prospective analysis of prevention‐effective adherence

Introduction: Adherence is essential for pre‐exposure prophylaxis (PrEP) to protect against HIV acquisition, but PrEP use need not be life‐long. PrEP is most efficient when its use is aligned with periods of risk – a concept termed prevention‐effective adherence. The objective of this paper is to describe prevention‐effective adherence and predictors of adherence within an open‐label delivery project of integrated PrEP and antiretroviral therapy (ART) among HIV serodiscordant couples in Kenya and Uganda (the Partners Demonstration Project). Methods : We offered PrEP to HIV‐uninfected participants until the partner living with HIV had taken ART for ≥6 months (a strategy known as “PrEP as a bridge to ART”). The level of adherence sufficient to protect against HIV was estimated in two ways: ≥4 and ≥6 doses/week (per electronic monitoring). Risk for HIV acquisition was considered high if the couple reported sex with <100% condom use before six months of ART, low if they reported sex but had 100% condom use and/or six months of ART and very low if no sex was reported. We assessed prevention‐effective adherence by cross‐tabulating PrEP use with HIV risk and used multivariable regression models to assess predictors of ≥4 and ≥6 doses/week. Results : A total of 985 HIV‐uninfected participants initiated PrEP; 67% were male, median age was twenty‐nine years, and 67% reported condomless sex in the month before enrolment. An average of ≥4 doses and ≥6 doses/week were taken in 81% and 67% of participant‐visits, respectively. Adherence sufficient to protect against HIV acquisition was achieved in 75–88% of participant‐visits with high HIV risk. The strongest predictor of achieving sufficient adherence was reporting sex with the study partner who was living with HIV; other statistically significant predictors included no concerns about daily PrEP, pregnancy or pregnancy intention, females aged > 25 years, older male partners and desire for relationship success. Predictors of not achieving sufficient adherence were no longer being a couple, delayed PrEP initiation, >6 months  of follow‐up, ART use > 6 months  by the partner living with HIV and problem alcohol use. Conclusions: Over three‐quarters of participant‐visits by HIV‐uninfected partners in serodiscordant couples achieved prevention‐effective adherence with PrEP. Greater adherence was observed during months with HIV risk and the strongest predictor of achieving sufficient adherence was sexual activity.     

A novel Online‐to‐Offline (O2O) model for pre‐exposure prophylaxis and HIV testing scale up

Introduction : PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high‐risk groups is a critical priority. This study evaluates the effect of a novel Adam's Love Online‐to‐Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake. Methods : The O2O model was piloted by Adam's Love ( www.adamslove.org ) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam's Love online staff, received real‐time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto‐generated site‐ and service‐specific e‐tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check‐in by offline site staff. Service uptake and participant's socio‐demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression. Results : Between January 10th and April 11th, 2016, Adam's Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e‐tickets. There were 325 (76.5%) MSM and TG who checked‐in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e‐ticket and checking‐in was 3 (0–7) days. Of 316 HIV‐negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14–4.66; p = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19–3.54; p = 0.009), being aware of sexual partners’ HIV status (OR 2.37, 95%CI 1.29–4.35; p = 0.008), ever previously using post‐exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19–5.09; p = 0.01), and enrolment at Adam's Love clinic compared to the other three sites (OR 3.79, 95%CI 2.06–6.95; p < 0.001) were independently associated with PrEP uptake. Conclusions : Adam's Love O2O model is highly effective in linking online at‐risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations.     

Same day HIV diagnosis and antiretroviral therapy initiation affects retention in Option B+ prevention of mother-to-child transmission services at antenatal care in Zomba District,Malawi

Introduction

Data from the Option B+ prevention of mother-to-child transmission (PMTCT) program in Malawi show considerable variation between health facilities in retention on antiretroviral therapy (ART). In a programmatic setting, we studied whether the “model of care,” based on the degree of integration of antenatal care (ANC), HIV testing and counselling (HTC) and ART service provision–influenced uptake of and retention on ART.

Methods

We conducted a retrospective cohort study of pregnant women seeking ANC at rural primary health facilities in Zomba District, Malawi. Data were extracted from standardized national ANC registers, ART registers and ART master cards. The “model of care” of Option B+ service delivery was determined at each health facility, based on the degree of integration of ANC, HTC and ART. Full integration (Model 1) of HTC and ART initiation at ANC was compared with integration of HTC only into ANC services (Model 2) with subsequent referral to an existing ART clinic for treatment initiation.

Results and discussion

A total of 10,528 women were newly registered at ANC between October 2011 and March 2012 in 23 rural health facilities (12 were Model 1 and 11 Model 2). HIV status was ascertained in 8,572 (81%) women. Among 914/8,572 (9%) HIV-positive women enrolling at ANC, 101/914 (11%) were already on ART; of those not on treatment, 456/813 (56%) were started on ART. There was significantly higher ART uptake in Model 1 compared with Model 2 sites (63% vs. 51%; p=0.001), but significantly lower ART retention in Model 1 compared with Model 2 sites (79% vs. 87%; p=0.02). Multivariable analysis showed that initiation of ART on the same day as HIV diagnosis, but not model of care, was independently associated with reduced retention in the first six months (adjusted odds ratio 2.27; 95% CI: 1.34–3.85; p=0.002).

Conclusions

HIV diagnosis and treatment on the same day was associated with reduced retention on ART, independent of the level of PMTCT service integration at ANC.     

High self‐reported non‐adherence to antiretroviral therapy amongst adolescents living with HIV in Malawi: barriers and associated factors

Introduction : Globally adolescents and young adults account for more than 40% of new HIV infections, and HIV‐related deaths amongst adolescents increased by 50% from 2005 to 2012. Adherence to antiretroviral therapy (ART) is critical to control viral replication and preserve health; however, there is a paucity of research on adherence amongst the growing population of adolescents living with HIV/AIDS (ALHIV) in Southern Africa. We examined levels of self‐reported ART adherence, barriers to adherence, and factors associated with non‐adherence amongst ALHIV in Malawi. Methods : Cross‐sectional study of 519 ALHIV (12–18 years) attending two large HIV clinics in central and south‐eastern Malawi. Participants self‐reported missed doses (past week/month), barriers to adherence, and completed questionnaires on past traumatic events/stressors, disclosure, depression, substance use, treatment self‐efficacy, and social support. Biomedical data were retrieved from existing medical records. Multivariate logistic regression was performed to identify factors independently associated with self‐reported ART adherence (7 day recall). Results : The mean age of participants (SD) was 14.5 (2) years and 290 (56%) were female. Of the 519 participants, 153 (30%) reported having missed ART doses within the past week, and 234 (45%) in the past month. Commonly reported barriers to adherence included forgetting (39%), travel from home (14%), busy with other things (11%), feeling depressed/overwhelmed (6%), feeling stigmatized by people outside (5%) and within the home (3%). Factors found to be independently associated with missing a dose in the past week were drinking alcohol in the past month (OR 4.96, 95% CI [1.41–17.4]), missed clinic appointment in the past 6 months (OR 2.23, 95% CI [1.43–3.49]), witnessed or experienced violence in the home (OR 1.86, 95% CI [1.08–3.21]), and poor treatment self‐efficacy (OR 1.55 95% CI [1.02–2.34]). Sex and age were not associated with adherence. Conclusions : In our study, nearly half of all ALHIV reported non‐adherence to ART in the past month. Violence in the home or alcohol use in the past year as well as poor treatment self‐efficacy were associated with worse adherence. Sub‐optimal adherence is a major issue for ALHIV and compromise treatment outcomes. Programmes specifically tailored to address those challenges most pertinent to ALHIV may help improve adherence to ART.     

HIV viral load as an independent risk factor for tuberculosis in South Africa: collaborative analysis of cohort studies

Introduction : Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART). Methods : We included all HIV‐positive adult patients (≥16 years) in care between 2000 and 2014 at three ART programmes in South Africa. Patients with previous TB were excluded. Missing CD4 cell counts and HIV‐RNA viral loads at ART start (baseline) and during follow‐up were imputed. We used parametric survival models to assess TB incidence (pulmonary and extrapulmonary) by CD4 cell and HIV‐RNA levels, and estimated the rate ratios for TB by including age, sex, baseline viral loads, CD4 cell counts, and WHO clinical stage in the model. We also used Poisson general additive regression models with time‐updated CD4 and HIV‐RNA values, adjusting for age and sex. Results : We included 44,260 patients with a median follow‐up time of 2.7 years (interquartile range [IQR] 1.0–5.0); 3,819 incident TB cases were recorded (8.6%). At baseline, the median age was 34 years (IQR 28–41); 30,675 patients (69.3%) were female. The median CD4 cell count was 156 cells/µL (IQR 79–229) and the median HIV‐RNA viral load 58,000 copies/mL (IQR 6,000–240,000). Overall TB incidence was 26.2/1,000 person‐years (95% confidence interval [CI] 25.3–27.0). Compared to the lowest viral load category (0–999 copies/mL), the adjusted rate ratio for TB was 1.41 (95% CI 1.15–1.75, p < 0.001) in the highest group (>10,000 copies/mL). Time‐updated analyses for CD4/HIV‐RNA confirmed the association of viral load with the risk for TB. Conclusions : Our results indicate that ongoing HIV replication is an important risk factor for TB, regardless of CD4 cell counts, and underline the importance of early ART start and retention on ART.     

Multicentre analysis of second‐line antiretroviral treatment in HIV‐infected children: adolescents at high risk of failure

Introduction : The number of HIV‐infected children and adolescents requiring second‐line antiretroviral treatment (ART) is increasing in low‐ and middle‐income countries (LMIC). However, the effectiveness of paediatric second‐line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second‐line ART outcomes for children and assessed the need for paediatric third‐line ART. Methods : We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second‐line ART in LMIC, contacting the corresponding study groups and including patient‐level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second‐line treatment. Results : We included 12 cohorts representing 928 children on second‐line protease inhibitor (PI)‐based ART in 14 countries in Asia and sub‐Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person‐years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first‐line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months). Conclusions : In LMIC, paediatric PI‐based second‐line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI‐based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.     

Towards elimination of mother-to-child transmission of HIV: performance of different models of care for initiating lifelong antiretroviral therapy for pregnant women in Malawi (Option B+)

Introduction

Malawi introduced a new strategy to improve the effectiveness of prevention of mother-to-child HIV transmission (PMTCT), the Option B+ strategy. We aimed to (i) describe how Option B+ is provided in health facilities in the South East Zone in Malawi, identifying the diverse approaches to service organization (the “model of care”) and (ii) explore associations between the “model of care” and health facility–level uptake and retention rates for pregnant women identified as HIV-positive at antenatal (ANC) clinics.

Methods

A health facility survey was conducted in all facilities providing PMTCT/antiretroviral therapy (ART) services in six of Malawi''s 28 districts to describe and compare Option B+ service delivery models. Associations of identified models with program performance were explored using facility cohort reports.

Results

Among 141 health facilities, four “models of care” were identified: A) facilities where newly identified HIV-positive women are initiated and followed on ART at the ANC clinic until delivery; B) facilities where newly identified HIV-positive women receive only the first dose of ART at the ANC clinic, and are referred to the ART clinic for follow-up; C) facilities where newly identified HIV-positive women are referred from ANC to the ART clinic for initiation and follow-up of ART; and D) facilities serving as ART referral sites (not providing ANC). The proportion of women tested for HIV during ANC was highest in facilities applying Model A and lowest in facilities applying Model B. The highest retention rates were reported in Model C and D facilities and lowest in Model B facilities. In multivariable analyses, health facility factors independently associated with uptake of HIV testing and counselling (HTC) in ANC were number of women per HTC counsellor, HIV test kit availability, and the “model of care” applied; factors independently associated with ART retention were district location, patient volume and the “model of care” applied.

Conclusions

A large variety exists in the way health facilities have integrated PMTCT Option B+ care into routine service delivery. This study showed that the “model of care” chosen is associated with uptake of HIV testing in ANC and retention in care on ART. Further patient-level research is needed to guide policy recommendations.     

Five year neurodevelopment outcomes of perinatally HIV‐infected children on early limited or deferred continuous antiretroviral therapy

Introduction

Early antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV‐infected (HIV‐positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long‐term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIV‐infected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART‐Def); immediate time‐limited ART for 40 weeks (ART‐40W) or 96 weeks (ART‐96W). ART was restarted in the time‐limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants.

Methods

A prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery‐Buktenica developmental tests for visual motor integration at 60 months. HIV‐exposed uninfected (HEU) and HIV‐unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms.

Results

In this study, 28 ART‐Def, 35 ART‐40W, 33 ART‐96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART‐Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV‐infected children (mean standard scores: 75.8 ART‐Def, 79.8 ART‐40W, 75.9 ART‐96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)).

Conclusions

Early locomotor delay in the ART‐Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV‐infected children on early time‐limited ART were similar to uninfected controls, apart from visual perception where HIV‐infected children scored lower. Poorer visual perception performance warrants further investigation.

     

Alcohol use,viral hepatitis and liver fibrosis among HIV‐positive persons in West Africa: a cross‐sectional study

Introduction : Liver fibrosis is often the first stage of liver disease in people living with HIV (PLWHIV) in industrialized countries. However, little is known about liver fibrosis and its correlates among PLWHIV in sub‐Saharan Africa. Methods : The study was undertaken in three HIV referral clinics in Côte d’Ivoire, Senegal and Togo. Enrolled PLWHIV underwent a non‐invasive assessment of liver fibrosis combining liver stiffness measure (LSM) with transient elastography and the aspartate aminotransferase‐to‐platelet ratio index (APRI). Significant liver fibrosis was defined as LSM ≥7.1 kPa. Patients were screened for alcohol use (alcohol use disorder identification test (AUDIT)‐C questionnaire), hepatitis B virus (HBV) antigen, hepatitis Delta virus (HDV) antibody and anti‐hepatitis C (HCV) antibody. A logistic regression model was used to identify the factors associated with significant liver fibrosis. Results : A total of 807 PLWHIV were screened at a median age of 43 years (interquartile range (IQR): 36–50). Their median CD4 count was 393 cells/mm³ (IQR: 234–563) and 682 (84.5%) were on antiretroviral therapy (ART). The prevalence of significant fibrosis was 5.3% (3.8–6.7). Infections with HBV and HCV were identified in 74 (9.2%) and nine (1.1%) participants. Main factors associated with liver fibrosis were alcohol use (AUDIT‐C >6): (odds ratio (OR) = 4.0, confidence interval (CI): 1.2–14.0), (Ref. AUDIT‐C <4) and HBV infection (OR = 2.9, CI: 1.2–7.2). Of the 74 patients positively screened for HBV, 50.0% were on a tenofovir‐based ART regimen. Overall, 10% of HIV/HBV coinfected patients were detected with a positive HDV antibody with a higher prevalence in patients with a significant liver fibrosis (43.0%) compared to others (6.3%) (p = 0.01). Conclusions : Considering the WHO recommendations to screen for HBV infection and treat co‐infected patients with tenofovir‐based ART, screening of alcohol use and brief interventions to prevent alcohol abuse should be implemented in West Africa, especially in HBV/HIV co‐infected patients.     

Retention on ART and predictors of disengagement from care in several alternative community‐centred ART refill models in rural Swaziland

Introduction

A broad range of community‐centred care models for patients stable on anti‐retroviral therapy (ART) have been proposed by the World Health Organization to better respond to patient needs and alleviate pressure on health systems caused by rapidly growing patient numbers. Where available, often a single alternative care model is offered in addition to routine clinical care. We operationalized several community‐centred ART delivery care models in one public sector setting. Here, we compare retention in care and on ART and identify predictors of disengagement with care.

Methods

Patients on ART were enrolled into three community‐centred ART delivery care models in the rural Shiselweni region (Swaziland), from 02/2015 to 09/2016: Community ART Groups (CAGs), comprehensive outreach care and treatment clubs. We used Kaplan–Meier estimates to describe crude retention in care model and retention on ART (including patients who returned to clinical care). Multivariate Cox proportional hazard models were used to determine factors associated with all‐cause attrition from care model and disengagement with ART.

Results

A total of 918 patients were enrolled. CAGs had the most participants with 531 (57.8%). Median age was 44.7 years (IQR 36.3 to 54.4), 71.8% of patients were female, and 62.6% fulfilled eligibility criteria for community ART. The 12‐month retention in ART was 93.7% overall; it was similar between model types (p = 0.52). A considerable proportion of patients returned from community ART to clinical care, resulting in lower 12 months retention in care model (82.2% overall); retention in care model was lowest in CAGs at 70.4%, compared with 86.3% in outreach and 90.4% in treatment clubs (p < 0.001). In multivariate Cox regression models, patients in CAGs had a higher risk of disengaging from care model (aHR 3.15, 95% CI 2.01 to 4.95, p < 0.001) compared with treatment clubs. We found, however, no difference in attrition in ART between alternative model types.

Conclusions

Concurrent implementation of three alternative community‐centred ART models in the same region was feasible. Although a considerable proportion of patients returned back to clinical care, overall ART retention was high and should encourage programme managers to offer community‐centred care models adapted to their specific setting.

     

Loss to follow‐up among children and adolescents growing up with HIV infection: age really matters

Introduction : Globally, increasing numbers of HIV‐infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss‐to‐follow‐up (LTFU) from HIV care services among children as they transition from childhood through adolescence. Methods : Individuals aged 5–19 years initiated on ART in a public‐sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age‐bands namely: 5–9 (children), 10–14 (young adolescents) and 15–19 (older adolescents). The effect of age at ART initiation, current age (using a time‐updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression. Results : Of 2273 participants, 1013, 875 and 385 initiated ART aged 5–9, 10–14 and 15–19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age‐band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94–2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05–3.07). In older adolescents, the LTFU rate among those who started ART in that age‐band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age‐groups. Conclusions : Adolescents had higher rates of LTFU compared to other age‐groups, with older adolescents at particularly high risk in all analyses. Age‐updated analyses that examine movement across narrow age‐bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes.     

HIV testing and the care continuum among transgender women: population estimates from Rio de Janeiro,Brazil

Introduction : Evidence suggests that, of all affected populations, transgender women (transwomen) may have the heaviest HIV burden worldwide. Little is known about HIV linkage and care outcomes for transwomen. We aimed to estimate population‐level indicators of the HIV cascade of care continuum, and to evaluate factors associated with viral suppression among transwomen in Rio de Janeiro, Brazil. Methods : We conducted a respondent‐driven sampling (RDS) study of transwomen from August 2015 to January 2016 in Rio de Janeiro, Brazil and collected data on linkage and access to care, antiretroviral treatment and performed HIV viral load testing. We derived population‐based estimates of cascade indicators using sampling weights and conducted RDS‐weighted logistic regression analyses to evaluate correlates of viral suppression (viral load ≤50 copies/mL). Results : Of the 345 transwomen included in the study, 89.2% (95% CI 55–100%) had been previously tested for HIV, 77.5% (95% CI 48.7–100%) had been previously diagnosed with HIV, 67.2% (95% CI 39.2–95.2) reported linkage to care, 62.2% (95% CI 35.4–88.9) were currently on ART and 35.4% (95% CI 9.5–61.4%) had an undetectable viral load. The final adjusted RDS‐weighted logistic regression model for viral suppression indicated that those who self‐identified as black (adjusted odds ratio [aOR] 0.06, 95% CI 0.01–0.53, p < 0.01), reported earning ≤U$160/month (aOR 0.11, 95% CI 0.16–0.87, p = 0.04) or reported unstable housing (aOR 0.08, 95% CI 0.01–0.43, p < 0.01) had significantly lower odds of viral suppression. Conclusions : Our cascade indicators for transwomen showed modest ART use and low viral suppression rates. Multi‐level efforts including gender affirming care provision are urgently needed to decrease disparities in HIV clinical outcomes among transwomen and reduce secondary HIV transmission to their partners.     

A prospective “test‐and‐treat” demonstration project among people who inject drugs in Vietnam

Introduction

Modelling suggests that early diagnosis and immediate antiretroviral therapy (ART) among key populations would have a substantial impact in reducing HIV transmission and mortality in Vietnam. An implementation research project of “test‐and‐treat” among people who inject drugs (PWID) was developed to inform effective roll‐out of such interventions.

Methods

“Test‐and‐treat” was offered to PWID in two high burden provinces, Thai Nguyen and Thanh Hoa. The interventions comprised the offer of biannual HIV testing and immediate ART, irrespective of CD4 count. PWID were enrolled between April 2014 and July 2015 and followed up for 12 months, and retention, HIV viral load (VL) and risk behaviours were assessed. Retention in care of this prospective cohort was compared with the retention among men enrolled in care in the preceding period (April 2012 to March 2013) at the same clinics when ART was initiated at CD4 cell count ≤350 cells/mm³.

Results

In total, 287 HIV positive PWID started immediate ART. The majority (98%) were men; median age was 34; and median (interquartile range) CD4 count was 199 (50 to 402) cells/mm³. After 12 months, 238 participants (83%) were retained on ART, and 205 achieved viral suppression (<1000 copies/mL) (92% among those in whom VL was measured, 71% overall). Baseline CD4 count ≤100 cells/mm³ and history of imprisonment were associated with lower retention and viral suppression, while engagement in methadone maintenance was associated with higher retention. Retention in care was higher in the “test‐and‐treat” cohort (83%) compared with men enrolled in care in the preceding period (78%), primarily because lost‐to‐follow‐up during pre‐ART care was eliminated. No decline in consistent condom use and clean needle use was observed.

Conclusions

Early ART initiation resulted in successful treatment outcomes among PWID, with no observed increase in self‐reported risk behaviours, suggesting feasibility and potential effectiveness of “test‐and‐treat” approach. The results also call for differentiated care for PWID, including promoting early diagnosis and engagement in methadone maintenance therapy while enhancing care for those with advanced HIV disease and history of imprisonment.

     

Comprehensiveness of HIV care provided at global HIV treatment sites in the IeDEA consortium: 2009 and 2014

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