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Background Women who are newly diagnosed with HIV infection during pregnancy may not be ready to immediately initiate lifelong antiretroviral therapy (ART; called Option B +) as is recommended. Lack of “readiness” drives early disengagement from care and undermines prevention of HIV transmission to infants. Several studies have shown high early attrition of women initiating ART in pregnancy. Although poor ART uptake and adherence have been attributed to various factors including stigma, disclosure issues and structural issues, there is no standard way of determining which pregnant woman will face challenges and therefore need additional support. We developed and validated a novel ART readiness tool in Lusaka, Zambia. Methods The aim of this study was to develop and validate a tool that could be used to assess how ready a newly diagnosed pregnant woman living with HIV would be to initiate ART on the day of diagnosis. Using a mixed method design, we conducted this study in three public-setting health facilities in Lusaka, Zambia. Informed by qualitative research and literature review, we identified 27 candidate items. We assessed content validity using expert and target population judgment approaches. We administered the 27-item questionnaire to 454 newly diagnosed pregnant women living with HIV, who were enrolled into a randomized trial (trials number NCT02459678). We performed item reduction analysis and used Cronbach’s alpha coefficient of 0.70 as threshold for reliability. Results A total of 454 pregnant women living with HIV enrolled in the study between March 2017 and December 2017; 452 had complete data for analysis. The correlation coefficient between the 27 items on the completed ART readiness scale ranged from 0.31 to 0.70 while item discrimination index ranged from -0.01 to 2.38. Sixteen items were selected for the final scale, representing three domains, which we classified as “internalized and anticipated HIV stigma”, “partner support” and “anticipated structural barriers”. Conclusion We developed and validated a tool that could be used to assess readiness of newly diagnosed women living with HIV to initiate ART. This ART readiness tool could allow clinics to tailor limited resources to pregnant women living with HIV needing additional support to initiate and remain on ART.

This randomized controlled trial tested the efficacy of a multi-session, evidence-based, lay counselor-delivered transdiagnostic therapy, the Common Elements Treatment Approach (CETA), in reducing unhealthy alcohol use and comorbidities among persons living with HIV (PLWH) in Zambia. Adult PLWH with (a) unhealthy alcohol use plus mental health or substance use comorbidities, or (b) severe unhealthy alcohol use were randomized to receive a single-session alcohol brief intervention (BI) alone or BI plus referral to CETA. Outcomes were measured at baseline and a 6-month follow-up and included Alcohol Use Disorders Identification Test (AUDIT) score (primary), depression and trauma symptoms, and other substance use (secondary). We enrolled 160 participants; 78 were randomized to BI alone and 82 to BI plus CETA. Due to COVID-19, the trial ended early before 36 participants completed. Statistically and clinically significant reductions in mean AUDIT score from baseline to 6-month follow-up were observed in both groups, however, participants assigned to BI plus CETA had significantly greater reductions compared to BI alone (- 3.2, 95% CI - 6.2 to - 0.1; Cohen's d: 0.48). The CETA effect size for AUDIT score increased in line with increasing mental health/substance use comorbidity (0 comorbidities d = 0.25; 1-2 comorbidities d = 0.36; 3+ comorbidities d = 1.6). Significant CETA treatment effects were observed for depression, trauma, and several other substances. BI plus referral to CETA was feasible and superior to BI alone for unhealthy alcohol use among adults with HIV, particularly among those with comorbidities. Findings support future effectiveness testing of CETA for HIV outcomes among PLWH with unhealthy alcohol use.Clinical Trials Number: NCT03966885.

Through a nationally-representative household survey, we measured the prevalence and correlates of unhealthy alcohol use (UAU) in Zambia and its association with the HIV care continuum. Adolescent and adult (ages 15-59 years) data, including the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), from the 2016 Zambia Population-based HIV Impact Assessment, were analyzed. UAU was defined as AUDIT-C of 3 + points for women and 4 + for men. Among 20,923 participants, 15.3% had UAU; this was 21.6% among people living with HIV (PLWH). Male sex, increasing age, being employed, urban residence, and having HIV were independent correlates of UAU (all

Background In low- and middle-income countries (LMIC), there is a substantial gap in the treatment of mental and behavioral health problems, which is particularly detrimental to adolescents and young adults (AYA). The Common Elements Treatment Approach (CETA) is an evidence-based, flexible, transdiagnostic intervention delivered by lay counselors to address comorbid mental and behavioral health conditions, though its effectiveness has not yet been tested among AYA. This paper describes the protocol for a randomized controlled trial that will test the effectiveness of traditional in-person delivered CETA and a telehealth-adapted version of CETA (T-CETA) in reducing mental and behavioral health problems among AYA in Zambia. Non-inferiority of T-CETA will also be assessed. Methods This study is a hybrid type 1 three-arm randomized trial to be conducted in Lusaka, Zambia. Following an apprenticeship model, experienced non-professional counselors in Zambia will be trained as CETA trainers using a remote, technology-delivered training method. The new CETA trainers will subsequently facilitate technology-delivered trainings for a new cohort of counselors recruited from community-based partner organizations throughout Lusaka. AYA with mental and behavioral health problems seeking services at these same organizations will then be identified and randomized to (1) in-person CETA delivery, (2) telehealth-delivered CETA (T-CETA), or (3) treatment as usual (TAU). In the superiority design, CETA and T-CETA will be compared to TAU, and using a non-inferiority design, T-CETA will be compared to CETA, which is already evidence-based in other populations. At baseline, post-treatment (approximately 3–4 months post-baseline), and 6 months post-treatment (approximately 9 months post-baseline), we will assess the primary outcomes such as client trauma symptoms, internalizing symptoms, and externalizing behaviors and secondary outcomes such as client substance use, aggression, violence, and health utility. CETA trainer and counselor competency and cost-effectiveness will also be measured as secondary outcomes. Mixed methods interviews will be conducted with trainers, counselors, and AYA participants to explore the feasibility, acceptability, and sustainability of technology-delivered training and T-CETA provision in the Zambian context. Discussion Adolescents and young adults in LMIC are a priority population for the treatment of mental and behavioral health problems. Technology-delivered approaches to training and intervention delivery can expand the reach of evidence-based interventions. If found effective, CETA and T-CETA would help address a major barrier to the scale-up and sustainability of mental and behavioral treatments among AYA in LMIC. Trial registration ClinicalTrials.govNCT03458039. Prospectively registered on May 10, 2021

We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naive pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30 days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30 days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91–1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02–1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support. This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.

Background Zambia recently achieved UNAIDS 90-90-90 treatment targets for HIV epidemic control; however, inpatient facilities continue to face a large burden of patients with advanced HIV disease and HIV-related mortality. Management of advanced HIV disease, following guidelines from outpatient settings, may be more difficult within complex inpatient settings. We evaluated adherence to HIV guidelines during hospitalization, including opportunistic infection (OI) screening, treatment, and prophylaxis. Methods We reviewed inpatient medical records of people living with HIV (PLHIV) admitted to the University Teaching Hospital in Lusaka, Zambia between December 1, 2018 and April 30, 2019. We collected data on patient demographics, antiretroviral therapy (ART), HIV biomarkers, and OI screening and treatment—including tuberculosis (TB), Cryptococcus, and OI prophylaxis with co-trimoxazole (CTX). Screening and treatment cascades were constructed based on the 2017 WHO Advanced HIV Guidelines. Results We reviewed files from 200 charts of patients with advanced HIV disease; of these 92% (184/200) had been on ART previously; 58.1% (107/184) for more than 12 months. HIV viral load (VL) testing was uncommon but half of VL results were high. 39% (77/200) of patients had a documented CD4 count result. Of the 172 patients not on anti-TB treatment (ATT) on admission, TB diagnostic tests (either sputum Xpert MTB/RIF MTB/RIF or urine TB-LAM) were requested for 105 (61%) and resulted for 60 of the 105 (57%). Nine of the 14 patients (64%) with a positive lab result for TB died before results were available. Testing for Cryptococcosis was performed predominantly in patients with symptoms of meningitis. Urine TB-LAM testing was rarely performed. Conclusions At a referral hospital in Zambia, CD4 testing was inconsistent due to laboratory challenges and this reduced recognition of AHD and implementation of AHD guidelines. HIV programs can potentially reduce mortality and identify PLHIV with retention and adherence issues through strengthening inpatient activities, including reflex VL testing, TB-LAM and serum CrAg during hospitalization.

BACKGROUND Hazardous alcohol use is a predictor of intimate partner violence (IPV), and both are increasingly prevalent in sub-Saharan Africa. The accurate measurement of alcohol consumption is therefore critical in IPV intervention studies that target hazardous drinking. Collecting a collateral report in addition to self-report is one convergent validity approach to improve alcohol measurement. We investigated concordance between self- and partner-reported alcohol use among women who reported recent IPV and their male partners in Zambia. METHODS Data were from the baseline of a randomized IPV intervention trial of 247 heterosexual couples in which a woman has reported recent IPV and her male partner has recent hazardous alcohol use. Both partners completed the Alcohol Use Disorders Identification Test (AUDIT) in reference to their own drinking and in reference to their partner's drinking. We calculated percent agreement across a range of outcomes: any use, quantity, frequency, and hazardous use. We also compared self- and partner-reported AUDIT scores using t-tests. RESULTS Concordance was poor across most outcomes. Percent agreement with respect to the women's drinking ranged from 60% to 65% across outcomes and with respect to the men's drinking from 51% to 89%. Women's average partner-reported AUDIT score (20.7) was statistically significantly (p

Among 284 human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected adults starting tenofovir-based antiretroviral therapy (ART) in Zambia, median baseline CD4+ count was 202 cells/mm3 and 41.6% were hepatitis B e-antigen positive. Within 2 years of therapy, 29 (10.2%) participants experienced HBV functional cure (confirmed loss of hepatitis B surface antigen). In multivariable analysis, baseline CD4 count

Background Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs. Methods We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points. Results For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity. Conclusions Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.

BackgroundThough antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery.MethodsWe conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted a total of 28 in-depth interviews among women and 2 focus group discussions among male partners. Data was transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework.ResultsMen thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one’s children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women’s intrinsic motivation.ConclusionThe results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men’s role in couples’ joint decision-making and women’s maternal love as motivators for adherence.

As the response to the HIV epidemic in sub-Saharan Africa continues to mature, a growing number of people living with HIV (PLHIV) are aging and risk for non-communicable diseases increases. Routine laboratory tests of serum creatinine have been conducted to assess HIV treatment (ART) suitability. Here we utilize those measures to assess kidney function impairment among those initiating ART. Identification of non-communicable disease (NCD) risks among those in HIV care creates opportunity to improve public health through care referral and/or NCD/HIV care integration. We estimated glomerular filtration rates (eGFR) using routinely collected serum creatinine measures among a cohort of PLHIV with an HIV care visit at one of 113 Centre for Infectious Disease Research Zambia (CIDRZ) supported sites between January 1, 2011 and December 31, 2017, across seven of the ten provinces in Zambia. We used mixed-effect Poisson regression to assess predictors of eGFR 2allowing random effects at the individual and facility level. Additionally, we assessed agreement between four eGFR formulae with unadjusted CKD-EPI as a standard using Scott/Fleiss method across five categories of kidney function. A total of 72,933 observations among 68,534 individuals met the inclusion criteria for analysis. Of the 68,534, the majority were female 41,042 (59.8%), the median age was 34 (interquartile range [IQR]: 28–40), and median CD4 cell count was 292 (IQR: 162–435). The proportion of individuals with an eGFR 2was 6.9% (95% CI: 6.7–7.1%) according to the unadjusted CKD-EPI equation. There was variation in agreement across eGFR formulas considered compared to unadjusted CKD-EPI (χ2p-value

We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naïve pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30 days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30 days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91-1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02-1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support.This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.

Summary Background The proportion of children living with HIV and receiving antiretroviral therapy (ART) in sub-Saharan Africa has increased greatly since 2006, yet the changes in their demographic characteristics and treatment outcomes have not been well described. We examine the trends in characteristics and outcomes of children living with HIV who were younger than 5 years at ART initiation, and compare outcomes over time and across country income groups. Methods We conducted a retrospective cohort analysis of data from children living with HIV who were younger than 5 years at ART initiation from 45 paediatric sites in 16 low-income, lower-middle-income, and upper-middle-income countries in sub-Saharan Africa (Benin, Burundi, Cote d'Ivoire, Democratic Republic of the Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia, and Zimbabwe). Outcomes were trends in patient characteristics at ART initiation (age, weight, height, and CD4%), and comparisons of mortality and loss to follow-up during ART over time and in various economic settings. We identified risk factors for mortality using Cox proportional hazards models. Each participating region had relevant institutional ethics review board approvals to contribute data to the analysis. Findings We included 32 221 children living with HIV and initiating ART younger than 5 years between Jan 1, 2006, and Dec 31, 2017. Median age at ART initiation was 20·4 months (IQR 9·4–36·0) in 2006–10, 19·2 months (8·3–33·6) in 2011–13, and 19·2 months (8·8–33·7) in 2014–17. Median age at ART initiation was 13·2 months (IQR 4·7–26·8) in upper-middle-income countries, 22·6 months (13·2–37·5) in lower-middle-income countries and 24·2 months (13·5–39·1) in low-income countries. The proportion of children initiating ART younger than 3 months increased from 770 (5·1%) of 14 943 children in 2006–10 to 728 (10·0%) of 7290 children in 2014–17. The proportion of children initiating ART with severe immunosuppression decreased from 5469 (74·7%) of 7314 children for whom CD4% data were available in 2006–10 to 2353 (55·2%) of 4269 children in 2014–17. Mortality at 24 months on ART decreased from 970 (6·5%) of 14 943 children in 2006–10 to 214 (2·9%) of 7290 children in 2014–17. Loss to follow-up was 20·5% (95% CI 20·1–21·0) overall, and was similar across time periods. In multivariable analysis, lower mortality was observed for more recent ART initiation cohorts (adjusted hazard ratio 0·70, 95% CI 0·63–0·79 for 2011–13; 0·53, 0·45–0·72 for 2014–17 vs 2006–10) and for those residing in an upper-middle-income country (0·42, 0·35–0·49 vs low-income countries). Interpretation Mortality declined significantly after universal ART recommendations for children younger than 2 years in 2010 and children younger than 5 years in 2013. However, substantial variations persisted across country income groups, and one in five children continue to be lost to follow-up. Targeted interventions are required to improve outcomes of children living with HIV, especially in the poorest countries. Funding National Institute of Allergy and Infectious Disease.

Highlights • Unhealthy alcohol use is common among persons living with HIV (PLWH). • In sub-Saharan Africa, there are limited treatment options for unhealthy alcohol use. • This RCT tests multiple interventions at reducing unhealthy alcohol use in SSA., Aims Prevalence of unhealthy alcohol use and co-occurring mental health problems is high among persons living with HIV (PLWH) in sub-Saharan Africa (SSA). Yet, there is a dearth of evidence-based treatment options that can address both unhealthy alcohol use and comorbidities in SSA HIV care settings. Recent studies testing single-session alcohol brief interventions (BIs) among PLWH in SSA have suggested that more robust treatments are needed. This paper describes the protocol of a pilot randomized controlled superiority trial that will test the effectiveness of an evidence-based transdiagnostic multi-session psychotherapy, the Common Elements Treatment Approach (CETA), compared to a control condition consisting of a single session brief alcohol intervention (BI) based on CETA, at reducing unhealthy alcohol use, mental health problems, and other substance use among PLWH in urban Zambia. Methods The study is a single-blind, parallel, individually randomized trial conducted in HIV treatment centers in Lusaka. 160 PLWH who meet criteria for unhealthy alcohol use + mental health or substance use comorbidities and/or have a more severe alcohol use disorder are eligible. Participants are randomized 1:1 to receive the single-session BI or CETA. Outcomes are assessed at baseline and a six-month follow-up and include unhealthy alcohol use, depression, trauma symptoms, and other substance use. Conclusions The trial is a first step in establishing the effectiveness of CETA at reducing unhealthy alcohol use and comorbidities among PLWH in SSA. If effectiveness is demonstrated, a larger trial featuring long-term follow-ups and HIV treatment outcomes will be undertaken.

BACKGROUND After first-line antiretroviral therapy failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second line is uncertain due to the high potency of protease inhibitors used in second line. SETTING We used clinical data from 6290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Southern Africa cohort. METHODS We included patients who initiated on standard first-line antiretroviral therapy and had evidence of first-line failure. We used propensity score-adjusted Cox proportional-hazards models to evaluate the impact of change in NRTI on second-line failure compared with remaining on the same NRTI in second line. In South Africa, where viral load monitoring was available, treatment failure was defined as 2 consecutive viral loads >1000 copies/mL. In Zambia, it was defined as 2 consecutive CD4 counts

In East and Southern Africa, where 5-10% have chronic hepatitis B virus (HBV) infection, incidence of human immunodeficiency virus (HIV) infection remains unacceptably high. This introduces challenges and opportunities for implementation of HBV care and treatment. We now describe new HIV diagnoses made within an HBV monoinfection cohort in Zambia and their relevance to broader HBV policy implementation. This article is protected by copyright. All rights reserved.

Background: We investigated changes in hepatic fibrosis, based on transient elastography (TE), among human immunodeficiency virus (HIV)-infected patients with and without hepatitis B virus (HBV) coinfection on antiretroviral therapy (ART) in Zambia. Methods: Patients' liver stiffness measurements (LSM; kiloPascals [kPa]) at ART initiation were categorized as no or minimal fibrosis (equivalent to Metavir F0-F1), significant fibrosis (F2-F3), and cirrhosis (F4). TE was repeated following 1 year of ART. Stratified by HBV coinfection status (hepatitis B surface antigen positive at baseline), we described LSM change and the proportion with an increase/decrease in fibrosis category. Using multivariable logistic regression, we assessed correlates of significant fibrosis/cirrhosis at 1 year on ART. Results: Among 463 patients analyzed (61 with HBV coinfection), median age was 35 years, 53.7% were women, and median baseline CD4+ count was 240 cells/mm3. Nearly all (97.6%) patients received tenofovir disoproxil fumarate-containing ART, in line with nationally recommended first-line treatment. The median LSM change was -0.70 kPa (95% confidence interval, -3.0 to +1.7) and was similar with and without HBV coinfection. Significant fibrosis/cirrhosis decreased in frequency from 14.0% to 6.7% (P < .001). Increased age, male sex, and HBV coinfection predicted significant fibrosis/cirrhosis at 1 year (all P < .05). Conclusion: The percentage of HIV-infected Zambian adults with elevated liver stiffness suggestive of significant fibrosis/cirrhosis decreased following ART initiation-regardless of HBV status. This suggests that HIV infection plays a role in liver inflammation. HBV-coinfected patients were more likely to have significant fibrosis/cirrhosis at 1 year on ART. Clinical Trials Registration: NCT02060162.

Cirrhosis commonly complicates portal hypertension worldwide but in Zambia hepatosplenic schistosomiasis (HSS) dominates as the cause of portal hypertension. We need easier and non-invasive ways to assess HSS. Transient elastography (TE), a measure of liver stiffness can diagnose liver cirrhosis. TE remains unexplored in HSS patients, who generally have normal liver parenchyma. We aimed to explore liver stiffness in HSS. This nested case control study was conducted at the University Teaching Hospital, Lusaka, Zambia between January 2015 and January 2016. We enrolled 48 adults with HSS and 22 healthy controls. We assessed liver stiffness using TE while plasma hyaluronan was used to assess liver fibrosis. Plasma tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) were used to assess inflammation. The median (interquartile range) liver stiffness was higher in patients, 9.5 kPa (7.8, 12.8) than in controls, 4.7 kPa (4.0, 5.4), P < 0.0001. We noted linear correlations of hyaluronan and TNFR1 with the liver stiffness, P = 0.0307 and P = 0.0003 respectively. HSS patients seem to have higher liver stiffness than healthy controls. TE may be useful in identifying fibrosis in HSS. The positive correlations of inflammatory markers with TE suggest that HSS has both periportal and parenchymal pathophysiology., Metabolism; Liver stiffness; Hepatosplenic schistosomiasis; Fibrosis.

Background: Suboptimal retention may undermine the individual and public health benefits of immediate lifelong antiretroviral therapy (ART) for HIV-positive pregnant women (i.e., Option B+). We evaluated the effect of an intervention called the B-plus Enhanced Adherence Package (BEAP) on early ART uptake and short-term retention among newly diagnosed HIV-positive pregnant women in Lusaka, Zambia. Methods: Pregnant women at 3 public sector facilities in Lusaka urban district who were 18+ years old, HIV-positive, and ART naA¯ve were enrolled between March 02, 2017 and December 18, 2017 and randomized 1:1 to BEAP versus standard of care (SOC) services. All participants were eligible for Option B+ per national guidelines. BEAP involved early (within 1-2 weeks of eligibility for option B+) phone calls and home visits from a male-female pair of community health workers (CHW) to provide additional counseling, engage male partners in HIV testing, and follow-up any missed ART appointments. CHW documented all BEAP activities. The primary outcome, initiation and retention on ART per pharmacy records at 30 days after Option B+ eligibility, was compared by study arm in an intention to treat (ITT) analysis using logistic regression. In a per protocol analysis we also assessed the impact of BEAP on initiation and retention among those women who were confirmed to have received BEAP services. In pre-planned subgroup analyses, we also evaluated the BEAP's impact according to participant age, parity, baseline HIV partner disclosure status and baseline CD4+ count. Findings: Among 454 women enrolled, 229 were randomized to BEAP and 225 to SOC. The two arms were balanced with respect to age (p=0.16) and gestational age (p=0.09). Within 30 days of Option B+ eligibility, 445 (98.2%) initiated ART; however, only 369 (82.9%) of those women who started ART were still in care at 30 days. In ITT analysis, the proportion initiating and remaining on ART at 30 days was similar between women randomized to BEAP versus SOC (82.5% versus 80.4%; crude relative risk [RR], 1.03; 95% confidence interval [CI], 0.91-1.16). After exclusion of 92 participants (40.2%) due to not receiving BEAP services based on CHW documentation and 1 participant due to ineligibility, BEAP was associated with being on ART at 30 days versus SOC (91.9.0% versus 80.4%; crude RR 1.14; 95% CI, 1.02-1.29). No significant variation was found in the effect of BEAP in subgroup analyses based on parity, age, baseline HIV disclosure status, and/or baseline CD4+ count. Interpretation: Uptake of Option B+ within 30 days of eligibility was nearly universal among HIV-positive pregnant women in urban Zambia. Women who received the BEAP intervention were statistically more likely to be on ART at 30 days compared to those receiving standard services. This difference, though modest, supports the potential of targeted early interventions to optimize the implementation of Option B+. Trial Registration: The trial was also registered at ClinicalTrials.gov (trials number NCT02459678). Funding Statement: This research has been supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC) under the terms of cooperative agreement number U01GH000530. Additional investigator support was provided by the National Institutes of Health (K24 AI120796). Declaration of Interests: MM declares that the Centre for Infectious Disease Research in Zambia (CIDRZ), received a grant from the Centers for Disease Control and Prevention (CDC) (grant number: GH000530) to carry out this study. The rest of the authors declare no conflict of interest. Ethics Approval Statement: Approval for the study was obtained from the University of Zambia Biomedical Research Ethics Committee (Lusaka, Zambia) and the University of North Carolina at Chapel Hill Instituitional Review Board (Chapel Hill, NC, USA). The study was reviewed in accordance with the Centers for Disease Control and Prevention (CDC) human research protection procedures and was determined to be research, but CDC investigators did not interact with human subjects or have access to identifiable data or specimens for research purposes. Women who were eligible and agreed to participate provided written informed consent.

Access to hepatitis B viral load (VL) testing is poor in sub-Saharan Africa (SSA) due to economic and logistical reasons.To demonstrate the feasibility of testing dried blood spots (DBS) for hepatitis B virus (HBV) VL in a laboratory in Lusaka, Zambia, and to compare HBV VLs between DBS and plasma samples.Paired plasma and DBS samples from HIV-HBV co-infected Zambian adults were analyzed for HBV VL using the COBAS AmpliPrep/COBAS TaqMan HBV test (Version 2.0) and for HBV genotype by direct sequencing. We used Bland-Altman analysis to compare VLs between sample types and by genotype. Logistic regression analysis was conducted to assess the probability of an undetectable DBS result by plasma VL.Among 68 participants, median age was 34 years, 61.8% were men, and median plasma HBV VL was 3.98logIU/ml (interquartile range, 2.04-5.95). Among sequenced viruses, 28 were genotype A1 and 27 were genotype E. Bland-Altman plots suggested strong agreement between DBS and plasma VLs. DBS VLs were on average 1.59logIU/ml lower than plasma with 95% limits of agreement of -2.40 to -0.83log IU/ml. At a plasma VL ≥2,000IU/ml, the probability of an undetectable DBS result was 1.8% (95% CI: 0.5-6.6). At plasma VL ≥20,000IU/ml this probability reduced to 0.2% (95% CI: 0.03-1.7).In a Zambian laboratory, we observed strong agreement between DBS and plasma VLs and high sensitivity in DBS at plasma VL ≥2,000IU/ml. As HBV treatment expands, DBS could increase access to HBV VL testing and care in SSA settings.

IntroductionWe evaluated antiviral therapy (AVT) eligibility in a population-based sample of adults with chronic hepatitis B virus (HBV) infection in Zambia.Materials and methodsUsing a household survey, adults (18+ years) were tested for hepatitis B surface antigen (HBsAg). Sociodemographic correlates of HBsAg-positivity were identified with multivariable regression. HBsAg-positive individuals were referred to a central hospital for physical examination, elastography, and phlebotomy for HBV DNA, hepatitis B e antigen, serum transaminases, platelet count, and HIV-1/2 antibody. We determined the proportion of HBV monoinfected adults eligible for antiviral therapy (AVT) based on European Association for the Study of the Liver (EASL) 2017 guidelines. We also evaluated the performance of two alternative criteria developed for use in sub-Saharan Africa, the World Health Organization (WHO) and Treat-B guidelines.ResultsAcross 12 urban and 4 rural communities, 4,961 adults (62.9% female) were tested and 182 (3.7%) were HBsAg-positive, 80% of whom attended hospital follow-up. HBsAg-positivity was higher among men (adjusted odds ratio [AOR], 1.37; 95% confidence interval [CI], 0.99-1.87) and with decreasing income (AOR, 0.89 per household asset; 95% CI, 0.81-0.98). Trends toward higher HBsAg-positivity were also seen at ages 30-39 years (AOR, 2.11; 95% CI, 0.96-4.63) and among pregnant women (AOR, 1.74; 95% CI, 0.93-3.25). Among HBV monoinfected individuals (i.e., HIV-negative) evaluated for AVT, median age was 31 years, 24.6% were HBeAg-positive, and 27.9% had HBV DNA >2,000 IU/ml. AVT-eligibility was 17.0% by EASL, 10.2% by WHO, and 31.1% by Treat-B. Men had increased odds of eligibility. WHO (area under the receiver operating curve [AUROC], 0.68) and Treat-B criteria (AUROC, 0.76) had modest accuracy. Fourteen percent of HBsAg-positive individuals were HIV coinfection, and most coinfected individuals were taking tenofovir-containing antiretroviral therapy (ART).ConclusionApproximately 1 in 6 HBV monoinfected adults in the general population in Zambia may be AVT-eligible. Men should be a major focus of hepatitis B diagnosis and treatment. Further development and evaluation of HBV treatment criteria for resource-limited settings is needed. In settings with overlapping HIV and HBV epidemics, scale-up of ART has contributed towards hepatitis B elimination.

AIM To characterize antiviral therapy eligibility among hepatitis B virus (HBV)-infected adults at a university hospital in Zambia. METHODS Hepatitis B surface antigen-positive adults ( = 160) who were HIV-negative and referred to the hospital after a routine or clinically-driven HBV test were enrolled. Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), platelet count, hepatitis B e-antigen, and HBV DNA were measured. Liver fibrosis/cirrhosis was assessed by physical examination, AST-to-platelet ratio index, and transient elastography. In antiviral therapy-naive individuals, we described HBV stages and antiviral therapy eligibility per World Health Organization (WHO) and by HBV test (routine clinical). Elevated ALT was > 19 in women and > 30 U/L in men. Among treatment-experienced individuals, we described medication side effects, adherence, and viral suppression. RESULTS The median age was 33 years, 71.9% were men, and 30.9% were diagnosed with HBV through a clinically-driven test with the remainder identified routine testing (at the blood bank, community events, .). Among 120 treatment-naive individuals, 2.5% were categorized as immune tolerant, 11.7% were immune active, 35.6% were inactive carriers, and 46.7% had an indeterminate phenotype. Per WHO guidelines, 13 (10.8%) were eligible for immediate antiviral therapy. The odds of eligibility were eight times higher for those diagnosed at clinical routine settings (adjusted odds ratio, 8.33; 95%CI: 2.26-29.41). Among 40 treatment-experienced HBV patients, virtually all took tenofovir, and a history of mild side effects was reported in 20%. Though reported adherence was good, 12 of 29 (41.4%) had HBV DNA > 20 IU/mL. CONCLUSION Approximately one in ten HBV-monoinfected Zambians were eligible for antivirals. Many had indeterminate phenotype and needed clinical follow-up.

INTRODUCTION Excessive alcohol consumption leads to unfavourable outcomes in people living with HIV (PLHIV), including reduced adherence to antiretroviral therapy (ART) and engagement into care. However, there is limited information on alcohol consumption patterns among PLHIV in sub-Saharan Africa. METHODS Using a cross-sectional approach, the Alcohol Use Disorders Identification Test (AUDIT-C) was administered to PLHIV attending HIV clinics in Cote d'Ivoire, Togo, Senegal and Zambia (2013 to 2015). Hazardous drinking was defined as an AUDIT-C score ≥4 for men or ≥3 for women, and binge drinking as ≥6 drinks at least once per month. The prevalence of binge drinking was compared to estimates from the general population using data from the World Health Organization. Factors associated with binge drinking among persons declaring any alcohol use in the past year were assessed using a logistic regression model to estimate odds ratio (OR) and their corresponding 95% confidence intervals (CI). RESULTS Among 1824 PLHIV (median age 39 years, 62.8% female), the prevalence of hazardous alcohol use ranged from 0.9% in Senegal to 38.4% in Zambia. The prevalence of binge drinking ranged from 14.3% among drinkers in Senegal to 81.8% in Zambia, with higher estimates among PLHIV than in the general population. Male sex (OR 2.4, 95% CI 1.6 to 3.7), tobacco use (OR 1.7, 95% CI 1.0 to 2.9) and living in Zambia were associated with binge drinking. CONCLUSIONS Alcohol consumption patterns varied widely across settings and binge drinking was more frequent in HIV-positive individuals compared to the general population. Interventions to reduce excessive alcohol use are urgently needed to optimize adherence in the era of universal ART.

In an HIV-hepatitis B virus (HIV-HBV) coinfection cohort in Zambia, we piloted a qualitative point-of-care (POC) test for urine Ethyl glucuronide (uEtG), assessed concordance between uEtG and alcohol use disorders identification test-consumption (AUDIT-C), and identified epidemiological factors associated with underreporting (defined as uEtG-positivity with last reported drink > 7 days prior). Among 211 participants (40.8% women), there were 44 (20.8%) lifetime abstainers, 32 (15.2%) former drinkers, and 135 (64.0%) current drinkers, including 106 (50.2%) with unhealthy drinking per AUDIT-C. Eighty-seven (41.2%) were uEtG-positive including 64 of 65 (98.5%) who drank ≤ 3 days prior and 17 of 134 (12.7%) underreported, all of whom admitted to recent drinking when results were discussed. uEtG was moderately concordant with AUDIT-C. Past drinking (versus lifetime abstinence) and longer time on antiretrovirals (≥ 12 months) were associated with underreporting. These data support further use of POC alcohol biomarkers in HIV and hepatitis research and clinical settings.

We assessed attitudes and preferences toward HIV self-testing (HIVST) among Zambian adolescents and adults. We conducted a population-based survey of individuals aged 16–49 years old in Lusaka Province, Zambia. HIVST was shown to participants through a short video on oral fluid-based self-testing. In addition to demographics, HIV risk perceptions, and HIV testing history, we assessed participants' acceptability and concerns regarding HIVST. Using a discrete choice experiment, we investigated preferences for the location of self-test pickup, availability of counseling, and cost. After reviewing an instructional sheet or an additional video, we assessed participants' understanding of self-test performance. Among 1617 participants, 647 (40.0%) were male, 269 (16.6%) were adolescents and 754 (46.6%) were nontesters (i.e., no HIV test in the past 12 months). After viewing the video, 1392 (86.0%) reported that HIVST would make them more likely to test and while 35.0% reported some concerns with HIVST, only 2% had serious concerns. Participants strongly preferred HIVST over finger prick testing as well as having counseling and reported willingness to pay out-of-pocket (US$3.5 for testers and US$5.5 for nontesters). Viewing an HIVST demonstration video did not improve participant understanding of self-test usage procedures compared to an instructional sheet alone, but it increased confidence in the ability to self-test. In conclusion, HIVST was highly acceptable and desirable, especially among those not accessing existing HIV testing services. Participants expressed a strong preference for counseling and a willingness to pay for test kits. These data can guide piloting and scaling-up of HIVST in Zambia and elsewhere in Africa.

The prevalence of high blood pressure (HBP) and hypertension (HTN), awareness of the diagnoses, and use of anti-hypertensive drugs were examined among human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy (ART) in Zambia’s capital Lusaka. Within a prospective cohort based at two public sector ART clinics, BP was measured at ART initiation and every 6 months thereafter as a routine clinic procedure. Predictors of HBP (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) during one year on ART were analyzed using logistic regression, and the proportion with HTN (2+ episodes of HBP >3 months apart) described. A phone survey was used to understand patient awareness of HBP, use of anti-hypertensive drugs, and history of cardiovascular events (CVE; myocardial infarction or stroke). Among 896 cohort participants, 887 (99.0%) had at least one BP measurement, 98 (10.9%) had HBP, and 57 (6.4%) had HTN. Increasing age (10-year increase in age: adjusted odds ratio [AOR] = 1.50; 95% confidence interval [CI] 1.20–1.93), male sex (AOR = 2.33, 95% CI 1.43–3.80), and overweight/obesity (AOR = 4.07; 95% CI 1.94–8.53) were associated with HBP. Among 66 patients with HBP, 35 (53.0%) reported awareness of the condition, and nine (25.7%) of these reported having had a CVE. Only 14 (21.2%) of those reached reported ever taking an anti-hypertensive drug, and one (1.5%) was currently on treatment. These data suggest that major improvements are needed in the management of HBP among HIV-infected individuals in settings such as Zambia.

Background Africa has a high prevalence of both Human Immunodeficiency Virus and Non Communicable Diseases (NCDs) but in Zambia there are few data on co-morbid NCDs like Diabetes Mellitus (DM) among HIV-infected individuals. We aimed to identify risk factors for impaired fasting glucose or diabetes among HIV-infected Zambians on long-term Combined Antiretroviral Treatment (cART). Methods This was a cross sectional study of adult HIV patients in five health facilities of Copperbelt Province in Zambia. HIV/AIDS patients aged 18 years and above, enrolled in care at those health facilities and had been on cART for more than 2 years were included. All patients known to have Diabetes mellitus were excluded from the study. Participants underwent assessment of random blood sugar levels at enrolment and returned the following morning for fasting glucose measured by glucometers. The primary outcome was proportion with impaired fasting glucose or DM. Multivariable logistic regression was used to examine if demographics, time on ART, type of ART regimen, body mass index and baseline CD4 count were predictors of impaired fasting glucose. Results Overall (n = 270) there were 186 females (69%) and 84 males (31%). The prevalence of impaired fasting blood sugar or diabetes after 8 h of fasting was 15% (95%CI: 11.1, 20.0). Ten percent (26/270) had impaired fasting glucose and 5 % (14/270) had diabetes. Impaired fasting glucose was higher in males than females [AOR = 3.26, (95% CI: 1.15–9.25; p-value = 0.03)]; as well as among patients on second line treatment than those on first line [AOR = 3.87 (95% CI 1.16–12.9); p-value = 0.03]. In contrast those with less likelihood of impaired fasting glucose included patients with a normal BMI (18.5–24.9) than overweight or obese patients [AOR = 0.09 (95% CI 0.03–0.31; p-value

We analyzed the association of age at antiretroviral therapy (ART) initiation with CD4(+) T cell count recovery, death, and loss to follow-up (LTFU) among HIV-infected adults in Zambia. We compared baseline characteristics of patients by sex and age at ART initiation [categorized as 16-29 years, 30-39 years, 40-49 years, 50-59 years, and 60 years and older]. We used the medication possession ratio to assess adherence and analysis of covariance to measure the adjusted change in CD4(+) T cell count during ART. Using Cox proportional hazard regression, we examined the association of age with death and LTFU. In a secondary analysis, we repeated models with age as a continuous variable. Among 92,130 HIV-infected adults who initiated ART, the median age was 34 years and 6,281 (6.8%) were aged ≥50 years. Compared with 16-29 year olds, 40-49 year olds (-46 cells/mm(3)), 50-59 year olds (-53 cells/mm(3)), and 60+ year olds (-60 cells/mm(3)) had reduced CD4(+) T cell gains during ART. The adjusted hazard ratio (AHR) for death was increased for individuals aged ≥40 years (AHR 1.25 for 40-49 year olds, 1.56 for 50-59 year olds, and 2.97 for 60+ year olds). Adherence and retention in care were poorest among 16-29 year olds but similar in other groups. As a continuous variable, a 5-year increase in age predicted reduced CD4(+) T cell count recovery and increased risk of death. Increased age at ART initiation was associated with poorer clinical outcomes, while age30 years was associated with a higher likelihood of being lost to follow-up. HIV treatment guidelines should consider age-specific recommendations.

OBJECTIVE To describe the liver disease epidemiology among HIV-infected individuals in Zambia. METHODS We recruited HIV-infected adults (≥18 years) at antiretroviral therapy initiation at two facilities in Lusaka. Using vibration controlled transient elastography we assessed liver stiffness, a surrogate for fibrosis/cirrhosis, and analyzed liver stiffness measurements (LSM) according to established thresholds (>7.0 kPa for significant fibrosis and >11.0 kPa for cirrhosis). All participants underwent standardized screening for potential causes of liver disease including chronic hepatitis B (HBV) and C virus co-infection, herbal medicine, and alcohol use. We used multivariable logistic regression to identify factors associated with elevated liver stiffness. RESULTS Among 798 HIV-infected patients, 651 had a valid LSM (median age, 34 years; 53% female). HBV co-infection (12%) and alcohol use disorders (41%) were common and hepatitis C virus co-infection (7.0 kPa (all P11.0 kPa. Among HIV-HBV patients, those with elevated ALT and HBV viral load were more likely to have significant liver fibrosis than patients with normal markers of HBV activity. CONCLUSIONS HBV co-infection was the most important risk factor for liver fibrosis and cirrhosis and should be diagnosed early in HIV care to optimize treatment outcomes. This article is protected by copyright. All rights reserved.

Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication.

ObjectivesThe aim of this study was to estimate the frequency of disclosure to and testing of contacts of patients with hepatitis B virus (HBV) in Zambia.DesignWe used a convergent parallel mixed-method research design including a quantitative survey and focus group discussions with patients with HBV.SettingA university hospital in Lusaka, Zambia.Participants79 hepatitis B surface antigen (HBsAg)-positive, HIV-negative, adults (18+ years) receiving HBV care completed a quantitative survey and 32 also participated in a focus group discussion.Outcomes and analysisContacts of patients with HBV were enumerated and patient-reported disclosure, contact testing and contact HBV test results were used to develop a testing cascade. Using multivariable logistic regression, we identified factors associated with disclosure of HBV status. In focus groups, we explored how index patient knowledge and awareness of their condition shaped perspectives on contact disclosure and testing. Focus groups coding and analysis followed a thematic analysis approach.ResultsAmong 79 patients with HBV (median age 35 years; 26.6% women), the majority reported disclosure to ≥1 contact. According to the index patients’ knowledge, of 776 contacts enumerated, 326 (42.1%) were disclosed to, 77 (9.9%) were tested, 67 (8.6%) received results and 8 (11.9%) were HBsAg-positive. Increased stigma score was associated with reduced disclosure. In focus groups, HBV awareness, knowledge and stigma emerged as barriers to disclosure and referral of contacts for testing. Association of HBV with HIV-related stigma was also reported as a strong barrier to contact disclosure and testing and to taking antivirals for HBV monoinfection.ConclusionsHBV contact disclosure and testing were feasible and yielded new diagnoses in Zambia. A better understanding of barriers to seeking HBV testing and treatment is needed to scale-up this important intervention in Africa.Trials registration numberNCT03158818.

Hepatitis B virus (HBV) is endemic in Africa, where it may occur as an HIV coinfection. Data remain limited on HIV–HBV epidemiology in Africa, particularly in children. Using programmatic data from pediatric HIV clinics in Lusaka, Zambia during 2011–2014, we analyzed the prevalence of chronic HBV coinfection (defined as a single positive hepatitis B surface antigen [HBsAg] test) and its impact on immune recovery and liver enzyme elevation (LEE) during the first year of antiretroviral therapy. Among 411 children and adolescents, 10.4% (95% confidence interval, 7.6–14.1) had HIV–HBV. Coinfected patients were more likely to have World Health Organization stage 3/4, LEE and CD4

Dear Editor, In sub-Saharan Africa (SSA), approximately 3 million HIV-infected individuals have chronic hepatitis B virus (HBV) co-infection [1]. HIV–HBV-co-infected patients experience increased mortality, reduced immune recovery and increased risk of hepatotoxicity during antiretroviral therapy (ART) compared to those with HIV alone [2–4]. The World Health Organization (WHO) recommends HBV screening with a hepatitis B surface antigen (HBsAg) test for all HIV-infected individuals at the time of linkage to care and/or prior to ART initiation [5]. According to these guidelines, HIV–HBV patients with advanced liver disease should initiate ART regardless of CD4+ count. Despite its recommendation by the majority of national ART guidelines, HBV screening has not been widely implemented in most ART programmes in SSA; as a result, the epidemiology and outcomes of HIV–HBV co-infection remain poorly characterized in the region. In 2010, the Zambian Ministry of Health (MOH) [6] HIV treatment policy shifted from targeted HBsAg testing to routine baseline testing at enrolment. HBsAg-positive patients with ALT > 2.5 times normal were ART eligible regardless of CD4+ count and WHO stage. In this report, we describe HBV screening and initial treatment practices among public sector HIV clinics in Zambia's capital city Lusaka during 2008–2012. In each calendar quarter (Q), we determined the proportion of newly enrolled patients who received an HBsAg test at baseline (defined as within 6 months of enrolment and prior to ART initiation) or during follow-up and compared these proportions over time using a Jonckheere–Terpstra test for trend. In the period after dissemination of the 2010 guidelines, using multivariable logistic regression, we identified factors associated with baseline testing including age, sex, WHO clinical stage, ALT, CD4+ count and facility volume, which we defined as the number of new patient enrolments per year. We also modelled patient demographic and clinical correlates of HBsAg positivity. We used Stata version 12 (Statacorp, College Station, TX, USA) for analysis. The ethics committees of the University of Zambia (Lusaka, Zambia) and the University of North Carolina at Chapel Hill (North Carolina, USA) approved the study. From 1 January 2008 to 31 December 2012, 60 060 HIV-infected patients enrolled across 15 treatment facilities in Lusaka district. There was a rapid and substantial increase in HBsAg testing following dissemination of the MOH's 2010 HIV treatment guidelines (Fig. 1). The overall percentage of patients tested increased from 1.0% in Q1 of 2008 to 46.8% in Q4 of 2012 (P for trend < 0.001). During this time, the percentage of HBsAg tests that occurred at baseline increased from 16.1% to 99.7% (P for trend < 0.001). Fig. 1 Rapid increase in the percent of HIV-infected individuals screened for hepatitis B surface antigen in Lusaka district following release of the Zambian Ministry of Health 2010 HIV guidelines. At the facility level, there was a wide variation in HBsAg testing in the 24 months following the guideline change, with only six of 15 facilities increasing testing rates (Fig. 1). Among the six facilities that increased baseline testing, by Q4 of 2012, nearly 80% of newly enrolled patients were HBsAg tested. The nine sites that did not increase HBsAg testing had similar patient volumes to those in the sites that increased testing. Among facilities that increased testing, during 2011–2012, adults [16+ years old; adjusted odds ratio (AOR) 6.09; 95% confidence interval (CI), 4.55–8.14] and males (AOR 1.13; 95% CI, 1.02–1.25) were more likely to be HBsAg tested, whereas patients with tuberculosis (AOR 0.60; 95% CI, 0.49–0.72) and/or WHO stage 3 or 4 (AOR 0.87; CI, 0.78–0.97) had reduced odds of testing. The percentage of positive HBsAg tests decreased (16.4% in 2008–2010 vs 11.8% in 2011–2012, P 40 U/L (AOR 2.35; 95% CI, 1.87–2.96) and CD4+ count

Although AST-to-platelet ratio index (APRI) and FIB-4 have been compared with liver biopsy in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), HIV/HCV co-infection, and HIV/HBV co-infection, Johannessen and Lemoine stress that they have not been validated in HIV mono-infected populations in SSA. However, this is unlikely to occur because liver biopsy does not play a role in HIV management and the procedure carries its own risks for complication. Clinicians using APRI and FIB-4 in this setting should be aware of this limitation and should interpret test results in the context of each patient’s clinical scenario. While it elevates APRI or FIB-4 scores, HIV-associated thrombocytopenia (HAT) does not fully explain the association of these markers with mortality. In our analysis, an elevated APRI score at start of antiretroviral therapy predicted all-cause mortality — even among patients with WHO clinical stage 1 or 2 and CD4+ counts >200 cells/mm2 who were unlikely to have HAT [1]. In a sensitivity analysis not included in the primary manuscript, we replaced each patient’s platelet count with the median value of 238 × 109/L. As expected, the percentage with APRI ≥1.5 decreased from 5.1% to 1.9%; however, the association with mortality was similar (adjusted hazard ratio 1.62; 95% CI, 1.29-2.05). In their letter to the editor, Johannessen and Lemoine speculate that the excess mortality experienced by patients with elevated APRI was unlikely a direct result of liver disease. Unfortunately, as is common in Africa, causes of death were not available in our large observational cohort, making this a difficult question to answer. However liver-related mortality was plausible, since HIV itself can interact with and infect multiple liver cell types [2,3] with potential clinical consequences [4] that are not fully understood, and chronic HBV, the leading cause of advanced liver disease in Africa, was not comprehensively screened for in our cohort. Further investigation is needed to better understand the contribution of liver disease to all-cause mortality among patients on HIV treatment. Finally, it is important to note that APRI and FIB-4 independently predicted ART mortality in our analysis and may thus have a prognostic role in HIV care in SSA. As our colleagues suggest, further research is certainly needed to better define underlying biological mechanisms to determine how to incorporate their use at scale. Given the limited capacity for diagnosis and management of liver disease, however, such non-invasive metrics appear highly promising for future work.

Background We investigated the impact of community tracing as recommended in national guidelines on outcomes within a prospective HIV cohort in Zambia. Methods HIV-positive, antiretroviral therapy-naive adults were enrolled at 2 Lusaka clinics. Per national guidelines we collected detailed baseline patient locator information including patient phone number, address, church, and a map from the clinic to their home. Study visits were aligned with routine ART program schedules and 3 telephonic attempts were made if visits were missed. Per guidelines, a lay health worker conducted a community home visit on lost to follow-up (LTFU) patients. Transfers to other clinics and deaths were ascertained when reported by the clinic staff, patients, or family members. At one year, we measured the percentage retained, transferred out, withdrawn (stopped ART), dead, and LTFU (>6 months absent). A lay health worker went into the community to make a home visit on LTFU patients. We recorded the change in mortality after tracing. We also estimated the time and costs per patient traced. Results We enrolled 795 patients (median age 34 years; 53.7% were female; median CD4 228 cell/mm3). Prior to tracing, we recorded 45 deaths, 23 transfers, 1 withdrawal, and 83 LTFU who could not be reached by phone. At 63 attempted home visits, we learnt that 9 (14.3%) had died, 5 (7.9%) had transferred, and 2 had withdrawn. We could not locate 32 (50.8%) but neighbours/family reported that 12 of these had relocated (HIV care status unknown). After successful tracing, 15 (23.8%) returned to clinic and HIV care. Community tracing increased known mortality from 5.7% to 6.8% (95% CI: 5.1–8.8%) and increased retention at 1-year from 80.9% to 82.8%. Tracing required an average of 5 person-hours and K150.00 (∼15 USD) in bus/taxi fares per patient. Conclusions Community tracing was limited by patient mobility and had a modest impact on cohort mortality and retention.

Background Hepatosplenic schistosomiasis (HSS) and hepatitis B virus (HBV) are both endemic in sub-Saharan Africa but the clinical epidemiology of co-infection is not well-characterised. Within a current HIV cohort study, we assessed the prevalence of HSS and its impact on markers of liver fibrosis in HIV-HBV co-infected individuals. Methods At two urban HIV care facilities in Zambia9s capital Lusaka, we screened for HBV co-infection using a hepatitis B surface antigen (HBsAg) test and for lifetime infection with Schistosoma mansoni using an IgG enzyme-linked immunoassay (Abcam, Cambridge, UK). Among HIV-HBV patients, we also performed abdominal ultrasonography. We defined HSS as evidence of periportal hepatic fibrosis on ultrasound regardless of IgG result. Patient characteristics, including liver fibrosis markers (ALT and transient elastography) were measured and stratified by HSS. We used Wilcoxon rank sum test for continuous and chi-square test for categorical comparisons between groups. Results Among 895 HIV-infected adults, lifetime exposure to S. mansoni was observed in 23.3%. Within the cohort 92 HBsAg-positives underwent assessment for HSS. Median age among these was 34.7 years (interquartile range [IQR], 28.9–39.9), 48% were men, CD4 count was 247 cells/mm3 (IQR, 145–335), HBV viral load was 2.87 (IQR, 1.00–5.18) log10 IU/mL, and liver stiffness was 5.5 kilopascals (IQR, 4.7–6.9). On ultrasound, 1 patient had cirrhosis and 36 (39.1%) had evidence of HSS. HBV-HSS patients had a non-significant trend toward higher portal vein diameter (8.5 versus 10.2; p=0.15) compared to those without HSS but ALT (18.5 vs 20 U/L), and liver stiffness (5.3 vs 5.0 kPa) were similar between groups (both p >0.05). Conclusions Lifetime S. mansoni exposure and current HSS were common among HIV-infected patients with HBV co-infection in Zambia. Mild HSS did not appear to alter non-invasive markers of liver fibrosis. Further research on the impact of more advanced HSS on HBV co-infection is needed.

Background In Zambia, we evaluated the field performance of a rapid point-of-care test for hepatitis B surface antigen (HBsAg) which could support decentralisation and scale-up of care and treatment of chronic hepatitis B virus (HBV) infection in sub-Saharan Africa. Methods At two urban public health facilities in Zambia9s capital Lusaka, we screened a cohort of HIV-infected adults for HBsAg per national guidelines. A subset was tested with both Determine HBsAg (Alere, USA), using finger prick in the clinic, and HBsAg serology (Access2Analyser, Beckman Coulter), using serum sent to a reference laboratory. If either test was reactive, we measured HBV viral load (VL) and determined HBV genotype with Sanger sequencing. We described patient demographic and clinical characteristics (including liver fibrosis biomarkers) and assessed the sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the Determine test. In secondary analyses, we assessed sensitivity among patients with replicating HBV (VL >20 IU/mL) and with high HBV VL (>20,000 IU/mL). Results Among 412 participants with both HBsAg tests, median age was 34 years, 51% were women, and median CD4 was 208 cells/mm3. By serology, 66 (16%) were HBsAg-positive. HBV genotypes were A1 (n=21; 52.5%) and E (n=19; 47.5%) among successfully sequenced samples. Overall, the Determine test had 87.9% sensitivity (95% CI: 84.7–91.0%), 99.7% specificity, 98.3% PPV, and 97.7% NPV. The majority of patients (6/8) with false negative results had undetectable HBV VL and no evidence of significant liver fibrosis. Test sensitivity increased to 95.9% among the 51 with replicating HBV and to 100% among the 28 with high HBV VL. Conclusions The Determine HBsAg test accurately diagnosed HBsAg-emia in the majority of field-tested HIV patients, particularly those with higher HBV VL. False negatives tended to have inactive HBV infection further supporting the use of this low-cost test in public health settings in sub-Saharan Africa.

Methods We prospectively enrolled HIV-infected treatment naive adults in Lusaka, Zambia. At enrolment, we recorded patient9s demographics, body mass index (BMI), WHO clinical stage, CD4+ count, and hepatitis B surface antigen (HBsAg) status. In HBsAg-positive patients we measured HBV viral loads (VL; Roche, COBAS® AmpliPrep/COBAS® Taqman® Assay, Pleasanton, California). We defined active HBV co-infection as having an HBV VL 320 IU/ml. TDF-based ART was the preferred first-line regimen. Follow-up visits occurred per national guidelines and we used phone and community tracing to optimise retention. Deaths were ascertained by clinic, family member, or community health worker report and losses to follow-up (LFTU) were defined as absences from clinic for 6+ months. Using multivariable Cox regression, we assessed the mortality risk among patients with HBV co-infection, adjusting for age, sex, WHO stage, BMI, and CD4+ count. Results During 2013–2014, 822 patients were enrolled and analysed at 1 year after ART initiation. Among this group, 438 (53.1%) were women, median age was 34 years (interquartile range, 29–40), 367 (44.8%) had WHO stage 3 or 4, 229 (28.2%) had BMI Conclusions In Southern Africa, HBV co-infection is a mortality risk factor and these patients should be diagnosed and those with replicating virus may need closer monitoring. Further investigation of the causes of death in HIV-HBV patients is needed.

Background In sub-Saharan Africa, the prevalence of hepatitis B virus (HBV) is between 6–20%. In Zambia, prevalence of HIV and HBV co-infection has been reported to be between 7.1% and 31.1%. Patients infected with HBV are at increased risk of experiencing elevated alanine transaminase enzyme (ALT) and HIV-HBV co-infection may lead to further reduced CD4 cell count before initiating antiretroviral therapy (ART). We investigated the relation of HBV with CD4 cell count and ALT enzyme in HIV-positive antiretroviral therapy-naive patients. Methods This was a cross-sectional study conducted in 15 government clinics in Lusaka. There were 5436 adult patients who initiated antiretroviral therapy between 2011 and 2013. Cases were described as HIV-positive patients who tested HBsAg-positive and controls as HIV-positive patients who tested HBsAg-negative. HIV-HBV co-infection was defined as the number of patients who tested HBsAg-positive divided by the total tested (with 95% CI). Laboratory measures of CD4 and ALT were categorised in the analysis. Elevated ALT was defined as ALT≥66 IU/ml. CD4 cell count was dichotomised CD4 of >200 cells/µl. Results The median age was 35 (29–41) years. The median CD4 cell count was 202 (102–305) cells/µl with the median ALT being 20 (14–30) IU/ml. HIV−HBV prevalence was 12.3% (95% CI: 11.4−13.1). Elevated ALT was reported in 11.1% cases and 4.7% in controls (p-value Conclusions Prevalence of HBV is high among HIV-infected persons in Zambia. There is need to explore the interactions of these co-infections and their impact on CD4 cell count and ALT.

BACKGROUND AND AIMS We investigated the association between significant liver fibrosis, determined by AST-to-platelet ratio index (APRI), and all-cause mortality among HIV-infected patients prescribed antiretroviral therapy (ART) in Zambia METHODS: Among HIV-infected adults who initiated ART, we categorized baseline APRI scores according to established thresholds for significant hepatic fibrosis (APRI ≥1.5) and cirrhosis (APRI ≥2.0). Using multivariable logistic regression we identified risk factors for elevated APRI including demographic characteristics, body mass index (BMI), HIV clinical and immunologic status, and tuberculosis. In the subset tested for hepatitis B surface antigen (HBsAg), we investigated the association of hepatitis B virus co-infection with APRI score. Using Kaplan-Meier analysis and Cox proportional hazards regression we determined the association of elevated APRI with death during ART. RESULTS Among 20,308 adults in the analysis cohort, 1,027 (5.1%) had significant liver fibrosis at ART initiation including 616 (3.0%) with cirrhosis. Risk factors for significant fibrosis or cirrhosis included male sex, BMI

Department of Medicine, University of Alabama at Birmingham, USA Centre for Infectious Disease Research in Zambia, Lusaka, Zambia School of Medicine, University of Zambia, Lusaka, Zambia Institute of Infectious Diseases, University of Bern, Switzerland Department of Infectious Diseases, University Hospital Bern, Switzerland Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, USA Institute of Social and Preventive Medicine, University of Bern, Switzerland Department of Infectious Diseases, University of Dakar, Senegal

To the Editor—In their recent article, Shorr and colleagues present a new clinical tool to predict risk of drug-resistant bacterial pneumonia in patients presenting to emergency departments [1]. Improving risk assessment and minimizing inappropriate antibiotic use are necessary given the increasing prevalence of resistant pathogens and the risk of selecting for further resistance through overuse of broad-spectrum antibiotics, but this new risk score has several weaknesses. A weighted risk score is an attractive strategy to improve clinical decision making, but the authors overstate its advantages over the existing healthcare-associated pneumonia (HCAP) definition. Although the authors assert that their new risk score is superior to HCAP criteria because it incorporates weighting of risk factors, the cutoff of 0 turns the risk score into a dichotomous tool by which the presence of any risk factor yields a score considered positive rather than a stratified risk score. Under this conclusion, the predictive ability of the new tool is comparable (but not superior) to the current HCAP definition. Using a dichotomous risk tool ignores the information contained in a scoring system, and such a tool cannot be compared directly with the HCAP criteria. To compare the two, cutoff points should be contrasted for persons meeting 1, 2, or more HCAP or risk score criteria. The authors could further improve the predictive ability of their score by presenting likelihood ratios for each of the risk scores of the new tool. The authors present single positive and negative predictive values based on a risk score of 0, but these statistics could be calculated for other scores as well. Because of the effect of prevalence on the performance of diagnostic tests, we are concerned that the prevalence of drug-resistant pathogens reported in the study is inaccurate due to verification bias that occurs when the action of performing a test is affected by the pretest probability of disease [2]. The authors report a 47% prevalence of drug-resistant pathogens, likely an overestimation. A medical history suggesting a person had high risk for drug-resistant bacterial infection might influence physicians’ decisions to obtain cultures, a criterion for inclusion in the study. Persons without significant healthcare exposure might be deemed low-risk by clinicians, who would not order cultures, leading to underrepresentation of these patients in this study. Verification bias results in overestimation of the sensitivity and underestimation of the specificity of the new risk score. Unfortunately it is difficult to confirm that verification bias has occurred; however, the authors could have performed sensitivity analyses or controlled for culture collection to assess this problem. Finally, the most appropriate cutoff for risk score is determined by weighing the costs of further testing or broad-spectrum antibiotic use in patients who do not need them against benefits of appropriate early therapy in those infected with drug-resistant pathogens. This balance will depend on the clinical characteristics and risk factors of the patients, societal views of medical care, and economic considerations. Although the HCAP definition reaches an imperfect balance, the authors’ clinical risk score fails to improve upon that standard.

Seasonal influenza causes substantial mortality and morbidity in the United States, with approximately 365,000 hospitalizations and 50,000 deaths per year ([8][1], [9][2]). Multiple influenza virus types and subtypes cause human infection, and currently circulating subtypes of influenza A virus