Matthew R. Lamb

High attrition before and after ART initiation among youth (15-24 years of age) enrolled in HIV care.

Objectives:To compare pre and post-ART attrition between youth (15–24 years) and other patients in HIV care, and to investigate factors associated with attrition among youth. Design:Cohort study utilizing routinely collected patient-level data from 160 HIV clinics in Kenya, Mozambique, Tanzania, and Rwanda. Methods:Patients at least 10 years of age enrolling in HIV care between 01/05 and 09/10 were included. Attrition (loss to follow-up or death 1 year after enrollment or ART initiation) was compared between youth and other patients using multivariate competing risk (pre-ART) and traditional (post-ART) Cox proportional hazards methods accounting for within-clinic correlation. Among youth, patient-level and clinic-level factors associated with attrition were similarly assessed. Results:A total of 312 335 patients at least 10 years of age enrolled in HIV care; 147 936 (47%) initiated ART, 17% enrolling in care and 10% initiating ART were youth. Attrition before and after ART initiation was substantially higher among youth compared with other age groups. Among youth, nonpregnant women experienced lower pre-ART attrition than men [sub-division hazard ratio = 0.90, 95% confidence interval (CI): 0.86–0.94], while both pregnant [adjusted hazard ratio (AHR) = 0.85, 95% CI: 0.74–0.97] and nonpregnant (AHR = 0.79, 95% CI: 0.73–0.86) female youth experienced lower post-ART attrition than men. Youth attending clinics providing sexual and reproductive health services including condoms (AHR = 0.47, 95% CI: 0.32–0.70) and clinics offering adolescent support groups (AHR = 0.73, 95% CI: 0.52–1.0) experienced significantly lower attrition after ART initiation. Conclusion:Youth experienced substantially higher attrition before and after ART initiation compared with younger adolescents and older adults. Adolescent-friendly services were associated with reduced attrition among youth, particularly after ART initiation.

Prenatal Exposure to Polychlorinated Biphenyls and Postnatal Growth: A Structural Analysis

Normal endocrine function in utero and early in childhood influences later height and weight attainment. Polychlorinated biphenyls (PCBs) are persistent environmental contaminants with suspected endocrine-disrupting properties. PCBs may mimic or inhibit hormone and endocrine processes based in part on their structural configuration, with non-ortho-substituted PCBs having a coplanar orientation and ortho-substituted PCBs becoming increasingly noncoplanar. Coplanar and noncoplanar PCBs have known differences in biologic effect. Animal studies link prenatal PCB exposure to adverse birth and early-life growth outcomes, but epidemiologic studies are conflicting. We examined whether prenatal exposure to PCBs, categorized by their degree of ortho-substitution, affected childhood height and weight attainment in 150 children (109 boys and 41 girls) with African-American mothers born at the Columbia-Presbyterian Hospital from 1959 through 1962. Stratifying by sex, we used regression models for repeated measures to investigate associations between maternal levels of PCBs and height and weight through 17 years of age. Maternal levels of ortho-substituted PCBs were associated with reduced weight through 17 years of age among girls but not among boys. Tri-ortho-substituted PCBs were marginally associated with increased height in boys. Although limited by sample size, our results suggest that prenatal exposure to PCBs may affect growth, especially in girls, and that ortho-substitution is an important determinant of its effect on growth.

Association of Adherence Support and Outreach Services with Total Attrition, Loss to Follow-Up, and Death among ART Patients in Sub-Saharan Africa

Background Loss to follow-up (LTF) after antiretroviral therapy (ART) initiation is common in HIV clinics. We examined the effect of availability of adherence support and active patient outreach services on patient attrition following ART initiation. Methods and Findings This ecologic study examined clinic attrition rates (total attrition, LTF, and death) among 232,389 patients initiating ART at 349 clinics during 2004–2008 in 10 sub-Saharan African countries, and cohort attrition (proportion retained at 6 and 12 months after ART initiation) among a subset of patients with follow-up information (n = 83,389). Log-linear regression compared mean rates of attrition, LTF, and death between clinics with and without adherence support and outreach services. Cumulative attrition, LTF, and death rates were 14.2, 9.2, and 4.9 per 100 person-years on ART, respectively. In multivariate analyses, clinic availability of >2 adherence support services was marginally associated with lower attrition rates (RRadj = 0.59, 95%CI: 0.35–1.0). Clinics with availability of counseling services (RRadj = 0.62, 95%CI: 0.42–0.92), educational materials (RRadj = 0.73, 95%CI: 0.63–0.85), reminder tools (RRadj = 0.79, 95%CI: 0.64–0.97), and food rations (RRadj = 0.72, 95%CI: 0.58–0.90) had significantly lower attrition, with similar results observed for LTF. Outreach services were not significantly associated with attrition. In cohort analyses, attrition was significantly lower at clinics offering >2 adherence support services (RRadj,6m = 0.84, 95%CI: 0.73–0.96), dedicated pharmacy services (RRadj,6m = 0.78, 95%CI: 0.69–0.90), and active patient outreach (RRadj,6m = 0.85, 95%CI: 0.73–0.99). Availability of food rations was marginally associated with increased retention at 6 (RRadj,6m  = 0.82, 95%CI: 0.64–1.05) but not 12 months (RRadj,12m  = 0.98, 95%CI: 0.78–1.21). Conclusions Availability of adherence support services, active patient outreach and food rations at HIV care clinics may improve retention following ART initiation.

Retention of HIV-infected children on antiretroviral treatment in HIV care and treatment programs in Kenya Mozambique Rwanda and Tanzania.

Background:Retention of children in HIV care is essential for prevention of disease progression and mortality. Methods:Retrospective cohort of children (aged 0 to <15 years) initiating antiretroviral treatment (ART) at health facilities in Kenya, Mozambique, Rwanda, and Tanzania, from January 2005 to June 2011. Retention was defined as the proportion of children known to be alive and attending care at their initiation facility; lost to follow-up (LTF) was defined as no clinic visit for more than 6 months. Cumulative incidence of ascertained survival and retention after ART initiation was estimated through 24 months using Kaplan–Meier methods. Factors associated with LTF and death were assessed using Cox proportional hazard modeling. Results:A total of 17,712 children initiated ART at 192 facilities: median age was 4.6 years [interquartile ratio (IQR), 1.9–8.3], median CD4 percent was 15% (IQR, 10–20) for children younger than 5 years and 265 cells per microliter (IQR, 111–461) for children aged 5 years or older. At 12 and 24 months, 80% and 72% of children were retained with 16% and 22% LTF and 5% and 7% known deaths, respectively. Retention ranged from 71% to 95% at 12 months and from 62% to 93% at 24 months across countries, respectively, and was lowest for children younger than 1 year (51% at 24 months). LTF and death were highest in children younger than 1 year and children with advanced disease. Conclusions:Retention was lowest in young children and differed across country programs. Young children and those with advanced disease are at highest risk for LTF and death. Further evaluation of patient- and program-level factors is needed to improve health outcomes.

Use of a Comprehensive HIV Care Cascade for Evaluating HIV Program Performance: Findings From 4 Sub-Saharan African Countries

Background:The traditional HIV treatment cascade has been noted to have limitations. A proposed comprehensive HIV care cascade that uses cohort methodology offers additional information as it accounts for all patients. Using data from 4 countries, we compare patient outcomes using both approaches. Methods:Data from 390,603 HIV-infected adults (>15 years) enrolled at 217 facilities in Kenya, Mozambique, Rwanda, and Tanzania from 2005 to 2011 were included. Outcomes of all patients at 3, 6, and 12 months after enrollment were categorized as optimal, suboptimal, or poor. Optimal outcomes included retention in care, antiretroviral therapy (ART) initiation, and documented transfer. Suboptimal outcomes included retention in care without ART initiation among eligible patients or those without eligibility data. Poor outcomes included loss to follow-up and death. Results:The comprehensive HIV care cascade demonstrated that at 3, 6 and 12 months, 58%, 51%, and 49% of patients had optimal outcomes; 22%, 12%, and 7% had suboptimal outcomes, and 20%, 37% and 44% had poor outcomes. Of all patients enrolled in care, 56% were retained in care at 12 months after enrollment. In comparison, the traditional HIV treatment cascade found 89% of patients enrolled in HIV care were assessed for ART eligibility, of whom 48% were determined to be ART-eligible with 70% initiating ART, and 78% of those initiated on ART retained at 12 months. Conclusions:The comprehensive HIV care cascade follows outcomes of all patients, including pre-ART patients, who enroll in HIV care over time and uses quality of care parameters for categorizing outcomes. The comprehensive HIV care cascade provides complementary information to that of the traditional HIV treatment cascade and is a valuable tool for monitoring HIV program performance.

Characteristics and outcomes among older HIV-positive adults enrolled in HIV programs in four sub-Saharan African countries.

Background Limited information exists on adults ≥50 years receiving HIV care in sub-Saharan Africa. Methodology Using routinely-collected longitudinal patient-level data among 391,111 adults ≥15 years enrolling in HIV care from January 2005–December 2010 and 184,689 initiating ART, we compared characteristics and outcomes between older (≥50 years) and younger adults at 199 clinics in Kenya, Mozambique, Rwanda, and Tanzania. We calculated proportions over time of newly enrolled and active adults receiving HIV care and initiating ART who were ≥50 years; cumulative incidence of loss to follow-up (LTF) and recorded death one year after enrollment and ART initiation, and CD4+ response following ART initiation. Findings From 2005–2010, the percentage of adults ≥50 years newly enrolled in HIV care remained stable at 10%, while the percentage of adults ≥50 years newly initiating ART (10% [2005]-12% [2010]), active in follow-up (10% [2005]-14% (2010]), and active on ART (10% [2005]-16% [2010]) significantly increased. One year after enrollment, older patients had significantly lower incidence of LTF (33.1% vs. 32.6%[40–49 years], 40.5%[25–39 years], and 56.3%[15–24 years]; p-value<0.0001), but significantly higher incidence of recorded death (6.0% vs. 5.0% [40–49 years], 4.1% [25–39 years], and 2.8% [15–24 years]; p-valve<0.0001). LTF was lower after vs. before ART initiation for all ages, with older adults experiencing less LTF than younger adults. Among 85,763 ART patients with baseline and follow-up CD4+ counts, adjusted average 12-month CD4+ response for older adults was 20.6 cells/mm3 lower than for adults 25–39 years of age (95% CI: 17.1–24.1). Conclusions The proportion of patients who are ≥50 years has increased over time and been driven by aging of the existing patient population. Older patients experienced less LTF, higher recorded mortality and less robust CD4+ response after ART initiation. Increased programmatic attention on older adults receiving HIV care in sub-Saharan Africa is warranted.

A combination strategy for enhancing linkage to and retention in HIV care among adults newly diagnosed with HIV in Mozambique: study protocol for a site-randomized implementation science study

BackgroundDespite the extraordinary scale up of HIV prevention, care and treatment services in sub-Saharan Africa (SSA) over the past decade, the overall effectiveness of HIV programs has been significantly hindered by high levels of attrition across the HIV care continuum. Data from “real-life” settings are needed on the effectiveness of an easy to deliver package of services that can improve overall performance of the HIV care continuum.Methods/DesignWe are conducting an implementation science study using a two-arm cluster site-randomized design to determine the effectiveness of a combination intervention strategy (CIS) using feasible, evidence-based, and practical interventions—including (1) point-of-care (POC) CD4 count testing, (2) accelerated antiretroviral therapy initiation for eligible individuals, and (3) SMS reminders for linkage to and retention in care—as compared to the standard of care (SOC) in Mozambique in improving linkage and retention among adults following HIV diagnosis. A pre-post intervention two-sample design is nested within the CIS arm to assess the incremental effectiveness of the CIS plus financial incentives (CIS + FI) compared to the CIS without FI on study outcomes. Randomization is done at the level of the study site, defined as a primary health facility. Five sites are included from the City of Maputo and five from Inhambane Province. Target enrollment is a total of 2,250 adults: 750 in the SOC arm, 750 in the CIS cohort of the intervention arm and 750 in the CIS + FI cohort of the intervention arm (average of 150 participants per site). Participants are followed for 12 months from time of HIV testing to ascertain a combined endpoint of linkage to care within 1 month after testing and retention in care 12 months from HIV test. Cost-effectiveness analyses of CIS compared to SOC and CIS + FI compared to CIS will also be conducted.DiscussionStudy findings will provide evidence on the effectiveness of a CIS and the incremental effectiveness of a CIS + FI in a “real-life” service delivery system in a SSA country severely impacted by HIV.Trial registrationClinicaltrials.gov, NCT01930084

Effectiveness of a combination strategy for linkage and retention in adult HIV care in Swaziland: The Link4Health cluster randomized trial

Background Gaps in the HIV care continuum contribute to poor health outcomes and increase HIV transmission. A combination of interventions targeting multiple steps in the continuum is needed to achieve the full beneficial impact of HIV treatment. Methods and findings Link4Health, a cluster-randomized controlled trial, evaluated the effectiveness of a combination intervention strategy (CIS) versus the standard of care (SOC) on the primary outcome of linkage to care within 1 month plus retention in care at 12 months after HIV-positive testing. Ten clusters of HIV clinics in Swaziland were randomized 1:1 to CIS versus SOC. The CIS included point-of-care CD4+ testing at the time of an HIV-positive test, accelerated antiretroviral therapy (ART) initiation for treatment-eligible participants, mobile phone appointment reminders, health educational packages, and noncash financial incentives. Secondary outcomes included each component of the primary outcome, mean time to linkage, assessment for ART eligibility, ART initiation and time to ART initiation, viral suppression defined as HIV-1 RNA < 1,000 copies/mL at 12 months after HIV testing among patients on ART ≥6 months, and loss to follow-up and death at 12 months after HIV testing. A total of 2,197 adults aged ≥18 years, newly tested HIV positive, were enrolled from 19 August 2013 to 21 November 2014 (1,096 CIS arm; 1,101 SOC arm) and followed for 12 months. The median participant age was 31 years (IQR 26–39), and 59% were women. In an intention-to-treat analysis, 64% (705/1,096) of participants at the CIS sites achieved the primary outcome versus 43% (477/1,101) at the SOC sites (adjusted relative risk [RR] 1.52, 95% CI 1.19–1.96, p = 0.002). Participants in the CIS arm versus the SOC arm had the following secondary outcomes: linkage to care regardless of retention at 12 months (RR 1.08, 95% CI 0.97–1.21, p = 0.13), mean time to linkage (2.5 days versus 7.5 days, p = 0.189), retention in care at 12 months regardless of time to linkage (RR 1.48, 95% CI 1.18–1.86, p = 0.002), assessment for ART eligibility (RR 1.20, 95% CI 1.07–1.34, p = 0.004), ART initiation (RR 1.16, 95% CI 0.96–1.40, p = 0.12), mean time to ART initiation from time of HIV testing (7 days versus 14 days, p < 0.001), viral suppression among those on ART for ≥6 months (RR 0.97, 95% CI 0.88–1.07, p = 0.55), loss to follow-up at 12 months after HIV testing (RR 0.56, 95% CI 0.40–0.79, p = 0.002), and death (N = 78) within 12 months of HIV testing (RR 0.80, 95% CI 0.46–1.35, p = 0.41). Limitations of this study include a small number of clusters and the inability to evaluate the incremental effectiveness of individual components of the combination strategy. Conclusions A combination strategy inclusive of 5 evidence-based interventions aimed at multiple steps in the HIV care continuum was associated with significant increase in linkage to care plus 12-month retention. This strategy offers promise of enhanced outcomes for HIV-positive patients. Trial registration ClinicalTrials.gov NCT01904994.

Impact of a youth-friendly HIV clinic: 10 years of adolescent outcomes in Port-au-Prince, Haiti

Adolescents account for over 40% of new HIV infections in Haiti. This analysis compares outcomes among HIV‐positive adolescents before and after implementation of an adolescent HIV clinic in Port‐au‐Prince, Haiti.

A combination intervention strategy to improve linkage to and retention in HIV care following diagnosis in Mozambique: A cluster-randomized study

Background Concerning gaps in the HIV care continuum compromise individual and population health. We evaluated a combination intervention strategy (CIS) targeting prevalent barriers to timely linkage and sustained retention in HIV care in Mozambique. Methods and findings In this cluster-randomized trial, 10 primary health facilities in the city of Maputo and Inhambane Province were randomly assigned to provide the CIS or the standard of care (SOC). The CIS included point-of-care CD4 testing at the time of diagnosis, accelerated ART initiation, and short message service (SMS) health messages and appointment reminders. A pre–post intervention 2-sample design was nested within the CIS arm to assess the effectiveness of CIS+, an enhanced version of the CIS that additionally included conditional non-cash financial incentives for linkage and retention. The primary outcome was a combined outcome of linkage to care within 1 month and retention at 12 months after diagnosis. From April 22, 2013, to June 30, 2015, we enrolled 2,004 out of 5,327 adults ≥18 years of age diagnosed with HIV in the voluntary counseling and testing clinics of participating health facilities: 744 (37%) in the CIS group, 493 (25%) in the CIS+ group, and 767 (38%) in the SOC group. Fifty-seven percent of the CIS group achieved the primary outcome versus 35% in the SOC group (relative risk [RR]CIS vs SOC = 1.58, 95% CI 1.05–2.39). Eighty-nine percent of the CIS group linked to care on the day of diagnosis versus 16% of the SOC group (RRCIS vs SOC = 9.13, 95% CI 1.65–50.40). There was no significant benefit of adding financial incentives to the CIS in terms of the combined outcome (55% of the CIS+ group achieved the primary outcome, RRCIS+ vs CIS = 0.96, 95% CI 0.81–1.16). Key limitations include the use of existing medical records to assess outcomes, the inability to isolate the effect of each component of the CIS, non-concurrent enrollment of the CIS+ group, and exclusion of many patients newly diagnosed with HIV. Conclusions The CIS showed promise for making much needed gains in the HIV care continuum in our study, particularly in the critical first step of timely linkage to care following diagnosis. Trial registration ClinicalTrials.gov NCT01930084