Feasibility and acceptability of point of care testing for sexually transmitted infections in outpatient clinics offering integrated services in Eswatini.

BACKGROUND: Lack of point of care testing (POCT) for sexually transmitted infections (STIs) is a continuing missed opportunity in Sub-Saharan Africa. We assessed feasibility and acceptability of STI POCT in Eswatini. METHODS: STI POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) was piloted among sexually active adults 18-45 years attending two urban outpatient clinics offering HIV services. Females were randomized 1:1 to provide urine or vaginal swab and all males provided urine samples for CT/NG testing using Cepheid CT/NG cartridges on existing GeneXpert platforms. Results were returned in-person or by telephone call. We assessed duration of procedures and participant and healthcare worker acceptability of services (5-point Likert scale), time spent on STI POCT services, and correlates of CT/NG infection. RESULTS: Of 250 adults triaged, 99% (248/250) accepted STI POCT, including 44% (109/248) people living with HIV. STI POCT procedures took a median of 3:22 hours. Most adults (90%, 224/248), received results within a day (61% same day, 29% next day). CT/NG was detected among 22% (55/248): 31/55 CT, 21/55 NG and 3/55 coinfections. Youth 18-25 years, history of any sexual intercourse, and condom-less sex within the previous 7 days were significantly associated with CT/NG detected (p < 0.05). Most adults with CT/NG were treated (51/55, 93%). Most participants were satisfied with STI POCT (217/241, 90%), and would accept again/recommend it. All 32 healthcare workers who participated were satisfied with STI POCT. CONCLUSION: STI POCT was feasible, acceptable, and identified a high prevalence of STIs, highlighting the urgent need for this testing.

Effects of the Coronavirus Disease 2019 Pandemic on Human Immunodeficiency Virus Services: Findings from 11 Sub-Saharan African Countries.

BACKGROUND: Due to concerns about the effects of the coronavirus disease 2019 (COVID-19 pandemic on health services, we examined its effects on human immunodeficiency virus (HIV) services in sub-Saharan Africa. METHODS: Quarterly data (Q1, 10/2019-12/2019; Q2, 1/2020-3/2020; Q3, 4/2020-6/2020; Q4, 7/2020-9/2020) from 1059 health facilities in 11 countries were analyzed and categorized by stringency of pandemic measures. We conducted a difference-in-differences assessment of HIV service changes from Q1-Q2 to Q3-Q4 by higher vs lower stringency. RESULTS: There was a 3.3% decrease in the number HIV tested from Q2 to Q3 (572 845 to 553 780), with the number testing HIV-positive declining by 4.9% from Q2 to Q3. From Q3 to Q4, the number tested increased by 10.6% (612 646), with an increase of 8.8% (23 457) in the number testing HIV-positive with similar yield (3.8%). New antiretroviral therapy (ART) initiations declined by 9.8% from Q2 to Q3 but increased in Q4 by 9.8%. Across all quarters, the number on ART increased (Q1, 419 028 to Q4, 476 010). The number receiving viral load (VL) testing in the prior 12 months increased (Q1, 255 290 to Q4, 312 869). No decrease was noted in VL suppression (Q1, 87.5% to Q4, 90.1%). HIV testing (P < .0001) and new ART initiations (P = .001) were inversely associated with stringency. CONCLUSIONS: After initial declines, rebound was brisk, with increases noted in the number HIV tested, newly initiated or currently on ART, VL testing, and VL suppression throughout the period, demonstrating HIV program resilience in the face of the COVID-19 crisis.

Low rates of prior HIV testing among HIV-positive adults accessing outpatient services in Eswatini.

Prior HIV testing and awareness of HIV-positive status were assessed among HIV-positive adults at 20 clinics in Eswatini. Of 2196 HIV-positive adults, 1183 (53.8%) reported no prior HIV testing, and 1948 (88.7%) were unaware of their HIV-positive status. Males [adjusted odds ratio, AOR, (95% confidence interval): 0.7 (0.5-0.9)], youth 18-25 years [AOR 0.6 (0.4-0.95)], adults ≥ 50 years [AOR 0.5 (0.3-0.9)], those needing family support [AOR 0.6 (0.5-0.8)], and those living ≥ 45 min from clinic [AOR 0.5 (0.4-0.8)] were less likely to know their HIV-positive status. More HIV testing is needed to achieve 95-95-95 targets, with targeted strategies for those less likely to test for HIV.

Healthcare worker experiences with Option B+ for prevention of mother-to-child HIV transmission in eSwatini: findings from a two-year follow-up study.

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) across sub-Saharan Africa has rapidly shifted towards Option B+, an approach in which all HIV+ pregnant and breastfeeding women initiate lifelong antiretroviral therapy (ART) independent of CD4+ count. Healthcare workers (HCW) are critical to the success of Option B+, yet little is known regarding HCW acceptability of Option B+, particularly over time. METHODS: Ten health facilities in the Manzini and Lubombo regions of eSwatini transitioned from Option A to Option B+ between 2013 and 2014 as part of the Safe Generations study examining PMTCT retention. Fifty HCWs (5 per facility) completed questionnaires assessing feasibility and acceptability: (1) prior to transitioning to Option B+, (2) two months post transition, and (3) approximately 2 years post Option B+ transition. This analysis describes HCW perceptions and experiences two years after transitioning to Option B+. RESULTS: Two years after transition, 80% of HCWs surveyed reported that Option B+ was easy for HCWs, noting that it was particularly easy to explain and coordinate. Immediate ART initiation also reduced delays by eliminating need for laboratory tests prior to ART initiation. Additionally, HCWs reported ease of patient follow-up (58%), documentation (56%), and counseling (58%) under Option B+. Findings also indicate that a majority of HCWs reported that their workloads increased under Option B+. Sixty-eight percent of HCWs at two years post-transition reported more work under Option B+, specifically noting increased involvement in adherence counseling, prescribing/monitoring medications, and appointment scheduling/tracking. Some HCWs attributed their higher workloads to increased client loads, now that all HIV-positive women were initiated on ART. New barriers to patient uptake, and issues related to retention, adherence, and follow-up were also noted as challenges face by HCW when implementing Option B+. CONCLUSIONS: Overall, HCWs found Option B+ to be acceptable and feasible while providing critical insights into the practical issues of universal ART. Further strengthening of the healthcare system may be necessary to alleviate worker burden and to ensure effective monitoring of client retention and adherence. HCW perceptions and experiences with Option B+ should be considered more broadly as countries implement Option B+ and consider universal treatment for all HIV+ individuals. TRIAL REGISTRATION: http://clinicaltrials.gov NCT01891799 , registered on July 3, 2013.

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.

Transitioning to Country Ownership of HIV Programs in Rwanda.

Agnes Binagwaho and colleagues describe how Rwanda achieved country ownership of its HIV programs.

Mobile device for disease diagnosis and data tracking in resource-limited settings.

BACKGROUND: Collection of epidemiological data and care of patients are hampered by lack of access to laboratory diagnostic equipment and patients' health records in resource-limited settings. We engineered a low-cost mobile device that combines cell-phone and satellite communication technologies with fluid miniaturization techniques for performing all essential ELISA functions. METHODS: We assessed the device's ability to perform HIV serodiagnostic testing in Rwanda and synchronize results in real time with electronic health records. We tested serum, plasma, and whole blood samples collected in Rwanda and on a commercially available sample panel made of mixed antibody titers. RESULTS: HIV testing on 167 Rwandan patients evaluated for HIV, viral hepatitis, and sexually transmitted infections yielded diagnostic sensitivity and specificity of 100% and 99%, respectively. Testing on 40 Rwandan whole-blood samples-using 1 µL of sample per patient-resulted in diagnostic sensitivity and specificity of 100% and 100%. The mobile device also successfully transmitted all whole-blood test results from a Rwandan clinic to a medical records database stored on the cloud. For all samples in the commercial panel, the device produced results in agreement with a leading ELISA test, including detection of weakly positive samples that were missed by existing rapid tests. The device operated autonomously with minimal user input, produced each result 10 times faster than benchtop ELISA, and consumed as little power as a mobile phone. CONCLUSIONS: A low-cost mobile device can perform a blood-based HIV serodiagnostic test with laboratory-level accuracy and real-time synchronization of patient health record data.

HIV incidence, viremia, and the national response in Eswatini: Two sequential population-based surveys.

With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA <1000 copies/mL among all seropositive adults) and unsuppressed viremia (HIV RNA ≥1000 copies/mL among all, regardless of HIV status) and assessed for temporal changes by conducting a trend analysis of the log ratio of proportions, using a Z statistic distribution. HIV prevalence remained stable from 2011 to 2016 [32% versus 30%, p = 0.10]. HIV incidence significantly declined 48% [2.48% versus 1.30%, p = 0.01]. Incidence remained higher among women than men [2011: 3.16% versus 1.83%; 2016: 1.76% versus 0.86%], with a smaller but significant relative reduction among women [44%; p = 0.04] than men [53%; p = 0.09]. The proportion of seropositive adults with viral load suppression significantly increased from 35% to 71% [p < .001]. The proportion of the total adult population with unsuppressed viremia decreased from 21% to 9% [p < .001]. National HIV incidence in Eswatini decreased by nearly half and viral load suppression doubled over a five-year period. Unsuppressed viremia in the total population decreased 58%. These population-based findings demonstrate the national impact of expanded HIV services in a hyperendemic country.

Comparing two service delivery models for the prevention of mother-to-child transmission (PMTCT) of HIV during transition from single-dose nevirapine to multi-drug antiretroviral regimens.

BACKGROUND: Mother-to-child transmission (MTCT) of HIV has been eliminated from the developed world with the introduction of multi-drug antiretroviral (md-ARV) regimens for the prevention of MTCT (PMTCT); but remains the major cause of HIV infection among sub-Saharan African children. This study compares two service delivery models of PMTCT interventions and documents the lessons learned and the challenges encountered during the transition from single-dose nevirapine (sd-nvp) to md-ARV regimens in a resource-limited setting. METHODS: Program data collected from 32 clinical sites was used to describe trends and compare the performance (uptake of HIV testing, CD4 screening and ARV regimens initiated during pregnancy) of sites providing PMTCT as a stand-alone service (stand-alone site) versus sites providing PMTCT as well as antiretroviral therapy (ART) (full package site). CD4 cell count screening, enrollment into ART services and the initiation of md-ARV regimens during pregnancy, including dual (zidovudine [AZT] +sd-nvp) prophylaxis and highly active antiretroviral therapy (HAART) were analysed. RESULTS: From July 2006 to December 2008, 1,622 pregnant women tested HIV positive (HIV+) during antenatal care (ANC). CD4 cell count screening during pregnancy increased from 60% to 70%, and the initiation of md-ARV regimens increased from 35.5% to 97% during this period. In 2008, women attending ANC at full package sites were 30% more likely to undergo CD4 cell count assessment during pregnancy than women attending stand-alone sites (relative risk (RR) = 1.3; 95% confidence interval (CI): 1.1-1.4). Enrollment of HIV+ pregnant women in ART services was almost twice as likely at full package sites than at stand-alone sites (RR = 1.9; 95% CI: 1.5-2.3). However, no significant differences were detected between the two models of care in providing md-ARV (RR = 0.9; 95% CI: 0.9-1.0). CONCLUSIONS: All sites successfully transitioned from sd-nvp to md-ARV regimens for PMTCT. Full package sites offer the most efficient model for providing immunological assessment and enrollment into care and treatment of HIV+ pregnant women. Strengthening the capacity of stand-alone PMTCT sites to achieve the same objectives is paramount.

Engagement in care among women and their infants lost to follow-up under Option B+ in eSwatini.

BACKGROUND: Universal antiretroviral treatment (ART) for pregnant women with HIV, Option B+, has been adopted widely for prevention of mother-to-child HIV transmission (PMTCT). Some evidence shows high loss to follow-up (LTF) under this model. However, gaps in data systems limit this evidence. We collected additional information for women and infants LTF from Option B+ in Eswatini to assess more accurate outcomes. METHODS: LTF at 6-months postpartum was assessed using facility data. Additional data was gathered from: 1) the national ART database and paper records; 2) patient tracing; and 3) interviews and abstraction from patient-held records. Engagement in care was defined as any clinic visit within 91 days before or after 6-months postpartum or completion of a documented transfer; or, for those traced but not completing study interviews, visits at 6-months postpartum or later (for infants), or visits within 3-months of tracing (for women). Multivariable loglinear models were used to identify correlates of engagement. RESULTS: One-hundred-ninety-four (44.7%) of 434 LTF women had outcomes ascertained, including 122 (62.9%) women engaged in care. Among 510 LTF infants, 265 (52.0%) had ascertained outcomes, including 143 (54.0%) engaged in care, 47 (17.7%) pregnancy losses, and 18 (6.8%) deaths. Seventy-two of 189 live infants (38.1%) with ascertained outcomes had a 6-week early infant diagnostic (EID) test. Among women with ascertained outcomes, gestational age of 20+ weeks (vs. fewer than 20 weeks, aRR 0.80; 95% CI 0.68-0.94) and age 25-29 years (vs. 15-24 years, aRR 0.81; 95% CI 0.67-0.97), were associated with lower engagement; initiating ART after first ANC visit was associated with higher engagement (vs. at first ANC visit, aRR 1.12; 95% CI 1.04-1.21). Among infants with ascertained outcomes, mother not initiating ART was associated with lower engagement (vs. ART at first ANC visit, aRR 0.71; 95% CI 0.54-0.91). CONCLUSION: Substantial numbers of women and infants classified as LTF under Option B+ were engaged in care, though a suboptimal level of 6-week EID testing was observed. These findings highlight a need to improve coverage of routine EID testing, and improve data systems to better capture PMTCT patient outcomes.

Impact of universal antiretroviral therapy for pregnant and postpartum women on antiretroviral therapy uptake and retention.

OBJECTIVE: Universal eligibility for lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') has been widely adopted, but concerns remain. We tested the hypothesis that the change from CD4+-guided ART eligibility ('Option A'), to Option B+, would improve maternal ART uptake and retention. DESIGN: A stepped-wedge evaluation at 12 health facilities in eSwatini. METHODS: Primary outcome was maternal retention: proportion of women attending clinic within 56 days of delivery (antenatal retention) and clinic attendance within 84 days of 6-months postpartum (postnatal retention). Generalized estimating equations examined impact of Option B+ vs. Option A. RESULTS: Between 19 August 2013 and 29 August 2014, 2347 HIV-positive women, 55% (n = 1296) Option A, 45%, (n = 1051) Option B+ were included. ART initiation was observed in 36% (n = 469) of Option A women vs. 94% (n = 983) under Option B+ (P < 0.001). Overall 39% (n = 912) were retained from first ANC visit through 6-months postpartum. Retention was higher under Option B+ (53%, n = 559) vs. Option A (24%, n = 353) with variation by site and study month. Adjusting for age, gestational age, previous HIV diagnosis, and CD4+, Option B+ women were significantly more likely to be retained antenatally (aRR 1.32; 95% CI 1.18-1.49; P < 0.001) and postnatally (aRR 2.11; 95% CI 1.79-2.49) compared with Option A. Restricted to women initiating ART, retention was lower under Option B+ (57%, n = 558) vs. Option A (66%, n = 309; aRR, 0.82; 95% CI 0.70-0.95; P < 0.0001). CONCLUSION: Compared with CD4+-guided ART eligibility, universal ART resulted in substantial increases in pregnant women initiating ART and retained in care through 6 months postpartum.

Cost-effectiveness of a combination strategy to enhance the HIV care continuum in Swaziland: Link4Health.

INTRODUCTION: Link4Health, a cluster-RCT, demonstrated the effectiveness of a combination strategy targeting barriers at various HIV continuum steps on linkage to and retention in care; showing effectiveness in achieving linkage to HIV care within 1 month plus retention in care at 12 months after HIV testing for people living with HIV (RR 1.48, 95% CI 1.19-1.96, p = 0.002). In addition to standard of care, Link4Health included: 1) Point-of-care CD4+ count testing; 2) Accelerated ART initiation; 3) Mobile phone appointment reminders; 4) Care and prevention package including commodities and informational materials; and 5) Non-cash financial incentive. Our objective was to evaluate the cost-effectiveness of a scale-up of the Link4Health strategy in Swaziland. METHODS AND FINDINGS: We incorporated the effects and costs of the Link4Health strategy into a computer simulation of the HIV epidemic in Swaziland, comparing a scenario where the strategy was scaled up to a scenario with no implementation. The simulation combined a deterministic compartmental model of HIV transmission with a stochastic microsimulation of HIV progression calibrated to Swaziland epidemiological data. It incorporated downstream health costs potentially saved and infections potentially prevented by improved linkage and treatment adherence. We assessed the incremental cost-effectiveness ratio of Link4Health compared to standard care from a health sector perspective reported in US$2015, a time horizon of 20 years, and a discount rate of 3% in accordance with WHO guidelines.[1] Our results suggest that scale-up of the Link4Health strategy would reduce new HIV infections over 20 years by 11,059 infections, a 7% reduction from the projected 169,019 cases and prevent 5,313 deaths, an 11% reduction from the projected 49,582 deaths. Link4Health resulted in an incremental cost per infection prevented of $13,310 and an incremental cost per QALY gained of $3,560/QALY from the health sector perspective. CONCLUSIONS: Using a threshold of <3 x per capita GDP, the Link4Health strategy is likely to be a cost-effective strategy for responding to the HIV epidemic in Swaziland.

Enrollment in HIV Care Two Years after HIV Diagnosis in the Kingdom of Swaziland: An Evaluation of a National Program of New Linkage Procedures.

To improve early enrollment in HIV care, the Swaziland Ministry of Health implemented new linkage procedures for persons HIV diagnosed during the Soka Uncobe male circumcision campaign (SOKA, 2011-2012) and the Swaziland HIV Incidence Measurement Survey (SHIMS, 2011). Abstraction of clinical records and telephone interviews of a retrospective cohort of HIV-diagnosed SOKA and SHIMS clients were conducted in 2013-2014 to evaluate compliance with new linkage procedures and enrollment in HIV care at 92 facilities throughout Swaziland. Of 1,105 clients evaluated, within 3, 12, and 24 months of diagnosis, an estimated 14.0%, 24.3%, and 37.0% enrolled in HIV care, respectively, after adjusting for lost to follow-up and non-response. Kaplan-Meier functions indicated lower enrollment probability among clients 14-24 (P = 0.0001) and 25-29 (P = 0.001) years of age compared with clients >35 years of age. At 69 facilities to which clients were referred for HIV care, compliance with new linkage procedures was low: referral forms were located for less than half (46.8%) of the clients, and few (9.6%) were recorded in the appointment register or called either before (0.3%) or after (4.9%) their appointment. Of over one thousand clients newly HIV diagnosed in Swaziland in 2011 and 2012, few received linkage services in accordance with national procedures and most had not enrolled in HIV care two years after their diagnosis. Our findings are a call to action to improve linkage services and early enrollment in HIV care in Swaziland.

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.

Time to initiation of antiretroviral therapy among patients who Are ART eligible in Rwanda: improvement over time.

BACKGROUND: Delayed initiation of antiretroviral therapy (ART) in eligible patients is a concern in resource-limited countries. METHODS: We analyzed data on HIV-positive patients ≥15 years enrolled at 41 ICAP-supported health care facilities in Rwanda, 2005-2010, to determine time to ART initiation among patients eligible at enrollment compared with those ineligible or of indeterminate eligibility who become eligible during follow-up. ART eligibility was based on CD4 cell count (CD4) and WHO staging; patients lacking CD4 and WHO stage were considered indeterminate. Cumulative incidence of reaching ART eligibility and to ART initiation after eligibility was generated using competing risk estimators. RESULTS: A total of 31,033 ART-naive adults were enrolled; 64.2% were female. At enrollment, 10,158 (32.7%) patients were ART eligible, 13,372 (43.1%) were ineligible for ART, and 7503 (24.2%) patients were indeterminate. Among patients retained in care pre-ART eligibility, 17.9% [95% confidence interval (CI): 17.2 to 18.6] of ineligible and 22.8% (95% CI: 21.7 to 23.8) of indeterminate patients at enrollment reached ART eligibility within 12 months. Cumulative incidence of ART initiation within 3 months for patients eligible at enrollment was 77.2% (95% CI: 76.4 to 78.0) compared with 67.9% (95% CI: 66.4 to 69.3) for ineligible and 63.8% (95% CI: 61.9 to 65.8) for patients with indeterminate eligibility at enrollment (P < 0.05). Over the study period, there was more rapid ART initiation for patients who became ART eligible. CONCLUSIONS: We found higher rates of ART initiation within 3 months among patients who were ART eligible at enrollment compared with those who reached eligibility during follow-up. From 2006 to 2011, earlier initiation of ART after eligibility was observed likely reflecting improved program quality.

Implementation and Operational Research: Evaluation of Swaziland's Hub-and-Spoke Model for Decentralizing Access to Antiretroviral Therapy Services.

BACKGROUND: In 2007, Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access. Decentralization was facilitated through (1) down-referral of stable ART patients from overburdened central facilities (hubs) to primary health care clinics (spokes) and (2) ART initiation at spokes (spoke initiation). METHODS: We conducted a nationally representative retrospective cohort study among adult ART enrollees during 2004-2010 to assess the effect of down-referral and spoke-initiation on rates of loss to follow-up (LTFU), death, and attrition (death or LTFU). Sixteen of 31 hubs were randomly selected using probability-proportional-to-size sampling. Seven selected facilities had initiated the hub-and-spoke model by study start. At these facilities, 1149 of 24,782 hub-initiated and maintained and 878 of 7722 down-referred or spoke-initiated patient records were randomly selected and analyzed. At the 9 hub-only facilities, 483 of 6638 records were randomly selected and analyzed. Multivariable proportional hazards regression was used to assess effect of down-referral (a time-varying covariate) and spoke-initiation on outcomes. RESULTS: At ART initiation, median age was 35, 65% were female, and median CD4 count was 147 cells per microliter. Controlling for known confounders, down-referral was strongly protective against LTFU [adjusted hazard ratio (AHR) 0.38; 95% confidence interval (CI): 0.29 to 0.50] and attrition (AHR = 0.50; 95% CI: 0.34 to 0.76) but not mortality. Compared with hub-initiated and maintained patients, spoke-initiated patients had lower LTFU (AHR 0.59; 95% CI: 0.45 to 0.77) and attrition rates (AHR 0.60; 95% CI: 0.47 to 0.77), but not mortality. CONCLUSIONS: Down-referral and spoke-initiation within a hub-and-spoke ART decentralization model were protective against LTFU and overall attrition and could facilitate future ART program expansion.

The Link4Health study to evaluate the effectiveness of a combination intervention strategy for linkage to and retention in HIV care in Swaziland: protocol for a cluster randomized trial.

BACKGROUND: Gaps in the HIV care continuum contribute to suboptimal individual health outcomes and increased risk of HIV transmission at the population level. Implementation science studies are needed to evaluate clinic-based interventions aimed at improving retention of patients across the continuum. METHODS/DESIGN: Link4Health uses an unblended cluster site-randomized design to evaluate the effectiveness of a combination intervention strategy (CIS) as compared to standard of care on linkage to and retention in care among HIV-diagnosed adults in Swaziland. The CIS intervention targets a multiplicity of structural, behavioral, and biomedical barriers through five interventions: (1) point-of-care CD4 testing at time of HIV testing, (2) accelerated antiretroviral therapy (ART) initiation for eligible patients, (3) mobile phone appointment reminders, (4) care and prevention packages, and (5) non-cash financial incentives for linkage and retention. The unit of randomization is a network of HIV clinics inclusive of a secondary facility coupled with an affiliated primary facility. Ten study units were randomized based on implementing partner, geographic location, and historic volume of HIV patients. Target enrollment was 2200 individuals, each to be followed for 12 months. Eligibility criteria includes HIV-positive test, age >18 years, willing to receive HIV care at a clinic in the study unit and consent to study procedures. Exclusion criteria included previous HIV care in the past 6 months, planning to leave the community, and current pregnancy. The primary study outcome is linkage within 1 month and retention at 12 months after testing HIV positive. Secondary outcomes include viral load suppression at 12 months, time to ART eligibility and initiation, participant acceptability, and cost-effectiveness. The trial status is that study enrollment is complete and follow-up procedures are ongoing. DISCUSSION: Link4Health evaluates a novel and pragmatic combination intervention strategy to improve linkage to and retention in care among adults with HIV in Swaziland. If the strategy is found to be effective, this study has the potential to inform HIV service delivery in resource-limited settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT01904994.

Determinants of mortality and loss to follow-up among adults enrolled in HIV care services in Rwanda.

BACKGROUND: Antiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs. METHODS: We analyzed routinely-collected data on HIV-infected patients ≥ 15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART. RESULTS: 31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9-11.6%) and 2.9% for death (95%CI 2.7-3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1-1.5) and death (aSHR 1.7, 95%CI 1.4-2.1). Low CD4 count (CD4<100 vs. ≥ 350 aSHR 0.2, 95%CI 0.1-0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2-0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4-4.5%) and 6.3% (95%CI 6.2-6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2-1.7) and death (AHR1.3, 95%CI 1.2-1.5). Mortality was higher for ART patients ≥ 40 years and in those with lower CD4 count at ART initiation. CONCLUSIONS: Low rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment.

High retention among HIV-infected children in Rwanda during scale-up and decentralization of HIV care and treatment programs, 2004 to 2010.

BACKGROUND: Efforts to scale-up HIV treatment in high burden countries have resulted in wider access to care, improved survival and decreased morbidity for HIV-infected children. The country of Rwanda has made significant achievements in expanding coverage of pediatric HIV services. METHODS: We describe the extent of and factors associated with mortality and lost to follow-up (LTF) in children (<15 years) enrolled in HIV care at 39 ICAP-supported facilities across Rwanda from 2004 to 2010 by antiretroviral treatment (ART) status. We estimated the 1-year cumulative incidence of death and LTF among all children enrolled in care (pre-ART) and children on ART. Survival analysis was used to evaluate factors associated with death and LTF in both groups. RESULTS: Between January 2004 and June 2010, 3244 children with a median age of 5.7 years (interquartile range 2.8-9.6) enrolled in HIV care. One-year cumulative incidence for death and LTF among pre-ART children was 4% (95% confidence interval [CI]: 3-5%) and 5% (95% CI: 4-6%), respectively. Overall, 2035 (63%) children initiated ART, median age 6.3 years (interquartile range 3.3-10.4): 1-year Kaplan-Meier estimates of death and LTF were 3% (95% CI: 3-4%) and 1% (95% CI: 1-2%), respectively. Factors associated with an increased hazard for death among pre-ART children included being <18 months old versus ≥5 years (adjusted sub hazard ratio [aSHR] = 4.4, 95% CI: 2.9-6.8) and World Health Organization stage IV versus I (aSHR = 4.1, 95% CI: 2.0-8.4), whereas children entering care through prevention of mother-to-child transmission had lower hazard than those from voluntary counseling and testing (aSHR = 0.50, 95% CI: 0.25-1.0). Markers of advanced disease, including severe immunosuppression (aSHR = 0.25, 95% CI: 0.12-0.54), and enrollment in care in rural versus urban clinics (aSHR = 0.71, 95% CI: 0.53-0.97) were protective against LTF. For children on ART, factors associated with hazard of death included younger age (adjusted hazard ratio [aHR] <18 months versus ≥5 years = 2.1, 95% CI: 1.3-3.6), severe malnutrition versus not malnourished (aHR = 3.2, 95% CI: 1.3-8.1), advanced World Health Organization stage (aHR IV versus I = 9.8, 95% CI: 3.5-27.4) and severe immunodeficiency versus no evidence (aHR = 2.3, 95% CI: 1.7-3.3). No associations were observed with LTF among children on ART. CONCLUSIONS: The results demonstrate very high retention among children enrolled in HIV care in Rwanda. Younger children continue to be particularly vulnerable, underscoring the urgent need for early identification, rapid treatment initiation and long-term retention in care.

Microfluidics-based diagnostics of infectious diseases in the developing world.

One of the great challenges in science and engineering today is to develop technologies to improve the health of people in the poorest regions of the world. Here we integrated new procedures for manufacturing, fluid handling and signal detection in microfluidics into a single, easy-to-use point-of-care (POC) assay that faithfully replicates all steps of ELISA, at a lower total material cost. We performed this 'mChip' assay in Rwanda on hundreds of locally collected human samples. The chip had excellent performance in the diagnosis of HIV using only 1 µl of unprocessed whole blood and an ability to simultaneously diagnose HIV and syphilis with sensitivities and specificities that rival those of reference benchtop assays. Unlike most current rapid tests, the mChip test does not require user interpretation of the signal. Overall, we demonstrate an integrated strategy for miniaturizing complex laboratory assays using microfluidics and nanoparticles to enable POC diagnostics and early detection of infectious diseases in remote settings.