Ruben Sahabo

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

BackgroundMother-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.MethodsProgram 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, enrolment 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.ResultsFrom 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). Enrolment 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).ConclusionsAll 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 enrolment into care and treatment of HIV+ pregnant women. Strengthening the capacity of stand-alone PMTCT sites to achieve the same objectives is paramount.

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.

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.

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.

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.

Transitioning to Country Ownership of HIV Programs in Rwanda

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

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.

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.

Tuberculosis in Rwanda: challenges to reaching the targets.

Rwanda has a generalized HIV epidemic: 3.1% of adults are living with HIV/AIDS.1 Care, treatment and prevention services for the approximately 183 558 adults and 13 901 children living with HIV/AIDS have been rapidly scaled up over the past three years under the guidance of the Rwandan Ministry of Health’s Treatment Research for AIDS Center. By November 2006, almost 33 000 HIV-infected adults and children were receiving antiretroviral therapy.2 Expansion and enhancement of DOTS in the six-point Stop TB Strategy described by Laserson & Wells have been implemented in Rwanda by the health ministry’s national integrated programme to combat leprosy and TB since 1990. Through recent programme improvements, treatment success rates have increased from 58% in 2003 to 81% by the third quarter of 2006; however, case detection was an estimated 24% in 2005.3–5 Thus, Rwanda is close to achieving the WHO target for treatment success, but is below the target for case detection. Concerted efforts are being made to ensure that effective smear microscopy and directly-observed therapy are available nationwide. Further efforts are needed to reach the goals, especially for case detection. A recent national survey showing that the prevalence of multidrug resistance among new TB patients is 3.9% gives cause for concern.6

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.