Chloe A. Teasdale

Scale-up of HIV Treatment Through PEPFAR: A Historic Public Health Achievement

Abstract: Since its inception in 2003, the US Presidents Emergency Plan for AIDS Relief (PEPFAR) has been an important driving force behind the global scale-up of HIV care and treatment services, particularly in expansion of access to antiretroviral therapy. Despite initial concerns about cost and feasibility, PEPFAR overcame challenges by leveraging and coordinating with other funders, by working in partnership with the most affected countries, by supporting local ownership, by using a public health approach, by supporting task-shifting strategies, and by paying attention to health systems strengthening. As of September 2011, PEPFAR directly supported initiation of antiretroviral therapy for 3.9 million people and provided care and support for nearly 13 million people. Benefits in terms of prevention of morbidity and mortality have been reaped by those receiving the services, with evidence of societal benefits beyond the anticipated clinical benefits. However, much remains to be accomplished to achieve universal access, to enhance the quality of programs, to ensure retention of patients in care, and to continue to strengthen health systems.

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.

Characteristics and outcomes of HIV-infected youth and young adolescents enrolled in HIV care in Kenya.

Background:The number of youth and adolescents (10–24 years) with HIV infection has increased substantially presenting unique challenges to effective health service delivery. Methods:We examined routinely collected patient-level data for antiretroviral treatment (ART)-naive HIV-infected patients, aged 10–24 years, enrolled in care during 2006–2011 at 109 ICAP-supported health facilities in three provinces in Kenya. Loss to follow-up (LTF) was defined as having no clinic visit for 12 months prior to ART initiation (pre-ART) and 6 months for ART patients. Competing risk and Kaplan–Meier estimators were used to calculate LTF and death rates. Sub-distributional and Cox proportional-hazards models were used to identify potential predictors of death and LTF. Results:Overall 22 832 patients were enrolled in care at 10–24 years of age, 69.5% were aged 20–24 years, and 82% were female. Median CD4+ cell count was 332 cells/&mgr;l (interquartile range 153–561); 70.8% were WHO stage I/II. Young adolescents (10–14 years) had more advanced WHO stage and lower median CD4+ cell count compared to youth (15–24 years) at enrollment (284 vs. 340 cells/&mgr;l; P < 0.0001). Cumulative incidence of LTF and death at 24 months for pre-ART patients was 46.1% [95% confidence interval (CI) 45.4–46.8%) and 2.1% (95% CI 1.9–2.3%), respectively. For those on ART, 32.2% (95% CI 31.1–33.3%) were LTF and 3.9% (95% CI 1.7–2.3%) died within 24 months. LTF among pre-ART and ART patients was twice as high among youth compared to young adolescents. Conclusion:LTF of young people with HIV in this Kenyan cohort was high and notably greater among youth compared to young adolescents. Novel strategies targeting these populations are urgently needed to improve retention.

Mother and child both matter: reconceptualizing the prevention of mother-to-child transmission care continuum.

Purpose of reviewTo propose a prevention of mother-to-child transmission (PMTCT) care continuum that defines the programmatic steps necessary to provide HIV care to the HIV-infected pregnant woman and her infant during the risk period for HIV transmission. Recent findingsThere are several complexities of PMTCT care that should be considered in the care continuum, including the evolution in the population of women entering PMTCT care, various models of PMTCT service delivery and patterns of PMTCT care, and the critical step of transfer of womens HIV care from PMTCT programs to adult HIV clinics. SummaryWe propose a reconceptualized PMTCT care continuum that accounts for the complexities of PMTCT care. We also propose a combined outcome for pregnant women and their infants across an interlinked PMTCT continuum to measure both maternal and child health outcomes.

PEPFAR scale-up of pediatric HIV services: Innovations, achievements, and challenges

Abstract: HIV/AIDS has had a profound impact on children around the world since the start of the epidemic. There are currently 3.4 million children under the age of 15 years living with HIV globally, and more than 450,000 children currently receiving lifesaving antiretroviral treatment. This article describes efforts supported by the Presidents Emergency Plan for AIDS Relief (PEPFAR) to expand access to treatment for children living with HIV in high-burden countries. The article also highlights a series of case studies that illustrate the impact that the PEPFAR initiative has had on the pediatric HIV epidemic. Through its support of host governments and partner organizations, the PEPFAR initiative has expanded HIV testing and treatment for pregnant women to reduce vertical transmission of HIV, increased access to early infant diagnosis for HIV-exposed infants, improved training and resources for clinicians who provide pediatric care and antiretroviral treatment, and, through public–private partnerships with pharmaceutical manufacturers, helped increase the number of medications available for the treatment of HIV-infected children in resource-limited settings.

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.

Impact of Youth and Adolescent Friendly Services on Retention of 10-24-Year-Olds in HIV Care and Treatment Programs in Nyanza, Kenya.

To the Editors:There are an estimated 2.9 million 10–24-year-olds living with HIV in sub-Saharan Africa,1 and these numbers are expected to increase with improved survival among perinatally infected children and as a result of new behaviorally acquired infections among older adolescents and youth.2

Adherence and Viral Suppression among Infants and Young Children Initiating Protease Inhibitor-Based Antiretroviral Therapy

Background: High levels of adherence to antiretroviral therapy are considered necessary to achieve viral suppression. We analyzed data from a cohort of HIV-infected children who were <2 years of age receiving protease inhibitor–based antiretroviral therapy to investigate associations between viral suppression and adherence ascertained using different methods. Methods: Data were from the prerandomization phase of a clinical trial in South Africa of HIV-infected children initiating either ritonavir-boosted lopinavir (LPV/r) or ritonavir-based antiretroviral therapy. At scheduled visits during the first 24 weeks of enrollment, study pharmacists measured quantities of medications returned to the clinic. Caregivers answered questionnaires on missed doses and adherence barriers. Associations between adherence and viral suppression (HIV-1 RNA <400 copies/mL) were investigated by regimen. Results: By 24 weeks, 197 of the 269 (73%) children achieved viral suppression. There was no association between viral suppression and caregiver reported missed doses or adherence barriers. For children receiving the LPV/r-based regimen, medication return adherence to each of the 3 drugs in the regimen (LPV/r, lamivudine or stavudine) individually or together was associated with viral suppression at different adherence thresholds. For example, <85% adherence to any of the 3 medications significantly increased odds of lack of viral suppression (odds ratio: 2.30, 95% confidence interval: 1.30–4.07, P = 0.004). In contrast, for children receiving the ritonavir-based regimen, there was no consistent pattern of association between medication return and viral suppression. Conclusions: Caregiver reports of missed doses did not predict virologic response to treatment. Pharmacist medication reconciliation correlated strongly with virologic response for children taking a LPV/r-based regimen and appears to be a valid method for measuring pediatric adherence.

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.

Outcomes Among Children Enrolled in Hiv Care in Mozambique 2009–2013

Background: Scale-up of HIV care and antiretroviral therapy (ART) services for children has expanded access, but significant gaps and challenges remain. We examined lost to follow-up (LTF) and mortality in a large cohort of children enrolled in HIV care in Mozambique. Methods: Routinely collected medical data on children 0–14 years enrolled in care 2009–2013 at ICAP-supported health facilities in 5 provinces of Mozambique were used. Children not receiving ART (pre-ART) were considered LTF if they did not a have a visit within 12 months of the end of data collection; for those receiving ART, LTF was no visit within 6 months. Competing risk and Kaplan-Meier estimators were used, respectively, to estimate pre-ART and on ART LTF and mortality. Results: A total of 13,695 children enrolled in HIV care at 64 health facilities (48.6%, <2 years), and 7733 (56.5%) initiated ART during follow-up. Cumulative incidence of pre-ART LTF was 32.9% [95% confidence interval (CI): 32.1–33.7] and 34.4% (95% CI: 33.6–35.2) by 12 and 24 months, respectively, and was highest in children <5 years (12-month LTF in children 2–4 years, 34.2%, 95% CI: 32.6–35.9). Pre-ART mortality at 12 months was 3.3% (95% CI: 3.0–3.6) and was highest in children <2 years (4.1%, 95% CI: 3.6–4.6). On ART, LTF was 28.6% (95% CI: 27.6–29.7) and 37.6 (95% CI: 36.4–38.8) at 12 and 24 months, and 12 months mortality after ART was 8.0% (95% CI: 7.3–8.7). Conclusions: High rates of LTF were observed in this large cohort of HIV-infected children accessing care in Mozambique both before and after ART initiation highlighting the urgent need for interventions to improve retention in routine care settings.