Caring for perinatally HIV-infected children: call for mental care for the children and the caregivers.

Antiretroviral therapy has dramatically improved the survival rate of perinatally HIV-infected children. For them to thrive, it is necessary to understand better their mental health issues. Caregivers play an important role in children's daily care and caregiver mental health may relate to children's mental health. However, this association has rarely been studied. Accordingly, the present study examined the associations between depression of caregivers and that of perinatally HIV-infected children in Kigali, Rwanda. We conducted a cross-sectional study of 475 perinatally HIV-infected children aged 7-14 years and their caregivers. We collected children's depression score data via face-to-face interviews with children using the Beck Depression Inventory for Youth. We also collected sociodemographic data using a semi-structured questionnaire with caregivers. In addition, we measured children's weight, height, and collected their clinical records. Data were analyzed via linear and logistic regression analyses. Of all children, 22% had symptoms of depression. Among those who had depressive symptoms (n= 105), 49% had never received psychological support. In both the linear and logistic regression analysis, caregiver's high depression scores were positively associated with children's higher depression scores (AOR: 3.064, 95% CI: 1.723, 4.855, and AOR: 1.759, 95% CI: 1.129, 2.740, respectively). Taking Efavirenz and low height-for-age were also positively associated with higher depression scores among HIV-infected children. Mental health needs to be addressed to improve quality of life of perinatally HIV-infected children. Caregiver's depression was positively associated with children's depressive symptoms. Caring for both children and the caregivers' mental health may prevent the mutual fostering of depression.

A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans.

Background. Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy. Methods. We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%. Results. Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, -7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm. Conclusions. A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.

HIV drug resistance mutations among patients failing second-line antiretroviral therapy in Rwanda.

BACKGROUND: Studies of patients failing second-line antiretroviral therapy (ART) in resource-limited settings (RLS) are few. Evidence suggests most patients who appear to be virologically failing do so not due to drug resistance but to poor adherence, which, if properly addressed, could allow continued use of less expensive first- and second-line regimens. Drug resistant mutations (DRMs) were characterized among patients virologically failing second-line ART in Rwanda. METHODS: A total of 128 adult patients receiving second-line ART for at least 6 months were invited to participate; 74 agreed and had HIV-1 viral load (VL) measured. Resistance genotypes were conducted in patients with virological failure (VF; that is, VL ≥1,000 copies/ml). RESULTS: In total, 35 patients met the criteria for VF. The median time on lopinavir/ritonavir-based second-line ART was 2.7 years. Of 30 successful resistance genotype analyses, 13 (43%) had ≥1 nucleoside reverse transcriptase inhibitor (NRTI) mutation, 18 (60%) had at least 1 non-NRTI mutation and 5 (17%) had at least 1 major protease inhibitor mutation. Eleven (37%) had virus without significant mutations that would be fully sensitive to first-line ART; 12 (40%) had DRM to first-line ART but sensitive to second-line ART. Only 7 patients (23%) demonstrated a DRM profile requiring third-line ART. CONCLUSIONS: Among 30 genotyped samples of patients with VF on second-line ART, more than one-third had no significant DRMs, implicating poor adherence as the primary cause of VF. The majority of patients (77%) would not have required third-line ART. These findings reinforce the need for intensive adherence assessment and counselling for patients who appear to be failing second-line ART in RLS.

What makes orphans in Kigali, Rwanda, non-adherent to antiretroviral therapy? Perspectives of their caregivers.

INTRODUCTION: Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. METHODS: We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. RESULTS: The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans' caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. CONCLUSIONS: Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children.

Scaling up intensified tuberculosis case finding in HIV clinics in Rwanda.

BACKGROUND: Tuberculosis (TB) is the leading cause of morbidity and mortality among people living with HIV (PLHIV) in sub-Saharan Africa. Early TB detection and treatment is key to saving lives of PLHIV. Rwanda began implementing intensified TB case finding (ICF) in 2005 in line with World Health Organization policy on TB/HIV collaborative activities. We aimed to describe trends of ICF in PLHIV newly enrolled into HIV clinics. METHODS: We used routinely collected program data on ICF from facility-based pre-antiretroviral therapy/antiretroviral therapy registers in Rwandan HIV clinics from 2006 to 2011. Semiannual, active data collection for PLHIV newly enrolled into HIV care included proportion screened for TB, proportion screened positive, and percentage with active TB and started anti-TB drugs. RESULTS: The number of health facilities reporting TB screening indicators increased 16-fold, from 20 facilities in the first semester of 2006 to 328 facilities by the end of 2011. The proportion of patients screened increased progressively from 77% of newly enrolled patients in first semester of 2006 to 94% at the end of 2011 (P < 0.001). The proportion of patients who screened positive decreased over time, from 23% in the first semester of 2006 to 10% at the end of 2011 (P < 0.001). The proportion of active TB cases remained relatively constant over time at 2.2%. CONCLUSIONS: Rwanda has increased the proportion of newly enrolled PLHIV screened for TB using a simple screening protocol. Countries with limited resources but high HIV and TB disease prevalence should implement ICF as part of their integrated HIV-TB treatment programs.

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.

High risk of ART non-adherence and delay of ART initiation among HIV positive double orphans in Kigali, Rwanda.

BACKGROUND: To reduce HIV/AIDS related mortality of children, adherence to antiretroviral treatment (ART) is critical in the treatment of HIV positive children. However, little is known about the association between ART adherence and different orphan status. The aims of this study were to assess the ART adherence and identify whether different orphan status was associated with the child's adherence. METHODS: A total of 717 HIV positive children and the same number of caregivers participated in this cross-sectional study. Children's adherence rate was measured using a pill count method and those who took 85% or more of the prescribed doses were defined as adherent. To collect data about adherence related factors, we also interviewed caregivers using a structured questionnaire. RESULTS: Of all children (N = 717), participants from each orphan category (double orphan, maternal orphan, paternal orphan, non-orphan) were 346, 89, 169, and 113, respectively. ART non-adherence rate of each orphan category was 59.3%, 44.9%, 46.7%, and 49.7%, respectively. The multivariate analysis indicated that maternal orphans (AOR 0.31, 95% CI 0.12-0.80), paternal orphans (AOR 0.35, 95% CI 0.14-0.89), and non-orphans (AOR 0.45, 95% CI 0.21-0.99) were less likely to be non-adherent compared to double orphans. Double orphans who had a sibling as a caregiver were more likely to be non-adherent. The first mean CD4 count prior to initiating treatment was 520, 601, 599, and 844 (cells/ml), respectively (p<0.001). Their mean age at sero-status detection was 5.9, 5.3, 4.8, and 3.9 (year old), respectively (p<0.001). CONCLUSIONS: Double orphans were at highest risk of ART non-adherence and especially those who had a sibling as a caregiver had high risk. They were also in danger of initiating ART at an older age and at a later stage of HIV/AIDS compared with other orphan categories. Double orphans need more attention to the promote child's adherence to ART.

Cell phone-based and internet-based monitoring and evaluation of the National Antiretroviral Treatment Program during rapid scale-up in Rwanda: TRACnet, 2004-2010.

BACKGROUND: Monitoring and evaluation of antiretroviral treatment (ART) scale-up has been challenging in resource-limited settings. We describe an innovative cell-phone-based and internet-based reporting system (TRACnet) utilized in Rwanda. METHODS: From January 2004 to June 30, 2010, all health facilities with ART services submitted standardized monthly aggregate reports of key indicators. National cohort data were analyzed to examine trends in characteristics of patients initiating ART and cumulative cohort outcomes. Estimates of HIV-infected patients eligible for ART were obtained from Joint United Nations Program on HIV/AIDS (Estimation and Projection Package-Spectrum, 2010). RESULTS: By June 30, 2010, 295 (65%) of 451 health centers, District and referral hospitals provided ART services; of these, 255 (86%) were located outside Kigali, the capital. Cell phone-based and internet-based reporting was used by 253 (86%) and 42 (14%), respectively. As of June 30, 2010, 83,041 patients were alive on ART, 6171 (6%) had died, and 9621 (10%) were lost-to-follow-up. Of those alive on ART, 7111 (8.6%) were children, 50,971 (61.4%) were female, and 1823 (2.2%) were on a second-line regimen. The proportion of all patients initiating ART at World Health Organization clinical stages 3 and 4 declined from 65% in 2005 to 27% in 2010. National ART coverage of eligible patients increased from 13% in 2005 to 79% in 2010. CONCLUSIONS: Rwanda has successfully expanded ART access and achieved high national ART coverage among eligible patients. TRACnet captured essential data about the ART program during rapid scale-up. Cell phone-based and internet-based reporting may be useful for monitoring and evaluation of similar public health initiatives in other resource-limited settings.