Although industrialized countries have nearly eliminated new Human Immunodeficiency Virus (HIV) infections in children, new pediatric HIV infections and high HIV-related mortality continue in sub-Saharan Africa.1 In Malawi, one of the most severely affected countries, 12.7% of adults are HIV-infected and approximately 90,000 children are living with HIV.1,2 Since 2004, more than 270,000 Malawians have started antiretroviral therapy (ART), although access for HIV-infected children has been disproportionately lower.3–5 Starting in 2007, Malawi adopted policies to improve ART access for children, including routine HIV testing (provider-initiated opt-out HIV testing and counseling [PITC]),6 DNA polymerase chain reaction (PCR) testing for infant HIV diagnosis, and in late 2008, universal ART for HIV-infected infants less than 1 year of age.7
Although there is high pediatric HIV-related disease burden in African hospitals,8–10 most clinical interventions target outpatient HIV care. In 2007, the Baylor International Pediatric AIDS Initiative (BIPAI) began caring for hospitalized HIV-infected and HIV-exposed uninfected children, and in 2008, BIPAI implemented inpatient pediatric PITC (BIPAI-PITC) at Kamuzu Central Hospital (KCH) in Malawi.11 Program outcomes for this and similar initiatives established in-hospital PITC is acceptable, feasible, and has the potential to increase pediatric HIV care enrollment.11–13
However, the influence of inpatient PITC on access to pediatric HIV services remains unknown. Our objective was to assess whether BIPAI-PITC compared with nonroutine HIV testing (NRT) improves access to pediatric HIV care. We also analyzed outcomes of patients identified by inpatient HIV testing to help assess whether BIPAI-PITC and similar routine testing approaches merit wider implementation.
MATERIALS AND METHODS
KCH is a busy, urban referral facility with more than 13,000 pediatric admissions annually and an 8.5% inpatient pediatric HIV-infection prevalence.11 In 2005, 1 year after the introduction of NRT at KCH,14 BIPAI opened an outpatient HIV clinic, the Baylor College of Medicine-Abbott Fund Clinical Centre of Excellence (COE), that currently treats more than 5000 children.15
BIPAI-PITC has been described in detail11 and is compared with NRT in Figure 1. Briefly, BIPAI-PITC and NRT used the same number of HIV counselors and pediatric HIV-trained clinicians. BIPAI-PITC added 4 volunteer patient escorts and used a nonanonymous HIV testing register that included patient names and hospital bed locations to facilitate linkage between testing and care. Patient escorts were caregivers of HIV-infected children who displayed competent language skills. They coordinated patient flow and encouraged caregivers by sharing their own HIV experiences. Each escort received remuneration (2 USD per day) for food and transportation to work. During NRT, healthcare providers offered HIV testing based on the child's clinical presentation or physical examination findings, whereas during BIPAI-PITC, testing was routinely offered irrespective of these factors.11,14
To compare the 2 HIV testing strategies while minimizing selection bias from seasonal admission patterns, we analyzed data from all hospitalized children at KCH from September 1 to December 31, 2007 (NRT), and from September 1 to December 31, 2008 (BIPAI-PITC). The entire pediatric inpatient population was included in the initial analysis because neither the HIV status of every child nor the total number of children eligible to access HIV care was known. To assess the influence of the HIV testing models on in-hospital and 1-year patient outcomes, we further studied children who received BIPAI inpatient care but had not received HIV care before hospitalization (Fig. 2).
Children classified as HIV-infected were either DNA PCR-positive (if younger than 18 months of age), antibody-positive (if older than 18 months of age), or produced valid HIV-infected test results. HIV-exposed infants were either breast-feeding from their HIV-infected mother within 6 weeks of a negative DNA PCR test, or born to an HIV-infected mother but without a test result. Alternatively, their HIV-exposed status was known but they were ineligible for another DNA PCR due to a pending test. If an HIV-exposed infant tested DNA PCR-positive during hospitalization, the child's status was reclassified as HIV infected. In addition, if the inpatient DNA PCR result was negative and they had last breast-fed outside the 6-week window period, then the patient was re-identified as HIV-uninfected and excluded from the outcomes analysis. Only the first hospitalization was analyzed for patients admitted more than once during the study period, irrespective of the child's HIV-status.
Two BIPAI clinicians reviewed inpatients on a daily basis, assigning a World Health Organization (WHO) clinical stage to each HIV-infected child and WHO Integrated Management of Childhood Illness-based diagnoses to every child upon hospital discharge.16 Because this study took place at a resource-limited hospital, laboratory tests were inconsistently available for most conditions. At the time of hospital discharge, BIPAI clinicians offered HIV-infected and HIV-exposed patients referral to the COE clinic. Patient outcomes were re-evaluated 1 year after hospital discharge, and patients who did not return to the COE clinic for 3 months were considered lost to follow-up. One-year outcome data were obtained for subjects who attended the COE clinic after hospital discharge.
Continuous, normally distributed variables were described by mean and standard deviation, and compared by student's t test. Non-normally distributed continuous variables were described with median and interquartile range, and compared by Mann-Whitney U test. Categorical variables were analyzed using Pearson χ2 test, and when more than 2 variable categories were present, a significant global test (alpha = 0.05) was followed by post hoc pairwise χ2 tests, using Bonferroni correction to adjust alpha for multiple variable levels. A comparison was considered significant only when the P value was smaller than the corrected alpha. All analyses were performed using SPSS software (version 17.0, SPSS Inc, Chicago, IL).
The Malawi National Health Sciences Research Committee and Baylor College of Medicine Institutional Review Board approved this study. Nationally certified HIV counselors obtained verbal consent for HIV testing from caregivers according to national guidelines.17 Consent was waived for study participation because data were collected retrospectively from existing patient medical files.
Children admitted to the pediatric ward during both periods of study were similar with respect to age and gender. Sepsis, gastroenteritis, and severe anemia were more frequently diagnosed in all children hospitalized during BIPAI-PITC (P < 0.001), irrespective of HIV status, whereas malaria comprised the most common diagnosis in either group (Table 1). There was a trend toward increased mortality in all patients admitted to KCH during BIPAI-PITC (P = 0.080).
During BIPAI-PITC, 2693 hospitalized children accepted HIV counseling and were either HIV tested or produced valid HIV test results, representing 81% of all admissions, an increase from the 33.3% of hospital admissions that accepted HIV counseling with NRT (P < 0.001, Table 2). No differences were found with respect to age, gender, WHO clinical stage, CD4-positive cell count percentage, in-hospital mortality, COE clinic enrollment, or ART initiation between the 2 identified HIV-infected cohorts (Table 3). In the BIPAI-PITC cohort, severe acute malnutrition was only half as prevalent as in the NRT cohort (24.2% vs. 43.1%, P = 0.005), whereas sepsis (40.3% vs. 23.1%, P = 0.015) and malaria (24.2% vs. 12.3%, P = 0.048) were nearly twice as prevalent. Although a smaller proportion of hospitalized HIV-exposed infants was diagnosed with bacterial meningitis during BIPAI-PITC (2.0% vs. 13.0%, P = 0.045), there were no differences with respect to other baseline characteristics or clinical outcomes (Table 4).
HIV-infected African children continue to be denied ART due to inadequate and inaccessible HIV services. Our results show that with a relatively modest investment of resources, BIPAI-PITC not only increased HIV testing rates, but also increased access to inpatient pediatric HIV clinicians, outpatient pediatric HIV care, DNA PCR, and ART. Furthermore, increasing access to inpatient and outpatient pediatric HIV care for hospitalized HIV-exposed infants during BIPAI-PITC is particularly important in this era of new prevention of mother-to-child transmission strategies such as extended postnatal antiretroviral prophylaxis during breast-feeding.18–22
BIPAI-PITC, compared with NRT, better used skilled healthcare personnel in a setting with inadequate number of healthcare providers. During BIPAI-PITC, the total number of HIV-infected and HIV-exposed patients identified by inpatient HIV testing increased by 163, and those receiving inpatient and outpatient pediatric HIV care increased by 161 and 58, respectively, compared with NRT. These results were achieved with the same staffing levels of HIV counselors and pediatric HIV-trained clinicians, aided by 4 unskilled volunteer patient escorts during BIPAI-PITC.
Given that early ART reduces disease progression and reduces mortality among HIV-infected children,23–27 the higher proportion of hospitalized children accessing ART during BIPAI-PITC achieved a key program objective. Along with the incorporation of recently revised WHO guidelines that expand ART eligibility for children,28 wider implementation of similar inpatient PITC strategies could narrow the gap between children in need of ART and prevention of mother-to-child transmission and those who have access to it.
BIPAI-PITC also identified HIV-infected patients with a different set of clinical presentations. In particular, HIV-infected children during BIPAI-PITC had a higher proportion of malaria and a lower proportion of severe acute malnutrition, despite these diagnoses being equally represented in both periods at KCH. These data suggest that NRT misses many HIV-infected children hospitalized with malaria. One explanation is that these patients may lack the physical stigmata typical of HIV infection, including marasmus. A nonroutine HIV testing system that relies solely on clinical judgment to refer patients for HIV testing is therefore more likely to miss HIV-infected patients with nonspecific febrile syndromes.
However, BIPAI-PITC fell short of its ART potential. More than 85% of all identified HIV-infected patients were ART-eligible during hospitalization, but none were started on ART in the hospital, and only half of those enrolling in outpatient care initiated ART within 1 year of hospital discharge. Furthermore, although BIPAI-PITC improved DNA PCR access, >70% of ART-eligible HIV-infected infants less than 18 months of age who followed up at the COE clinic failed to start ART within 1 year of enrollment despite the broadening of ART eligibility guidelines during BIPAI-PITC. Routine in-hospital ART initiation for eligible children is one potential means of addressing these shortcomings, but the feasibility of this strategy needs further evaluation.
Additionally, we observed high in-hospital and outpatient mortality in the HIV-infected and HIV-exposed cohorts regardless of the testing approach, confirming reports from comparable settings.8–10 This high mortality could reflect the severity of disease observed in HIV-infected children at the time of testing. Specifically, children in both cohorts presented with advanced WHO clinical stages, low mean CD4-positive cell count percentages, severe acute malnutrition, severe forms of pneumonia, and sepsis, all of which are highly predictive of in-hospital mortality in HIV-infected and HIV-exposed children (Preidis GA, McCollum ED et al, unpublished data). Case management guidelines of HIV-infected children with these diagnoses, while based upon the best available evidence, are in need of further examination to refine best practices in resource-limited inpatient and outpatient settings.29–31
Although BIPAI-PITC increased access to pediatric HIV care for all hospitalized children, we did not find that a higher proportion of identified HIV-infected and HIV-exposed patients received in-hospital or outpatient HIV care during BIPAI PITC, compared with NRT. These observations highlight the challenges associated with resource-limited health systems, rather than inefficiencies of access to care specific to BIPAI-PITC, for 2 reasons. First, BIPAI inpatient clinicians nearly tripled their workload to meet the greater inpatient clinical demands of BIPAI-PITC but were still unable to review every hospitalized patient. While training additional KCH clinicians in HIV could further increase the proportion of HIV-infected patients receiving in-hospital HIV care, high government-mandated training fees along with poor retention of hospital staff would have inflated program costs beyond what was available at KCH. Second, the high outpatient attrition rate during BIPAI-PITC, while similar to NRT and other reports,32–34 suggests that the hospital's current strategy to reduce the number of patients lost-to-follow-up, which uses vehicles to visit defaulted patients, needs re-evaluation. For instance, mechanisms of tracking defaulted patients could be made more successful and less costly with greater utilization of community volunteers or mobile phone technology.35
There are limitations to this study. Evaluating overall access to pediatric HIV care with the general pediatric inpatient population as a common denominator is limited by the inclusion of HIV-uninfected children. However, this cohort was the most appropriate to assess HIV care access, given that each testing period includes comparable proportions of unidentified HIV-infected patients, based upon stable national HIV prevalence data.36 Undiagnosed HIV-infected children were also likely to distort the in-hospital outcomes of the HIV-exposed group, given that 37% of HIV-exposed uninfected children did not have a negative inpatient DNA PCR test result to confirm their current hospital HIV status (data not shown). Although a potential confounder, this situation accurately reflects the typical clinical environment encountered by healthcare providers working in government facilities in resource-constrained countries.
In summary, we found that transitioning from NRT to BIPAI-PITC led to improvements in hospitalized children's access to HIV testing, DNA PCR, inpatient and outpatient pediatric HIV care, and ART, without increasing the number of HIV counselors or pediatric HIV-trained clinicians. Where resources allow, even greater improvements in access to pediatric HIV care may be realized by increasing the number of HIV-trained clinicians and using improved defaulter-tracking methods. Therefore, the expansion of BIPAI-PITC or similar systems of inpatient PITC would improve utilization of global pediatric HIV services.
The authors would like to thank the children and caregivers whom we serve at the Pediatric Department of Kamuzu Central Hospital and the Baylor College of Medicine-Abbott Fund Children's Clinical Centre of Excellence, as well as acknowledge the following individuals for their important contributions to this work: Ms. Charity Kanga, Mr. Andrea Tembo, Ms. Effie Phanga, Mr. Paul Kalionde, Ms. Gertrude Chaponda, Ms. Lonely Kalinde, Mr. Gift Chidathawa, Ms. Christina Ngozo, Ms. Gladys Mwenechanya, Ms. Lennie Nkhata, Mark M. Kabue, PhD, Mr. Emmanuel B. M. Singogo, the Baylor International Pediatric AIDS Initiative Pediatric AIDS Corps physicians, the Baylor College of Medicine-Abbott Fund Children's Clinical Centre of Excellence clinical and administrative staff, and the healthcare providers and administration at Kamuzu Central Hospital.
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