Treatment outcomes among children younger than five years living with HIV in rural Zambia, 2008-2018: a cohort study.

BACKGROUND: HIV testing and treatment guidelines for children in sub-Saharan Africa have evolved over time, such that children are now treated at younger ages. The objective of this study was to describe the treatment experience for immunologic, virologic, and growth outcomes among HIV-infected Zambian children younger than 5 years of age from 2008 to 2018. METHODS: Participants enrolled in a clinical cohort study in Macha, Zambia and initiating antiretroviral treatment before 5 years of age between 2008 and 2015 were included in the analysis and followed up to the end of 2018. Outcomes, including growth, CD4+ T-cell percentage, viral suppression, and mortality, were evaluated among all children using longitudinal and survival analyses. Comparisons by age at treatment initiation (< 1, 1 to < 2, and 2 to < 5 years) were also evaluated. RESULTS: Three hundred eighty-one children initiating treatment before 5 years of age between 2008 and 2015 were included in the analysis. Growth metrics and CD4+ T-cell percentage improved over time after treatment initiation. However, 20% of children remained underweight and 40% of children remained stunted after the first 36 months of treatment. 85% of children had a viral load < 400 copies/mL after 12 months of treatment. However, children < 1 year at treatment initiation were more likely to have a detectable viral load in the first 12 months of treatment and less likely to achieve viral suppression compared to older children. Mortality was highest in the first 12 months of treatment, among underweight children, and among children initiating treatment in 2008-2010 compared to 2011-2015. CONCLUSIONS: Most children initiating antiretroviral treatment from 2008 to 2015 in rural Zambia responded well to treatment. However, many children remained underweight and stunted, and experienced high mortality rates during the first few months of treatment. This supports continued efforts to improve early infant diagnosis, nutritional support, and pediatric drug formulations.

Food and water insecurity in households of children and adolescents living with HIV and receiving care in a rural Zambian hospital: A mixed-methods study.

Approximately 62,000 Zambian children are living with HIV. HIV care and treatment is generally more limited in rural areas, where a heavy reliance on rain-fed subsistence agriculture also places households at risk of food and water insecurity. We nested a mixed methods study with an explanatory sequential design in a clinical cohort of children and adolescents living with HIV (CHIV) in rural Zambia. We used validated questionnaires to assess household food and water insecurity and examined associations between indicators derived from those scales, household characteristics, and HIV treatment adherence and outcomes using log-binomial regression. We identified caregivers and older CHIV from food insecure households for in-depth interviews. Of 186 participants completing assessments, 72% lived in moderately or severely food insecure households and 2% in water insecure households. Food insecurity was more prevalent in households of lower socioeconomic status (80% vs. 59% for higher scores; p = 0.02) and where caregivers had completed primary (79%) vs. secondary school or higher (62%; p = 0.01). No other characteristics or outcomes were associated with food insecurity. Parents limited both the quality and quantity of foods they consumed to ensure food availability for their CHIV. Coping strategies included taking on piecework or gathering wild foods; livestock ownership was a potential buffer. Accessing sufficient clean water was less of a concern. During periods of drought or service interruption, participants travelled further for drinking water and accessed water for other purposes from alternative sources or reduced water use. Community contributions afforded some protection against service interruptions. Overall, while food insecurity was prevalent, strategies used by parents may have protected children from a measurable impact on HIV care or treatment outcomes. Reinforcing social protection programs by integrating livestock ownership and strengthening water infrastructure may further protect CHIV in the case of more extreme food or water system shocks.

The Evolving Pediatric HIV Epidemic in Rural Southern Zambia: The Beneficial Impact of Advances in Prevention and Treatment at a District Hospital From 2007 to 2019.

BACKGROUND: Remarkable progress has been made in expanding access to services addressing the pediatric HIV epidemic, including programs to prevent mother-to-child transmission, early diagnosis and treatment for children living with HIV. Few long-term data are available from rural sub-Saharan Africa to assess implementation and impact of national guidelines. METHODS: Results from 3 cross-sectional studies and 1 cohort study conducted at Macha Hospital in Southern Province, Zambia from 2007 to 2019 were summarized. For infant diagnosis, maternal antiretroviral treatment, infant test results and turnaround times for results were evaluated by year. For pediatric HIV care, the number and age of children initiating care and treatment, and treatment outcomes within 12 months were evaluated by year. RESULTS: Receipt of maternal combination antiretroviral treatment increased from 51.6% in 2010-2012 to 93.4% in 2019, and the proportion of infants testing positive decreased from 12.4% to 4.0%. Turnaround times for results returning to clinic varied but were shorter when labs consistently used a text messaging system. The proportion of mothers receiving results was higher when a text message intervention was piloted. The number of children living with HIV enrolled into care and the proportion initiating treatment with severe immunosuppression and dying within 12 months decreased over time. CONCLUSIONS: These studies demonstrate the long-term beneficial impact of implementing a strong HIV prevention and treatment program. While expansion and decentralization brought challenges, the program succeeded in decreasing the rate of mother-to-child transmission and ensuring that children living with HIV benefit from access to life-saving treatment.

Weight and height z-scores improve after initiating ART among HIV-infected children in rural Zambia: a cohort study.

BACKGROUND: Deficits in growth observed in HIV-infected children in resource-poor settings can be reversed with antiretroviral treatment (ART). However, many of the studies have been conducted in urban areas with older pediatric populations. This study was undertaken to evaluate growth patterns after ART initiation in a young pediatric population in rural Zambia with a high prevalence of undernutrition. METHODS: Between 2007 and 2009, 193 HIV-infected children were enrolled in a cohort study in Macha, Zambia. Children were evaluated every 3 months, at which time a questionnaire was administered, height and weight were measured, and blood specimens were collected. Weight- and height-for-age z-scores were constructed from WHO growth standards. All children receiving ART at enrollment or initiating ART during the study were included in this analysis. Linear mixed effects models were used to model trajectories of weight and height-for-age z-scores. RESULTS: A high proportion of study children were underweight (59%) and stunted (72%) at treatment initiation. Improvements in both weight- and height-for-age z-scores were observed, with weight-for-age z-scores increasing during the first 6 months of treatment and then stabilizing, and height-for-age z-scores increasing consistently over time. Trajectories of weight-for-age z-scores differed by underweight status at treatment initiation, with children who were underweight experiencing greater increases in z-scores in the first 6 months of treatment. Trajectories of height-for-age z-scores differed by age, with children older than 5 years of age experiencing smaller increases over time. CONCLUSIONS: Some of the effects of HIV on growth were reversed with ART initiation, although a high proportion of children remained underweight and stunted after two years of treatment. Partnerships between treatment and nutrition programs should be explored so that HIV-infected children can receive optimal nutritional support.

Timing of and factors associated with HIV disclosure among perinatally infected children in rural Zambia.

OBJECTIVE: This study was conducted to understand the process of disclosure among HIV-infected children receiving care in rural Zambia. DESIGN: Cross-sectional and longitudinal analyses were conducted within an ongoing clinical cohort study of HIV-infected children receiving care in Macha, Zambia from 2007 to 2016. METHODS: Children receiving HIV care were enrolled into the cohort study and assessed every 3 months. At each study visit, disclosure status was ascertained through questionnaire. Disclosure was categorized as none (child did not know they were chronically ill), partial (child knew they were chronically ill but not of their HIV infection status), or full (child knew they had HIV infection). Barriers to disclosure, and the timing of and factors associated with disclosure, were evaluated among children 5-15 years of age. RESULTS: At study entry, the prevalence of full disclosure increased with age, from 2.1 to 76.2% among children 5-6 and 13-15 years of age, respectively. Reasons provided by caregivers for not disclosing the child's status included they felt the child was too young, they were afraid to, or they did not know how to tell the child. During follow-up, the median age at full disclosure was 9.0 years. Among children with full disclosure, 89.5% first had partial disclosure at a median age of 7.4 years. Factors associated with disclosure included being female, sharing responsibility for taking their own medication, and low weight-for-age z-score. CONCLUSION: Given the complexity of the disclosure process and potential for health benefits, interventions and protocols are needed to support caregivers through the disclosure process.

Barriers to the care of HIV-infected children in rural Zambia: a cross-sectional analysis.

BACKGROUND: Successful antiretroviral treatment programs in rural sub-Saharan Africa may face different challenges than programs in urban areas. The objective of this study was to identify patient characteristics, barriers to care, and treatment responses of HIV-infected children seeking care in rural Zambia. METHODS: Cross-sectional analysis of HIV-infected children seeking care at Macha Hospital in rural southern Zambia. Information was collected from caretakers and medical records. RESULTS: 192 HIV-infected children were enrolled from September 2007 through September 2008, 28% of whom were receiving antiretroviral therapy (ART) at enrollment. The median age was 3.3 years for children not receiving ART (IQR 1.8, 6.7) and 4.5 years for children receiving ART (IQR 2.7, 8.6). 91% travelled more than one hour to the clinic and 26% travelled more than 5 hours. Most participants (73%) reported difficulties accessing the clinic, including insufficient money (60%), lack of transportation (54%) and roads in poor condition (32%). The 54 children who were receiving ART at study enrollment had been on ART a median of 8.6 months (IQR: 2.7, 19.5). The median percentage of CD4+ T cells was 12.4 (IQR: 9.2, 18.6) at the start of ART, and increased to 28.6 (IQR: 23.5, 36.1) at the initial study visit. However, the proportion of children who were underweight decreased only slightly, from 70% at initiation of ART to 61% at the initial study visit. CONCLUSION: HIV-infected children in rural southern Zambia have long travel times to access care and may have poorer weight gain on ART than children in urban areas. Despite these barriers, these children had a substantial rise in CD4+ T cell counts in the first year of ART although longer follow-up may indicate these gains are not sustained.

Turnaround time for early infant HIV diagnosis in rural Zambia: a chart review.

BACKGROUND: Early infant HIV diagnosis is challenging in sub-Saharan Africa, particularly in rural areas where laboratory capacity is limited. Specimens must be transported to central laboratories for testing, leading to delays in diagnosis and initiation of antiretroviral therapy. This study was undertaken in rural Zambia to measure the turnaround time for confirmation of HIV infection and identify delays in diagnosis. METHODS: Chart reviews were conducted from 2010-2012 for children undergoing early infant HIV diagnosis at Macha Hospital in Zambia. Relevant dates, receipt of drugs by mother and child for the prevention of mother-to-child transmission (PMTCT), and test results were abstracted. RESULTS: 403 infants provided 476 samples for early infant diagnosis. The median age at the "6-week" and "6-month" assessments was 8.1 weeks and 7.0 months, respectively. The majority of mothers (80%) and infants (67%) received PMTCT. The median time between sample collection and arrival at the central laboratory in Lusaka was 17 days (IQR: 10, 28); arrival at the central laboratory to testing was 6 days (IQR: 5, 11); testing to return of results to the clinic was 29 days (IQR: 17, 36); arrival of results at the clinic to return of results to the caregiver was 45 days (IQR: 24, 79). The total median time from sample collection to return of results to the caregiver was 92 days (IQR: 84, 145). The proportion of HIV PCR positive samples was 12%. The total median turnaround time was shorter for HIV PCR positive as compared to negative or invalid samples (85 vs. 92 days; p = 0.08). CONCLUSIONS: Delays in processing and communicating test results were identified, particularly in returning results from the central laboratory to the clinic and from the clinic to the caregiver. A more efficient process is needed so that caregivers can be provided test results more rapidly, potentially resulting in earlier treatment initiation and better outcomes for HIV-infected infants.

Scaling-up access to antiretroviral therapy for children: a cohort study evaluating care and treatment at mobile and hospital-affiliated HIV clinics in rural Zambia.

BACKGROUND: Travel time and distance are barriers to care for HIV-infected children in rural sub-Saharan Africa. Decentralization of care is one strategy to scale-up access to antiretroviral therapy (ART), but few programs have been evaluated. We compared outcomes for children receiving care in mobile and hospital-affiliated HIV clinics in rural Zambia. METHODS: Outcomes were measured within an ongoing cohort study of HIV-infected children seeking care at Macha Hospital, Zambia from 2007 to 2012. Children in the outreach clinic group received care from the Macha HIV clinic and transferred to one of three outreach clinics. Children in the hospital-affiliated clinic group received care at Macha HIV clinic and reported Macha Hospital as the nearest healthcare facility. RESULTS: Seventy-seven children transferred to the outreach clinics and were included in the analysis. Travel time to the outreach clinics was significantly shorter and fewer caretakers used public transportation, resulting in lower transportation costs and fewer obstacles accessing the clinic. Some caretakers and health care providers reported inferior quality of service provision at the outreach clinics. Sixty-eight children received ART at the outreach clinics and were compared to 41 children in the hospital-affiliated clinic group. At ART initiation, median age, weight-for-age z-scores (WAZ) and CD4(+) T-cell percentages were similar for children in the hospital-affiliated and outreach clinic groups. Children in both groups experienced similar increases in WAZ and CD4(+) T-cell percentages. CONCLUSIONS: HIV care and treatment can be effectively delivered to HIV-infected children at rural health centers through mobile ART teams, removing potential barriers to uptake and retention. Outreach teams should be supported to increase access to HIV care and treatment in rural areas.

Effectiveness of efavirenz-based regimens in young HIV-infected children treated for tuberculosis: a treatment option for resource-limited settings.

BACKGROUND: Antiretroviral treatment (ART) options for young children co-infected with HIV and tuberculosis are limited in resource-poor settings due to limited data on the use of efavirenz (EFV). Using available pharmacokinetic data, an EFV dosing schedule was developed for young co-infected children and implemented as the standard of care at Macha Hospital in Southern Province, Zambia. Treatment outcomes in children younger than 3 years of age or weighing less than 10 kg receiving either EFV-based ART plus anti-tuberculous treatment or nevirapine-based (NVP) ART were compared. METHODS: Treatment outcomes were measured in a cohort of HIV-infected children seeking care at Macha Hospital in rural Zambia from 2007 to 2010. Information on the diagnosis and treatment of tuberculosis was abstracted from medical records. RESULTS: Forty-five children treated for tuberculosis initiated an EFV-based regimen and 69 children initiated a NVP-based regimen, 7 of whom also were treated for tuberculosis. Children receiving both regimens were comparable in age, but children receiving EFV started ART with a lower CD4(+) T-cell percentage and weight-for-age z-score. Children receiving EFV experienced increases in both CD4(+) T-cell percentage and weight-for-age z-score during follow-up, such that levels were comparable to children receiving NVP after two years of ART. Cumulative survival after 12 months of ART did not differ between groups (NVP:87%;EFV:80%;p = 0.25). Eleven children experienced virologic failure during follow-up.The adjusted hazard ratio of virologic failure comparing EFV to NVP was 0.25 (95% CI:0.05,1.24) and 0.13 (95% CI:0.03,0.62) using thresholds of 5000 and 400 copies/mL, respectively.Five children receiving EFV were reported to have had convulsions after ART initiation compared to only one child receiving NVP (p = 0.04). CONCLUSIONS: Despite poorer health at ART initiation, children treated for tuberculosis and receiving EFV-based regimens showed significant improvements comparable to children receiving NVP-based regimens. EFV-based regimens should be considered for young HIV-infected children co-infected with tuberculosis in resource-limited settings.

HIV-infected children in rural Zambia achieve good immunologic and virologic outcomes two years after initiating antiretroviral therapy.

BACKGROUND: Many HIV-infected children in sub-Saharan Africa reside in rural areas, yet most research on treatment outcomes has been conducted in urban centers. Rural clinics and residents may face unique barriers to care and treatment. METHODS: A prospective cohort study of HIV-infected children was conducted between September 2007 and September 2010 at the rural HIV clinic in Macha, Zambia. HIV-infected children younger than 16 years of age at study enrollment who received antiretroviral therapy (ART) during the study were eligible. Treatment outcomes during the first two years of ART, including mortality, immunologic status, and virologic suppression, were assessed and risk factors for mortality and virologic suppression were evaluated. RESULTS: A total of 69 children entered the study receiving ART and 198 initiated ART after study enrollment. The cumulative probabilities of death among children starting ART after study enrollment were 9.0% and 14.4% at 6 and 24 months after ART initiation. Younger age, higher viral load, lower CD4+ T-cell percentage and lower weight-for-age z-scores at ART initiation were associated with higher risk of mortality. The mean CD4(+) T-cell percentage increased from 16.3% at treatment initiation to 29.3% and 35.0% at 6 and 24 months. The proportion of children with undetectable viral load increased to 88.5% and 77.8% at 6 and 24 months. Children with longer travel times (≥ 5 hours) and those taking nevirapine at ART initiation, as well as children who were non-adherent, were less likely to achieve virologic suppression after 6 months of ART. CONCLUSIONS: HIV-infected children receiving treatment in a rural clinic experienced sustained immunologic and virologic improvements. Children with longer travel times were less likely to achieve virologic suppression, supporting the need for decentralized models of ART delivery.

Risk factors for pre-treatment mortality among HIV-infected children in rural Zambia: a cohort study.

BACKGROUND: Many HIV-infected children in sub-Saharan Africa enter care at a late stage of disease. As preparation of the child and family for antiretroviral therapy (ART) can take several clinic visits, some children die prior to ART initiation. This study was undertaken to determine mortality rates and clinical predictors of mortality during the period prior to ART initiation. METHODS: A prospective cohort study of HIV-infected treatment-naïve children was conducted between September 2007 and September 2010 at the HIV clinic at Macha Hospital in rural Southern Province, Zambia. HIV-infected children younger than 16 years of age who were treatment-naïve at study enrollment were eligible for analysis. Mortality rates prior to ART initiation were calculated and risk factors for mortality were evaluated. RESULTS: 351 children were included in the study, of whom 210 (59.8%) were eligible for ART at study enrollment. Among children ineligible for ART at enrollment, 6 children died (mortality rate: 0.33; 95% CI:0.15, 0.74). Among children eligible at enrollment, 21 children died before initiation of ART and their mortality rate (2.73 per 100 person-years; 95% CI:1.78, 4.18) was significantly higher than among children ineligible for ART (incidence rate ratio: 8.20; 95% CI:3.20, 24.83). In both groups, mortality was highest in the first three months of follow-up. Factors associated with mortality included younger age, anemia and lower weight-for-age z-score at study enrollment. CONCLUSIONS: These results underscore the need to increase efforts to identify HIV-infected children at an earlier age and stage of disease progression so they can enroll in HIV care and treatment programs prior to becoming eligible for ART and these deaths can be prevented.