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Opportunities for Closing the Gap in HIV Diagnosis, Treatment, and Viral Load Suppression in Children in Malawi: Results From a 2015–2016 Population-based HIV Impact Assessment Survey

Jonnalagadda, Sasi PhD*; Auld, Andrew MD; Jahn, Andreas MD; Saito, Suzue PhD§; Bello, George PhD; Sleeman, Katrina PhD*; Ogollah, Francis M. MSc§; Cuervo-Rojas, Juliana MD, PhD§,¶; Radin, Elizabeth PhD§; Kayira, Dumbani MBBS; Kim, Evelyn PhD; Payne, Danielle MPH; Burnett, Janet MPH*; Hrapcak, Susan MD*; Patel, Hetal MSc*; Voetsch, Andrew C. PhD*; for the MPHIA Study Team

Author Information
The Pediatric Infectious Disease Journal: November 2021 - Volume 40 - Issue 11 - p 1011-1018
doi: 10.1097/INF.0000000000003288

Abstract

Diagnosing and treating children living with HIV (CLHIV) continues to be a public health challenge. In 2019, there were an estimated 1.8 (1.3–2.2) million CLHIV globally, with only half (53%; 37%–73%) of them receiving antiretroviral (ARV) treatment (ART).1

In Malawi, there were an estimated 65,000 (50,000–78,000) CLHIV in 2019.1 Based on program data, 68% of CLHIV were on ART and, among children on ART, 61% had suppressed viral load (VL) at the end of 2018.2 Gaps in diagnosis of CLHIV are difficult to ascertain from program data and opportunities to identify undiagnosed CLHIV are not well characterized in Malawi. The Malawi Population-based HIV Impact Assessment (MPHIA) 2015–2016 results among adults 15–64 years of age showed remarkable progress toward achieving the Joint United National Programme of HIV/AIDS (UNAIDS) 90-90-90 targets: 77% of HIV-positive adults were aware of their status, of whom 91% were on ART, and 91% of those on ART were virally suppressed.3 The same degree of progress has been difficult to achieve in children in spite of concerted efforts to improve pediatric HIV diagnosis and treatment coverage.4,5

The MPHIA was the first national population-based survey in Malawi to measure HIV infection outcomes in children <15 years of age.3 MPHIA survey data were used to measure HIV prevalence in children, to obtain a population-level estimate of CLHIV, and to identify the gaps in achieving the UNAIDS 90-90-90 targets in children in Malawi.

MATERIALS AND METHODS

MPHIA 2015–2016 was a nationally representative cross-sectional household survey designed to measure the impact of Malawi’s HIV epidemic response. Measuring the national HIV prevalence in children <15 years of age was a secondary survey objective. Details of survey methods and procedures are provided in the survey report.3 Briefly, MPHIA used a two-stage cluster sample design; the first stage of sampling involved selection of enumeration areas and the second stage involved selection of households within each enumeration area. Half of the total sampled households were randomly selected for HIV testing of children <15 years of age. Children were eligible for survey participation if they were in the household the night before the survey and had parent/guardian consent.

Data Collection on Children

Parent/guardian Reported Data

Questions pertaining to children were included in the adult (15–64 years of age) questionnaire. In all participating households, all residing children were rostered and, if eligible, a parent or guardian provided information on demographics, HIV testing history, HIV status of the child, and ART use if the child was known to have HIV infection.3

HIV Testing

Children age ≤18 months were screened for HIV exposure using Determine HIV-1/2 (Abbott Molecular Inc., Des Plaines, IL) at the household, and confirmed through HIV total nucleic acid polymerase chain reaction using the Abbott Real-Time HIV-1 Qualitative Assay (Abbott Molecular, Wiesbden, Germany). Children age >18 months were tested at the household using the HIV national algorithm: Determine HIV-1/2 (Abbott Molecular, Des Plaines, IL) as a screening test, followed by Uni-Gold (Trinity Biotech, plc., Wicklow, Ireland) if the screening test was reactive. Specimens testing positive with both tests from the national algorithm underwent confirmation using the Geenius HIV 1/2 Supplemental Assay (Bio-Rad, Hercules, CA) at the survey satellite laboratory.3

Viral Load Measurement

Children with confirmed HIV-positive status underwent VL testing at the survey central laboratory in Malawi, using the Abbott Real-Time HIV-1 assay with either plasma or dried blood spots (DBS) using the optimized 1 spot protocol for DBS.6 HIV-1 VL (HIV RNA copies per mL) was measured using the fully automated Abbott m2000 System (Abbott Molecular, Des Plaines, IL).3

Detection of Antiretroviral Medication

To determine recent exposure to ART, DBS collected from children who participated in MPHIA and confirmed as having HIV infection were tested for presence of selected ARVs using high-resolution liquid chromatography coupled with tandem mass spectrometry, at the University of Cape Town, South Africa.7 Efavirenz, atazanavir, and lopinavir were used as markers of first- and second-line regimens, based on contemporaneous international and national guidelines. Specimens in which none of these 3 drugs were detected were tested for nevirapine, a component of the most common first-line ART regimen for children in Malawi at the time of MPHIA (2015–2016).

Analysis

Household, interview, and biomarker datasets were merged to create an analytic dataset.8 A linkage between the child and a biologic parent was established through the household roster and adult interview data.8 Data used for this analysis were weighted to adjust for the probability of selection and nonresponse. Chi-square Automatic Interaction Detection tree classification scheme, which identifies predictors of response, was used to adjust for noncoverage.8,9 Jackknife replicate weights were used for variance estimation.8 Data analysis was conducted in R version 4.0.3, using the survey package.10,11

The analysis used confirmed HIV infection (confirmed through polymerase chain reaction or Geenius testing conducted in MPHIA) to calculate HIV infection prevalence. Prevalence ratios and 95% confidence intervals (CI) were estimated using survey-weighted generalized linear model (svyglm) function in the survey package in R.11 The survey-weighted number of CLHIV in Malawi was estimated using poststratification weights based on the age-sex distribution from the 2016 population projections based on the 2008 national census of Malawi.12

Diagnosis or awareness of HIV infection (first 90) was estimated as percent of all CLHIV who were guardian-reported as HIV-infected or had detectable ARVs. Being on ART was defined as guardian-reported ART or detection of ARV(s) and was estimated among all CLHIV (ART coverage) and among those who were diagnosed (second 90). Viral load suppression (VLS) (<1000 HIV RNA copies/mL) was estimated among all CLHIV and among CLHIV on ART (third 90). Analysis of the 90-90-90 indicators was restricted to children with complete data for diagnosis, ART status, and VLS.

The MPHIA protocol was reviewed and approved by the Institutional Review Boards at the United States Centers for Disease Control and Prevention, Columbia University, Westat, and National Health Sciences Research Committee in Malawi.

RESULTS

In the 11,386 households that participated in MPHIA 2015–2016, 20,683 children were rostered, 9300 were eligible for participation, 6166 provided a blood sample, and 99 children tested HIV-positive (Fig. 1). From an unweighted comparison, the children who participated in MPHIA were older but otherwise comparable with the nonparticipants (data not shown).

FIGURE 1.
FIGURE 1.:
Study population, <15 years of age, Malawi population-based HIV impact assessment 2015–2016. *Half of the sampled households were sub-selected for blood collection among children <15 years of age.

HIV Prevalence Among Children

The national pediatric HIV prevalence measured through MPHIA was 1.5% (95% CI: 1.1–1.9) (Table 1). The HIV prevalence of 1.5% in children extrapolates to 119,501 (95% CI: 89,028–149,974) CLHIV in Malawi during the period of 2015–2016. HIV prevalence among children ages 5–9 and 10–14 years was 1.4 and 1.9 times as high as the HIV prevalence among those age <5 years, respectively (Table 1; Figure, Supplemental Digital Content 1, http://links.lww.com/INF/E498).

TABLE 1. - HIV Prevalence Among Children <15 years, Malawi Population-based HIV Impact Assessment 2015–2016
n Weighted Prevalence 95% CI Prevalence Ratio 95% CI Total*
Total 99 1.5 1.1–1.9 6166
Age
 0–4 yrs 20 1.1 0.5–1.7 1868
 5–9 yrs 37 1.6 0.8–2.3 1.4 0.7–2.9 2201
 10–14 yrs 42 2.1 1.3–2.9 1.9 1.0–3.6 2097
Sex
 Male 46 1.5 0.9–2.1 3005
 Female 53 1.5 1.1–2.0 1.0 0.6–1.6 3161
Residence
 Urban 37 2.2 1.2–3.1 1923
 Rural 62 1.4 1.0–1.8 0.7 0.4–1.1 4243
Zone
 North 10 1.0 0.3–1.7 1067
 Central East 7 0.9 0.2–1.4 0.8 0.3–2.2 900
 Central West 4 0.5 0.0–1.1 0.5 0.1–1.8 645
 Lilongwe City 14 1.4 0.6–2.2 1.4 0.6–3.3 888
 South East 19 2.9 1.5–4.4 2.9 1.2–6.8 720
 South West 27 2.2 1.3–3.0 2.1 1.0–4.7 1151
 Blantyre City 18 2.5 1.4–3.6 2.5 1.1–5.6 795
Maternal HIV status
 Positive 57 8.0 5.6–10.5 73.6 22.4–241.0 783
 Negative 5 0.1 0.0–0.2 4151
 Unknown 37 3.0 1.9–4.2 27.8 8.4–92.8 1232
Father’s HIV status§
 Positive 19 4.5 2.2–6.7 8.8 3.8–20.4 386
 Negative 14 0.5 0.2–0.8 2528
HIV prevalence among orphaned children
 Both parents alive 67 1.2 0.8–1.5 5600
 One parent dead 23 5.3 1.7–8.9 4.6 2.1–10.3 485
 Both parents dead 9 15.2 4.2–26.3 13.2 6.3–27.6 57
HIV prevalence among children in HIV affected households
 Household with no HIV-positive adult 27 0.5 0.3–0.7 4821
 Household with at least 1 HIV-positive adult 46 6.0 3.9–8.1 11.2 6.6–19.0 924
 Household with 2+ HIV-positive adult 20 5.8 2.8–8.8 10.9 5.8–20.4 313
HIV testing history
 Yes 66 6.8 4.6–8.9 1076
 No 20 0.3 0.1–0.5 0.04 0.03–0.08 4695
HIV testing history among children of HIV-positive mother
 Yes 45 12.6 8.4–16.8 389
 No 11 3.0 0.9–5.1 0.2 0.1–0.5 382
*Total for each stratifier may not add up to the overall total of 6166 because of missing values.
Based on HIV testing in MPHIA 2015–2016.
Maternal HIV status is unknown because the mother who was linked to the child did not participate in blood draw in MPHIA or was not eligible for MPHIA participation, or child-mother data link could not be established.
§Father-to-child link was not available for 3252 children (6166 – [386 + 2528]).
This analysis is among the subset of children of HIV-positive mothers, with nonmissing data on HIV testing history of the child.

HIV prevalence among the 783 children whose mothers tested HIV-positive in MPHIA was 8.0% (95% CI: 5.6–10.5). HIV prevalence in children with both biologic parents deceased or with 1 biologic parent deceased was 13.2- and 4.6-times as high as the prevalence in children with both parents alive, respectively (Table 1). From the survey sample, we extrapolated 28,324 (95% CI: 8048–48,601) CLHIV with 1 deceased parent and 8251 (95% CI: 1795–14,707) CLHIV with both parents decreased (not shown in Table 1).

Among the 4821 children in a household with no HIV-positive adult, 27 (0.5%) tested HIV-positive in MPHIA. HIV prevalence among children living in households with at least 1 HIV-positive adult was 11.2-times as high as the prevalence in children in households where no adult tested HIV-positive during the survey.

Parent-reported HIV testing history was available for 5771 children, of whom 16.7% (95% CI: 15.3–18.2) of the children had received an HIV test (results not shown in Table 1). Of the 1076 children with an HIV testing history, 6.8% tested HIV-positive in MPHIA and of the 4695 children without an HIV testing history, 0.3% tested HIV positive in MPHIA (Table 1).

Of the 771 children with a mother who tested HIV-positive in MPHIA, 50.6% (95% CI: 45.5–55.8) were previously tested for HIV (not shown in Table 1). Of the 389 children with an HIV-positive mother and who had previously been tested for HIV, 12.6% tested HIV-positive in MPHIA. About 50% (382) of children with an HIV-positive mother were not previously tested for HIV; 3.0% of these children tested HIV-positive in MPHIA.

From the survey sample, we extrapolated 28,324 (95% CI: 8048–48,601) CLHIV with 1 deceased parent and 8251 (95% CI: 1795–14,707) CLHIV with both parents deceased in Malawi in 2015–2016 (not shown in Table 1).

Status of 90-90-90 Indicators Among CLHIV in Malawi

HIV Diagnosis

Among all CLHIV in Malawi, 30.7% (95% CI: 20.3–41.1) were undiagnosed (Table 2; Fig. 2). The percent of undiagnosed CLHIV extrapolates to 35,546 undiagnosed CLHIV in Malawi in 2015–2016 (not shown in Table 2).

TABLE 2. - Characteristics of HIV-positive Children 0–14 Years of Age, by HIV Diagnosis (or Awareness of HIV-positive Status), Malawi Population-based HIV Impact Assessment 2015–2016
Variable n Undiagnosed or Unaware of HIV Status 95% CI n Diagnosed or Aware of HIV Status 95% CI Total
All, 0–14 yrs 28 30.7 20.3–41.1 67 69.3 58.9–79.7 95*
Age
 0–4 8 31.4 6.1–56.7 12 68.6 43.3–93.9 20
 5–9 9 27.8 6.5–49.0 28 72.2 51.0–93.5 37
 10–14 11 33.0 12.6–53.4 27 67.0 46.6–87.4 38
Sex
 Male 8 19.5 4.9–34.0 36 80.5 66.0–95.1 44
 Female 20 41.8 28.4–55.1 31 58.2 44.9–71.6 51
Residence
 Urban 11 29.6 9.6–49.7 24 70.4 50.3–90.4 35
 Rural 17 31.0 19.3–42.6 43 69.0 57.4–80.7 60
Child ever tested for HIV
 Yes 12 17.3 6.3–28.2 53 82.7 71.8–93.7 65
 No 14 83.0 66.1–100.0 6 17.0 0.0–33.9 20
Orphan status
 Both parents alive 19 30.2 16.2–44.1 47 69.8 55.8–83.8 66
 One parent dead 9 41.9 10.6–73.2 12 58.1 26.8–89.5 21
 Both parents dead 8 100.0 100.0–100.0 8
Mother’s HIV status
 Positive 18 28.8 12.1–45.6 39 71.2 54.4–87.9 57
 Negative 1 22.0 0.0–64.1 4 78.0 35.9–100.0 5
 Unknown 9 35.2 11.3–59.1 24 64.8 40.9–88.7 33
Father’s HIV status
 Positive 6 25.5 4.4–46.5 13 74.5 53.5–95.6 19
 Negative 5 41.0 11.4–70.6 9 59.0 29.4–88.6 14
Mother aware of her own HIV status
 Mother aware 15 24.6 7.6–41.5 39 75.4 58.5–92.4 54
 Mother unaware 3 100.0 0.00 3
 Unknown 1 18.4 0.0–51.2 5 81.6 48.8–100.0 6
Mother with suppressed viral load
 Yes 15 29.9 10.2–49.7 31 70.1 50.3–89.8 46
 No 3 24.9 0.0–51.5 8 75.1 48.5–100.0 11
HIV-positive adults in the household
 None 8 40.7 12.1–69.4 17 59.3 30.7–88.0 25
 1 13 29.0 10.3–47.7 33 71.0 52.3–89.7 46
 2+ 7 24.9 5.1–44.6 13 75.1 55.4–94.9 20
Total for each stratifier may not add up to the overall total due to missing values.
*This table includes 95 of the 99 HIV-positive children with nonmissing data on HIV diagnosis.
Based on HIV testing in MPHIA 2015–2016.
Maternal HIV status is unknown because the mother who was linked to the child did not participate in blood draw in MPHIA or was not eligible for MPHIA participation, or child-mother link could not be established.

FIGURE 2.
FIGURE 2.:
90-90-90 cascade for CLHIV in Malawi, Malawi population-based HIV impact assessment 2015–2016. Of the 99 children who tested HIV-positive in MPHIA, 95 were included in this analysis/figure of the 90-90-90 cascade because they had complete information for the cascade of awareness of HIV status, ART use and viral load suppression. The 95 children in this analysis represents a weighted total of 115,791 CLHIV shown in the first bar. Second to fourth bars—The lower (darker) part of each stacked bar represents children living with HIV who are aware, on ART and have suppressed viral load, respectively. The upper part of each stacked bar represents children who are not aware, not on ART and not VLS, respectively. Children living with HIV who are aware and not aware of their HIV status add up to the total number of CLHIV for this analysis of the 90-90-90 cascade. CLHIV who are on ART and not on ART add up to the CLHIV who are aware. CLHIV who are virally suppressed and not suppressed add up to the number on ART. The dashed arrows and the percentages represent the percent of CLHIV who were aware or diagnosed (69.3%), on ART (59.6%) and virally suppressed (34.5%). The solid arrows represent the percent of CLHIV who are on ART, among those who were diagnosed or aware of their HIV status (86.1%) and the percent who had suppressed viral load, among those on ART (57.9%).

Among the 21 HIV-positive children with 1 biologic parent dead, 41.9% were undiagnosed, while among 66 HIV-positive children with both parents alive, 30.2% were undiagnosed (Table 2).

Larger percentage of children born to mothers with unknown HIV status were undiagnosed compared with children born to HIV-positive mothers (35.2% versus 28.8%). Among children born to mothers who were aware of their own HIV-positive status, 24.6% were undiagnosed and 29.9% of children born to mothers who were virally suppressed (implying mother was aware and on treatment) were undiagnosed. The median age of children with an HIV-positive mother who was aware of her own status (based on self-report or detectable ARVs) but the child never received an HIV test was 10 years (not shown in Table 2).

The proportion of HIV-positive children who were previously undiagnosed was greater in the 25 households where the survey did not identify an HIV-positive adult (40.7%) compared with the 46 households where 1 or 20 households where ≥2 HIV-positive adults were identified in the survey (29.0% and 24.9%, respectively) (Table 2).

On ART

This study estimates that among all CLHIV, 59.6% (95% CI: 47.0–72.29) were on ART. ART coverage among children 0–4 years, 5–9 years, and 10–14 years was 64.5% (95% CI: 37.8–91.1), 54.8% (95% CI: 35.7–73.8), and 60.4% (95% CI: 39.3–81.5), respectively (not shown in tables or figures). Among diagnosed CLHIV, 86.1% (95% CI: 76.6–95.6) were on ART (Fig. 2).

The median age at initiation of ART was 3 years (interquartile range [IQR]: 1.9–4.6) for all CLHIV. Median age at ART initiation was 1.2 (IQR: 0.0–2.0), 3.1 (IQR: 2.1–4.0), and 5.0 (IQR: 3.7–10.1) years for children <5, 5–9, and 10–14 years of age at the time of the survey, respectively (Table, Supplemental Digital Content 2, http://links.lww.com/INF/E498).

ART coverage of 59.6% in CLHIV extrapolates to 69,061 CLHIV (95% CI: 43,454–94,668) on ART in Malawi in early 2016 (Fig. 2).

Viral Load Suppression

Among all CLHIV, 57.7% (95% CI: 45.0–70.5) had unsuppressed VL. Unsuppressed VL was greatest among CLHIV <5 years of age (79.5%) and among those living in urban areas (74.7%). Among children of mothers who were virally suppressed, 59.6% had unsuppressed VL (Table 3).

TABLE 3. - Viral Load Suppression (<1000 copies/mL) among Children 0–14 Years of Age Living With HIV in Malawi, Malawi Population-Based HIV Impact Assessment 2015–2016
Variable n Unsuppressed Viral Load 95% CI Total
All, 0–14 yrs 50 57.7 45.0–70.5 96*
Age
 0–4 14 79.5 58.5–100.0 18
 5–9 18 48.2 29.4–66.9 37
 10–14 18 50.8 30.9–70.7 41
Sex
 Male 25 62.0 44.9–79.2 46
 Female 25 53.2 36.3–70.1 50
Residence
 Urban 22 74.7 58.8–90.5 35
 Rural 28 53.5 38.4–68.6 61
Treatment status
 On ART 18 42.1 25.6–58.6 57
 Not on ART§ 29 78.7 61.3–96.0 36
Mother virally suppressed
 Yes 24 59.6 42.8–76.3 46
 No 8 86.7 57.7–100.0 9
Total for each stratifier may not add up to the overall total due to missing values.
*3 HIV-positive children were missing viral load results.
This variable is restricted to children with complete data for the 90-90-90 cascade variables.
Parent reports the child is on ART, ARVs detected, or both.
§Parent reports the child is not on ART and ARVs not detected or parent is unaware of child’s HIV-positive status and ARV detection data is missing or not detected so child classified as not on ART.

Restricting to CLHIV on ART, 42.1% (95% CI: 25.6–58.6) or 29,082 had unsuppressed VL in 2015–2016 in Malawi (Fig. 2).

DISCUSSION

HIV prevalence among children <15 years in Malawi was 1.5%, based on the MPHIA survey conducted in 2015–2016. This extrapolates to 119,501 CLHIV in Malawi in 2015–2015 of whom, 35,546 CLHIV were undiagnosed and 57.7% of all CLHIV had unsuppressed viral load. Children are making slower progress toward the 90-90-90 goals measured at 69-86-58 compared with adults in whom these indicators were 77-91-91 in MPHIA 2015–2016.3

CLHIV Estimates From MPHIA 2015–2016

HIV pediatric ART program planning in Malawi has relied on the number of CLHIV derived from the Spectrum model, which is frequently updated to improve the accuracy of estimates.13 According to the 2019 Spectrum model estimates, there were 85,000 (65,000–100,000) (Malawi Spectrum file from 2019) CLHIV in Malawi in 2016, lower than that estimated by MPHIA (although with overlapping CIs). Spectrum model derives the number of CLHIV using demographic data, surveillance and survey data, epidemic characteristics, breast-feeding patterns, and other program data (eg, women on ART), which is combined with global measurements of disease progression, mortality among children, and mother-to-child transmission probabilities.13 Changes in modeled CLHIV estimates from year to year indicate the challenges in estimating the number of CLHIV. This impacts planning and resource allocation for pediatric HIV services and, ultimately, the achievement of 90-90-90 targets. MPHIA provided a direct measurement of HIV prevalence in children and the number of CLHIV living in Malawi in 2016 and has been a valuable reference point for program planning.

HIV Diagnosis in Children

Our results highlight the missed opportunities for HIV diagnosis in children born to HIV-positive mothers; half of the children with an HIV-positive mother had not received an HIV test and a substantial proportion of undiagnosed CLHIV had mothers who were linked to care and virally suppressed and were living in households with HIV-positive adults. Improving coverage of testing in children of HIV-positive mothers, especially older children who may be perceived as low risk and not yet tested, is a key strategy to diagnose CLHIV.14,15 As HIV prevalence was higher in the older children, and median age for undiagnosed children of HIV-positive mothers was 10 years, index testing strategies should emphasize to caregivers that older children have higher risk of undiagnosed HIV, and HIV testing should be offered to children with unknown status. This analysis also supports the use of a mother-centered testing approach to help diagnose children in the household who are living with HIV; among mothers who were virally suppressed, 30% had children who were undiagnosed.15 Although all HIV-positive orphans with both parents deceased were previously diagnosed in our analysis, there were missed opportunities in diagnosing children with 1 deceased parent.15 Irrespective of the diagnosis status, our analysis identified a substantial number of orphans, highlighting the need for family-based and orphans and vulnerable children programming, given the vulnerability and poor clinical outcomes for HIV-positive orphans.

ART Coverage Among CLHIV

Based on Malawi’s program data, 45,450 (68%) of CLHIV were on ART in 2018.2 Through MPHIA, we measured that 60% of all CLHIV in Malawi were receiving ART in 2015–2016 and among CLHIV who have been diagnosed, linkage to ART was high at 86%. We noted a delay in treatment initiation across all age-groups; immediate initiation of ART is critical because of high-risk of mortality in children in absence of treatment.16 While this may be partly explained due to evolving ART initiation criteria particularly in older children, the median age at ART initiation of 1.2 years in children <5 years of age is of concern. Initiating treatment from early infancy is important for better neurologic and growth outcomes as well as reduced viral reservoirs.17–19 This highlights in the importance of strengthening early infant testing, return of results and immediate initiation of treatment to avoid loss to follow-up of infants from the diagnosis and treatment cascade.

Viral Suppression Among CLHIV

Multiple studies report viral suppression in children on ART but estimates at a community level, not limited to those in care, are lacking.20 Among CLHIV with a mother who was virally suppressed, 60% were not virally suppressed, highlighting a missed opportunity in diagnosis and effective treatment of children, when the mother is linked to care and virally suppressed. Among children on ART, 42% had unsuppressed VL, indicating ineffective ART regimens and challenges related to adherence to ART. At the time of the survey, most children in Malawi were on nevirapine-based ART regimens.2 In our survey, 83% of children with detectable ARVs had detectable nevirapine. According to the 2019 report on HIV drug resistance, 69% of infants <18 months in Malawi had detectable pretreatment drug resistance to nevirapine or efavirenz.21 These children would likely not be able to achieve VLS, even with good adherence due to the low genetic barrier to developing drug resistance in presence of nevirapine.22,23 Regardless of ART regimen, to achieve VLS, adherence in children should be routinely assessed and supported, addressing the unique challenges children and their caregivers face.

This analysis has the following limitations. Although MPHIA was designed to generate a valid and precise estimate of pediatric HIV prevalence at the national level, it was not designed to estimate VLS and 90-90-90 outcomes among CLHIV, which are based on small denominators (the survey identified 99 HIV-positive children) and should be interpreted with caution. The data link between mother and child is not perfect, as seen with the 5 infected children linked to an HIV negative mother. Further, if a biologic parent refused survey participation or is not a usual household member or has died, the HIV status of that parent is marked as unknown. This has the potential to underestimate HIV exposure and HIV prevalence among HIV-exposed in children included in this analysis.

Although we adjusted for under-reporting of awareness and ART status through detectable ARVs, this adjustment does not help with mis-reported diagnosis when not on ART. This may result in an underestimate of awareness of status and an overestimate of ART status among those aware. Although we matched the ARVs tested to the recommended regimen in Malawi in 2015–2016, we may have missed detection of ARVs because of poor adherence to ART resulting in undetectable levels of ARVs in the sample. This might explain the 21.3% of children who were not on ART but were virally suppressed. Young children have a higher VL set-point and therefore, time from initiation of ART to viral suppression could be well beyond 6 months. This is particularly important in the young children whose ART initiation may be recent and may explain some of the low viral suppression seen in the youngest age group of <5 years. Finally, these results may need to be taken in context of any programmatic changes in the intervening 5 years since the completion of the MPHIA 2015–2016 survey, which may have addressed the gaps presented here.

The MPHIA 2015–2016 results confirmed the low viral load suppression in CLHIV seen in routine VL monitoring in Malawi and resulted in prioritization of the WHO-recommended lopinavir/ritonavir (LPV/r) pellets for newly diagnosed HIV-positive children <3 years of age and >6 kg, or LPV/r syrup for children <6 kg (PEPFAR Malawi Country Operational Plan 2017). Scale-up of LPV/r syrup has been challenging given the need for refrigeration and the bad taste of the syrup.24,25 The Malawi HIV treatment program therefore introduced LPV/r as first-line treatment for infants and young children <3 years, initially using the pellet formulation at a few pilot facilities in 2018. A nationwide scale-up of LPV/r as first line to all children weighing <20 kg using granule formulation for those that are unable to swallow tablets and transition of all children weighing ≥20 kg onto a dolutegravir (DTG)-based first-line regimen was initiated in January 2020.26,27 At the beginning of 2019, 96% of children receiving a pediatric first-line formulation were using nevirapine-based regimens; however, following successful scale-up of LPV/r-based regimen, only 9% of CLHIV were on NVP-based pediatric formulation as of December 2020. Plans for transitioning to DTG-based first-line regimens for children <20 kg by late 2021 are also underway (PEPFAR Malawi planning documents; unpublished).2

MPHIA was the first national household-based survey in Malawi to include measurement of pediatric HIV prevalence and VLS and provide a population-level status of the 90-90-90 indicators in CLHIV. Based on our results, there were a greater number of CLHIV in Malawi than previously estimated, in whom viral suppression is low. These first empirical HIV prevalence estimates for children have been tremendously useful for comparison with the Spectrum model estimates of CLHIV. Our results reinforce evidence that strengthening index testing of children whose biologic parent is engaged in care is a strategic approach for improving HIV case finding among children. Strengthening testing strategies in children has been highlighted in various national HIV program plans since 2017 including the most recent 2021 PEPFAR strategy. Achieving 90-90-90 targets in children have proven to be far more challenging than in adults, and it is critical for national programs to implement high-quality evidence-based interventions to improve HIV testing, care and treatment to end the pediatric HIV epidemic.

ACKNOWLEDGMENTS

The MPHIA study team was led by the Government of Malawi through the Ministry of Health (MOH), conducted with funding from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) and technical assistance through the U.S. Centers for Disease Control and Prevention (CDC). The survey was implemented by ICAP at Columbia University in collaboration with the Centre for Social Research (CSR) at the University of Malawi, the National Statistical Office (NSO), and the College of Medicine-Johns Hopkins Project (COM-JHP) at the University of Malawi.

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Keywords:

pediatric HIV; HIV diagnosis in children; viral load suppression; children living with HIV

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