Survival and HIV-Free Survival Among Children Aged ≤3 Years — Eight Sub-Saharan African Countries, 2015–2017

Although mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is preventable through antiretroviral treatment (ART) during pregnancy and postpartum, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 160,000 new HIV infections occurred among children in 2018 (1). Child survival and HIV-free survival rates* are standard measures of progress toward eliminating MTCT^† (2). Nationally representative Population-based HIV Impact Assessment (PHIA)^§ survey data, pooled from eight sub-Saharan African countries^¶ were used to calculate survival probability among children aged ≤3 years by maternal HIV status during pregnancy and HIV-free survival probability among children aged ≤3 years born to women with HIV infection, stratified by maternal ART** status during pregnancy. Survival probability was significantly lower among children born to women with HIV infection (94.7%) than among those born to women without HIV infection (97.6%). HIV-free survival probability of children born to women with HIV infection differed significantly by the timing of initiation of maternal ART: 93.0% among children whose mothers received ART before pregnancy, 87.8% among those whose mothers initiated ART during pregnancy, and 53.4% among children whose mothers did not receive ART during pregnancy. Focusing on prevention of HIV acquisition and, among women of reproductive age with HIV infection, on early diagnosis of HIV infection and ART initiation when applicable, especially before pregnancy, can improve child survival and HIV-free survival.

Females aged ≥15 years who provided consent^†† to survey participation answered questions about the most recent pregnancy that resulted in a live birth in the 3 years preceding the interview (i.e., births occurring during 2012–2017, depending on the date of the survey). Questions asked whether any antenatal care was received, timing of HIV testing and HIV status (HIV diagnosis before pregnancy; during pregnancy, labor, or delivery; or did not have a diagnosis of HIV infection), and ART use among mothers with HIV infection (initiated ART before pregnancy; initiated ART during pregnancy, labor, or delivery; or did not receive ART). All mothers provided the child’s date of birth; whether the child was living or deceased, and if deceased, the date of death or age at death; and HIV status of living children. All mothers and a random subsample of children underwent HIV testing in the household using country-specific HIV rapid testing algorithms. Positive rapid test results were confirmed using Geenius HIV-1/2 confirmatory assay (Bio-Rad) (for children aged ≥18 months).^§§ Infants aged <18 months were screened for HIV exposure using rapid tests; a positive rapid test result was confirmed using total nucleic acid polymerase chain reaction. HIV test results were provided to the participants along with referral to HIV treatment services. Survey protocols for each of the eight countries were reviewed by the CDC Institutional Review Board (IRB), the Columbia University Medical Center IRB, and the IRB in each country.

Children were classified according to maternal report of HIV status during pregnancy to determine survival by maternal HIV status. For the HIV-free survival analysis, children born to mothers with HIV infection were classified according to maternal self-reported ART use during pregnancy. Mothers whose response to HIV status during pregnancy was missing but who had positive test results for HIV (0.8%), were classified as having HIV infection during pregnancy. Mothers with HIV infection who were missing information on ART use during pregnancy (5%) were classified as not having received ART during pregnancy.

HIV status of children in this analysis was determined by HIV testing during the survey (74%) or maternal report for nonsampled children (26%). Date of the child’s HIV diagnosis was based on the survey test date for sampled children and on mothers’ report of first HIV test date with positive results for nonsampled children. Mothers reported the date of death or age at death for children who had died. HIV status of deceased children was not recorded uniformly across surveys and was therefore not included in the analysis. Children without a survey-confirmed HIV status and without mothers’ report were excluded.

Kaplan-Meier survival analyses were used to estimate overall survival and HIV-free survival probability (3). Interview data about mothers’ last pregnancy were used to determine the outcomes of children using the age of the child at the time of events of interest. To estimate survival, children were censored at the age at death or age at time of survey. To estimate HIV-free survival, children of mothers with HIV infection were censored at their age at death, their age at HIV diagnosis, or their age at the time of survey. A sensitivity analysis was conducted to estimate HIV-free survival rates after excluding children currently breastfeeding who were still at risk for HIV infection through breast milk transmission. The analyses were unweighted. Analyses were performed using SAS (version 9.4; SAS Institute) and Stata (version 14.2; StataCorp) statistical software.

Among 36,278 live births, data for the survival analysis were available for 33,863 (93%), including 30,703 (91.0%) children born to mothers without HIV infection, 3,020 (9.0%) born to mothers with HIV infection, and 140 (0.4%) children whose mothers’ HIV status was unknown (Table 1). Among children born to mothers with HIV infection, 108 (3.6%) died; 552 (1.8%) mothers without HIV infection and five (3.6%) mothers with unknown HIV status also died. Cumulative probability of survival up to 3 years among children born to mothers with HIV infection was 94.7% and among children born to mothers without HIV infection was 97.6% (p<0.001) (Figure) (Table 2).

Among the 3,020 children born to mothers with HIV infection, 2,373 (78.6%) had complete HIV data (HIV status and diagnosis date) and death data available and were included in the HIV-free survival analysis. Among these 2,373 children, mothers of 1,252 (52.8%) received ART before pregnancy; 842 (35.5%) initiated ART during pregnancy, labor, or delivery; and 276 (11.6%) did not receive ART during pregnancy, labor, or delivery (Table 1). Overall, 127 (5.4%) of these children had HIV infection, 2,138 (90.1%) did not, and 108 (4.6%) had died.

HIV-free survival probability in children born to mothers with HIV infection was 85.3%. HIV-free survival rates among children whose mothers initiated ART before pregnancy, during pregnancy, and who did not receive ART during pregnancy were 93.0%, 87.8%, and 53.4%, respectively (log-rank p-value <0.001) (Figure). Excluding children who were currently breastfeeding did not alter the HIV-free survival estimates.

Corresponding author: Sasi Jonnalagadda, wau4@cdc.gov, 404-639-2249.

¹CDC; ²ICAP at Columbia University, New York, New York; ³Eswatini Ministry of Health; ⁴Malawi Ministry of Health; ⁵Namibia Ministry of Health; ⁶Tanzania National AIDS Control Program; ⁷Uganda Ministry of Health; ⁸Zambia Ministry of Health; ⁹Zimbabwe Ministry of Health; ¹⁰CDC-Eswatini; ¹¹CDC-Lesotho; ¹²CDC-Malawi; ¹³CDC-Namibia; ¹⁴CDC-Tanzania; ¹⁵CDC-Uganda; ¹⁶CDC-Zambia; ¹⁷CDC-Zimbabwe.

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Abbreviations: ART = antiretroviral therapy; HIV = human immunodeficiency virus.
* Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe.
^† Eligibility requirements for inclusion in this analysis were that mothers be aged ≥15 years, had a live birth in the most recent delivery within the 3 years preceding the PHIA survey, and had age information on the children.
^§ Percentages were calculated using only total of children with reported characteristics as the denominator.
^¶ Percentages were calculated using total of all reported children as the denominator.
** Among 665 children’s deaths, five (9.8%) children were HIV-infected, 23 (3.5%) were not HIV-infected, and for 637 (97.3%), HIV status was not known.
^†† As determined by HIV testing conducted during the survey or on mothers’ report of child’s HIV status if child was not sampled for survey HIV testing.
^§§ Child was not tested for HIV during the survey, and mother’s report of child’s status was missing.

FIGURE. Probability of survival (A)*^,† and HIV-free survival (B)^§ among children aged ≤3 years at the time of the Population-based HIV Impact Assessment (PHIA) survey — eight sub-Saharan African countries,^¶ 2015–2017

Abbreviations: ANC = antenatal care; ART = antiretroviral therapy; CI = confidence interval; HIV = human immunodeficiency virus.

* Excludes 140 children out of 33,863 whose mothers had unknown HIV status.

^† Excludes 11 deaths among children not exposed to HIV that took place after 3 years.

^§ Out of 2,373 children born to mothers with HIV infection, three were born to mothers with missing ART use data.

^¶ Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe.

Abbreviation: CI = confidence Interval.
* Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe.
^† HIV status is unknown for mothers of 140 children, who are excluded from the survival analysis by maternal HIV status.