Pediatric HIV–HBV Coinfection in Lusaka, Zambia: Prevalence and Short-Term Treatment Outcomes: Table 1.

Hepatitis B virus (HBV) is endemic in Africa, where it may occur as an HIV coinfection. Data remain limited on HIV–HBV epidemiology in Africa, particularly in children. Using programmatic data from pediatric HIV clinics in Lusaka, Zambia during 2011–2014, we analyzed the prevalence of chronic HBV coinfection (defined as a single positive hepatitis B surface antigen [HBsAg] test) and its impact on immune recovery and liver enzyme elevation (LEE) during the first year of antiretroviral therapy. Among 411 children and adolescents, 10.4% (95% confidence interval, 7.6–14.1) had HIV–HBV. Coinfected patients were more likely to have World Health Organization stage 3/4, LEE and CD4 <14% at care entry (all p < 0.05). During treatment, CD4 increases and LEE incidence were similar by HBsAg status. HBsAg positivity decreased (11.8% vs. 6.6%; p = 0.24) following HBV vaccine introduction. These findings support screening pediatric HIV patients in Africa for HBV coinfection. Dedicated cohorts are needed to assess long-term outcomes of coinfection

Immunologic Risk Factors for Early Mortality After Starting Antiretroviral Therapy in HIV-Infected Zambian Children

To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4+ and CD8+ T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4+ T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8+ effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4+ central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ≥85% for early and overall mortality, with bootstrapped sensitivities of 82–85% upon validation, supporting the predictive accuracy of the models. CD4+ and CD8+ T cell subsets may be more accurate predictors of early mortality than CD4+ T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART

Duration of cART Before Delivery and Low Infant Birthweight Among HIV-Infected Women in Lusaka, Zambia

To estimate the association between duration of combination antiretroviral therapy (cART) during pregnancy and low infant birthweight (LBW), among women ≥37 weeks gestation

Implementation and Operational Research: Distance From Household to Clinic and Its Association With the Uptake of Prevention of Mother-to-Child HIV Transmission Regimens in Rural Zambia

In rural settings, HIV-infected pregnant women often live significant distances from facilities that provide prevention of mother-to-child transmission (PMTCT) services

Non-virologic algorithms for predicting HIV infection among HIV-exposed infants under 12 weeks of age

Early initiation of antiretroviral therapy (ART) has been shown to reduce mortality among perinatally HIV-infected infants, but availability of virologic testing remains limited in many settings

A risk score to identify HIV-infected women most likely to become lost to follow-up in the postpartum period

Access to lifelong combination antiretroviral therapy (cART) is expanding among HIV-infected pregnant and breastfeeding women throughout sub-Saharan Africa. For this strategy to meaningfully improve maternal HIV outcomes, retention in HIV care is essential. We developed a risk score to identify women with high likelihood of loss to follow-up (LTFU) at 6 months postpartum from HIV care, using data from public health facilities in Lusaka, Zambia. LTFU was defined as not presenting for HIV care within 60 days of the last scheduled appointment. We used logistic regression to assess demographic, obstetric, and HIV predictors of LTFU and to develop a simple risk score. Sensitivity and specificity were assessed at each risk score cut-point. Among 2,029 pregnant women initiating cART between 2009 and 2011, 507 (25%) were LTFU by 6 months postpartum. Parity, education, employment status, WHO clinical stage, duration of cART during pregnancy, and number of antenatal care visits were associated with LTFU (p-value<0.10). A risk score cut-point of 11 (42nd percentile) had 85% sensitivity (95% CI 82%, 88%) and 22% specificity (95% CI 20%, 24%) to detect women LTFU and would exclude 20% of women from a retention intervention. A risk score cut-point of 18 (69th percentile) identified the 23% of women with the highest probability of LTFU and had sensitivity 32% (95% CI 28%, 36%) and specificity 80% (95% CI 78%, 82%). A risk score approach may be useful to triage a subset of women most likely to be LTFU for targeted retention interventions

Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia

Background Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. Methods We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6–10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. Results Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6–10 weeks were lower among infants who were HEU vs HU [β = − 0.29 (95% CI: − 0.46, − 0.12) and [β = − 0.42 (95% CI: − 0.68, − 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [β = − 0.28 CI: − 0.50, − 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6–10 weeks, [β = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [β = − 0.30 CI: − 0.59, − 0.01)] at 6 months, without other anthropometric differences at either site. Conclusion Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU

The epidemiology of adolescents living with perinatally acquired HIV: A cross-region global cohort analysis

Background Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia. Methods and findings Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria. Conclusion To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses

Contraceptive use among HIV-infected women and men receiving antiretroviral therapy in Lusaka, Zambia: a cross-sectional survey

Abstract Background Family planning (FP) is an essential health service and an important part of comprehensive HIV care. However, there is limited information about the contraceptive needs of people living with HIV in sub-Saharan Africa, which in turn has hampered efforts to expand and integrate FP services into existing HIV programs. Methods We performed a cross-sectional survey to determine FP prevalence and predictors among HIV-positive women and men attending 18 public antiretroviral therapy (ART) clinics in Lusaka, Zambia. Trained peer counselors administered the 10-question survey to those seeking care for five days at each of the target sites. Results From February to April 2014, we surveyed 7,046 HIV-infected patients receiving routine HIV services. Use of modern contraception was reported by 69 % of female ART patients and 79 % of male ART patients. However, highly effective contraceptive use and dual method use were low among women (38 and 25 %, respectively) and men (19 and 14 %, respectively). HIV disclosure status (adjusted odds ratio (AOR) = 4.91, 95 % confidence interval (CI) = 3.32–7.24 for women, AOR = 3.58, 95 % CI = 2.39–5.38 for men) and sexual activity in the last 6 months (AOR = 5.80, 95 % CI = 4.51–7.47 for women, AOR = 6.24, 95 % CI = 3.51–11.08 for men) were associated with modern contraceptive use in multivariable regression. Most respondents said they would access FP services if made available within ART clinic. Conclusions While FP-ART integration may be a promising strategy for increasing FP service uptake, such services must focus on assessing sexual activity and advocating for dual method use to increase effective contraceptive use and prevent unintended pregnancies

Development and validation of a novel scale for antiretroviral therapy readiness among pregnant women in urban Zambia with newly diagnosed HIV infection

Abstract Background Women who are newly diagnosed with HIV infection during pregnancy may not be ready to immediately initiate lifelong antiretroviral therapy (ART; called Option B +) as is recommended. Lack of “readiness” drives early disengagement from care and undermines prevention of HIV transmission to infants. Several studies have shown high early attrition of women initiating ART in pregnancy. Although poor ART uptake and adherence have been attributed to various factors including stigma, disclosure issues and structural issues, there is no standard way of determining which pregnant woman will face challenges and therefore need additional support. We developed and validated a novel ART readiness tool in Lusaka, Zambia. Methods The aim of this study was to develop and validate a tool that could be used to assess how ready a newly diagnosed pregnant woman living with HIV would be to initiate ART on the day of diagnosis. Using a mixed method design, we conducted this study in three public-setting health facilities in Lusaka, Zambia. Informed by qualitative research and literature review, we identified 27 candidate items. We assessed content validity using expert and target population judgment approaches. We administered the 27-item questionnaire to 454 newly diagnosed pregnant women living with HIV, who were enrolled into a randomized trial (trials number NCT02459678). We performed item reduction analysis and used Cronbach’s alpha coefficient of 0.70 as threshold for reliability. Results A total of 454 pregnant women living with HIV enrolled in the study between March 2017 and December 2017; 452 had complete data for analysis. The correlation coefficient between the 27 items on the completed ART readiness scale ranged from 0.31 to 0.70 while item discrimination index ranged from -0.01 to 2.38. Sixteen items were selected for the final scale, representing three domains, which we classified as “internalized and anticipated HIV stigma”, “partner support” and “anticipated structural barriers”. Conclusion We developed and validated a tool that could be used to assess readiness of newly diagnosed women living with HIV to initiate ART. This ART readiness tool could allow clinics to tailor limited resources to pregnant women living with HIV needing additional support to initiate and remain on ART