Benzathine penicillin G stockouts and other barriers to documented syphilis treatment in pregnancy in Zambia.

OBJECTIVE: The prevalence of syphilis in Zambia remains high and is a critical public health concern. The Zambian Ministry of Health recommends universal screening and same-day treatment for syphilis in pregnancy, yet the syphilis screening rate is low, and treatment is poorly documented. The goal of this study was to document syphilis treatment rates and associated factors among pregnant women in care in Zambia. METHODS: This retrospective cohort study included pregnant women diagnosed with syphilis according to rapid plasma reagin (RPR) screening during routine antenatal care (ANC) in Lusaka, Zambia in 2018-2019. The main outcome of interest was lack of documented BPG treatment during pregnancy. Additional information about pregnancy and neonatal outcomes, partner referral for therapy, and facility level stockout data were included. Patient characteristics were compared by treatment status using Pearson Chi-Square Test and logistic regression models were created to estimate the association between individual level-factors, facility type, and lack of BPG treatment. A Cochran-Mantel-Haenszel test was used to evaluate facility-level data with significance set at p<0.05. RESULTS: Among 1,231 pregnant women who screened positive for syphilis at clinic, 643 (52%) lacked documented antibiotic treatment at the facility. BPG was the only antibiotic used to treat syphilis in the cohort and 8% of sex partners had evidence of referral for therapy. Preterm delivery rates were higher in women without documented BPG (43% vs 32%; p = 0.003). In adjusted models, only calendar year and hospital facility type were associated with lack of treatment. At the facility level, annual syphilis screening rates ranged from 37-65% and most (7/10) clinics reported at least one stockout of BPG. CONCLUSION: Treatment rates for syphilis in pregnancy in Zambia were low and BPG medication stockouts at the facility level were common. A consistent supply of BPG at all ANC facilities is needed to facilitate timely treatment and improve birth outcomes.

Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.

BACKGROUND: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. RESULTS: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.

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

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.

Genital Tract Infections in Women, Pregnancy and Neonates.

Treatable genital tract infections in women are common and most are transmitted via sexual contact with the potential for vertical transmission during pregnancy. Adverse infection outcomes include pelvic inflammatory disease, infertility, ectopic pregnancy, preterm delivery, and congenital or neonatal infection. Highly sensitive molecular diagnostic testing for genital tract infections is now recommended in many countries. Unfortunately, this testing is not yet widely available in low- and middle-income countries because of cost. Improved access to early diagnosis and treatment for curable genital tract infections is critical to improving women's health and reaching global STI elimination targets by 2030.

Temporal changes in paediatric and adolescent HIV outcomes across the care continuum in Zambia: an interrupted time-series analysis.

BACKGROUND: Paediatric and adolescent HIV treatment programmes in sub-Saharan Africa have rapidly expanded and evolved over the past decade. Real-world evidence of how the implementation of new policies over time has affected treatment outcomes is inadequate, but is crucial for guiding the implementation of the next phases of the HIV treatment response for children. We examined how treatment outcomes in Zambia's national paediatric and adolescent HIV treatment programmes have changed over time as new policies were implemented. METHODS: We used data from Zambia's routine electronic health record to analyse children and adolescents living with HIV who were antiretroviral therapy (ART) naive between the ages of 0 and 19 years who were newly enrolled in care between Jan 1, 2011, and March 31, 2019, at 102 health facilities in Lusaka and Western provinces supported by the Centre for Infectious Disease Research in Zambia. Sociodemographic factors, clinical data, facility-level data, and visit history were obtained from the national electronic health record and laboratory systems used in routine HIV care in Zambia. We aimed to characterise the changes in the distribution of the age and sex of new enrolees over time. We used an interrupted time-series design to examine the rates of ART initiation, retention in care, time to ART initiation, and first-line ART regimens among new enrolees across different age strata as they changed over time with the adoption of new ART guidelines in 2014 and 2017. FINDINGS: Between Jan 1, 2011, and March 31, 2019, 26 214 children and adolescents living with HIV who were ART naïve were newly enrolled at one of 102 ART facilities in two provinces in Zambia. Rates of new enrolees increased by 25-35% among children younger than 15 years over time, but by 92·3% between 2011 and 2017 among adolescents, with the largest absolute increase among adolescent girls. Rates of ART initiation increased steadily and in parallel across all age groups from before the implementation of the 2014 guidelines to after the implementation of the 2017 guidelines (<2 years, 42·4% for 2014 and 81·6% for 2017; 2 to <5 years, 39·3% for 2014 and 82·8% for 2017; 5 to <15 years, 49·2% for 2014 and 86·6% for 2017; 15 to 19 years, 52·4% for 2014 and 86·2% for 2017); median time to ART initiation went from 2-3 months to same-day initiation during this same time period. Rates of retention on ART 6 months after linkage saw much smaller improvements over time (<2 years, 35·4% for 2014 and 52·0% for 2017; 2 to <5 years, 40·2% for 2014 and 54·4% for 2017; 5 to <15 years, 46·7% for 2014 and 63·4% for 2017; 15 to 19 years, 40·1% for 2014 and 52·7% for 2017). INTERPRETATION: Improvements in ART initiation occurred largely in parallel across age groups over time, despite universal treatment being implemented at different timepoints for different ages. Although the rates of ART initiation reach high levels, retention on ART was low. This analysis provides a comprehensive examination of how paediatric and adolescent outcomes have evolved over the past decade in Zambia and identifies where more targeted efforts will be needed over the next decade. FUNDING: National Institutes of Health.

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 [ß = - 0.29 (95% CI: - 0.46, - 0.12) and [ß = - 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 [ß = - 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, [ß = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [ß = - 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.

Identifying barriers to ART initiation and adherence: An exploratory qualitative study on PMTCT in Zambia.

BACKGROUND: Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery. METHODS: We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework. RESULTS: Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one's children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women's intrinsic motivation. CONCLUSION: The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men's role in couples' joint decision-making and women's maternal love as motivators for adherence.

Effect on growth of exposure to maternal antiretroviral therapy in breastmilk versus extended infant nevirapine prophylaxis among HIV-exposed perinatally uninfected infants in the PROMISE randomized trial.

BACKGROUND: Malnutrition is highly prevalent in HIV-exposed perinatally uninfected infants (HEUs) increasing the risk of morbidity and mortality throughout the life course. We set out to compare the effect of postnatal exposure to maternal antiretroviral therapy (mART) in breastmilk versus infant Nevirapine prophylaxis (iNVP) on somatic growth of HEUs in the randomized PROMISE trial. METHODS AND FINDINGS: We randomized 2431 mothers with HIV and their 2444 HEUs from six African countries and India 6-14 days after delivery to mART or iNVP for prevention of breastmilk HIV transmission. The mART regimen contained tenofovir/emtricitabine (99%) plus lopinavir/ritonavir. Infant growth parameters were compared at postnatal week 10, 26, 74 and 104 using World Health Organization (WHO) z-scores for length-for-age (LAZ), weight-for-age (WAZ), and head circumference-for-age (HCAZ). Week 26 LAZ was the primary endpoint measure. Student T-tests compared mean LAZ, WAZ, and HCAZ; estimated mean and 95% confidence interval (CI) are presented. Maternal and infant baseline characteristics were comparable between study arms. The estimated median breastfeeding duration was 70 weeks. After a mean follow-up of 88 weeks, mean LAZ and WAZ were below the WHO reference population mean at all timepoints, whereas mean HCAZ was not. The mART and iNVP arms did not differ for the primary outcome measure of LAZ at week 26 (p-value = 0.39; estimated mean difference (95%CI) of -0.05 (-0.18, 0.07)) or any of the other secondary growth outcome measures or timepoints (all p-values≥0.16). Secondary analyses of the primary outcome measure adjusting for week 0 LAZ and other covariates did not change these results (all p-values≥0.09). However, infants assigned to mART were more likely to have stunting compared to iNVP infants at week 26 (odds ratio (95% CI): 1.28 (1.05, 1.57)). CONCLUSIONS: In HEUs, growth effects from postnatal exposure to mART compared to iNVP were comparable for measures on length, weight and head circumference with no clinically relevant differences between the groups. Despite breastfeeding into the second year of life, length and weight were below reference population means at all ages in both arms. Further investment is needed to optimize postnatal growth of infants born to women with HIV. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT01061151.

Effect of Enhanced Adherence Package on Early ART Uptake Among HIV-Positive Pregnant Women in Zambia: An Individual Randomized Controlled Trial.

We evaluated the effect of an option B-plus Enhanced Adherence Package (BEAP), on early ART uptake in a randomized controlled trial. HIV-positive, ART naïve pregnant women in Lusaka, Zambia, were randomized to receive BEAP (phone calls/home visits, additional counseling, male partner engagement and missed-visit follow-up) versus standard of care (SOC). The primary outcome was initiating and remaining on ART at 30 days. Analysis was by intention to treat (ITT) using logistic regression. Additional per protocol analysis was done. We enrolled 454 women; 229 randomized to BEAP and 225 to SOC. Within 30 days of eligibility, 445 (98.2%) initiated ART. In ITT analysis, 82.5% BEAP versus 80.4% SOC participants reached primary outcome (crude relative risk [RR] 1.03; 95% confidence interval [CI] 0.91-1.16; Wald test statistic = 0.44; p-value = 0.66). In per protocol analysis, (92 participants (40.2%) excluded), 91.9% BEAP versus 80.4% SOC participants reached primary outcome (crude RR 1.14; 95% CI 1.02-1.29; Wald test statistic = 2.23; p-value = 0.03). Early ART initiation in pregnancy was nearly universal but there was early drop out suggesting need for additional adherence support.This trial was registered at ClinicalTrials.gov (trials number NCT02459678) on May 14, 2015.

The impact of short term Antiretroviral Therapy (ART) interruptions on longer term maternal health outcomes-A randomized clinical trial.

BACKGROUND: Given well documented challenges faced by pregnant women living with HIV taking lifetime ART, it is critical to understand the impact of short-term ART exposure followed by treatment interruption on maternal health outcomes. METHODS: HIV+ breastfeeding (BF) and Formula Feeding (FF) women with CD4 counts > 350 cells/mm3, enrolled in the 1077BF/1077FF PROMISE trial were followed to assess the effect of ART during pregnancy and breastfeeding respectively. The first analysis compared ART use limited to the antepartum period (AP-only) relative to women randomized to Zidovudine. The second analysis included women with no pregnancy combination ART exposure; and compared women randomized to either ART or no ART during postpartum (PP-only). Both analyses included follow-up time beyond breastfeeding period. The primary outcome was progression to AIDS and/or death. Secondary outcomes included adverse events and HIV-related events. RESULTS: 3490 and 1137 HIV+ women were enrolled from 14 sites in Africa and India from April 2011 through September 2014 in cohort AP-only and PP-only, respectively. Most were Black African (96%); median age was 27 years; 97% were WHO Clinical Stage I; and most had a screening CD4 count ≥500 cells/mm3 (78%). The rate of progression to AIDS and/or death was similar and low across all comparison arms (AP comparison, HR = 1.14, 95%CI (0.44, 2.96), p-value = 0.79). In the PP-only cohort, the rate of WHO stage 2-3 events was lower for women randomized to ART(HR = 0.65, 95% CI 0.42, 1.01, p-value = 0.05). CONCLUSION: The incidence of AIDS and/or death was low in pregnant/postpartum HIV+ women with highCD4 cell counts for all comparison arms. This provides some reassurance that there were limited consequences for short term ART interruption in this group of asymptomatic HIV+ women during up to 4 years of follow up; and underscores that even short term ART exposure postpartum may reduce the risk of WHO grade 2-3 disease progression.

Stunting and growth velocity of adolescents with perinatally acquired HIV: differential evolution for males and females. A multiregional analysis from the IeDEA global paediatric collaboration.

INTRODUCTION: Stunting is a key issue for adolescents with perinatally acquired HIV (APH) that needs to be better understood. As part of the IeDEA multiregional consortium, we described growth evolution during adolescence for APH on antiretroviral therapy (ART). METHODS: We included data from sub-Saharan Africa, the Asia-Pacific, and the Caribbean, Central and South America regions collected between 2003 and 2016. Adolescents on ART, reporting perinatally acquired infection or entering HIV care before 10 years of age, with at least one height measurement between 10 and 16 years of age, and followed in care until at least 14 years of age were included. Characteristics at ART initiation and at 10 years of age were compared by sex. Correlates of growth defined by height-for-age z-scores (HAZ) between ages 10 and 19 years were studied separately for males and females, using linear mixed models. RESULTS: Overall, 8737 APH were included, with 46% from Southern Africa. Median age at ART initiation was 8.1 years (interquartile range (IQR) 6.1 to 9.6), 50% were females, and 41% were stunted (HAZ<-2 SD) at ART initiation. Males and females did not differ by age and stunting at ART initiation, CD4 count over time or retention in care. At 10 years of age, 34% of males were stunted versus 39% of females (p < 0.001). Females had better subsequent growth, resulting in a higher prevalence of stunting for males compared to females by age 15 (48% vs. 25%) and 18 years (31% vs. 15%). In linear mixed models, older age at ART initiation and low CD4 count were associated with poor growth over time (p < 0.001). Those stunted at 10 years of age or at ART initiation had the greatest growth improvement during adolescence. CONCLUSIONS: Prevalence of stunting is high among APH worldwide. Substantial sex-based differences in growth evolution during adolescence were observed in this global cohort, which were not explained by differences in age of access to HIV care, degree of immunosuppression or region. Other factors influencing growth differences in APH, such as differences in pubertal development, should be better documented, to guide further research and inform interventions to optimize growth and health outcomes among APH.

Impact of the Umoyo mother-infant pair model on HIV-positive mothers' social support, perceived stigma and 12-month retention of their HIV-exposed infants in PMTCT care: evidence from a cluster randomized controlled trial in Zambia.

BACKGROUND: Public health systems in resource-constrained settings have a critical role to play in the elimination of HIV transmission but are often financially constrained. This study is an evaluation of a mother-infant-pair model called "Umoyo," which was designed to be low cost and scalable in a public health system. Facilities with the Umoyo model dedicate a clinic day to provide services to only HIV-exposed infants (HEIs) and their mothers. Such models are in operation with reported success in Zambia but have not been rigorously tested. This work establishes whether the Umoyo model would improve 12-month retention of HEIs. METHODS: A cluster randomized trial including 28 facilities was conducted across two provinces of Zambia to investigate the impact on 12-month retention of HEIs in care. These facilities were offering Prevention of Mother-to-Child-Transmission (PMTCT) services and supported by the same implementing partner. Randomization was achieved by use of the covariate-constrained optimization technique. Secondary outcomes included the impact of Umoyo clinics on social support and perceived HIV stigma among mothers. For each of the outcomes, a difference-in-difference analysis was conducted at the facility level using the unweighted t test. RESULTS: From 13 control (12-month retention at endline: 45%) and 11 intervention facilities (12-month retention at endline: 33%), it was found that Umoyo clinics had no impact on 12-month retention of HEIs in the t test (- 11%; 99% CI - 40.1%, 17.2%). Regarding social support and stigma, the un-weighted t test showed no impact though sensitivity tests showed that Umoyo had an impact on increasing social support (0.31; 99% CI 0.08, 0.54) and reducing perceived stigma from health care workers (- 0.27; 99% CI - 0.46, - 0.08). CONCLUSION: The Umoyo approach of having a dedicated clinic day for HEIs and their mothers did not improve retention of HEIs though there are indications that it can increase social support among mothers and reduce stigma. Without further support to the underlying health system, based on the evidence generated through this evaluation, the Umoyo clinic day approach on its own is not considered an effective intervention to increase retention of HIV-exposed infants. TRIAL REGISTRATION: Pan African Clinical Trial Registry, ID: PACTR201702001970148 . Prospectively registered on 13 January 2017.

Access to antiretroviral therapy in HIV-infected children aged 0-19 years in the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium, 2004-2015: A prospective cohort study.

INTRODUCTION: Access to antiretroviral therapy (ART) is a global priority. However, the attrition across the continuum of care for HIV-infected children between their HIV diagnosis and ART initiation is not well known. We analyzed the time from enrollment into HIV care to ART initiation in HIV-infected children within the International Epidemiology Databases to Evaluate AIDS (IeDEA) Global Cohort Consortium. METHODS AND FINDINGS: We included 135,479 HIV-1-infected children, aged 0-19 years and ART-naïve at enrollment, between 1 January 2004 and 31 December 2015, in IeDEA cohorts from Central Africa (3 countries; n = 4,948), East Africa (3 countries; n = 22,827), West Africa (7 countries; n = 7,372), Southern Africa (6 countries; n = 93,799), Asia-Pacific (6 countries; n = 4,045), and Latin America (7 countries; n = 2,488). Follow-up in these cohorts is typically every 3-6 months. We described time to ART initiation and missed opportunities (death or loss to follow-up [LTFU]: last clinical visit >6 months) since baseline (the date of HIV diagnosis or, if unavailable, date of enrollment). Cumulative incidence functions (CIFs) for and determinants of ART initiation were computed, with death and LTFU as competing risks. Among the 135,479 children included, 99,404 (73.4%) initiated ART, 1.9% died, 1.4% were transferred out, and 20.4% were lost to follow-up before ART initiation. The 24-month CIF for ART initiation was 68.2% (95% CI: 67.9%-68.4%); it was lower in sub-Saharan Africa-ranging from 49.8% (95% CI: 48.4%-51.2%) in Central Africa to 72.5% (95% CI: 71.5%-73.5%) in West Africa-compared to Latin America (71.0%, 95% CI: 69.1%-72.7%) and the Asia-Pacific (78.3%, 95% CI: 76.9%-79.6%). Adolescents aged 15-19 years and infants <1 year had the lowest cumulative incidence of ART initiation compared to other ages: 62.2% (95% CI: 61.6%-62.8%) and 66.4% (95% CI: 65.7%-67.0%), respectively. Overall, 49.1% were ART-eligible per local guidelines at baseline, of whom 80.6% initiated ART. The following children had lower cumulative incidence of ART initiation: female children (p < 0.01); those aged <1 year, 2-4 years, 5-9 years, and 15-19 years (versus those aged 10-14 years, p < 0.01); those who became eligible during follow-up (versus eligible at enrollment, p < 0.01); and those receiving care in low-income or lower-middle-income countries (p < 0.01). The main limitations of our study include left truncation and survivor bias, caused by deaths of children prior to enrollment, and use of enrollment date as a proxy for missing data on date of HIV diagnosis, which could have led to underestimation of the time between HIV diagnosis and ART initiation. CONCLUSIONS: In this study, 68% of HIV-infected children initiated ART by 24 months. However, there was a substantial risk of LTFU before ART initiation, which may also represent undocumented mortality. In 2015, many obstacles to ART initiation remained, with substantial inequities. More effective and targeted interventions to improve access are needed to reach the target of treating 90% of HIV-infected children with ART.

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

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.

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 (SSA). 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 2029 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 < .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.

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

OBJECTIVE: To estimate the association between duration of combination antiretroviral therapy (cART) during pregnancy and low infant birthweight (LBW), among women ≥37 weeks of gestation. DESIGN: We conducted a retrospective cohort study of HIV-infected women who met eligibility criteria based on CD4 count ≤350 but had not started cART at entry into antenatal care. Our cohort was restricted to births that occurred ≥37 weeks of gestation. METHODS: We used Poisson models with robust variance estimators to estimate risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Of 50,765 HIV-infected women with antenatal visits between January 2009 and September 2013, 4474 women met the inclusion criteria. LBW occurred in 302 pregnancies (7%). Nearly two-thirds of women (62%) eligible to initiate cART never started treatment. Overall, 14% were on cART for ≤8 weeks, 22% for 9-20 weeks, and 2% for 21-36 weeks. There was no evidence of an increased risk of LBW for women receiving cART for ≤8 weeks (RR = 1.22; 95% CI: 0.77 to 1.91), 9-20 weeks (RR = 1.23; 95% CI: 0.82 to 1.83), or 21-36 weeks (RR = 0.87; 95% CI: 0.22 to 3.46), compared with women who never initiated treatment. These findings were consistent across several sensitivity analyses. CONCLUSIONS: Longer duration of cART was not associated with poor fetal growth among term pregnancies in our cohort. However, the relationship between cART and adverse pregnancy outcomes remains complicated. Continued work is required to investigate causality. An understanding cART's impact on adverse pregnancy outcomes is essential as cART becomes the cornerstone of preventing mother-to-child transmission programs globally.

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.

BACKGROUND: In rural settings, HIV-infected pregnant women often live significant distances from facilities that provide prevention of mother-to-child transmission (PMTCT) services. METHODS: We offered universal maternal combination antiretroviral regimens in 4 pilot sites in rural Zambia. To evaluate the impact of services, we conducted a household survey in communities surrounding each facility. We collected information about HIV status and antenatal service utilization from women who delivered in the past 2 years. Using household Global Positioning System coordinates collected in the survey, we measured Euclidean (i.e., straight line) distance between individual households and clinics. Multivariable logistic regression and predicted probabilities were used to determine associations between distance and uptake of PMTCT regimens. RESULTS: From March to December 2011, 390 HIV-infected mothers were surveyed across four communities. Of these, 254 (65%) had household geographical coordinates documented. One hundred sixty-eight women reported use of a PMTCT regimen during pregnancy including 102 who initiated a combination antiretroviral regimen. The probability of PMTCT regimen initiation was the highest within 1.9 km of the facility and gradually declined. Overall, 103 of 145 (71%) who lived within 1.9 km of the facility initiated PMTCT versus 65 of 109 (60%) who lived farther away. For every kilometer increase, the association with PMTCT regimen uptake (adjusted odds ratio: 0.90, 95% confidence interval: 0.82 to 0.99) and combination antiretroviral regimen uptake (adjusted odds ratio: 0.88, 95% confidence interval: 0.80 to 0.97) decreased. CONCLUSIONS: In this rural African setting, uptake of PMTCT regimens was influenced by distance to health facility. Program models that further decentralize care into remote communities are urgently needed.

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

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.

Changes in cellular immune activation and memory T-cell subsets in HIV-infected Zambian children receiving HAART.

BACKGROUND: Increased exposure to a broad array of pathogens in children residing in sub-Saharan Africa may lead to heightened immune activation and increased proportions of memory T cells. Changes in the size of these cellular subsets have implications for restoration of normal immune function after treatment with highly active antiretroviral therapy (HAART) and are not well characterized in young sub-Saharan African children. METHODS: CD4⁺ and CD8⁺ T-cell subsets were measured by flow cytometry in 157 HIV-infected Zambian children before and at 3-month intervals during HAART for up to 30 months and in 34 control children at a single study visit. RESULTS: Before HAART, HIV-infected children had higher levels of activated and effector memory (EM) CD4⁺ and CD8⁺ T cells, and lower levels of naive T cells and CD8⁺ T cells expressing IL-7Rα, compared with control children. The median duration of follow-up was 14.9 months (interquartile range, 6.4-23.2) among 120 HIV-infected children with at least 1 study follow-up visit. Levels of immune activation and EM CD4⁺ T cells declined within 6 months of HAART, but the percentages of EM CD4 T cells and effector CD8⁺ T cells remained elevated through 30 months of HAART. IL-7Rα-expressing CD8⁺ T cells increased with HAART, suggesting expansion of memory capacity. CONCLUSIONS: HAART significantly reduced levels of immune activation and EM CD4⁺ T cells, and promoted reconstitution of naive T cells and IL-7Rα-expressing CD8⁺ T cells. However, persistently high levels of EM CD4⁺ T cells in HIV-infected children may reflect chronic perturbations in T-cell subset composition.