Prevalence of undiagnosed HIV among children in South Africa, Côte d'Ivoire and Zimbabwe: a model-based analysis to inform paediatric HIV screening programmes.

INTRODUCTION: To improve the diagnosis and survival of children living with HIV (CLWH), the World Health Organization recommends testing approaches beyond traditional infant HIV testing programmes. Information about undiagnosed HIV prevalence among children of varying ages in the general population is needed to guide innovative national/subnational case-finding and testing approaches. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to estimate the prevalence of undiagnosed HIV in 2-, 5- and 10-year-old children in South Africa, Côte d'Ivoire and Zimbabwe in 2018. We simulated cohorts of children born in 2008 (10-year-olds), 2013 (5-year-olds) and 2016 (2-year-olds). Country-/year-specific inputs for pregnant/breastfeeding women included: HIV prevalence (4.2-32.3%), HIV incidence (0.03-0.24%/month), knowledge of HIV status (27-89%) and antiretroviral drug coverage (36-95%). Paediatric inputs included early infant testing coverage (6-95%) and breastfeeding duration (0-20 months). We projected the proportion of surviving CLWH in whom HIV remained undiagnosed and the undiagnosed HIV prevalence among surviving children of each age in the general population. For children born in 2016, we projected survival and diagnosis of all CLWH through 2026. We conducted sensitivity analyses on model parameters. RESULTS: In 2018, the projected proportion of surviving CLWH whose HIV remained undiagnosed in South Africa/Côte d'Ivoire/Zimbabwe was 44.2%/55.8%/52.9% among 2-year-old CLWH; 29.0%/37.8%/33.2% among 5-year-old CLWH; and 18.3%/25.4%/23.1% among 10-year-old CLWH. Projected general population undiagnosed HIV prevalence in South Africa/Côte d'Ivoire/Zimbabwe was 0.44%/0.32%/0.68% among 2-year-olds; 0.25%/0.17%/0.41% among 5-year-olds; and 0.24%/0.14%/0.38% among 10-year-olds. Among all CLWH born in 2016, 50-54% were projected to die without HIV diagnosis (and subsequently without treatment) within 10 years after birth; 80-85% of these deaths occurred in the first 2 years. CONCLUSIONS: Projected population-level undiagnosed HIV prevalence is low and sharply decreases after age 2, with more CLWH dying than being diagnosed. Despite low undiagnosed prevalence in the general population of older children, we project that a large proportion of CLWH remain undiagnosed, suggesting that innovative strategies targeting untested children of all ages outside of health facility settings should be prioritized. Programmes could consider routine testing of the general population of children below 2 in all settings and children of all ages in high-prevalence settings.

Potential of Long-Acting Products to Transform the Treatment and Prevention of Human Immunodeficiency Virus (HIV) in Infants, Children, and Adolescents.

Long-acting antiretroviral products have the potential to transform human immunodeficiency virus (HIV) prevention and treatment approaches in pediatric populations. Broadly neutralizing antibodies and/or long-acting antiretroviral formulations by injection could dramatically improve provision of HIV prophylaxis and/or early treatment to newborns and infants at risk of HIV infection. Challenges in daily oral antiretroviral administration to toddlers and school age children living with HIV may be relieved by use of long-acting formulations, but the pharmacokinetics and safety of these products in children must be studied before they can enter routine clinical use. Although some initial studies of broadly neutralizing antibodies and injectable long-acting agents in infants and young children are underway, more studies of these and other long-acting products are needed. For many adolescents, compliance with daily medication administration is especially challenging. Long-acting products hold particular promise for adolescents living with HIV as well as those at high risk of HIV acquisition, and adolescents can usually be included in the drug development pipeline simultaneously with adults. Long-acting products have the potential to provide alternatives to lifelong daily oral drug administration across the pediatric age spectrum, leading to more effective prevention and treatment of HIV infection in infants, children, and adolescents.

Standardized Definitions of In Utero Human Immunodeficiency Virus and Antiretroviral Drug Exposure Among Children.

In countries with high human immunodeficiency virus (HIV) prevalence, up to 30% of pregnant women are living with HIV, with fetal exposure to both HIV and antiretroviral therapy during pregnancy. In addition, pregnant women without HIV but at high risk of HIV acquisition are increasingly receiving HIV preexposure antiretroviral prophylaxis (PrEP). Investments are being made to establish and follow cohorts of children to evaluate the long-term effects of in utero HIV and antiretroviral exposure. Agreement on a key set of definitions for relevant exposures and outcomes is important both for interpreting individual study results and for comparisons across cohorts. Harmonized definitions of in utero HIV and antiretroviral drug (maternal treatment or PrEP) exposure will also facilitate improved classification of these exposures in future observational studies and clinical trials. The proposed definitions offer a uniform approach to facilitate the consistent description and estimation of effects of HIV and antiretroviral exposures on key child health outcomes.

Antiretroviral Adherence, Elevated Viral Load, and Drug Resistance Mutations in Human Immunodeficiency Virus-infected Women Initiating Treatment in Pregnancy: A Nested Case-control Study.

BACKGROUND: Elevated viral load (VL) early after antiretroviral therapy (ART) initiation appears frequently in pregnant and postpartum women living with human immunodeficiency virus; however the relative contributions of pre-ART drug resistance mutations (DRMs) vs nonadherence in the etiology of elevated VL are unknown. METHODS: Within a cohort of women initiating ART during pregnancy in Cape Town, South Africa, we compared women with elevated VL after initial suppression (cases, n = 80) incidence-density matched to women who maintained suppression over time (controls, n = 87). Groups were compared on pre-ART DRMs and detection of antiretrovirals in stored plasma. RESULTS: The prevalence of pre-ART DRMs was 10% in cases and 5% in controls (adjusted odds ratio [aOR], 1.53 [95% confidence interval {CI}, .4-5.9]); all mutations were to nonnucleoside reverse transcriptase inhibitors. At the time of elevated VL, 19% of cases had antiretrovirals detected in plasma, compared with 87% of controls who were suppressed at a matched time point (aOR, 131.43 [95% CI, 32.8-527.4]). Based on these findings, we estimate that <10% of all elevated VL in the cohort may be attributable to pre-ART DRMs vs >90% attributable to ART nonadherence. CONCLUSIONS: DRMs account for a small proportion of all elevated VL among women occurring in the 12 months after ART initiation during pregnancy in this setting, with nonadherence appearing to drive most episodes of elevated VL. Alongside the drive for access to more robust antiretroviral agents in resource-limited settings, there is an ongoing need for effective strategies to support ART adherence in this patient population.

Re-recruiting postpartum women living with HIV into a follow-up study in Cape Town, South Africa.

OBJECTIVE: Recruitment and retention present major challenges to longitudinal research in maternal and child health, yet there are few insights into optimal strategies that can be employed in low-resource settings. Following prior participation in a longitudinal study following women living with HIV through pregnancy and breastfeeding in Cape Town, women were re-contacted at least 18 months after the last study contact and were invited to attend an additional follow-up visit. We describe lessons learnt and offer recommendations for a multiphase recruitment approach. RESULTS: Using telephone calls, home visits, clinic tracing and Facebook/WhatsApp messages, we located 387 of the 463 eligible women and successfully enrolled 353 (91% of those contacted). Phone calls were the most successful strategy, yielding 67% of enrolments. Over half of the women had changed their contact information since participation in the previous study. We recommend that researchers collect multiple contact details and use several recruitment strategies in parallel from the start of a study. Participants in longitudinal studies may require frequent contact to update contact information, particularly in settings where mobility is common.

Risks and Benefits of Dolutegravir- and Efavirenz-Based Strategies for South African Women With HIV of Child-Bearing Potential: A Modeling Study.

Background: Dolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception. Objective: To project clinical outcomes of ART policies for women of child-bearing potential in South Africa. Design: Model of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach). Data Sources: Published data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women). Target Population: 3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children. Time Horizon: 5 years. Perspective: Societal. Intervention: EFV, DTG, and WHO approach. Outcome Measures: Deaths among women and children, sexual and pediatric HIV transmissions, and NTDs. Results of Base-Case Analysis: Compared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths). Results of Sensitivity Analysis: Women's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater. Limitation: Uncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses. Conclusion: Although NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential. Primary Funding Source: National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Massachusetts General Hospital; and Harvard University Center for AIDS Research.

Experiences of HIV-positive postpartum women and health workers involved with community-based antiretroviral therapy adherence clubs in Cape Town, South Africa.

BACKGROUND: The rollout of universal, lifelong treatment for all HIV-positive pregnant and breastfeeding women ("Option B+") has rapidly increased the number of women initiating antiretroviral treatment (ART) and requiring ART care postpartum. In a pilot project in South Africa, eligible postpartum women were offered the choice of referral to the standard of care, a local primary health care clinic, or a community-based model of differentiated ART services, the adherence club (AC). ACs have typically enrolled only non-pregnant and non-postpartum adults; postpartum women had not previously been referred directly from antenatal care. There is little evidence regarding postpartum women's preferences for and experiences of differentiated models of care, or the capacity of this particular model to cater to their specific needs. This qualitative paper reports on feedback from both postpartum women and health workers who care for them on their respective experiences of the AC. METHODS: One-on-one in-depth qualitative interviews were conducted with 19 (23%) of the 84 postpartum women who selected the AC and were retained at approximately 12 months postpartum, and 9 health workers who staff the AC. Data were transcribed and thematically analysed using NVivo 11. RESULTS: Postpartum women's inclusion in the AC was acceptable for both participants and health workers. Health workers were welcoming of postpartum women but expressed concerns about prospects for longer term adherence and retention, and raised logistical issues they felt might compromise trust with AC members in general. CONCLUSIONS: Enrolling postpartum women in mixed groups with the general adult population is feasible and acceptable. Preliminary recommendations are offered and may assist in supporting the specific needs of postpartum women transitioning from antenatal ART care. TRIAL REGISTRATION: Number NCT02417675 clinicaltrials.gov/ct2/show/record/NCT02417675 (retrospective reg.).

Pediatric HIV Treatment Gaps in 7 East and Southern African Countries: Examination of Modeled, Survey, and Routine Program Data.

BACKGROUND: Remarkable success in the prevention and treatment of pediatric HIV infection has been achieved in the past decade. Large differences remain between the estimated number of children living with HIV (CLHIV) and those identified through national HIV programs. We evaluated the number of CLHIV and those on treatment in Lesotho, Malawi, Swaziland, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We assessed the total number of CLHIV, CLHIV on antiretroviral treatment (ART), and national and regional ART coverage gaps using 3 data sources: (1) Joint United Nations Programme on HIV/AIDS model-based estimates and national program data used as input values in the models, (2) population-based HIV impact surveys (PHIA), and (3) program data from the President's Emergency Plan for AIDS Relief (PEPFAR)-supported clinics. RESULTS: Across the 7 countries, HIV prevalence among children aged 0-14 years ranged from 0.4% (Uncertainty Bounds (UB) 0.2%-0.6%) to 2.8% (UB: 2.2%-3.4%) according to the PHIA surveys, resulting in estimates of 520,000 (UB: 460,000-580,000) CLHIV in 2016-2017 in the 7 countries. This compared with Spectrum estimates of pediatric HIV prevalence ranging from 0.5% (UB: 0.5%-0.6%) to 3.5% (UB: 3.0%-4.0%) representing 480,000 (UB: 390,000-550,000) CLHIV. CLHIV not on treatment according to the PEPFAR, PHIA, and Spectrum for the countries stood at 48% (UB: 25%-60%), 49% (UB: 37%-50%), and 38% (UB: 24%-47%), respectively. Of 78 regions examined across 7 countries, 33% of regions (PHIA data) or 41% of regions (PEPFAR data) had met the ART coverage target of 81%. CONCLUSIONS: There are substantial gaps in the coverage of HIV treatment in CLHIV in the 7 countries studied according to all sources. There is continued need to identify, engage, and treat infants and children. Important inconsistencies in estimates across the 3 sources warrant in-depth investigation.

A Global Research Agenda for Pediatric HIV.

BACKGROUND: Despite progress, 2016 still saw 160,000 new infections and 120,000 AIDS-related deaths among children. Evidence gaps on how to best diagnose, treat, and deliver services to children living with HIV remain. A global research prioritization exercise was undertaken by WHO and CIPHER to focus research efforts in the context of diminishing resources. METHODS: The Child Health and Nutrition Research Initiative methodology was adapted and used, as described by Irvine et al. Outcomes were reviewed by an expert group and 5 priority themes identified for testing, antiretroviral treatment, and service delivery, accounting for existing policies, published literature and ongoing research. RESULTS: A total of 749 questions were submitted by 269 individuals from 62 countries. For HIV testing, priority themes included strategies and interventions to improve access, uptake and linkage to care, including with novel diagnostic tools and entry points beyond antenatal care. For treatment, priorities included strategies to improve adherence, short- and long-term outcomes and management of coinfections, optimal drug formulations, and early ART. For service delivery, priorities included strategies or interventions to improve access, uptake and retention in care, including psychosocial and family support and approaches to HIV disclosure and reduction of stigma and discrimination. CONCLUSIONS: This is the largest Child Health and Nutrition Research Initiative exercise undertaken in HIV. The results provide guidance to focus future research in pediatric HIV for impact. Global commitment to support priority research, adequate investment, and strong leadership is urgently needed to improve the health and well-being of children living with and affected by HIV.

Simulation Modeling and Metamodeling to Inform National and International HIV Policies for Children and Adolescents.

OBJECTIVE AND APPROACH: Computer-based simulation models serve an important purpose in informing HIV care for children and adolescents. We review current model-based approaches to informing pediatric and adolescent HIV estimates and guidelines. FINDINGS: Clinical disease simulation models and epidemiologic models are used to inform global and regional estimates of numbers of children and adolescents living with HIV and in need of antiretroviral therapy, to develop normative guidelines addressing strategies for diagnosis and treatment of HIV in children, and to forecast future need for pediatric and adolescent antiretroviral therapy formulations and commodities. To improve current model-generated estimates and policy recommendations, better country-level and regional-level data are needed about children living with HIV, as are improved data about survival and treatment outcomes for children with perinatal HIV infection as they age into adolescence and adulthood. In addition, novel metamodeling and value of information methods are being developed to improve the transparency of model methods and results, as well as to allow users to more easily tailor model-based analyses to their own settings. CONCLUSIONS: Substantial progress has been made in using models to estimate the size of the pediatric and adolescent HIV epidemic, to inform the development of guidelines for children and adolescents affected by HIV, and to support targeted implementation of policy recommendations to maximize impact. Ongoing work will address key limitations and further improve these model-based projections.

Psychiatric Disorders, Antiretroviral Medication Adherence and Viremia in a Cohort of Perinatally HIV-Infected Adolescents and Young Adults.

BACKGROUND: Perinatally HIV-infected (PHIV+) adolescents and young adults (AYA) are at risk for suboptimal antiretroviral therapy (ART) adherence and mental health and substance use problems that, in HIV-infected adults, predict nonadherence. Studies on the relationship between psychiatric and substance use disorders (SUD) and adherence among PHIV+ AYA are limited, but may be important for informing evidence-based interventions to promote adherence. METHODS: Data were analyzed from 3 annual follow-up interviews (FU2-FU4, N = 179) in a longitudinal study of PHIV+ AYA. Psychiatric disorders (anxiety, disruptive behavior, mood and SUD) were assessed with the Diagnostic Interview Schedule for Children. Adherence was self-reported missed ART doses within the past week. Viral load (VL) results were abstracted from medical charts. Multiple logistic regression analyzed cross-sectional associations between psychiatric disorders and (1) missed ART dose and (2) VL > 1000 copies/mL. Multiple linear regression assessed associations between psychiatric disorders and proportion of VL values >1000 copies/mL over time. RESULTS: At FU2, 53% of PHIV+ AYA had any psychiatric disorder, 35% missed an ART dose in the past week and 47% had a VL > 1000 copies/mL. At FU2, behavioral disorders were associated with missed dose (P = 0.009) and VL > 1000 (P = 0.019), and mood disorders were associated with missed dose (P = 0.041). At FU4, behavioral disorders were associated with missed dose (P = 0.009). Behavioral disorders (P = 0.041), SUD (P = 0.016) and any disorder (P = 0.008) at FU2 were associated with higher proportion of VLs >1000 across FU2-FU4. CONCLUSIONS: Addressing psychiatric disorder and SUD among PHIV+ AYA may improve ART adherence outcomes in this population. Targeted interventions should be developed and tested.

Pregnant and breastfeeding women: A priority population for HIV viral load monitoring.

Landon Myer and colleagues discuss viral load monitoring for pregnant HIV-positive women and those breastfeeding; ART treatments can suppress viral load and are key to preventing transmission to the child.

HIV birth testing and linkage to care for HIV-infected infants.

: On 5-6 May 2016, the division of AIDS of the National Institute of Allergy and Infectious Diseases convened a workshop on 'HIV Birth Testing and Linkage to Care for HIV Infected Infants.' The goal of the workshop was to evaluate birth testing for early infant diagnosis (EID) of HIV, delineate technological resources for advancing a point-of-care (POC) HIV test implementable at birth and chart out the implementation hurdles for initiating early antiretroviral therapy to HIV-infected infants diagnosed at birth. The workshop addressed research and regulatory needs involved in the optimization of POC EID testing and challenges associated with implementation of EID, focusing on testing at birth. Scientific gaps and areas of intervention to accelerate and scale-up EID initiatives and birth testing were identified. These include discussion of the evidence supporting an early mortality peak among HIV-infected infant and justifying a role for birth HIV testing, including POC testing; evaluation of the current POC EID technology pipeline and test performance characteristics required for effective programmatic uptake; mathematical modeling of different testing scenarios and solutions with inclusion of birth testing; the adoption of setting-specific EID testing algorithms to achieve efficient linkage to care including early antiretroviral therapy initiation; the development of appropriate quality assurance programs to ensure accuracy of test results and enable sustainability of the testing program. Addressing these gaps and answering these challenges will be important in helping improve outcomes for HIV-infected infants and accelerate achieving the Joint United Nations Program for HIV and AIDS 90-90-90 targets in children.

Frequency of Viremic Episodes in HIV-Infected Women Initiating Antiretroviral Therapy During Pregnancy: A Cohort Study.

Background: The numbers of human immunodeficiency virus (HIV)-infected women initiating antiretroviral therapy (ART) in pregnancy are increasing rapidly with global policy changes. There are widespread concerns about ART adherence during pregnancy and postpartum but few data on viral suppression (VS) over time in these populations. Methods: We followed a cohort of 523 women in Cape Town, South Africa, initiating ART in pregnancy (once-daily tenofovir 300 mg, emtricitabine 200 mg, and efavirenz 600 mg) and achieving VS (<50 copies/mL). Participants provided specimens through 12 months postpartum for batched viral load (VL) testing separate from routine care. Analyses described the incidence of major (>1000 copies/mL) and minor (50-1000 copies/mL) viremic episodes (VEs) and factors associated with major VEs. Results: In the cohort (median age, 28 years; median pre-ART VL, 3.99 copies/mL; 3% previously defaulted ART; 24% with previous exposure to short-course antiretrovirals), the median time of follow-up from VS was 322 days. Overall, 70% maintained VS throughout follow-up, 8% experienced minor VEs only, and at least 1 major VE was documented in 22% of women. In women with VEs, peak viremia (median, 3.79 log10 copies/mL) was linearly related to pre-ART VL. The incidence of major VEs after initial VS was independently associated with younger age, ART initiation during the third trimester, previous defaulting on ART, and postpartum follow-up. Conclusions: Viremia appears to occur frequently, particularly postpartum, among HIV-infected women after initial VS in this setting. More intensive VL monitoring is warranted in this population; the immediate causes and long-term implications of VE require investigation.

Community-Based HIV and Health Testing for High-Risk Adolescents and Youth.

Adolescents account for 40% of new HIV infections, and HIV testing strategies to increase uptake of testing are needed. A community-based adolescent and youth HIV and health testing campaign was conducted in seven slum neighborhoods of Port-au-Prince, Haiti, from December 2014 to September 2015. Community health workers provided community sensitization and recruited 10- to 24-year-olds to test for HIV, syphilis, gonorrhea/chlamydia, and to screen for tuberculosis (TB) and pregnancy. HIV-infected individuals were escorted to the GHESKIO HIV clinic for same-day enrollment in care. Among 3425 individuals eligible for testing, 3348 (98%) accepted an HIV test. HIV prevalence was 2.65% (n = 89). Median age was 19 [interquartile range (IQR) 17-20]; 73% were female. HIV prevalence was 0.6-7.4% across slum neighborhoods. All HIV-infected individuals enrolled in care the same day as testing; median CD4 was 529 cells/µL [IQR 363-761]. Syphilis prevalence was 2.60% (65/2536) and gonorrhea/chlamydia prevalence was 6.25% (96/1536). Among 168 (5%) individuals who reported TB symptoms, 7.7% (13/168) had microbiologically confirmed disease. One hundred twenty-nine females (5% of all females) were pregnant. This community-based testing campaign identified an adolescent and youth population with an HIV prevalence six times higher than the estimated national adolescent HIV prevalence (0.4%) in Haiti, including perinatally infected adolescents. This type of community-based campaign for HIV testing within a package of services can serve as a model for other resource-poor settings to identify high-risk adolescents and youth, and curb the global HIV epidemic among adolescents.

Brief Report: Impact of Option B+ on the Infant PMTCT Cascade in Lilongwe, Malawi.

This observational study compared uptake of infant prevention of mother-to-child transmission of HIV services pre/post implementation of Option B+ in Lilongwe, Malawi. There were 845 (pre) and 998 (post) births. Post-B+, infants had longer median predelivery maternal antiretroviral therapy {62 days [interquartile range (IQR): 38-94] pre-B+ vs. 95 days [IQR: 61-131] post-B+; P < 0.0001} and improved polymerase chain reaction testing (82.0% vs. 86.5%; P = 0.01) at younger median age [7.6 weeks (IQR: 6.6-10.9) vs. 6.9 (IQR: 6.4-8.1); P < 0.0001]. Proportion testing polymerase chain reaction positive decreased (4.6% vs. 2.6%; P = 0.03). Proportion of HIV-infected infants starting antiretroviral therapy (75% vs. 77.3%) and age at initiation [19.7 weeks (IQR: 15.4-31.1) vs. 16 (IQR: 13.3-17.9)] remained unchanged. These findings suggest modest improvements in infant care with Option B+.

Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis.

BACKGROUND: In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children. METHODS: HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy for pregnant women, were being implemented. RESULTS: Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had nonnucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures, but resistance to NNRTI was detected in 24.0%, NRTI in 10.7%, and protease inhibitor in 1.3%. CONCLUSION: The new PMTCT strategies dramatically reduce the number of children who acquire infection, but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pretreatment drug resistance. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.

Timing of maternal HIV testing and uptake of prevention of mother-to-child transmission interventions among women and their infected infants in Johannesburg, South Africa.

BACKGROUND: By 2011, South African prevention of mother-to-child transmission (PMTCT) of HIV programs had reduced perinatal HIV transmission at 6 weeks of age to 2.7%. We investigated the profile of newly diagnosed vertically infected children and their mothers to identify shortfalls in the PMTCT program. METHODS: In this operational follow-up study, fieldworkers enrolled mothers of newly diagnosed HIV-infected children up to 2 years of age at 5 major health care facilities in Johannesburg. Structured questionnaires and clinical record reviews were conducted and analyzed to describe the population and assess factors associated with PMTCT uptake. RESULTS: Two hundred eighty-nine mother-child pairs were enrolled. Timing of maternal HIV diagnosis influenced PMTCT access and feeding choices and was associated with infants' age at HIV diagnosis (7 vs. 11 vs. 31 weeks where mothers tested before, during, or after the pregnancy, respectively; P < 0.0001). Women diagnosed before pregnancy (12%) were older (median, 31 years) than those diagnosed during the index pregnancy (53%; median, 27 years). Women diagnosed after delivery (35%) were younger (median, 25 years, P < 0.0001), of lower parity, and less likely to be South African citizens. In 81 cases (29%), late maternal diagnosis precluded any PMTCT access. Where women were diagnosed during or before pregnancy, the recommended PMTCT guidelines for mother and infant were followed in 86 (61%) pairs. CONCLUSIONS: Failure to diagnose maternal HIV infection before delivery was the main reason for missing PMTCT prophylaxis and early infant testing. Timely maternal diagnosis enables PMTCT uptake, but implementation and follow-up gaps require attention to improve infant outcomes.