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BACKGROUND: Following a decline in perinatal HIV transmission from 20% to 10% between 2010 and 2017 in Kenya, rates have since plateaued with an estimated 8% transmission rate in 2021. Between October 2016 and September 2021, Family AIDS Care & Education Services (FACES) supported HIV care and treatment services across 61 facilities in Kisumu County, Kenya with an emphasis on service strengthening for pregnant and postpartum women living with HIV to reduce perinatal HIV transmission. This included rigorous implementation of national HIV guidelines and implementation of 3 locally adapted evidence-based interventions targeted to the unique needs of women and their infants. We examined whether these person-centered program enhancements were associated with changes in perinatal HIV transmission at FACES-supported sites over time. METHODS AND FINDINGS: We conducted a repeated cross-sectional study of annually aggregated routinely collected documentation of perinatal HIV transmission risk through the end of breastfeeding at FACES-supported facilities between October 2016 and September 2021. Data included 12,599 women living with HIV with baseline antenatal care metrics, and, a separate data set of 11,879 mother-infant pairs who were followed from birth through the end of breastfeeding (overlapping with those in antenatal care 2 years prior). FACES implemented 3 interventions for pregnant and postpartum women living with HIV in 2019: (1) high-risk clinics; (2) case management; and (3) a mobile app to support treatment engagement. Our primary outcome was infant HIV acquisition by the end of breastfeeding (18 to 24 months). We compared infant HIV acquisition risk in the final year of the FACES program (2021) to the year before intervention scale-up and following implementation of the "Treat All" policy (2018). Mother-infant pair loss to follow-up was a secondary outcome. Program data were aggregated by year and site, thus in multivariable regression, we adjusted for site-level characteristics, including facility type, urban versus rural, number of women with HIV in antenatal care each year, and the proportion among them under 25 years of age. Between October 2016 and September 2021, 81,172 pregnant women received HIV testing at the initiation of antenatal care, among whom 12,599 (15.5%) were living with HIV, with little variation in HIV prevalence over time. The risk of infant HIV acquisition by 24 months of age declined from 4.9% (101/2,072) in 2018 to 2.2% (48/2,156) in 2021 (adjusted risk difference -2.6% [95% confidence interval (CI): -3.7, -1.6]; p < 0.001). Loss to follow-up declined from 9.9% (253/2,556) in 2018 to 2.5% (59/2,393) in 2021 (risk difference -7.5% [95% CI: -8.8, -6.2]; p < 0.001). During the same period, UNAIDS estimated rates of perinatal transmission in the broader Nyanza region and in Kenya as a whole did not decline. The main limitation of this study is that we lacked a comparable control group. CONCLUSIONS: These findings suggest that implementation of person-centered interventions was associated with significant declines in perinatal HIV transmission and loss to follow-up of pregnant and postpartum women.
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Infecções por HIV , Transmissão Vertical de Doenças Infecciosas , Sistema de Registros , Humanos , Quênia/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Feminino , Estudos Transversais , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Adulto , Recém-Nascido , Adulto Jovem , Complicações Infecciosas na Gravidez/epidemiologia , Lactente , Cuidado Pré-Natal , Assistência Centrada no PacienteRESUMO
INTRODUCTION: Human mobility is a critical aspect of existence and survival, but may compromise care engagement among people living with HIV (PLHIV). We examined the association between various forms of human mobility with retention in HIV care and antiretroviral treatment (ART) interruptions. METHODS: In a cohort of adult PLHIV in Kenya and Uganda, we collected surveys in 2016 about past 6-month travel and lifetime migration histories, including reasons and locations, and engagement in HIV care defined as (1) discontinuation of care, and (2) history of a treatment interruption among those who remained in care. We estimated associations between mobility and these care engagement outcomes via logistic regression, adjusted for sex, prior mobility, age, region, marital status, household wealth, and education. RESULTS: Among 1081 participants, 56 (5%) reported having discontinued care; among those in care, 104 (10%) reported treatment interruption. Past-year migration was associated with a higher risk of discontinuation of care (adjusted odds ratio [aOR] 1.98, 95% CI 1.08-3.63). In sex-stratified models, the association was somewhat attenuated in women, but remained robust among men. Past-year migration was associated with reduced odds of having a treatment interruption among men (aOR 0.51, 95% CI 0.34-0.77) but not among women (aOR 2.67, 95% CI 0.78, 9.16). Travel in the past 6 months was not associated with discontinuation of care or treatment interruptions. CONCLUSIONS: We observed both negative and protective effects of recent migration on care engagement and ART use that were most pronounced among men in this cohort. Migration can break ties to ongoing care, but for men, who have more agency in the decision to migrate, may foster new care and treatment strategies. Strategies that enable health facilities to support individuals throughout the process of transferring care could alleviate the risk of care disengagement.
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Disclosure to children living with HIV (CLHIV) about their own status is associated with positive outcomes such as treatment adherence, but prior cross-sectional studies in sub-Saharan Africa report disclosure rates of <50%. This study aims to assess pediatric disclosure over time. 548 CLHIV were followed from 2/2013-4/2018 in Johannesburg, South Africa. Cumulative incidence of disclosure was calculated with Kaplan-Meier analysis, and disclosure characteristics assessed with a Cox model. By end of follow-up, cumulative disclosure was 70.3% (95% confidence interval: 60.0-79.9). Median age at disclosure was 9 years (range: 3-13). Baseline predictors of disclosure included older child age and the child having a history of going hungry. Prior to disclosure, 98.0% of caregivers who disclosed had conversed with their child about their illness or an HIV-related topic, or their child had asked about HIV, versus 88.6% of caregivers who never disclosed. While many children did not receive disclosure during this relatively large, longitudinal study of South African CLHIV, caregivers who had not yet disclosed may have been preparing to do so by discussing their child's health or HIV generally with their child. This highlights the need for clinicians to consistently support caregivers throughout the incremental disclosure process.
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Revelação , Infecções por HIV , Humanos , Criança , Adolescente , Pré-Escolar , África do Sul/epidemiologia , Estudos Longitudinais , Infecções por HIV/epidemiologia , Estudos Transversais , Revelação da Verdade , CuidadoresRESUMO
BACKGROUND: We examined change in antiretroviral treatment (ART) adherence after breastfeeding (BF) cessation using hair tenofovir (TFV) concentrations as an objective metric of medication consumption. METHODS: A subset of postpartum women in Zimbabwe randomized in IMPAACT PROMISE to take ART while BF and post-BF cessation had hair TFV measured longitudinally. Using linear mixed-effect models, we estimated differences in hair TFV levels after BF cessation, accounting for trends in levels over time regardless of BF status and change in slope after breastfeeding cessation. We also estimated the relative risk of viremia (>50 copies/mL) per doubling of hair TFV concentration. RESULTS: Among 55 women (median age 26, interquartile range 24-29 years), hair TFV levels (n = 305) were available for a median of 9 visits per woman between 3 and 29 months postpartum. Hair TFV levels ranged from undetected to 0.25 ng/mg (median 0.04 ng/mg). Controlling for trends since delivery [decline of 2.2% per month, 95% confidence interval (CI): -5.3 to 1.0], TFV levels averaged 24.4% higher (95% CI: -5.1 to 63.1) post-BF cessation than during BF, with no change in slope (0.0% per month, 95% CI: -3.8 to 3.9). Postpartum, 42% of women were ever viremic. Higher TFV levels were strongly protective; relative risk of viremia per doubling of TFV was 0.52 (95% CI: 0.43 to 0.63; P < 0.0001). CONCLUSIONS: Leveraging an objective metric of ART use, we observed modestly declining adherence across the postpartum period, but no additional decline associated with breastfeeding cessation. High viremia frequency and varying postpartum TFV levels observed highlight the importance of enhanced adherence support with viral load monitoring among postpartum women.
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Fármacos Anti-HIV , Infecções por HIV , Adulto , Feminino , Humanos , Adulto Jovem , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Cabelo , Infecções por HIV/tratamento farmacológico , Adesão à Medicação , Tenofovir/uso terapêutico , Viremia/tratamento farmacológicoRESUMO
The aim of this study was to determine the association between lifetime anabolic-androgenic steroid (AAS) use and seven indicators of sexual health behaviors among a nationally representative sample of adolescent boys in the United States. Multiple modified Poisson regression analyses were conducted to determine the associations between any lifetime AAS use and seven indicators of sexual health behaviors among 2,095 sexually active adolescent boys from the 2019 National Youth Risk Behavior Survey. Sexually active boys who reported lifetime AAS use were at greater risk of having sexual intercourse before the age of 13 years (adjusted risk ratio [aRR] = 2.73, 95% confidence interval [CI] = [1.44, 5.17]), reporting ≥4 sexual partners in their lifetime (aRR = 1.96, 95% CI = [1.34, 2.89]) and in the past 3 months (aRR = 6.77, 95% CI = [3.19, 14.37]), having been tested for HIV in their lifetime (aRR = 2.49, 95% CI = [1.13, 4.73]), and having been tested for any sexually transmitted infection in the past 12 months (aRR = 3.14, 95% CI = [1.63, 6.03]). These findings align with prior research among adult men and have implications for public health and health care prevention efforts to reduce the use of AAS, as well as support the engagement in safe sexual health behaviors among adolescent boys.
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Comportamento do Adolescente , Adolescente , Adulto , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Assunção de Riscos , Comportamento Sexual , Esteroides , Congêneres da Testosterona , Estados UnidosRESUMO
OBJECTIVE: We examined whether human mobility was associated with antiretroviral treatment adherence, measured via antiretroviral hair concentrations. DESIGN: This is a cross-sectional analysis of adults on antiretroviral treatment in East Africa at baseline in an observational cohort study. METHODS: Participants reported recent mobility (overnight travel) and histories of migration (changes of residence), including reasons, frequency/duration, and locations. Hair antiretroviral concentrations were analyzed using validated methods. We estimated associations between mobility and antiretroviral concentrations via linear regression adjusted for age, sex, region, years on treatment. RESULTS: Among 383 participants, half were women and the median age was 40. Among men, 25% reported recent work-related mobility, 30% nonwork mobility, and 11% migrated in the past year (mostly across district boundaries); among women, 6 and 57% reported work-related and nonwork mobility, respectively, and 8% recently migrated (mostly within district). Those reporting work-related trips 2 nights or less had 72% higher hair antiretroviral levels (Pâ=â0.02) than those who did not travel for work; in contrast, nonwork mobility (any duration, vs. none) was associated with 24% lower levels (Pâ=â0.06). Intra-district migrations were associated with 59% lower antiretroviral levels than nonmigrants (Pâ=â0.003) while inter-district migrations were not (27% higher, Pâ=â0.40). CONCLUSION: We found that localized/intra-district migration and nonwork travel-more common among women-were associated with lower adherence, potentially reflecting care interruptions or staying with family/friends unaware of the participants' status. In contrast, short work-related trips-more common among men-were associated with higher adherence, perhaps reflecting higher income. Adherence interventions may require tailoring by sex and forms of mobility.
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Infecções por HIV , Adulto , África Oriental , Antirretrovirais , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Cooperação e Adesão ao TratamentoRESUMO
We investigated the first 152 laboratory-confirmed SARS-CoV-2 cases (125 primary and 27 secondary) and their 248 close contacts in Kisumu County, Kenya. Conducted June 10-October 8, 2020, this study included interviews and sample collection at enrolment and 14-21 days later. Median age was 35 years (IQR 28-44); 69.0% reported COVID-19 related symptoms, most commonly cough (60.0%), headache (55.2%), fever (53.3%) and loss of taste or smell (43.8%). One in five were hospitalized, 34.4% >25 years of age had at least one comorbidity, and all deaths had comorbidities. Adults ≥25 years with a comorbidity were 3.15 (95% CI 1.37-7.26) times more likely to have been hospitalized or died than participants without a comorbidity. Infectious comorbidities included HIV, tuberculosis, and malaria, but no current cases of influenza, respiratory syncytial virus, dengue fever, leptospirosis or chikungunya were identified. Thirteen (10.4%) of the 125 primary infections transmitted COVID-19 to 27 close contacts, 158 (63.7%) of whom resided or worked within the same household. Thirty-one percent (4 of 13) of those who transmitted COVID-19 to secondary cases were health care workers; no known secondary transmissions occurred between health care workers. This rapid assessment early in the course of the COVID-19 pandemic identified some context-specific characteristics which conflicted with the national line-listing of cases, and which have been substantiated in the year since. These included over two-thirds of cases reporting the development of symptoms during the two weeks after diagnosis, compared to the 7% of cases reported nationally; over half of cases reporting headaches, and nearly half of all cases reporting loss of taste and smell, none of which were reported at the time by the World Health Organization to be common symptoms. This study highlights the importance of rapid in-depth assessments of outbreaks in understanding the local epidemiology and response measures required.
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Performance-enhancing substance (PES) use is common among young men and prior research has documented cross-sectional associations between anabolic-androgenic steroid (AAS) use and sexual risk behaviors. However, this relationship remains understudied among a longitudinal cohort of young adult men, and research on prospective associations between legal PES (e.g., creatine) use and sexual risk behaviors is lacking. The current study addressed these oversights using data from the National Longitudinal Study of Adolescent to Adult Health (N = 5,451). AAS use and legal PES use were assessed at Wave III (ages 18-26) and 10 indicators of sexual risk behavior were assessed at seven-year follow up (Wave IV; ages 24-32). Linear and logistic regression analyses were conducted adjusting for demographic and behavioral confounders. Participants who reported AAS use and legal PES use had significantly higher number of one-time sexual partners and higher odds of multiple sex partners around the same time in the past 12 months. Participants who reported AAS use had higher odds of any STI in the past 12 months. These results extend prior research on the risk behaviors and adverse effects of PES use. Health care professionals should assess for PES use among young adult men and provide guidance on healthful sexual behaviors.
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Infecções por HIV , Substâncias para Melhoria do Desempenho , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Adulto , Estudos Transversais , Humanos , Estudos Longitudinais , Masculino , Substâncias para Melhoria do Desempenho/efeitos adversos , Estudos Prospectivos , Assunção de Riscos , Comportamento Sexual , Parceiros Sexuais , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Adherence to antiretroviral treatment (ART) among postpartum women with HIV is essential for optimal health and prevention of perinatal transmission. However, suboptimal adherence with subsequent viremia is common, and adherence challenges are often underreported. We aimed to predict viremia to facilitate targeted adherence support in sub-Saharan Africa during this critical period. METHODS: Data are from PROMISE 1077BF/FF, which enrolled perinatal women between 2011 and 2014. This analysis includes postpartum women receiving ART per study randomization or country-specific criteria to continue from pregnancy. We aimed to predict viremia (single and confirmed events) after 3 months on ART at >50, >400, and >1000 copies/mL within 6-month intervals through 24 months. We built models with routine clinical and demographic data using the least absolute shrinkage and selection operator and SuperLearner (which incorporates multiple algorithms). RESULTS: Among 1321 women included, the median age was 26 years and 96% were in WHO stage 1. Between 0 and 24 months postpartum, 42%, 31%, and 28% of women experienced viremia >50, >400, and >1000 copies/mL, respectively, at least once. Across models, the cross-validated area under the receiver operating curve ranged from 0.74 [95% confidence interval (CI): 0.72 to 0.76] to 0.78 (95% CI: 0.76 to 0.80). To achieve 90% sensitivity predicting confirmed viremia >50 copies/mL, 64% of women would be classified as high risk. CONCLUSIONS: Using routinely collected data to predict viremia in >1300 postpartum women with HIV, we achieved moderate model discrimination, but insufficient to inform targeted adherence support. Psychosocial characteristics or objective adherence metrics may be required for improved prediction of viremia in this population.
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Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez , Dados de Saúde Coletados Rotineiramente , Viremia , Adulto , Algoritmos , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Humanos , Aprendizado de Máquina , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Carga Viral , Viremia/diagnóstico , Viremia/tratamento farmacológicoRESUMO
BACKGROUND: Objective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption. METHODS: We identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8 ng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score. RESULTS: One third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8 ng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables. CONCLUSIONS: Among people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.
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Consumo de Bebidas Alcoólicas/sangue , Glicerofosfolipídeos/sangue , HumanosRESUMO
Stress and food insecurity (FI) are associated with poor perinatal and HIV outcomes. We hypothesized that FI would increase postpartum stress among women in Kenya, and that the impact would be greater in women with HIV. Among 371 pregnant women, we identified latent FI trajectories across the perinatal period, and estimated their association with postpartum stress. Stress metrics included the Perceived Stress Scale (PSS) and hair cortisol concentrations (HCC). We identified two FI trajectories: persistent moderate FI and persistent mild FI. Moderate FI (vs. mild) was associated with higher PSS; this association was stronger among HIV-negative women. We observed a trend towards higher HCC associated with moderate FI, which did not differ by HIV status. HCC and PSS were not correlated. In summary, moderate FI (vs. mild) was associated with increased stress. The lack of PSS-HCC correlation could reflect different physiological pathways. Interventions to mitigate FI could alleviate postpartum stress.
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Abastecimento de Alimentos/estatística & dados numéricos , Mães/psicologia , Assistência Perinatal , Gestantes/psicologia , Estresse Psicológico/epidemiologia , Adulto , Feminino , Infecções por HIV/psicologia , Cabelo/química , Humanos , Hidrocortisona/metabolismo , Quênia/epidemiologia , Período Pós-Parto , Gravidez , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
BACKGROUND: Antiretroviral treatment (ART) adherence is often suboptimal in the perinatal period. We measured hair tenofovir (TFV) concentrations as a metric of adherence in postpartum women to understand patterns and predictors of adherence throughout this critical period. In addition, we examined the association between hair TFV concentrations and virologic outcomes. METHODS: Between 12/2012 and 09/2016, hair samples were collected longitudinally from delivery through breastfeeding from women on ART in the Promoting Maternal and Infant Survival Everywhere study (NCT01061151) in sub-Saharan Africa. Hair TFV levels were measured using validated methods. Using generalized estimating equations, we estimated the association between hair TFV levels and virologic suppression (<400 copies/ml) over time and assessed predictors of hair TFV levels. RESULTS: Hair TFV levels were measured at 370 visits in 71 women from delivery through a median of 14 months (interquartile range 12-15) of breastfeeding. Levels ranged from below detection (0.002) to 1.067âng/mg (geometric mean: 0.047). After at least 90 days on ART, 69 women had at least one viral load measured (median 5 measures, range 1-9); 18 (26%) experienced viremia at least once. Each doubling of TFV level more than doubled odds of concurrent virologic suppression [odds ratio 2.35, 95% confidence interval (CI): 1.44-3.84, Pâ=â0.0006] and was associated with 1.43 times the odds of future suppression (95% CI: 0.75-2.73, Pâ=â0.28). Relative to the first 3 months after delivery, hair levels were highest in months 6-12 (1.42-fold higher, 95% CI: 1.09-1.85, Pâ=â0.01). CONCLUSION: Hair TFV levels strongly predicted concurrent virologic suppression among breastfeeding women. Objective adherence metrics can supplement virologic monitoring to optimize treatment outcomes in this important transition period.
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Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/análise , Infecções por HIV/tratamento farmacológico , Cabelo/química , Resposta Viral Sustentada , Tenofovir/administração & dosagem , Tenofovir/análise , Adulto , África Subsaariana , Aleitamento Materno , Feminino , Humanos , Estudos Longitudinais , Adesão à Medicação/estatística & dados numéricos , Período Pós-Parto , Gravidez , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
INTRODUCTION: "Treat All" - the treatment of all people with HIV, irrespective of disease stage or CD4 cell count - represents a paradigm shift in HIV care that has the potential to end AIDS as a public health threat. With accelerating implementation of Treat All in sub-Saharan Africa (SSA), there is a need for a focused agenda and research to identify and inform strategies for promoting timely uptake of HIV treatment, retention in care, and sustained viral suppression and addressing bottlenecks impeding implementation. METHODS: The Delphi approach was used to develop consensus around research priorities for Treat All implementation in SSA. Through an iterative process (June 2017 to March 2018), a set of research priorities was collectively formulated and refined by a technical working group and shared for review, deliberation and prioritization by more than 200 researchers, implementation experts, policy/decision-makers, and HIV community representatives in East, Central, Southern and West Africa. RESULTS AND DISCUSSION: The process resulted in a list of nine research priorities for generating evidence to guide Treat All policies, implementation strategies and monitoring efforts. These priorities highlight the need for increased focus on adolescents, men, and those with mental health and substance use disorders - groups that remain underserved in SSA and for whom more effective testing, linkage and care strategies need to be identified. The priorities also reflect consensus on the need to: (1) generate accurate national and sub-national estimates of the size of key populations and describe those who remain underserved along the HIV-care continuum; (2) characterize the timeliness of HIV care and short- and long-term HIV care continuum outcomes, as well as factors influencing timely achievement of these outcomes; (3) estimate the incidence and prevalence of HIV-drug resistance and regimen switching; and (4) identify cost-effective and affordable service delivery models and strategies to optimize uptake and minimize gaps, disparities, and losses along the HIV-care continuum, particularly among underserved populations. CONCLUSIONS: Reflecting consensus among a broad group of experts, researchers, policy- and decision-makers, PLWH, and other stakeholders, the resulting research priorities highlight important evidence gaps that are relevant for ministries of health, funders, normative bodies and research networks.
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Infecções por HIV/tratamento farmacológico , África Subsaariana/epidemiologia , Bases de Dados Factuais , Infecções por HIV/economia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Política de Saúde , Humanos , Formulação de Políticas , Saúde Pública/economia , Saúde Pública/legislação & jurisprudênciaRESUMO
The implementation of the 2013 World Health Organization Option B+ recommendations for HIV treatment during pregnancy has helped drive significant progress in achieving universal treatment for pregnant and postpartum women in sub-Saharan Africa (SSA). Yet, critical research and implementation gaps exist in achieving the UNAIDS 90-90-90 targets. To help guide researchers, programmers and policymakers in prioritising these areas, we undertook a comprehensive review of the progress, gaps and research needs to achieve the 90-90-90 targets for this population in the Option B+ era, including early infant HIV diagnosis (EID) for HIV-exposed infants. Salient areas where progress has been achieved or where gaps remain include: (1) knowledge of HIV status is higher among people with HIV in southern and eastern Africa compared to western and central Africa (81% versus 48%, UNAIDS); (2) access to antiretroviral therapy (ART) for pregnant women has doubled in 22 of 42 SSA countries, but only six have achieved the second 90, and nearly a quarter of pregnant women initiating ART become lost to follow-up; (3) viral suppression data for this population are sparse (estimates range from 30% to 98% peripartum), with only half of women maintaining suppression through 12 months postpartum; and (4) EID rates range from 15% to 62%, with only three of 21 high-burden SSA countries testing >50% HIV-exposed infants within the first 2 months of life. We have identified and outlined promising innovations and research designed to address these gaps and improve the health of pregnant and postpartum women living with HIV and their infants.
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BACKGROUND: Initiation of antiretroviral therapy (ART) following diagnosis of HIV infection at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. METHODS: From September, 2013 (era 1), only high-risk HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June, 2014 (era 2), all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October, 2014 (era 3), point of care (POC) diagnostic PCR tests were also done if staff availability allowed. We describe time to ART initiation, mortality, retention in care, and viral suppression among the HIV-infected infants identified across these eras. FINDINGS: We tested 5449 HIV-exposed infants who were born between Sept 1, 2013, and June 30, 2016. 88 neonates with confirmed HIV infection were identified and included in the study, of which 86 (98%) started ART. Median age at ART initiation decreased from 9 days (IQR 6-25) in eras 1 and 2 to 2 days (1-8) in era 3. In era 3, more neonates who were co-tested with POC testing started ART within 48 h of birth (29 [83%] of 35; median 1 day [IQR 1-2]) than infants who were not co-tested (one [4%] of 29; median 6 days [5-10]). The probability of mortality by 12 months across the eras was 14% (95% CI 8-24) and did not differ by era. Of the 72 infants who survived and initiated ART at the site, 56 (78%) were retained at 12 months. Of the 56 infants retained in care, 40 (71%) had a viral load less than 400 copies per mL at 12 months, with no differences between eras (p=0·23). INTERPRETATION: HIV-infected infants can be identified at birth and ART can be initiated within hours to days. Although most infants in our cohort started ART, mortality remained unacceptably high with suboptimal retention and viral suppression. Reducing mortality and improving retention and viral suppression remain urgent priorities. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Allergy and Infectious Disease, National Institutes of Health, USAID/PEPfAR, and the South African National HIV Programme.
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Antirretrovirais/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Animais , Estudos de Coortes , Feminino , Infecções por HIV/patologia , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Técnicas de Diagnóstico Molecular/métodos , Reação em Cadeia da Polimerase/métodos , Retenção nos Cuidados , África do Sul , Análise de Sobrevida , Resultado do Tratamento , Carga ViralRESUMO
INTRODUCTION: Mathematical models that incorporate HIV disease progression dynamics can estimate the potential impact of strategies that delay HIV disease progression and reduce infectiousness for persons not on antiretroviral therapy (ART). Suppressive treatment of HIV-positive persons co-infected with herpes simplex virus-2 (HSV-2) with valacyclovir, an HSV-2 antiviral, can lower HIV viral load, but the impact of partially-suppressive valacyclovir relative to fully-suppressive ART on population HIV transmission has not been estimated. METHODS: We modeled HIV disease progression as a function of changes in viral load and CD4 count over time among ART naïve persons. The disease progression Markov model was nested within a dynamic model of HIV transmission at population level. We assumed that valacyclovir reduced HIV viral load by 1.23 log copies/µL, and that persons treated with valacyclovir initiated ART more rapidly when their CD4 fell below 500 due to retention in HIV care. We estimated the potential impact of valacyclovir on onward transmission of HIV in three scenarios of different ART and valacyclovir population coverage. RESULTS: The average duration of HIV infection was 9.5 years. The duration of disease before reaching CD4 200cells/µL was 2.53 years longer for females than males. Relative to a baseline of ART initiation at CD4≤500cells/µL, the valacyclovir scenario resulted in 167,000 fewer HIV infections over ten years, with an incremental cost-effectiveness ratio (ICER) of $5276 per HIV infection averted. A Test and Treat scenario with 70% ART coverage and no valacyclovir resulted in 350,000 fewer HIV infections at an ICER of $2822 and $812 per HIV infection averted and QALY gained, respectively. CONCLUSION: Even when compared with valacyclovir suppression, a drug that reduces HIV viral load, universal treatment for HIV is the optimal strategy for averting new infections and increasing public health benefit. Universal HIV treatment would most effectively and efficiently reduce the HIV burden.
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Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Valaciclovir/uso terapêutico , Adulto , África Subsaariana/epidemiologia , Análise Custo-Benefício , Progressão da Doença , Feminino , Seguimentos , Infecções por HIV/transmissão , Humanos , Masculino , Cadeias de Markov , Carga Viral/efeitos dos fármacos , Carga Viral/estatística & dados numéricosAssuntos
Nevirapina , Ritonavir , Alcinos , Benzoxazinas , Criança , Ciclopropanos , HIV , Humanos , LopinavirRESUMO
INTRODUCTION: HIV-1 polymerase chain reaction (PCR) testing at birth aims to facilitate earlier initiation of antiretroviral therapy (ART) for HIV-infected neonates. Data from two years of universal birth testing implementation in a high-burden South African urban setting are presented to demonstrate the prevalence and outcomes of diagnostic challenges in this context. METHODS: HIV-exposed neonates born at Rahima Moosa Mother and Child Hospital between 5 June 2014 and 31 August 2016 were routinely screened at birth for HIV-1 on whole blood samples using the COBAS® AmpliPrep/COBAS® TaqMan (CAP/CTM) HIV-1 Qualitative Test, version 2.0 (Roche Molecular Systems, Inc., Branchburg, NJ, USA). Virological results were interpreted according to standard operating procedures with the South African National Health Laboratory Service. All neonates with non-negative results were actively followed-up and categorized according to HIV infection status as positive, negative, uncertain and lost to follow-up (LTFU). RESULTS: 104 (1.8%) of 5743 HIV-exposed neonates received a non-negative birth PCR result, for which laboratory data were available for 102 (98%) cases - 78 (76%) tested positive and 24 (24%) indeterminate. HIV infection status was confirmed positive in 83 (81%) infants, negative in 8 (8%), uncertain in 5 (5%) and LTFU in 6 (6%) cases. The positive predictive value (excluding cases of uncertain diagnosis and inadequate testing) following a non-negative HIV-1 PCR screening test at birth was 0.91 (83/91; 95% confidence interval: 0.85-0.96). Neonates testing positive at birth had significantly higher viral load (VL) results than those testing indeterminate at birth of 4.5 and 3.0 log copies/ml (p = 0.0007), respectively. Similarly, mothers of neonates with positive as compared to indeterminate birth test results had higher VLs of 4.5 and 2.7 log copies/ml (p = 0.0013), respectively. Half of neonates with an indeterminate birth test were shown to be HIV-infected on subsequent confirmatory testing, with time to final diagnosis 30 days longer for these neonates (p < 0.0001). CONCLUSION: Indeterminate HIV-1 PCR results accounted for a quarter of non-negative results at birth and were associated with a high risk of infection in comparison to the risk of in utero transmission. Indeterminate birth results with positive HIV PCR results on repeat testing were associated with later final diagnosis. The HIV-1 status remains uncertain in a minority of cases because of repeatedly indeterminate results, highlighting the need for more sensitive and specific virological tests.
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Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Doenças do Recém-Nascido/diagnóstico , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/virologia , Transmissão Vertical de Doenças Infecciosas , Perda de Seguimento , Masculino , Triagem Neonatal , Reação em Cadeia da Polimerase , Prevalência , Carga ViralRESUMO
OBJECTIVE: The US preexposure prophylaxis (PrEP) Demonstration Project (U.S. Demo) evaluated MSM on PrEP postmarketing and found low seroconversion rates. The objective of this study is to examine hair levels as an adherence measure to PrEP. DESIGN: Using an 'opt-in' design, participants of PrEP Demo were invited to enroll into a substudy where hair was collected quarterly. METHODS: Tenofovir concentrations were measured in hair by liquid chromatography/tandem mass spectrometry. Hair levels consistent with ≥4 doses/week (protective in other studies) defined adequate adherence. Mixed effects multivariate logistic regression models examined factors associated with ≥4 doses/week. Separate mixed effects models evaluated the relationship between hair PrEP levels and changes in creatinine clearance (CrCl) over time. RESULTS: Overall, 58% of U.S. Demo participants enrolled into this opt-in study; reasons for nonparticipation included insufficient hair (61%) and concerns about hairstyle (27%). Hair and dried blood spots levels consistent with ≥4 doses/week were highly concordant (84%). Hair levels showed adequate adherence in 87% of 875 person-visits (among 280 participants). Factors associated with adequate adherence in multivariate models were amphetamine use [adjusted odds ratio (aOR) 2.59 (0.97-6.9, P 0.06)], condomless receptive anal sex [aOR 2.28 (1.19-4.40, P 0.01)], and stable housing [aOR 2.63 (1.03-6.67), P 0.04]. Hair levels of tenofovir showed a monotonic relationship with decline in CrCl (P 0.01 for trend). CONCLUSION: In this substudy of the U.S. PrEP demonstration project, hair and dried blood spots levels were highly concordant and hair concentrations demonstrated adequate adherence 87% of the time, with stable housing and high-risk behavior associated with higher adherence. Daily PrEP drug taking is associated with modest declines in CrCl.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Uso de Medicamentos , Infecções por HIV/prevenção & controle , Cabelo/química , Adesão à Medicação , Profilaxia Pré-Exposição , Tenofovir/uso terapêutico , Adulto , Idoso , Fármacos Anti-HIV/análise , Análise Química do Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tenofovir/análise , Pessoas Transgênero , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Point-of-care testing (POCT) among HIV-exposed infants might improve linkage to care relative to laboratory-based testing (LABT). We evaluated HIV-1 POCT at birth in the context of universal LABT in a maternity hospital and describe our implementation experience. METHODS: We did a field evaluation study between Oct 1, 2014, and April 30, 2016, at the urban Rahima Moosa Mother and Child Hospital (RMMCH), Johannesburg, South Africa. We aimed to sample consecutive neonates at birth with POCT (Cepheid Xpert HIV-1 Qualitative test) and compared results with those of LABT (Roche COBAS TaqMan HIV-1 Qualitative test) with respect to performance in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's κ coefficient, result return, antiretroviral treatment (ART) initiation, and coverage. FINDINGS: 18â268 women delivered livebirths at RMMCH and 4267 (23%) were HIV-positive with 4336 HIV-exposed neonates delivered. Mothers of 4141 (96%) HIV-exposed neonates were offered infant birth testing. Mothers of 4112 (99%) neonates consented. In 78 neonates with consent (2%), a test was not done due to early neonatal death (n=13), mother departing before venesection, or staff unavailability. Among 3970 infants who had LABT, 57 (1%) tested positive, 3906 (99%) tested negative, two (<1%) were indeterminate, and five (<1%) had an error result. 2238 (56%) of these infants had concurrent POCT. POCT detected all 30 HIV-infected neonates (sensitivity 100%; 95% CI 88·4-100) with two additional false-positive results (specificity 99·9%; 99·7-100). All positive and 96·2% of negative POCT results were returned compared with 88·9% of positive and 52·8% of negative LABT results. Although every POCT required 90 min of instrument time, 2·6 h (IQR 2·3-3·1) elapsed between phlebotomy and result return. In days, median time of result return for POCT was 1 day, significantly earlier than 10 days for LABT (p<0·0001). ART was initiated in 30 neonates (100%) with positive POCT compared with 24 (88·9%, p=0·10) of 27 infants who had LABT only, with initiation occurring a median of 5 days earlier in the POCT group (p<0·0001). POCT implementation required additional staff and weekend cover. INTERPRETATION: Compared with LABT, POCT was associated with good performance, improved rates of result return, and reduced time to ART initiation. Resources needed to integrate POCT into a routine birth testing programme require further evaluation. FUNDING: National Institutes of Health.