HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women.

Importance: Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized. Objective: To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women. Design, Setting, and Participants: Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling. Exposures: F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory. Main Outcomes and Measures: HIV incidence. Results: Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632). Conclusions and Relevance: In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.

COVID-19 vaccine safety inquiries to the centers for disease control and prevention immunization safety office.

BACKGROUND: Following the authorization and recommendations for use of the U.S. COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC)'s Immunization Safety Office (ISO) responded to inquiries and questions from public health officials, healthcare providers, and the general public on COVID-19 vaccine safety. METHODS: We describe COVID-19 vaccine safety inquiries, by topic, received and addressed by ISO from December 1, 2020-August 31, 2022. RESULTS: Of the 1978 COVID-19 vaccine-related inquiries received, 1655 specifically involved vaccine safety topics. The most frequently asked-about topics included deaths following vaccination, myocarditis, pregnancy, and reproductive health outcomes, understanding or interpreting data from the Vaccine Adverse Event Reporting System (VAERS), and thrombosis with thrombocytopenia syndrome. CONCLUSIONS: Inquiries about vaccine safety generally reflect issues that receive media attention. ISO will continue to monitor vaccine safety inquiries and provide accurate and timely information to healthcare providers, public health officials, and the general public.

Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5-11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022.

Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).

Reported cases of multisystem inflammatory syndrome in children aged 12-20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the USA, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorisations. We aimed to investigate reports of individuals aged 12-20 years with MIS-C after COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to the US Centers for Disease Control and Prevention (CDC). METHODS: In this surveillance activity, we investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's MIS-C national surveillance system, the Vaccine Adverse Event Reporting System (co-administered by CDC and the US Food and Drug Administration), and CDC's Clinical Immunization Safety Assessment Project. A multidisciplinary team adjudicated cases by use of the CDC MIS-C definition. Any positive SARS-CoV-2 serology test satisfied case criteria; although anti-nucleocapsid antibodies indicate previous SARS-CoV-2 infection, anti-spike protein antibodies indicate either past or recent infection or COVID-19 vaccination. We describe the demographic and clinical features of cases, stratified by laboratory evidence of SARS-CoV-2 infection. To calculate the reporting rate of MIS-C, we divided the count of all individuals meeting the MIS-C case definition, and of those without evidence of SARS-CoV-2 infection, by the number of individuals aged 12-20 years in the USA who received one or more COVID-19 vaccine doses up to Aug 31, 2021, obtained from CDC national vaccine surveillance data. FINDINGS: Using surveillance results from Dec 14, 2020, to Aug 31, 2021, we identified 21 individuals with MIS-C after COVID-19 vaccination. Of these 21 individuals, median age was 16 years (range 12-20); 13 (62%) were male and eight (38%) were female. All 21 were hospitalised: 12 (57%) were admitted to an intensive care unit and all were discharged home. 15 (71%) of 21 individuals had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. As of Aug 31, 2021, 21 335 331 individuals aged 12-20 years had received one or more doses of a COVID-19 vaccine, making the overall reporting rate for MIS-C after vaccination 1·0 case per million individuals receiving one or more doses in this age group. The reporting rate in only those without evidence of SARS-CoV-2 infection was 0·3 cases per million vaccinated individuals. INTERPRETATION: Here, we describe a small number of individuals with MIS-C who had received one or more doses of a COVID-19 vaccine before illness onset; the contribution of vaccination to these illnesses is unknown. Our findings suggest that MIS-C after COVID-19 vaccination is rare. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. FUNDING: US Centers for Disease Control and Prevention.

Real-Time CDC Consultation during the COVID-19 Pandemic-United States, March-July, 2020.

CONTEXT: In response to the COVID-19 pandemic, the Centers for Disease Prevention and Control (CDC) clinicians provided real-time telephone consultation to healthcare providers, public health practitioners, and health department personnel. OBJECTIVE: To describe the demographic and public health characteristics of inquiries, trends, and correlation of inquiries with national COVID-19 case reports. We summarize the results of real-time CDC clinician consultation service provided during 11 March to 31 July 2020 to understand the impact and utility of this service by CDC for the COVID-19 pandemic emergency response and for future outbreak responses. DESIGN: Clinicians documented inquiries received including information about the call source, population for which guidance was sought, and a detailed description of the inquiry and resolution. Descriptive analyses were conducted, with a focus on characteristics of callers as well as public health and clinical content of inquiries. SETTING: Real-time telephone consultations with CDC Clinicians in Atlanta, GA. PARTICIPANTS: Health care providers and public health professionals who called CDC with COVID-19 related inquiries from throughout the United States. MAIN OUTCOME MEASURES: Characteristics of inquiries including topic of inquiry, inquiry population, resolution, and demographic information. RESULTS: A total of 3154 COVID-19 related telephone inquiries were answered in real-time. More than half (62.0%) of inquiries came from frontline healthcare providers and clinical sites, followed by 14.1% from state and local health departments. The majority of inquiries focused on issues involving healthcare workers (27.7%) and interpretation or application of CDC's COVID-19 guidance (44%). CONCLUSION: The COVID-19 pandemic resulted in a substantial number of inquiries to CDC, with the large majority originating from the frontline clinical and public health workforce. Analysis of inquiries suggests that the ongoing focus on refining COVID-19 guidance documents is warranted, which facilitates bidirectional feedback between the public, medical professionals, and public health authorities.

Demographic, clinical, and epidemiologic characteristics of persons under investigation for Coronavirus Disease 2019-United States, January 17-February 29, 2020.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020. METHODS: In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17-February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios. RESULTS: A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures. CONCLUSIONS: These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections.

Initial findings from a novel population-based child mortality surveillance approach: a descriptive study.

BACKGROUND: Sub-Saharan Africa and south Asia contributed 81% of 5·9 million under-5 deaths and 77% of 2·6 million stillbirths worldwide in 2015. Vital registration and verbal autopsy data are mainstays for the estimation of leading causes of death, but both are non-specific and focus on a single underlying cause. We aimed to provide granular data on the contributory causes of death in stillborn fetuses and in deceased neonates and children younger than 5 years, to inform child mortality prevention efforts. METHODS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network was established at sites in seven countries (Baliakandi, Bangladesh; Harar and Kersa, Ethiopia; Siaya and Kisumu, Kenya; Bamako, Mali; Manhiça, Mozambique; Bombali, Sierra Leone; and Soweto, South Africa) to collect standardised, population-based, longitudinal data on under-5 mortality and stillbirths in sub-Saharan Africa and south Asia, to improve the accuracy of determining causes of death. Here, we analysed data obtained in the first 2 years after the implementation of CHAMPS at the first five operational sites, during which surveillance and post-mortem diagnostics, including minimally invasive tissue sampling (MITS), were used. Data were abstracted from all available clinical records of deceased children, and relevant maternal health records were also extracted for stillbirths and neonatal deaths, to incorporate reported pregnancy or delivery complications. Expert panels followed standardised procedures to characterise causal chains leading to death, including underlying, intermediate (comorbid or antecedent causes), and immediate causes of death for stillbirths, neonatal deaths, and child (age 1-59 months) deaths. FINDINGS: Between Dec 10, 2016, and Dec 31, 2018, MITS procedures were implemented at five sites in Mozambique, South Africa, Kenya, Mali, and Bangladesh. We screened 2385 death notifications for inclusion eligibility, following which 1295 families were approached for consent; consent was provided for MITS by 963 (74%) of 1295 eligible cases approached. At least one cause of death was identified in 912 (98%) of 933 cases (180 stillbirths, 449 neonatal deaths, and 304 child deaths); two or more conditions were identified in the causal chain for 585 (63%) of 933 cases. The most common underlying causes of stillbirth were perinatal asphyxia or hypoxia (130 [72%] of 180 stillbirths) and congenital infection or sepsis (27 [15%]). The most common underlying causes of neonatal death were preterm birth complications (187 [42%] of 449 neonatal deaths), perinatal asphyxia or hypoxia (98 [22%]), and neonatal sepsis (50 [11%]). The most common underlying causes of child deaths were congenital birth defects (39 [13%] of 304 deaths), lower respiratory infection (37 [12%]), and HIV (35 [12%]). In 503 (54%) of 933 cases, at least one contributory pathogen was identified. Cytomegalovirus, Escherichia coli, group B Streptococcus, and other infections contributed to 30 (17%) of 180 stillbirths. Among neonatal deaths with underlying prematurity, 60% were precipitated by other infectious causes. Of the 275 child deaths with infectious causes, the most common contributory pathogens were Klebsiella pneumoniae (86 [31%]), Streptococcus pneumoniae (54 [20%]), HIV (40 [15%]), and cytomegalovirus (34 [12%]), and multiple infections were common. Lower respiratory tract infection contributed to 174 (57%) of 304 child deaths. INTERPRETATION: Cause of death determination using MITS enabled detailed characterisation of contributing conditions. Global estimates of child mortality aetiologies, which are currently based on a single syndromic cause for each death, will be strengthened by findings from CHAMPS. This approach adds specificity and provides a more complete overview of the chain of events leading to death, highlighting multiple potential interventions to prevent under-5 mortality and stillbirths. FUNDING: Bill & Melinda Gates Foundation.

Mortality Surveillance Methods to Identify and Characterize Deaths in Child Health and Mortality Prevention Surveillance Network Sites.

Despite reductions over the past 2 decades, childhood mortality remains high in low- and middle-income countries in sub-Saharan Africa and South Asia. In these settings, children often die at home, without contact with the health system, and are neither accounted for, nor attributed with a cause of death. In addition, when cause of death determinations occur, they often use nonspecific methods. Consequently, findings from models currently utilized to build national and global estimates of causes of death are associated with substantial uncertainty. Higher-quality data would enable stakeholders to effectively target interventions for the leading causes of childhood mortality, a critical component to achieving the Sustainable Development Goals by eliminating preventable perinatal and childhood deaths. The Child Health and Mortality Prevention Surveillance (CHAMPS) Network tracks the causes of under-5 mortality and stillbirths at sites in sub-Saharan Africa and South Asia through comprehensive mortality surveillance, utilizing minimally invasive tissue sampling (MITS), postmortem laboratory and pathology testing, verbal autopsy, and clinical and demographic data. CHAMPS sites have established facility- and community-based mortality notification systems, which aim to report potentially eligible deaths, defined as under-5 deaths and stillbirths within a defined catchment area, within 24-36 hours so that MITS can be conducted quickly after death. Where MITS has been conducted, a final cause of death is determined by an expert review panel. Data on cause of death will be provided to local, national, and global stakeholders to inform strategies to reduce perinatal and childhood mortality in sub-Saharan Africa and South Asia.

Characteristics associated with lack of HIV testing during pregnancy and delivery in 36 U.S. states, 2004-2013.

The Centers for Disease Control and Prevention and the American Congress of Obstetricians and Gynecologists recommend universal prenatal HIV testing to prevent perinatal HIV transmission in the U.S.; since the 1990s perinatal HIV transmission has declined. In 2006, 74% of women with a recent live birth reported testing for HIV prenatally or at delivery. We used Pregnancy Risk Assessment Monitoring System data from 36 states and New York City from 2004 to 2013 (N = 387,424) to assess characteristics associated with lack of self-reported testing and state-to-state variability in these associations. Overall, 75.2% (95% confidence interval [CI] 75.0-75.5) of women with a recent live birth reported an HIV test. There were significant differences in testing prevalence by state, ranging from 91.8% (95% CI 91.0-92.6) in New York to 42.3% (95% CI 41.7-43.5) in Utah. In adjusted analysis, characteristics associated with no reported testing included being married, white, non-Hispanic, multiparous, not smoking during pregnancy, and having neither Medicaid nor Special Supplemental Nutritional Program for Women, Infants, and Children. White married women were 57% (adjusted prevalence ratio [aPR] 1.57, 95% CI 1.52-1.63) more likely to report no test compared to white unmarried women. Multiparous married women were 57% (aPR 1.57, 95% CI 1.51-1.64) more likely to report no test compared to multiparous unmarried women. Women who were married, white, non-Hispanic, and multiparous women were 23% less likely to be tested than other women combined. Marital status was significantly associated with lower prevalence of testing in 35 of the 37 reporting areas, and race was significant in 30 of 35 states with race information. The prevalence of reported HIV testing during pregnancy or at delivery remains below 80%. Opportunities exist to increase HIV testing among pregnant women, particularly among certain subpopulations.

Prenatal HIV Testing and the Impact of State HIV Testing Laws, 2004 to 2011.

OBJECTIVE: This study aimed to analyze prenatal human immunodeficiency virus (HIV) testing rates over time and describe the impact of state HIV testing laws on prenatal testing. METHODS: During 2004-2011, self-reported prenatal HIV testing data for women with live births in 35 states and New York City were collected. Prevalence of testing was estimated overall and by state and year. An annual percent change was calculated in states with at least 6 years of data to analyze testing changes over time. An attorney-coder used WestlawNext to identify states with laws that direct prenatal care providers to screen all pregnant women or direct all women to be tested for HIV and document changes in laws to meet this threshold. RESULTS: The overall prenatal HIV testing rate for 2004 through 2011 combined was 75.7%. State-level data showed a wide range of testing rates (43.2%-92.8%) for 2004 through 2011 combined. In areas with 6 years of data, 4 experienced an annual drop in testing (Alaska, Arkansas, Colorado, and Illinois). States that changed laws to meet the threshold generally had the highest testing rates, averaging 80%, followed by states with a preexisting law, at approximately 70%. States with no law, or no law meeting the threshold, had an average prenatal testing rate of 65%. CONCLUSIONS: Prenatal HIV testing remained stable between 2004 and 2011 but remained below universal recommendations. Testing varied widely across states and was generally higher in areas that changed their laws to meet the threshold or had preexisting prenatal HIV testing laws, compared with those with no or limited prenatal HIV testing language.

Estimated Perinatal HIV Infection Among Infants Born in the United States, 2002-2013.

Importance: Perinatal transmission of human immunodeficiency virus (HIV) can be reduced through services including antiretroviral treatment and prophylaxis. Data on the national incidence of perinatal HIV transmission and missed prevention opportunities are needed to monitor progress toward elimination of mother-to-child HIV transmission. Objective: To estimate the number of perinatal HIV cases among infants born in the United States. Design, Setting, and Participants: Data were obtained from the National HIV Surveillance System on infants with HIV born in the United States (including the District of Columbia) and their mothers between 2002 and 2013 (reported through December 31, 2015). Estimates were adjusted for delay in diagnosis and reporting by weighting each reported case based on a model incorporating time from birth to diagnosis and report. Analysis was performed from April 1 to August 15, 2016. Exposures: Maternal HIV infection and antiretroviral medication, including maternal receipt prenatally or during labor/delivery and infant receipt postnatally. Main Outcomes and Measures: Diagnosis of perinatally acquired HIV infection in infants born in the United States. Infant and maternal characteristics, including receipt of perinatal HIV testing, treatment, and prophylaxis. Results: The estimated annual number of perinatally infected infants born in the United States decreased from 216 (95% CI, 206-230) in 2002 to 69 (95% CI, 60-83) in 2013. Among perinatally HIV-infected children born in 2002-2013, 836 (63.0%) of the mothers identified as black or African American and 243 (18.3%) as Hispanic or Latino. A total of 236 (37.5%) of the mothers had HIV infection diagnosed before pregnancy in 2002-2005 compared with 120 (51.5%) in 2010-2013; the proportion of mother-infant pairs receiving all 3 recommended arms of antiretroviral prophylaxis or treatment (prenatal, intrapartum, and postnatal) was 22.4% in 2002-2005 and 31.8% in 2010-2013, with approximately 179 (28.4%) (2002-2005) and 94 (40.3%) (2010-2013) receiving antiretroviral prophylaxis or treatment during pregnancy. Five Southern states (Florida, Texas, Georgia, Louisiana, and Maryland) accounted for 687 (38.0%) of infants born with HIV infection in the United States during the overall period. According to national data for live births, the incidence of perinatal HIV infection among infants born in the United States in 2013 was 1.75 per 100 000 live births. Conclusions and Relevance: Despite reduced perinatal HIV infection in the United States, missed opportunities for prevention were common among infected infants and their mothers in recent years. As of 2013, the incidence of perinatal HIV infection remained 1.75 times the proposed Centers for Disease Control and Prevention elimination of mother-to-child HIV transmission goal of 1 per 100 000 live births.

Perinatal Antiretroviral Exposure and Prevented Mother-to-child HIV Infections in the Era of Antiretroviral Prophylaxis in the United States, 1994-2010.

OBJECTIVES: Using published, nationally-representative estimates, we calculated the total number of perinatally HIV-exposed and HIV-infected infants born during 1978-2010, the number of perinatal HIV cases prevented by interventions designed for the prevention of mother-to-child transmission (PMTCT), and the number of infants exposed to antiretroviral (ARV) drugs during the prenatal and intrapartum periods. DESIGN: We calculated the number of infants exposed to ARV drugs since 1994, and the number of cases of mother-to-child HIV transmission prevented from 1994 to 2010 using published data. We generated confidence limits for our estimates by performing a simulation study. METHODS: Data were obtained from published, nationally-representative estimates from the Centers for Disease Control and Prevention. Model parameters included the annual numbers of HIV-infected pregnant women, the annual numbers of perinatally infected infants, the annual proportions of infants exposed to ARV drugs during the prenatal and intrapartum period and the estimated MTCT rate in the absence of preventive interventions. For the simulation study, model parameters were assigned distributions and we performed 1,000,000 repetitions. RESULTS: Between 1978 and 2010, an estimated 186,157 [95% confidence interval (CI): 185,312-187,003] HIV-exposed infants and approximately 21,003 (95% CI: 20,179-21,288) HIV-infected infants were born in the United States. Between 1994 and 2010, an estimated 124,342 (95% CI: 123,651-125,034) HIV-exposed infants were born in the US, and approximately 6083 (95% CI: 5931-6236) infants were perinatally infected with HIV. During this same period, about 100,207 (95% CI: 99,374-101,028) infants were prenatally exposed to ARV drugs. As a result of PMTCT interventions, an estimated 21,956 (95% CI: 20,191-23,759) MTCT HIV cases have been prevented in the United States since 1994. CONCLUSION: Although continued vigilance is needed to eliminate mother-to-child HIV transmission, PMTCT interventions have prevented nearly 22,000 cases of perinatal HIV transmission in the United States since 1994.

Maternal Highly Active Antiretroviral Therapy and Child HIV-Free Survival in Malawi, 2004-2009.

OBJECTIVES: Highly active antiretroviral therapy (HAART) provision to eligible HIV-infected pregnant and post-partum women is critical for optimizing maternal health. We assessed the impact of maternal HAART on HIV-free survival of breastfed infants in Malawi. METHODS: The post-exposure prophylaxis of infants-Malawi trial (2004-2009) enrolled mothers/infants during labor or immediately post-partum to evaluate 14-week extended infant antiretroviral prophylaxis for preventing HIV transmission through breastfeeding. Mothers meeting national HAART guidelines were referred for therapy. Child HIV-free survival-survival without HIV infection-was compared by maternal HAART status. RESULTS: Overall, 3022 mother-infant pairs contributed 4214 infant/person-years (PY) at-risk for HIV infection or death, with 532 events (incidence 12.6/100 PY, 95 % confidence interval [CI] 11.6-13.7). During follow-up, 349 mothers were HAART initiated; 581 remained HAART naïve with CD4 cell counts <250 cells/mm(3), and 2092 were never HAART-eligible. By 3 months, 11 % of infants with HAART naïve mothers (CD4 < 250) were infected with HIV or died versus 7 % of infants of HAART-initiated mothers and 4 % of infants of HAART-ineligible mothers. Maternal HAART was associated with a 46 % reduction in infant HIV infection or death as compared to infants with HAART naïve mothers (CD4 < 250) (adjusted hazards ratio 0.54, 95 % CI 0.36-0.81). Among HIV-exposed, uninfected infants, breastfeeding, but not HAART, was significantly associated with decreased child mortality. CONCLUSIONS: HIV infection and mortality are high during the first 3 months post-partum in infants of mothers with advanced HIV, and rapid maternal HAART initiation can significantly improve HIV-related infant outcomes. Clinical Trials Registration This study is registered at http://clinicaltrials.gov/ under trial number NCT00115648.

Outcomes in a cohort of women who discontinued maternal triple-antiretroviral regimens initially used to prevent mother-to-child transmission during pregnancy and breastfeeding--Kenya, 2003-2009.

BACKGROUND: In 2012, the World Health Organization (WHO) amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum. METHODS AND FINDINGS: The Kisumu Breastfeeding Study, 2003-2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naïve, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning-when tARV-PMTCT discontinued-by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P = 0.03). Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4-40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9-5.0) were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing. CONCLUSIONS: Considering the serious health risks to the woman's infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at antiretroviral initiation or 6-months postpartum can identify pregnant women who would most benefit from continuing cART in settings unable to implement WHO Option B+.

Factors associated with human immunodeficiency virus screening of women during pregnancy, labor and delivery, United States, 2005-2006.

The purpose of this study was to estimate prenatal human immunodeficiency virus (HIV) screening rates prior to and on admission to labor and delivery (L&D) and to examine factors associated with HIV screening, including hospital policies, with a comparison of HIV and hepatitis B prenatal screening practices and hospital policies. In March 2006, a survey of hospitals (n = 190) and review of paired maternal and infant medical records (n = 4,762) were conducted in 50 US states, DC, and Puerto Rico. Data from the survey and medical record review were analyzed using SAS software v9.2 (SAS Institute, Cary, NC). HIV testing before delivery occurred among 3,438 women (73.9%); African American and Hispanic women were more likely to be tested than white women [aOR 2.22, 95% CI (1.6-3.1) and aOR 1.55, 95% CI (1.1-2.2), respectively]. Among women without previous HIV testing, 138 (16.6%) were tested after admission to labor and delivery. Policies to test women with undocumented HIV status in at delivery were present in 65 (36.3%) hospitals. HIV testing after admission to L&D was more likely in hospitals with policies to test women with undocumented HIV status [aOR 5.91, 95% CI (2.0-17.8)]. Overall, policies and screening practices for HIV were consistently less prevalent than those for hepatitis B. Many women are not being routinely screened for HIV before or at delivery. Women with unknown HIV status were more likely to be tested in L&D in hospitals with testing policies.

Neutralization of HIV subtypes A and D by breast milk IgG from women with HIV infection in Uganda.

OBJECTIVES: Among HIV-exposed infants in resource-limited countries, 8-12% are infected postnatally by breastfeeding. However, most of those uninfected at birth remain uninfected over time despite daily exposure to HIV in breast milk. Thus, we assessed the HIV-inhibitory activity of breast milk. METHODS: We measured cross-clade neutralization in activated PBMC of Ugandan subtype A (92UG031) and D (92UG005) primary HIV by breast milk or purified milk IgG and IgA from 25 HIV-infected Ugandan women. Isotype-specific antigen recognition was resolved by immunoblot. We determined HIV subtype from envelope population sequences in cells from 13 milk samples by PCR. RESULTS: Milk inhibited p24 production by ≥50% (dose-dependent) by subtype A (21/25; 84%) and subtype D (11/25; 44%). IgG consistently reacted with multiple HIV antigens, including gp120/gp41, but IgA primarily recognized p24 alone. Depletion of IgG (n = 5), not IgA, diminished neutralization (mean 78 ± 33%) that was largely restored by IgG repletion. Mothers infected with subtype A more effectively neutralized subtype A than D. CONCLUSIONS: Breast milk from HIV-infected women showed homotypic and cross-subtype neutralization of HIV by IgG-dependent and -independent mechanisms. These data direct further investigations into mechanisms of resistance against postnatal transmission of HIV to infants from their mothers.

Pregnancy outcomes in HIV-infected women receiving long-term isoniazid prophylaxis for tuberculosis and antiretroviral therapy.

OBJECTIVE: While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART) are not established in human-immunodeficiency-virus-(HIV-) infected women who experience pregnancy during the course of therapy. DESIGN: Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. RESULTS: Among 196 pregnant women, 103 (52.6%) were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1-1095) of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3-1.1 and 1.8, 95% CI 0.9-3.6, resp.). CONCLUSIONS: Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

A review of evidence for transmission of HIV from children to breastfeeding women and implications for prevention.

BACKGROUND: Child-to-breastfeeding woman transmission (CBWT) of HIV occurs when an HIV-infected infant transmits the virus to an HIV-uninfected woman through breastfeeding. Transmission likely occurs as a result of breastfeeding contact during a period of epithelial disruption, such as maternal skin fissures and/or infant stomatitis. Despite extensive epidemiologic and phylogenetic evidence, however, CBWT of HIV continues to be overlooked. OBJECTIVE: This article summarizes the available evidence for CBWT from nosocomial outbreaks, during which nosocomially HIV-infected infants transmitted the virus to their mothers through breastfeeding. This article also explores the CBWT risk associated with HIV-infected orphans and their female caretakers, and the lack of guidance regarding CBWT prevention in infant feeding recommendations. METHODS: We searched online databases including PubMed and ScienceDirect for English language articles published from January 1975 to January 2011 using the search terms "HIV," "perinatal," "child-to-mother" and "breastfeeding." The citations from all selected articles were reviewed for additional studies. RESULTS: We identified 5 studies documenting cases of CBWT. Two studies contained data on the number of HIV-infected women, as well as the proportion breastfeeding. Rates of CBWT ranged from 40% to 60% among women reporting breastfeeding after their infants were infected. CONCLUSIONS: Poor infection control practices, especially in areas of high HIV prevalence, have resulted in pediatric HIV infections and put breastfeeding women at risk for CBWT. Current infant feeding guidelines and HIV prevention messages do not address CBWT, and fail to provide strategies to help women reduce their risk of acquiring HIV during breastfeeding.

Correlates of mother-to-child transmission of HIV in the United States and Puerto Rico.

OBJECTIVE: The goal of this study was to examine associations between demographic, behavioral, and clinical variables and mother-to-child HIV transmission in 15 US jurisdictions for birth years 2005 through 2008. METHODS: The study used Enhanced Perinatal Surveillance system data for HIV-infected women who gave birth to live infants. Multivariable logistic regression was used to assess variables associated with mother-to-child transmission. RESULTS: Among 8054 births, 179 infants (2.2%) were diagnosed with HIV infection. Half of the births had at least 1 missed prevention opportunity: 74.3% of infected infants, 52.1% of uninfected infants. Among 7757 mother-infant pairs with sufficient data for analysis, the odds of having an HIV-infected infant were higher for women who received late testing or no prenatal antiretroviral medications (odds ratio: 2.5 [95% confidence interval (CI): 1.5-4.0] and 3.5 [95% CI: 2.0-6.4], respectively). The odds for mothers who breastfed were 4.6 times (95% CI: 2.2-9.8) the odds for those who did not breastfeed. The adjusted odds for women with CD4 counts <200 cells per microliter were 2.4 times (95% CI: 1.4-4.2) those for women with CD4 counts ≥500 cells per microliter. The odds for women who abused substances were twice (95% CI: 1.4-2.9) those for women who did not. CONCLUSIONS: The odds of having an HIV-infected infant were higher among HIV-infected women who were tested late, had no antiretroviral medications, abused substances, breastfed, or had lower CD4 cell counts. Increases in earlier HIV diagnosis, substance abuse treatment, avoidance of breastfeeding, and use of prenatal antiretroviral medications are critical in eliminating perinatal HIV infections in the United States.

Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis.

BACKGROUND: In the Post Exposure Prophylaxis of Infants (PEPI)-Malawi trial, infants received up to 14 weeks of extended nevirapine (NVP) or extended NVP with zidovudine (NVP + ZDV) to prevent postnatal HIV transmission. We examined emergence and persistence of NVP resistance in HIV-infected infants who received these regimens prior to HIV diagnosis. METHODS: Infant plasma samples collected at 14 weeks of age were tested using the ViroSeq HIV Genotyping System and a sensitive point mutation assay, LigAmp (for K103N and Y181C). Samples collected at 6 and 12 months of age were analyzed using LigAmp. RESULTS: At 14 weeks of age, NVP resistance was detected in samples from 82 (75.9%) of 108 HIV-infected infants. Although the frequency of NVP resistance detected by ViroSeq was lower in the extended NVP + ZDV arm than in the extended NVP arm, the difference was not statistically significant (38/55 = 69.1% vs. 44/53 = 83.0%, P = 0.12). Similar results were obtained using LigAmp. Using LigAmp, the proportion of infants who still had detectable NVP resistance at 6 and 12 months was similar among infants in the two study arms (at 6 months: 17/20 = 85.0% for extended NVP vs. 21/26 = 80.8% for extended NVP + ZDV, P = 1.00; at 12 months: 9/16 = 56.3% for extended NVP vs.10/13 = 76.9% for extended NVP + ZDV, P = 0.43). CONCLUSION: Infants exposed to extended NVP or extended NVP + ZDV had high rates of NVP resistance at 14 weeks of age, and resistant variants frequently persisted for 6-12 months. Frequency and persistence of NVP resistance did not differ significantly among infants who received extended NVP only vs. extended NVP + ZDV prophylaxis.