Prevented perinatal HIV infections in the era of antiretroviral prophylaxis and treatment, United States, 1994-2020.

OBJECTIVE: The primary aim of this serial cross-sectional analysis is to estimate the total number of prevented perinatal HIV transmissions from the time of the initial recommendation for perinatal zidovudine (ZDV) prophylaxis in 1994 through 2020 in the US. METHODS: The estimated number of prevented transmissions was calculated as annual differences between expected and observed numbers of perinatal HIV transmissions. Annual expected number of transmissions was estimated by multiplying the annual number of births to women with HIV by 0.2255 (22.55%), i.e., the transmission rate of the control group in the ACTG Protocol 076 trial. We used published point estimates or, if only ranges were given, the midpoints of those ranges as the best estimates of the annual numbers of births to women with HIV and infants with perinatal HIV. When data were not available, we linearly interpolated or extrapolated the available data to obtain estimated numbers for each year. RESULTS: Between 1978 and 2020, the approximate number of live births to women with HIV was 191 267 (95% confidence interval [CI] 190 392-192 110) and for infants with diagnosed perinatal HIV, it was 21 379 (95% CI 21 088-21 695). Since 1994, the annual number of infants born with HIV decreased from 1263 (95% CI 1194-1333) to 33 in 2019 (95% CI 22-45) and 36 in 2020 (95% CI 25-48), corresponding to a 97% reduction. Cumulatively, an estimated total of 22 732 (95% CI 21 340-24 462) perinatal HIV infections were prevented from 1994 through to 2020. CONCLUSION: The elimination of perinatal HIV transmission-accompanied by the cumulative number of prevented cases exceeding that of perinatal HIV infections-is a major public health achievement in the US.

Factors Associated With Partner Notification, Testing, and Positivity in HIV Partner Services Programs in the United States, 2013 to 2017.

BACKGROUND: Human immunodeficiency virus (HIV) partner services are an essential component of comprehensive HIV prevention and care. We examined factors associated with partner notification, HIV testing, and HIV positivity among partners of HIV-diagnosed persons (index persons) contacted by Centers for Disease Control and Prevention (CDC)-funded state and local health departments. METHODS: We analyzed partner service data submitted to the CDC by 61 state and local health departments from 2013 to 2017. Using multivariate Poisson regression-adjusted for clustering effects among partners reported by a common index person-we assessed associations between 3 outcomes of interest (partner notification, HIV testing, and HIV positivity) and the demographic characteristics, risk behaviors, geographic region, and service year of index persons and their partners. RESULTS: A total of 51,368 sexual and/or needle-sharing partners were matched with 33,524 index persons. Of notifiable partners, 97.2% were notified of their potential HIV exposure, and 52.3% were tested for HIV. Among 21,842 notified and tested partners, 23.8% were newly diagnosed with an HIV infection. Partner notification, HIV testing, and HIV positivity were associated with both partner and index person characteristics (individually and interactively), geographic region, and year of service. CONCLUSIONS: Partner service programs provided through CDC-funded health departments were effective in both partner notification and identification of undiagnosed HIV infection among partners. However, HIV testing rate among notified partners remained low. Implementing strategies to address gaps in HIV testing can contribute toward ending the HIV epidemic in the United States.

Racial and Ethnic Disparities in COVID-19 Incidence by Age, Sex, and Period Among Persons Aged <25 Years - 16 U.S. Jurisdictions, January 1-December 31, 2020.

The COVID-19 pandemic has disproportionately affected racial and ethnic minority groups in the United States. Whereas racial and ethnic disparities in severe COVID-19-associated outcomes, including mortality, have been documented (1-3), less is known about population-based disparities in infection with SARS-CoV-2, the virus that causes COVID-19. In addition, although persons aged <30 years account for approximately one third of reported infections,§ there is limited information on racial and ethnic disparities in infection among young persons over time and by sex and age. Based on 689,672 U.S. COVID-19 cases reported to CDC's case-based surveillance system by jurisdictional health departments, racial and ethnic disparities in COVID-19 incidence among persons aged <25 years in 16 U.S. jurisdictions¶ were described by age group and sex and across three periods during January 1-December 31, 2020. During January-April, COVID-19 incidence was substantially higher among most racial and ethnic minority groups compared with that among non-Hispanic White (White) persons (rate ratio [RR] range = 1.09-4.62). During May-August, the RR increased from 2.49 to 4.57 among non-Hispanic Native Hawaiian and Pacific Islander (NH/PI) persons but decreased among other racial and ethnic minority groups (RR range = 0.52-2.82). Decreases in disparities were observed during September-December (RR range = 0.37-1.69); these decreases were largely because of a greater increase in incidence among White persons, rather than a decline in incidence among racial and ethnic minority groups. NH/PI, non-Hispanic American Indian or Alaska Native (AI/AN), and Hispanic or Latino (Hispanic) persons experienced the largest persistent disparities over the entire period. Ensuring equitable and timely access to preventive measures, including testing, safe work and education settings, and vaccination when eligible is important to address racial/ethnic disparities.

Resilience, condom use self-efficacy, internalized homophobia, and condomless anal sex among black men who have sex with men, New York City.

BACKGROUND: Black men who have sex with men, who account for less than 1% of the U.S. population, account for approximately 25% of new HIV infections annually. Condomless anal sex contributes to HIV infection among black men who have sex with men. The capacity to recover quickly from difficulties (resilience) may be protective against condomless anal sex, but has been understudied among black men who have sex with men. Psychosocial factors related to resilience, i.e., condom use self-efficacy and internalized homophobia, may also affect condomless anal sex. We assessed the association between resilience, condom use self-efficacy, internalized homophobia and condomless anal sex among black men who have sex with men. METHODS: Data are from a 2010-2011 study examining condomless anal sex (past 60 days) among black men who have sex with men in New York City. Validated scales assessed resilience (theoretical range = 0-100), condom use self-efficacy (theoretical range = 27-135), and internalized homophobia (theoretical range = 9-36). We described continuous variables using median and interquartile range (IQR). Univariable and multivariable Poisson regression models assuming a robust variance estimator were used to compute unadjusted and adjusted prevalence ratios, respectively, and their corresponding 95% confidence intervals (CI). Adjusted prevalence ratios (aPR) examined the association of resilience, condom use self-efficacy, and internalized homophobia with condomless anal sex, while controlling for potential confounders (e.g., having >1 sex partner). RESULTS: The median resilience score within our sample (N = 228) was 75 (IQR = 66-83). Many black men who have sex with men reported condomless anal sex (55.7%) and >1 sex partner (58.8%). Decreased condomless anal sex was associated with increased levels of condom use self-efficacy (aPR: 0.94 per 10-point increase in condom use self-efficacy score; CI: 0.90-0.97; p-value: 0.001). Condomless anal sex was not associated with resilience or internalized homophobia. CONCLUSIONS: Within this sample of black men who have sex with men, condomless anal sex was prevalent. Greater resilience was not protective against condomless anal sex. Interventions that support condom use are warranted for black men who have sex with men.

Time spent with HIV viral load above 1500 copies/ml among patients in HIV care, 2000-2014.

OBJECTIVE: Sexual HIV transmission is more likely to occur when plasma HIV RNA level (viral load) exceeds 1500 copies/ml. We assessed the percentage of person-time spent with viral load above 1500 copies/ml (pPT >1500) among adults with HIV in care. DESIGN: Observational cohort in eight United States HIV clinics. METHODS: Participants had at least one HIV Outpatient Study (HOPS) clinic visit and at least two viral loads during 2000-2014. We assessed pPT above 1500 in time intervals between consecutive viral load pairs, overall and by ART status. Trends in pPT above 1500 and associations between pPT above 1500 and chosen baseline demographics and clinical characteristics were analyzed using generalized estimating equations. RESULTS: There were 5873 patients contributing 37 794 person-years; 86.0% person-years had prescribed ART, with increasing coverage over time. Over 2000-2014 pPT above 1500 was 24.2%, decreasing from 38.3% in 2000-2002 to 11.3% in 2012-2014. During observation time with ART prescribed, pPT above 1500 was 16.4% overall, decreasing from 29.9% in 2000-2002 to 8.0% in 2012-2014. pPT above 1500 was higher in patients less than 35 vs. at least 50 years old (31.5 vs. 15.6%), women vs. men (30.8 vs. 22.3%), and black vs. white and Latino/Hispanic patients (32.7 vs. 19.9 and 23.7%, respectively). Multivariable correlates of higher pPT above 1500 included no prescribed ART, being younger, non-Hispanic black vs. white, baseline viral load above 1500 copies/ml or lower CD4 count, and baseline public vs. private insurance. CONCLUSION: pPT above 1500 declined during 2000-2014. Results support decreasing HIV transmission risk from persons in HIV care over the last decade, and the need to focus interventions on patient groups more consistently viremic.

Developing a Motion Comic for HIV/STD Prevention for Young People Ages 15-24, Part 2: Evaluation of a Pilot Intervention.

In the United States, young people (ages 15-24 years) are disproportionately affected by human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs), due at least in part to inadequate or incorrect HIV/STD-related knowledge, attitudes, beliefs, and behavioral intentions (KABI). Comic book narratives are a proven method of HIV/STD prevention communication to strengthen KABI for HIV/STD prevention. Motion comics, a new type of comic media, are an engaging and low-cost means of narrative storytelling. The objective of this study was to quantitatively evaluate the effectiveness of a pilot six-episode HIV/STD-focused motion comic series to improve HIV/STD-related KABI among young people. We assessed change in HIV/STD knowledge, HIV stigma, condom attitudes, HIV/STD testing attitudes, and behavioral intentions among 138 participants in 15 focus groups immediately before and after viewing the motion comic series. We used paired t-tests and indicators of overall improvement to assess differences between surveys. We found a significant decrease in HIV stigma (p < .001) and increases in both HIV knowledge (p = .002) and behavioral intentions to engage in safe sex (p < .001). In summary, this motion comic intervention improved HIV/STD-related KABI of young adult viewers by reducing HIV stigma and increasing behavioral intentions to engage in safer sex. Our results demonstrate the promise of this novel intervention and support its use to deliver health messages to young people.

Uptake of HIV Preexposure Prophylaxis Among Commercially Insured Persons-United States, 2010-2014.

BACKGROUND: Daily, oral use of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for preexposure prophylaxis (PrEP) is an effective strategy to prevent acquisition of human immunodeficiency virus (HIV) infection. It is important to monitor PrEP uptake at the national level to increase our understanding of trends in its utilization, but national HIV surveillance data do not include PrEP uptake. Our objective was to develop feasible methods to estimate PrEP uptake and to estimate uptake each year among commercially insured persons during 2010-2014. METHODS: We conducted a retrospective analysis of the 2010-2014 MarketScan database, a national sample of persons with commercial health insurance in the United States. We developed an algorithm to identify persons aged ≥16 years who were prescribed TDF-FTC for PrEP each year. We generated nationally representative estimates of prevalence of persons prescribed PrEP. RESULTS: We found a significantly increasing trend in the proportion of persons prescribed TDF-FTC for PrEP during the study period, with 417 users in 2010 and 9375 in 2014 (P < .001); 97% of PrEP users were male and 98% lived in metropolitan areas in 2014. During the study period, the numbers of women prescribed PrEP were low. CONCLUSIONS: Our analytic method provides the only feasible means to monitor PrEP uptake in the United States. Although a marked increasing trend in uptake was observed for men, the number of women who used PrEP remained very low during the study period. Interventions are needed to increase PrEP use by women at substantial risk of acquiring HIV infection.

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.

Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study.

Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated with the development of malignant mesothelioma on membranes surrounding the epididymis and on the testicular tunics, with the increase being significant at 2 mg furan/kg BW. There was also a dose-related increase in the incidence of mononuclear cell leukemia, with the increase in incidence being significant at 0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis, the frequency of which increased significantly at 0.2 mg furan/kg BW.

PrEP Awareness and Attitudes in a National Survey of Primary Care Clinicians in the United States, 2009-2015.

OBJECTIVES: As trials were assessing the safety and efficacy of daily oral antiretroviral preexposure prophylaxis (PrEP) for the prevention of HIV infection, there was a clear need to understand the evolution of knowledge of, and attitudes toward, PrEP among primary care clinicians. METHODS: Physicians and nurse practitioners were surveyed in 2009 (n = 1500), 2010 (n = 1504), 2012 (n = 1503), 2013 (n = 1507), 2014 (n = 1508) and 2015 (n = 1501) to assess their awareness of PrEP, willingness to prescribe PrEP, and whether they support use of public funds to pay for PrEP. Pharmacists (n = 251) were surveyed about PrEP in 2012 only. Descriptive statistics were computed for physician demographics and PrEP-related questions. Prevalence ratios for willingness to prescribe PrEP were computed using Poisson regression analysis. RESULTS: Awareness of PrEP was low among clinicians (2009: 24%, 2010: 29%) but increased after trials reported effectiveness (2012: 49%, 2013: 51%, 2014: 61%, 2015: 66%). Following a description of PrEP with an estimated effectiveness of 75%, across 6 of the study years 91% of clinicians indicated a willingness to prescribe PrEP to at least one group at high risk of HIV acquisition. A smaller majority of clinicians indicated support for public funding of PrEP in 2009: 59%, 2010: 53%, and 2013: 63%. CONCLUSIONS: In surveys conducted before and after the release of PrEP trial results, primary care clinicians were largely unaware of PrEP. They indicated high levels of willingness to prescribe it for patients at high risk of HIV acquisition and expressed interest in education about how to deliver this new clinical HIV prevention method. It will be important to continue monitoring clinician knowledge, attitudes, and practices as the use of PrEP increases in the US.

Trends in condom use among MSM in the United States: the role of antiretroviral therapy and seroadaptive strategies.

OBJECTIVE: Evaluate changes in condomless anal sex at last sex among men who have sex with men (MSM) and assess if these changes are associated with the adoption of serosorting and biomedical prevention. DESIGN: The National HIV Behavioral Surveillance is a crosssectional survey done in up to 21 cities in 2005, 2008, 2011 and 2014. METHODS: MSM were recruited through venue-based sampling. Among men reporting at least one male partner, we evaluated changes in condomless anal sex at last sex with a partner with (1) HIV-concordant (proxy for serosorting) or (2) HIV-discordant (discordant/unknown) status. We hypothesized that if concordant condomless sex was increasing while discordant was stable/declining, the increases could be driven by more men attempting to serosort. We used generalized estimating equations assuming a Poisson distribution and robust variance estimator to explore whether temporal changes in the outcomes varied by selected characteristics. We also assessed changes in condomless anal sex by antiretroviral therapy (ART) use among HIV-positive MSM. RESULTS: Among 5371 HIV-positive MSM, there were increases in concordant (19% in 2005 to 25% in 2014, P < 0.001) and discordant condomless sex (15 to 19%, P < 0.001). The increases were not different by ART use. Among 30 547 HIV-negative MSM, concordant (21 to 27%, P < 0.001) and discordant condomless sex (8 to 13%, P < 0.001) increased. CONCLUSION: Our data suggest that condom use decreased among MSM and that the trends are not explained by serosorting or ART. Promotion of condoms and increased access to preexposure prophylaxis are vital to ensure that the benefits of ART in reducing transmission of HIV are not undermined.

Carcinogenicity of glycidamide in B6C3F1 mice and F344/N rats from a two-year drinking water exposure.

Acrylamide is a contaminant in baked and fried starchy foods, roasted coffee, and cigarette smoke. Previously we reported that acrylamide is a multi-organ carcinogen in B6C3F1 mice and F344/N rats, and hypothesized that acrylamide is activated to an ultimate carcinogen through metabolism to the epoxide glycidamide. We have now examined the carcinogenic effects of glycidamide administered at 0, 0.0875, 0.175, 0.35 and 0.70 mM in drinking water to the same strains of rodents for two years. In male and female mice, there were significant increases in tumors of the Harderian gland, lung, forestomach, and skin. Female mice also had an increased incidence of tumors of the mammary gland and ovary. In male and female rats, there were significant increases in thyroid gland and oral cavity neoplasms and mononuclear cell leukemia. Male rats also had increases in tumors of the epididymis/testes and heart, while female rats demonstrated increases in tumors of the mammary gland, clitoral gland, and forestomach. A similar spectrum of tumors was obtained in mice and rats administered acrylamide. These data indicate that, under the conditions of these bioassays, acrylamide is efficiently metabolized to glycidamide and that the carcinogenic activity of acrylamide is due to its conversion into glycidamide.

Carcinogenicity of acrylamide in B6C3F(1) mice and F344/N rats from a 2-year drinking water exposure.

Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F(1) mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F(1) mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F(1) mice. Male B6C3F(1) mice also had a significantly increased incidence of forestomach tumors, while female B6C3F(1) mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide.

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Case-deletion diagnostics for maximum likelihood multipoint quantitative trait locus linkage analysis.

OBJECTIVES: Case-deletion diagnostic methods are tools that allow identification of influential observations that may affect parameter estimates and model fitting conclusions. The goal of this paper was to develop two case-deletion diagnostics, the exact case deletion (ECD) and the empirical influence function (EIF), for detecting outliers that can affect results of sib-pair maximum likelihood quantitative trait locus (QTL) linkage analysis. METHODS: Subroutines to compute the ECD and EIF were incorporated into the maximum likelihood QTL variance estimation components of the linkage analysis program MAPMAKER/SIBS. Performance of the diagnostics was compared in simulation studies that evaluated the proportion of outliers correctly identified (sensitivity), and the proportion of non-outliers correctly identified (specificity). RESULTS: Simulations involving nuclear family data sets with one outlier showed EIF sensitivities approximated ECD sensitivities well for outlier-affected parameters. Sensitivities were high, indicating the outlier was identified a high proportion of the time. Simulations also showed the enormous computational time advantage of the EIF. Diagnostics applied to body mass index in nuclear families detected observations influential on the lod score and model parameter estimates. CONCLUSIONS: The EIF is a practical diagnostic tool that has the advantages of high sensitivity and quick computation.