Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 141 Records) |
Query Trace: Kourtis AP[original query] |
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Trends in oral and injectable HIV preexposure prophylaxis prescriptions in the US, 2013-2023
Mann LM , Zhu W , Huang YA , Kourtis AP , Fanfair RN , Hoover KW . Jama 2024 This study examines the prescribing trends of 3 oral preexposure prophylaxis medications and a long-acting injectable option from 2013 to 2023. | eng |
Findings from the first year of a federally funded, direct-to-consumer HIV self-test distribution program - United States, March 2023-March 2024
Sanchez T , MacGowan RJ , Hecht J , Keralis JM , Ackah-Toffey L , Bourbeau A , Dana R , Lilo EA , Downey RS , Getachew-Smith H , Hannah M , Valencia R , Krebs E , Pingel ES , Gayden JJ , Norelli J , Mason Z , Mahn J , Cramer N , Bole R , Sullivan P , Nwaohiri AN , Stryker JE , Kourtis AP , DiNenno EA , Fanfair RN , Mermin JH , Delaney KP . MMWR Morb Mortal Wkly Rep 2024 73 (24) 558-564 In September 2022, CDC funded a nationwide program, Together TakeMeHome (TTMH), to expand distribution of HIV self-tests (HIVSTs) directly to consumers by mail through an online ordering portal. To publicize the availability of HIVSTs to priority audiences, particularly those disproportionately affected by HIV, CDC promoted this program through established partnerships and tailored resources from its Let's Stop HIV Together social marketing campaign. The online portal launched March 14, 2023, and through March 13, 2024, distributed 443,813 tests to 219,360 persons. Among 169,623 persons who answered at least one question on a postorder questionnaire, 67.9% of respondents were from priority audiences, 24.1% had never previously received testing for HIV, and 24.8% had not received testing in the past year. Among the subset of participants who initiated a follow-up survey, 88.3% used an HIVST themselves, 27.1% gave away an HIVST, 11.7% accessed additional preventive services, and 1.9% reported a new positive HIVST result. Mailed HIVST distribution can quickly reach large numbers of persons who have never received testing for HIV or have not received testing as often as is recommended. TTMH can help to achieve the goal of diagnosing HIV as early as possible and provides a path to other HIV prevention and care services. Clinicians, community organizations, and public health officials should be aware of HIVST programs, initiate discussions about HIV testing conducted outside their clinics or offices, and initiate follow-up services for persons who report a positive or negative HIVST result. |
Challenges, risks, and opportunities of antiretroviral drugs in women of reproductive potential
Henderson AC , Cholli P , Lampe MA , Kourtis AP . Expert Rev Anti Infect Ther 2024 1-15 INTRODUCTION: The HIV/AIDS epidemic has been one of the greatest challenges in global health, significantly affecting women of reproductive potential. Considerable advances in antiretroviral therapy for women living with HIV have contributed to improvements in quality of life, better reproductive and birth outcomes, and a reduced risk of perinatal transmission. AREAS COVERED: Despite the progress made, persistent challenges in access and adherence to antiretroviral drugs may limit their benefits for some women. More pharmacokinetic and safety studies in pregnant and lactating women are urgently needed, as are prospective surveillance systems to evaluate associations between fetal and infant antiretroviral exposures, drug-drug interactions, and pregnancy outcomes. EXPERT OPINION: Multipurpose technologies, such as combined HIV and other STI or unintended pregnancy prevention, and innovative delivery methods, such as the development of long-acting antiretrovirals, have the potential to reduce adherence challenges and enhance quality of life for women with HIV. Parallel advances in drug safety testing and surveillance are needed to ensure the health and safety of women with or at risk for HIV and children at risk for perinatal transmission. |
HIV preexposure prophylaxis provision among adolescents: 2018 to 2021
Kimball AA , Zhu W , Leonard J , Wei W , Ravichandran I , Tanner MR , Huang YA , Hoover KW , Kourtis AP . Pediatrics 2023 152 (5) BACKGROUND AND OBJECTIVES: HIV preexposure prophylaxis (PrEP) is safe, effective, and was approved for adolescents in 2018. Adolescents and young adults make up 20% of HIV diagnoses in the United States. Our objective was to describe trends in adolescents prescribed PrEP during 2018 through 2021 and characteristics of these adolescents and their PrEP providers. METHODS: We identified adolescents aged 13 to 19 years with oral PrEP prescriptions during 2018 through 2021 in a national pharmacy database using a validated algorithm. We assessed trends by calculating the overall percentage change and estimated annual percentage change with 95% confidence intervals. We described characteristics of adolescents and their PrEP providers in 2021. We performed χ2 analyses to assess differences by sex and age group. RESULTS: The number of adolescents prescribed PrEP increased 76.2% from 2018 to 2021 (estimated annual percentage change: 18.0% [95% confidence interval: 16.6-19.5]), despite decreases in 2020. We observed increases among all sex and age groups, with larger increases among older adolescents aged 18 to 19 years. The majority of the 6444 adolescents prescribed PrEP in 2021 were male (82.6%) and aged 18 to 19 years (87.8%). Among 2455 physician PrEP providers, 29.6% were pediatricians, with varying specialty distributions by adolescent age group (P < .001). Among the 217 pediatricians who prescribed PrEP to adolescents aged 13 to 17 years, 67.7% were general pediatricians. CONCLUSIONS: PrEP provision for adolescents has increased, largely among older and male adolescents. The availability of PrEP provides an important opportunity for pediatric providers to take an active role in HIV prevention. |
Vaginal microbiome, antiretroviral concentrations, and HIV genital shedding in the setting of hormonal contraception initiation in Malawi
Lantz AM , Cottrell ML , Corbett AH , Chinula L , Kourtis AP , Nelson JAE , Tegha G , Hurst S , Gajer P , Ravel J , Haddad LB , Tang JH , Nicol MR . AIDS 2023 37 (14) 2185-2190 OBJECTIVE: The aim of this study was to understand how vaginal microbiota composition affects antiretroviral concentrations in the setting of hormonal contraception initiation. METHODS: Cervicovaginal fluid (CVF) concentrations of tenofovir, lamivudine, and efavirenz from 73 Malawian women with HIV were compared before and after initiation of depot-medroxyprogesterone acetate (DMPA) or levonorgestrel implant. We evaluated antiretroviral concentrations and vaginal microbiota composition/structure in the context of contraception initiation and predicted genital shedding using multivariable repeated measurements models fit by generalized estimating equations. RESULTS: Mean lamivudine CVF concentrations decreased 37% 1 month after contraception initiation. Subgroup analyses revealed a 41% decrease in women 1 month after initiating levonorgestrel implant, but no significant difference was observed in DMPA group alone. Tenofovir, lamivudine, and efavirenz CVF concentrations were positively correlated with anaerobic bacteria associated with nonoptimal vaginal microbiota. Risk of genital HIV shedding was not significantly associated with tenofovir or lamivudine CVF concentrations [tenofovir relative risk (RR): 0.098, P = 0.75; lamivudine RR: 0.142, P = 0.54]. Lack of association between genital HIV shedding and efavirenz CVF concentrations did not change when adjusting for vaginal microbiota composition and lamivudine/tenofovir CVF concentrations (RR: 1.33, P = 0.531). CONCLUSION: No effect of hormone initiation on genital shedding provides confidence that women with HIV on either DMPA or levonorgestrel implant contraception will not have compromised ART efficacy. The unexpected positive correlation between antiretroviral CVF concentrations and certain bacterial taxa relative abundance requires further work to understand the mechanism and clinical relevance. |
Dolutegravir and pregnancy outcomes including neural tube defects in the USA during 2008-20: a national cohort study
Kourtis AP , Zhu W , Lampe MA , Huang YA , Hoover KW . Lancet HIV 2023 10 (9) e588-e596 BACKGROUND: A study from Botswana identified an increased risk of neural tube defects (NTDs) in infants of mothers with HIV who were treated with dolutegravir around the time of conception. We aimed to examine associations of dolutegravir use with NTDs and pregnancy loss using large health-care claims databases from the USA, a country with folic acid fortification of food. METHODS: In this cohort study, we analysed health-care claims data, recorded in the Merative MarketScan commercial database (MarketScan data) and Centers for Medicare & Medicaid Services Medicaid database (Medicaid data) from Jan 1, 2008, to Dec 31, 2020. We identified pregnancies with enrolment during their entire duration among women aged 15-49 years and we estimated time of conception. For each pregnancy, we determined HIV status and periconceptional exposure to dolutegravir or other antiretroviral agents. We estimated and compared the incidence rate of NTDs, stillbirths, and pregnancy loss (ie, spontaneous or induced abortions) by type of periconceptional antiretroviral exposure. We calculated adjusted risk ratios of the adverse outcomes using Poisson models adjusting for demographic and clinical factors. FINDINGS: Of 4 489 315 pregnancies in MarketScan data and 14 405 861 pregnancies in Medicaid data that had full enrolment, we identified 69 pregnancies in MarketScan data and 993 pregnancies in Medicaid data that were associated with HIV and periconceptional dolutegravir exposure. For women without HIV, the NTD rate was 4·1 per 10 000 live births (95% CI 3·9-4·3) in MarketScan and 5·7 per 10 000 live births (5·6-5·8) in Medicaid. No NTD cases were found among those with dolutegravir or non- dolutegravir antiretroviral drug exposure in the MarketScan data; only one NTD case was identified among women with dolutegravir, and three among women with non-dolutegravir antiretroviral exposure in Medicaid. After adjusting for covariates, there were no significant differences in risk ratios of NTD between groups with periconceptional dolutegravir or non-dolutegravir antiretroviral exposure and the group without HIV. However, compared with women without HIV, the risk of pregnancy loss was higher among women exposed to antiretroviral therapy: for dolutegravir exposure the adjusted risk ratio was 1·73 (95% CI 1·20-2·49) in MarketScan data and 1·41 (1·30-1·54) in Medicaid data; for non-dolutegravir antiretroviral exposure the adjusted risk ratio was 1·23 (1·10-1·37) in MarketScan data and 1·11 (1·07-1·15) in Medicaid data. INTERPRETATION: We studied the largest US cohort of women with periconceptional or early-pregnancy dolutegravir exposure. Our results do not show an increased risk of NTDs in exposed infants in the USA. Administrative databases can be used, with rigorous methodology, to study correlates of rare outcomes, such as NTDs, and to monitor for adverse pregnancy outcomes in women who receive antiretrovirals. FUNDING: US Centers for Disease Control and Prevention. |
Achieving elimination of perinatal HIV in the United States
Lampe MA , Nesheim SR , Oladapo KL , Ewing AC , Wiener J , Kourtis AP . Pediatrics 2023 151 (5) In 2012, the Centers for Disease Control and Prevention published a Framework for Elimination of Perinatal Transmission of HIV in the United States in Pediatrics, setting the goals of an incidence of <1 case of perinatal HIV per 100 000 live births, and a perinatal transmission rate of <1%. We used National HIV Surveillance System data to monitor the numbers of perinatally acquired HIV cases among US-born persons and perinatal HIV diagnosis rates per 100 000 live births to approximate incidence. Perinatal HIV transmission rates from 2010 to 2019 were calculated by using estimates of live births to women with an HIV diagnosis from the National Inpatient Sample, Healthcare Cost and Utilization Project. The annual estimated number of live births to women with diagnosed HIV decreased from 4587 in 2010 to 3525 in 2019, and the number of US-born infants with perinatally acquired HIV decreased from 74 in 2010 to 32 in 2019. Annual perinatal HIV diagnosis rates declined from 1.9 to 0.9 per 100 000 live births, and perinatal HIV transmission rates declined from 1.6% to 0.9%. Racial and ethnic disparities in HIV diagnosis rates persisted but declined substantially over the 10-year period. Both diagnosis and transmission rate elimination goals were first achieved in 2019. To maintain the elimination of perinatal HIV, and to eliminate racial disparities, the continued coordinated effort of health care and public health is required. The approach to perinatal HIV elimination is a public health model that can be replicated or expanded to areas beyond HIV. |
Identification of pregnancies and their outcomes in healthcare claims data, 2008-2019: An algorithm
Ailes EC , Zhu W , Clark EA , Huang YA , Lampe MA , Kourtis AP , Reefhuis J , Hoover KW . PLoS One 2023 18 (4) e0284893 Pregnancy is a condition of broad interest across many medical and health services research domains, but one not easily identified in healthcare claims data. Our objective was to establish an algorithm to identify pregnant women and their pregnancies in claims data. We identified pregnancy-related diagnosis, procedure, and diagnosis-related group codes, accounting for the transition to International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis and procedure codes, in health encounter reporting on 10/1/2015. We selected women in Merative MarketScan commercial databases aged 15-49 years with pregnancy-related claims, and their infants, during 2008-2019. Pregnancies, pregnancy outcomes, and gestational ages were assigned using the constellation of service dates, code types, pregnancy outcomes, and linkage to infant records. We describe pregnancy outcomes and gestational ages, as well as maternal age, census region, and health plan type. In a sensitivity analysis, we compared our algorithm-assigned date of last menstrual period (LMP) to fertility procedure-based LMP (date of procedure + 14 days) among women with embryo transfer or insemination procedures. Among 5,812,699 identified pregnancies, most (77.9%) were livebirths, followed by spontaneous abortions (16.2%); 3,274,353 (72.2%) livebirths could be linked to infants. Most pregnancies were among women 25-34 years (59.1%), living in the South (39.1%) and Midwest (22.4%), with large employer-sponsored insurance (52.0%). Outcome distributions were similar across ICD-9 and ICD-10 eras, with some variation in gestational age distribution observed. Sensitivity analyses supported our algorithm's framework; algorithm- and fertility procedure-derived LMP estimates were within a week of each other (mean difference: -4 days [IQR: -13 to 6 days]; n = 107,870). We have developed an algorithm to identify pregnancies, their gestational age, and outcomes, across ICD-9 and ICD-10 eras using administrative data. This algorithm may be useful to reproductive health researchers investigating a broad range of pregnancy and infant outcomes. |
An estimate of excess deaths among people with HIV during the COVID-19 pandemic in the United States, 2020
Zhu W , Huang YA , Song R , Wiener J , Neblett-Fanfair RN , Kourtis AP , Hoover KW . AIDS 2023 37 (5) 851-853 We developed an ad hoc method to estimate the number of excess deaths among persons with HIV (PWH) during the COVID-19 pandemic in the United States. Using this method, we estimated approximately 1,448 excess deaths from COVID-19 among PWH in 2020 in the United States. We also developed an Excel workbook for use as a tool to quickly assess excess deaths among PWH in settings with limited surveillance data. |
Influence of Hormonal Contraceptive Use and HIV on Cervicovaginal Cytokines and Microbiota in Malawi.
Haddad LB , Tang JH , Davis NL , Kourtis AP , Chinula L , Msika A , Tegha G , Hosseinipour MC , Nelson JAE , Hobbs MM , Gajer P , Ravel J , De Paris K . mSphere 2023 8 (1) e0058522 Important questions remain on how hormonal contraceptives alter the local immune environment and the microbiota in the female genital tract and how such effects may impact susceptibility to HIV infection. We leveraged samples from a previously conducted clinical trial of Malawian women with (n = 73) and without (n = 24) HIV infection randomized to depot medroxyprogesterone acetate (DMPA) or the levonogestrel implant in equal numbers within each group and determined the effects of these hormonal contraceptives (HCs) on the vaginal immune milieu and the composition of the vaginal microbiota. Longitudinal data for soluble immune mediators, measured by multiplex bead arrays and enzyme-linked immunosorbent assays (ELISAs), and vaginal microbiota, assessed by 16S rRNA gene amplicon, were collected prior to and over a period of 180 days post-HC initiation. DMPA and levonogestrel had only minimal effects on the vaginal immune milieu and microbiota. In women with HIV, with the caveat of a small sample size, there was an association between the median log(10) change in the interleukin-12 (IL-12)/IL-10 ratio in vaginal fluid at day 180 post-HC compared to baseline when these women were classified as having a community state type (CST) IV vaginal microbiota and were randomized to DMPA. Long-lasting alterations in soluble immune markers or shifts in microbiota composition were not observed. Furthermore, women with HIV did not exhibit increased viral shedding in the genital tract after HC initiation. Consistent with the results of the ECHO (Evidence for Contraceptive Options and HIV Outcomes) trial, our data imply that the progestin-based HC DMPA and levonorgestrel are associated with minimal risk for women with HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT02103660). IMPORTANCE The results of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, the first large randomized controlled clinical trial comparing the HIV acquisition risk of women receiving DMPA, the levonorgestrel (LNG) implant, or the copper intrauterine device (IUD), did not reveal an increased risk of HIV acquisition for women on any of these three contraceptives. Our study results confirm that the two different progestin-based hormonal contraceptives DMPA and levonogestrel will not increase the risk for HIV infection. Furthermore, DMPA and levonogestrel have only minimal effects on the immune milieu and the microbiota in the vaginal tract, attesting to the safety of these hormonal contraceptives. |
HIV services and outcomes during the COVID-19 pandemic - United States, 2019-2021
Hoover KW , Zhu W , Gant ZC , Delaney KP , Wiener J , Carnes N , Thomas D , Weiser J , Huang YA , Cheever LW , Kourtis AP . MMWR Morb Mortal Wkly Rep 2022 71 (48) 1505-1510 Increasing HIV testing, preexposure prophylaxis (PrEP), and antiretroviral therapy (ART) are pillars of the federal Ending the HIV Epidemic in the U.S. (EHE) initiative, with a goal of decreasing new HIV infections by 90% by 2030.* In response to the COVID-19 pandemic, a national emergency was declared in the United States on March 13, 2020, resulting in the closure of nonessential businesses and most nonemergency health care venues; stay-at-home orders also limited movement within communities (1). As unemployment increased during the pandemic (2), many persons lost employer-sponsored health insurance (3). HIV testing and PrEP prescriptions declined early in the COVID-19 pandemic (4-6); however, the full impact of the pandemic on use of HIV prevention and care services and HIV outcomes is not known. To assess changes in these measures during 2019-2021, quarterly data from two large U.S. commercial laboratories, the IQVIA Real World Data - Longitudinal Prescription Database (IQVIA),(†) and the National HIV Surveillance System (NHSS)(§) were analyzed. During quarter 1 (Q1)(¶) 2020, a total of 2,471,614 HIV tests were performed, 190,955 persons were prescribed PrEP, and 8,438 persons received a diagnosis of HIV infection. Decreases were observed during quarter 2 (Q2), with 1,682,578 HIV tests performed (32% decrease), 179,280 persons prescribed PrEP (6% decrease), and 6,228 persons receiving an HIV diagnosis (26% decrease). Partial rebounds were observed during quarter 3 (Q3), with 2,325,554 HIV tests performed, 184,320 persons prescribed PrEP, and 7,905 persons receiving an HIV diagnosis. The proportion of persons linked to HIV care, the number who were prescribed ART, and proportion with a suppressed viral load test (<200 copies of HIV RNA per mL) among those tested were stable during the study period. During public health emergencies, delivery of HIV services outside of traditional clinical settings or that use nonclinical delivery models are needed to facilitate access to HIV testing, ART, and PrEP, as well as to support adherence to ART and PrEP medications. |
Crush: A randomized trial to evaluate the impact of a mobile health app on adolescent sexual health
Martnez-Garca G , Ewing AC , Olugbade Y , DiClemente RJ , Kourtis AP . J Adolesc Health 2022 72 (2) 287-294 PURPOSE: Mobile technology allows delivery of sexual and reproductive health (SRH) information directly to youth. We tested the efficacy of Crush, a mobile application aimed at improving sexual health by promoting the use of SRH services and contraception among female adolescents. METHODS: We recruited 1,210 women aged 14-18years through social media advertising and randomized them into a Crush intervention group and a control group that received a wellness app. At 3 and 6months post randomization, we compared changes from baseline in behaviors, attitudes, self-efficacy, perceived social norms, birth control knowledge, perceived control and use intentions, and SRH service utilization. Odds ratios were estimated with multivariable logistic regression and adjusted for baseline outcome, age, race/ethnicity, mother's education, and sexual experience. RESULTS: There was no difference in accessing SRH services according to study group. Three months post baseline, Crush users had higher odds (p < .05) than control participants of reporting confidence in accessing SRH services (adjusted odds ratio [aOR]= 1.6, 95% confidence interval [CI]: 1.1-2.3) and of believing that it is a good thing to use birth control consistently (aOR= 2.3, 95% CI: 1.4-3.8). Six months after baseline, Crush users had higher odds than control participants of reporting they can control whether birth control is used every time they have sex (aOR= 1.8, 95% CI: 1.2-2.6) and perceiving they would get pregnant if they did not use birth control (aOR: 1.5, 95% CI: 1.1-2.2). Impacts on other behavioral constructs were also found. DISCUSSION: Crush was associated with improvements in knowledge, attitudes, and self-efficacy related to key SRH behaviors and may be a strategy to deliver SRH education to adolescent women. Studies including larger numbers of sexually active adolescents are needed to demonstrate behavioral impacts. |
2gether: A clinic-based intervention to increase dual protection from sexually transmitted infections and pregnancy in young African American females
Kottke MJ , Sales JM , Goedken P , Brown JL , Hatfield-Timajchy K , Koumans EH , Hardin JW , Kraft JM , Kourtis AP . J Womens Health (Larchmt) 2022 32 (1) 29-38 Background: To determine whether the 2gether intervention increases use of a dual protection (DP; concurrent prevention of pregnancy and sexually transmitted infections [STIs]) strategy and decreases pregnancy and STIs among young African American females, who disproportionately experience these outcomes. Materials and Methods: We conducted a randomized clinical trial comparing the 2gether intervention to standard of care (SOC). Participants were self-identified African American females aged 14-19 years who were sexually active with a male partner in the past 6 months. Participants were followed for 12 months; 685 were included in the analytic sample. The primary biologic outcome was time to any incident biologic event (chlamydia, gonorrhea, trichomonas infections, or pregnancy). The primary behavioral outcomes were use of and adherence to a DP strategy. Results: 2gether intervention participants had a decreased hazard of chlamydia, gonorrhea, trichomonas infections, or pregnancy during follow-up, hazard ratio=0.73 (95% confidence interval [CI] 0.58-0.92), and were more likely to report use of condoms plus contraception, generally, adjusted risk ratio (aRR)=1.61 (95% CI 1.15-2.26) and condoms plus an implant or intrauterine device (IUD), specifically, aRR=2.11 (95% CI 1.35-3.29) in the prior 3 months compared with those receiving SOC. 2gether participants were also more likely to report use of condoms plus an implant or IUD at last sex and consistently over the prior 3 months. Conclusions: 2gether was efficacious in increasing use of condoms with contraception and decreasing pregnancy or selected STIs in our participants. Implementation of this intervention in clinical settings serving young people with high rates of pregnancy and STIs may be beneficial. ClinicalTrials.gov, No. NCT02291224 (https://clinicaltrials.gov/ct2/show/NCT02291224term=2gether&draw=2&rank=5). |
Impact of tenofovir disoproxil fumarate use during pregnancy on maternal bone mineral density
Wang L , Kourtis AP , Wiener J , Chen L , Liu W , Fan B , Shepherd J , Bulterys M . Pediatr Infect Dis J 2022 41 (12) 976-978 Chronic hepatitis B virus (HBV) infection and HIV infection are diseases of great public health importance. Tenofovir disoproxil fumarate (TDF), a nucleotide analog reverse transcriptase inhibitor, is effective for the treatment of both HIV and HBV.1,2 However, information on the bone safety of TDF during pregnancy, a time with increased demands on bone metabolism, has not been systematically assessed. | We conducted a phase II randomized controlled trial (RCT) in Guangxi Zhuang Autonomous Region of the People’s Republic of China, to evaluate the bone mineral density (BMD) effects of TDF on women and their infants. Effects of TDF on bone health of infants have been reported elsewhere3; this report presents our findings on the effects of TDF on maternal BMD. |
Decreased human immunodeficiency virus diagnosis rates among Black and Hispanic or Latino men who have sex with men in US jurisdictions supported by the THRIVE Demonstration Project, 2014-2019
Iqbal K , Dong X , Zhu W , Wiener J , Dominguez KL , Tanner MR , Kourtis AP , Singh S , Hoover KW . Clin Infect Dis 2023 76 (2) 307-314 BACKGROUND: Black and Hispanic/Latino men who have sex with men (MSM) are disproportionately affected by human immunodeficiency virus (HIV). In the Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project, 7 community collaboratives were developed to provide comprehensive HIV prevention services for these populations. METHODS: We analyzed National HIV Surveillance System data to determine the number of HIV diagnoses for each year from 2014 to 2019 among Black, Hispanic/Latino, and White MSM in 7 THRIVE-eligible Metropolitan Statistical Areas (MSAs) that were awarded funding and 12 THRIVE-eligible MSAs that were not awarded funding. We used generalized linear Poisson regression models to estimate adjusted estimated annual percentage changes (EAPCs) with 95% confidence intervals for HIV diagnosis rates controlling for HIV prevalence, viral suppression, HIV testing rates, preexposure prophylaxis (PrEP) prescription rates, poverty, education, and insurance status. RESULTS: We found larger estimated decreases in HIV diagnosis rates in THRIVE jurisdictions compared with non-THRIVE jurisdictions. The adjusted EAPC among Black MSM was -8.2 (-11.7 to -4.6) in THRIVE MSAs compared with -4.2 (-7.8 to -0.4) in non-THRIVE MSAs. The adjusted EAPC among Hispanic/Latino MSM was -8.6 (-12.2 to -4.8) in THRIVE MSAs compared with -2.6 (-5.1 to -0.1)in non-THRIVE MSAs. The adjusted EAPC among White MSM was -7.6 (-12.0 to -3.1) in THRIVE MSAs compared with 5.9 (1.8-10.1) in non-THRIVE MSAs. CONCLUSIONS: The THRIVE community collaborative model was associated with a decrease in HIV diagnoses among Black and Hispanic/Latino MSM. To achieve the goals of the US Ending the HIV Epidemic initiative, effective interventions aimed to increase PrEP use need to be focused on Black and Hispanic/Latino MSM. |
U.S. Black women and human immunodeficiency virus preexposure prophylaxis implementation
Hoover KW , Kourtis AP , Smith DK . Obstet Gynecol 2022 140 (1) 106-109 Black women are disproportionately affected by the U.S. human immunodeficiency virus (HIV) epidemic. Preexposure prophylaxis (PrEP) is a safe and effective intervention for HIV prevention. Increased PrEP implementation is a pillar of the U.S. Department of Health and Human Services' Ending the HIV Epidemic in the U.S. initiative. However, PrEP has been used by a smaller proportion of women with PrEP indications compared with men. The goals of the Ending the HIV Epidemic in the U.S. initiative can be achieved only by increasing PrEP use among Black women. Obstetricians and gynecologists are uniquely poised to provide PrEP services for women. We describe the need for community-to-clinic models to overcome the barriers to PrEP use by Black women and a roadmap for clinician and community organization collaboration to increase access to and use of PrEP by Black women. |
Impact of the COVID-19 pandemic on prescriptions for antiretroviral drugs for HIV treatment in the United States, 2019-2021.
Zhu W , Huang YA , Weiner J , Neblett-Fanfair R , Kourtis AP , Hall HI , Hoover KW . AIDS 2022 36 (12) 1697-1705 OBJECTIVE: To access disruption in healthcare services for HIV treatment by national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic in the United States. DESIGN: Time-series analysis. METHODS: We analyzed the IQVIA Real World Data-Longitudinal Prescriptions Database and calculated time trends in the weekly number of persons with active antiretroviral (ARV) prescriptions for HIV treatment, and of persons who obtained ARV prescriptions during January 2017-March 2021. We used interrupted time-series models to estimate the impact of the COVID-19 pandemic on antiretroviral therapy (ART) use between March 2020 and March 2021. RESULTS: We found that the weekly number of persons with active ARV prescriptions decreased by an average 2.5% (95% confidence interval [CI]: -3.8% to -1.1%), compared to predicted use, during March 2020 through March 2021. The weekly number of persons who obtained ARV prescriptions decreased 4.5% (95% CI: -6.0% to -3.0%), compared to the predicted number. Men, persons aged ≤34 years, privately insured persons, and persons in medication assistance programs had greater decreases than other groups. CONCLUSIONS: We demonstrated a decrease in the number of persons with active ARV prescriptions during the first year of the COVID-19 pandemic and the number did not return to levels expected in the absence of the pandemic. Disruptions in HIV care and decreased ART may lead to lower levels of viral suppression and immunologic control, and increased HIV transmission in the community. |
Antibody-dependent cellular cytotoxicity (ADCC) responses along with ADCC susceptibility influence HIV-1 mother to child transmission.
Thomas AS , Coote C , Moreau Y , Isaac JE , Ewing AC , Kourtis AP , Sagar M . JCI Insight 2022 7 (9) BACKGROUND: HIV-1 vaccine efforts are primarily directed towards eliciting neutralizing antibodies (nAbs). However, vaccine trials and mother to child natural history cohort investigations indicate that antibody-dependent cellular cytotoxicity (ADCC), not nAbs, correlate with prevention. The ADCC characteristics associated with lack of HIV-1 acquisition remain unclear. METHODS: Here we examine ADCC and nAb properties in pre-transmission plasma from HIV-1 exposed infants and from the corresponding transmitting and non-transmitting mothers' breast milk and plasma. Breadth and potency (BP) is assessed against a panel of heterologous, non-maternal, variants. ADCC and neutralization sensitivity is estimated for the strains present in the infected mothers. RESULTS: Infants that eventually acquire HIV-1 and those that remain uninfected have similar pre-transmission ADCC BP. The viruses circulating in the transmitting and the non-transmitting mothers also have similar ADCC susceptibility. Infants with a combination of higher pre-transmission ADCC BP and exposure to more ADCC susceptible strains are less likely to acquire HIV-1. In contrast, higher pre-existing infant neutralization BP and greater maternal virus neutralization sensitivity does not associate with transmission. Infants have higher ADCC BP closer to birth and in the presence of high plasma IgG relative to IgA levels. Mothers with potent humoral responses against their autologous viruses harbor more ADCC sensitive strains. CONCLUSION: ADCC sensitivity of the exposure variants along with preexisting ADCC BP influence mother to child HIV-1 transmission during breastfeeding. Vaccination strategies that enhance ADCC responses are likely not sufficient to prevent HIV-1 transmission because strains present in chronically infected individuals can have low ADCC susceptibility. TRIAL REGISTRATION: NCT00164736 for BAN study. |
COVID-19 vaccines in children and adolescents
Maldonado YA , O'Leary ST , Ardura MI , Banerjee R , Bryant KA , Campbell JD , Caserta MT , John CC , Gerber JS , Kourtis AP , Ratner AJ , Romero JR , Shah SS , Zangwill KM , Kimberlin DW , Barnett ED , Lynfield R , Sawyer MH , Bernstein HH , Cohn AC , Farizo KM , Halasa NB , Kafer LM , Kim D , LpezMedina E , Moore D , Panagiotakopoulos L , Sauv L , Silverman NS , Starke JR , Tomashek KM , Frantz JM , CommitteeonInfectious Diseases . Pediatrics 2022 149 (1) Vaccines are safe and effective in protecting individuals and populations against infectious diseases. New vaccines are evaluated by a long-standing, rigorous, and transparent process through the US Food and Drug Administration and the Centers for Disease Control and Prevention (CDC), by which safety and efficacy data are reviewed before authorization and recommendation. |
Impact of COVID-19 on HIV Preexposure Prophylaxis Prescriptions in the United States - A Time Series Analysis.
Huang YA , Zhu W , Wiener J , Kourtis AP , Hall HI , Hoover KW . Clin Infect Dis 2022 75 (1) e1020-e1027 BACKGROUND: Uptake of HIV preexposure prophylaxis (PrEP) has been increasing in the United States since its FDA approval in 2012; however, the COVID-19 pandemic may have affected this trend. Our objective was to assess the impact of the COVID-19 pandemic on PrEP prescriptions in the United States. METHODS: We analyzed data from a national pharmacy database from January 2017 through March 2021 to fit an interrupted time-series model that predicted PrEP prescriptions and new PrEP users had the pandemic not occurred. Observed PrEP prescriptions and new users were compared with those predicted by the model. Main outcomes were weekly numbers of PrEP prescriptions and new PrEP users based on a previously developed algorithm. The impact of the COVID-19 pandemic was quantified by computing rate ratios and percent decreases between the observed and predicted counts during 3/15/2020 - 3/31/2021. RESULTS: In the absence of the pandemic, our model predicted that there would have been 1,058,162 PrEP prescriptions during 3/15/2020 - 3/31/2021. We observed 825,239 PrEP prescriptions, a 22.0% reduction (95% CI: 19.1%-24.8%) after the emergency declaration. The model predicted 167,720 new PrEP users during the same period; we observed 125,793 new PrEP users, a 25.0% reduction (95% CI: 20.9%-28.9%). The COVID-19 impact was greater among younger persons and those with commercial insurance. The impact of the pandemic varied markedly across states. CONCLUSION: The COVID-19 pandemic disrupted an increasing trend in PrEP prescriptions in the United States, highlighting the need for innovative interventions to maintain access to HIV prevention services during similar emergencies. |
Incidence of herpes simplex virus type 2 infection among African women using depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a nested randomized trial
Mugo NR , Stalter RM , Heffron R , Rees H , Scoville CW , Morrison C , Kourtis AP , Bukusi E , Beksinka M , Philip NM , Beesham I , Deese J , Edward V , Donnell D , Baeten JM . Clin Infect Dis 2021 75 (4) 586-595 BACKGROUND: Globally, women have higher herpes simplex type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM). METHODS: Within a randomized trial of the effect of three contraceptive methods - DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant - on HIV acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015-2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method. FINDINGS: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI] 0.65-0.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI 0.71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI 0.89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55, 95% CI 2.78-4.48). INTERPRETATION: In a randomized trial, we found no association between HSV-2 acquisition and use of three contraceptive methods. |
Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity.
Thomas AS , Moreau Y , Jiang W , Isaac JE , Ewing A , White LF , Kourtis AP , Sagar M . Cell Rep Med 2021 2 (10) 100412 In humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. Here, we evaluate antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1-exposed uninfected compared with HIV-1-exposed infected infants have higher ADCC and a combination of ADCC and nAb responses against their corresponding mother's strains. ADCC does not correlate with nAbs, suggesting they are independent activities. The infected infants with high ADCC compared with low ADCC, but not those with higher ADCC plus nAbs, have lower morbidity up to 1 year after birth. A higher IgA to IgG ratio, observed in BM supernatants and in a higher proportion of the infected compared with the uninfected infants, associates with lower ADCC. Against the exposure strains, ADCC, more than nAbs, associates with both lower mother-to-child transmission and decreased post-infection infant morbidity. |
Trends in the Number and Characteristics of HIV Pre-Exposure Prophylaxis Providers in the United States, 2014-2019
Zhu W , Huang YA , Kourtis AP , Hoover KW . J Acquir Immune Defic Syndr 2021 88 (3) 282-289 BACKGROUND: The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported. METHODS: We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%-86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers. RESULTS: The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers. CONCLUSIONS: An increasing number of providers prescribed PrEP during 2014-2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States. |
Factors Associated With HIV Testing Among High-School Girls in the U.S., 20152017
Cyrus AC , Dunville R , Kourtis AP , Hoover KW , Tucker P . Am J Prev Med 2021 61 (1) 20-27 INTRODUCTION: Few studies have examined the factors associated with HIV testing, specifically among U.S. high-school girls. METHODS: Investigators analyzed 2015 and 2017 Youth Risk Behavior Survey data to calculate the prevalence ratios and the corresponding 95% CIs for the association of HIV-related risk behaviors and other factors with HIV testing. Analyses were completed in March 2020. RESULTS: Approximately 1 in 10 high-school girls reported ever having had an HIV test. Ever having had an HIV test was most common among girls who had ≥4 lifetime sexual partners and those who had ever injected illegal drugs. CONCLUSIONS: High-school girls who engage in behaviors or experience other factors that put them at higher risk for HIV are more likely to have ever gotten tested. However, the prevalence of having ever had an HIV test remains relatively low, indicating that continued efforts may be warranted to reduce risk behaviors and increase testing among high-school girls. |
Motivations to use hormonal contraceptive methods and condoms among HIV-positive and negative women randomized to a progestin contraceptive in Malawi: a qualitative study
Bula AK , Hatfield-Timajchy K , Chapola J , Chinula L , Hurst SA , Kourtis AP , Tang JH . BMC Womens Health 2021 21 (1) 114 BACKGROUND: Although many countries have been promoting hormonal contraceptives to prevent unintended pregnancy and condom use to prevent HIV transmission, little is known about how women targeted by these messages have interpreted and internalized them. We describe HIV-positive and negative women's understanding of the benefits of contraception and condoms and their motivations to use them. METHODS: This is a qualitative sub-study from a clinical trial evaluating the effects of progestin contraception on HIV-positive and negative women aged 18-45 years randomly assigned to depot medroxyprogesterone acetate (DMPA) injection or levonorgestrel (LNG) implant. We purposively recruited 41 women to participate in in-depth interviews (IDIs) and focus group discussions (FGDs) after randomization into the main study. We conducted a total of 30 IDIs and 6 FGDs comprised of 4-7 women (N = 32). All women were counselled about potential risks for HIV acquisition/transmission with progestin-only contraception, drug-drug interactions between the implant and efavirenz-based ART, and the need to use condoms with their assigned contraceptive to help prevent pregnancy and HIV acquisition and transmission. RESULTS: All women understood that HIV is transmitted through unprotected sex and that HIV transmission can be prevented through condom use but not DMPA injection or LNG implant use. Nearly all HIV-positive women knew or suspected that their partners were also HIV-positive and were most interested in using condoms to prevent infection with a drug-resistant HIV strain to keep their HIV viral load low. Almost all reported that their partners agreed to condom use, but few used them consistently. Most women believed that condoms were effective at preventing both HIV and pregnancy if used consistently. Nearly all women considered contraception and condom use as important in preventing unintended pregnancy and HIV because partner disclosure of HIV status is low. CONCLUSION: Our results showed that both HIV-positive and negative women understood modes of HIV transmission and prevention and were aware that hormonal contraceptives are only effective for preventing pregnancy and not HIV. Although both HIV-negative and positive women were motivated to use condoms to prevent both HIV acquisition and infection with other HIV strains respectively, they all faced challenges from their partners in using condoms consistently. |
Women's perspectives on relationship dynamics with their partners and their role in HIV acquisition, HIV disclosure, hormonal contraceptive uptake, and condom use
Chapola JC , Hatfield-Timajchy K , Bula AK , Hurst S , Chinula L , Kourtis AP , Tang JH . Afr J AIDS Res 2021 20 (1) 61-69 Background: Limited information exists about relationship dynamics and their role in HIV acquisition, HIV disclosure, hormonal contraceptive uptake, and condom use among women in Malawi.Methods: Ninety-seven women aged 18-45 years were randomly assigned to initiate the depot medroxyprogesterone acetate injectable or levonorgestrel implant from May 2014 to April 2015 in Lilongwe, Malawi. Women were recruited after randomisation to participate in semi-structured interviews about HIV and family planning using purposive sampling. Interviews were thematically analysed using within and between group comparisons.Results: We conducted individual interviews and/or focus group discussions with 41 women: 30 (73%) women living with HIV and 11 (27%) women not living with HIV. Most women living with HIV who participated in in-depth interviews disclosed their status to their partners, and most partners agreed to get HIV tested only after disclosure. Nearly all women said their partners agreed to use condoms, but few used them consistently. Nearly all women believed their current and former partners had outside partners. Most women living with HIV who participated in in-depth interviews believed their current or other serious partners were the source of their infection. Some women thought their partner's infidelity was due to their partner's disinterest in sex with them during menstrual/ breakthrough bleeding. Some women included their partners in contraceptive decision-making when the partner was supportive.Discussion: Relationship dynamics affected decision-making for contraceptive and condom use, as well as serodisclosure for the women living with HIV in the study. All women reported challenges with consistent condom use with their male partners, although contraceptive use was generally more acceptable. Women included their partners in their decision-making concerning contraceptive use when they were supportive. |
Antibiotic multi-drug-resistance of Escherichia coli causing device- and procedure-related infections in the United States reported to the National Healthcare Safety Network (NHSN), 2013-2017
Kourtis AP , Sheriff EA , Weiner-Lastinger LM , Elmore K , Preston LE , Dudeck M , McDonald LC . Clin Infect Dis 2020 73 (11) e4552-e4559 BACKGROUND: Escherichia coli is one of the most common causes of healthcare-associated infections (HAI); multidrug resistance reduces available options for antibiotic treatment. We examined factors associated with the spread of multidrug-resistant E. coli phenotypes responsible for device- and procedure-related HAI from acute care hospitals, long term acute care hospitals and inpatient rehabilitation facilities, using isolate and antimicrobial susceptibility data reported to the National Healthcare Safety Network (NHSN) from 2013-2017. METHODS: We used multivariable logistic regression to examine associations between co-resistant phenotypes, patient and healthcare facility characteristics, and time. We also examined the geographic distributione of co-resistant phenotypes each year by state and by hospital referral region to identify hot spots. RESULTS: A total of 96,672 E. coli isolates were included. Patient median age was 62 years; 60% were females; over half (54%) were reported from catheter-associated urinary tract infections. From 2013-2017, 35% of the isolates were non-susceptible to FQs; 17% to ESCs; and 13% to both ESCs and FQs. The proportion of isolates co-resistant to ESCs and FQs was higher in 2017 (14%) than in 2013 (11%) (P<0.0001); overall prevalence and increases were heterogeneously distributed across healthcare referral regions. Co-resistance to FQs and ESCs was independently associated with male sex, central line-associated bloodstream infections, long-term acute care hospitals, and the 2016-17 (v. 2013-14) reporting period. CONCLUSIONS: Multidrug-resistance among E.coli causing device- and procedure-related HAIs has increased in the United States. FQ and ESC co-resistant strains appear to be spreading heterogeneously across hospital referral regions. |
Effect of efavirenz on levonorgestrel concentrations among Malawian levonorgestrel implant users for up to 30 months of concomitant use: a subanalysis of a randomized clinical trial
Tang JH , Davis NL , Corbett AH , Chinula L , Cottrell ML , Zia Y , Tegha G , Stanczyk FZ , Hurst S , Hosseinipour MC , Haddad LB , Kourtis AP . Contracept X 2020 2 100027 Objectives: Our primary objective was to compare geometric mean levonorgestrel concentrations between levonorgestrel implant users who were or were not taking the antiretroviral efavirenz, for up to 30 months after implant initiation. Our secondary objective was to evaluate the pregnancy rate among levonorgestrel implant users on efavirenz. Study design: We performed a subanalysis of 42 Malawian women randomized to initiate the levonorgestrel implant as part of a parent randomized clinical trial. Our subset included 30 HIV-infected women taking efavirenz and 12 HIV-uninfected women not taking efavirenz. They underwent urine pregnancy testing every 3 months and serum levonorgestrel testing at day 3 and months 1, 3, 6, 12, 18, 24, 27 and 30 after implant initiation. Geometric mean levonorgestrel concentrations were calculated for efavirenz users and non-efavirenz users at each time point. Results: The geometric mean levonorgestrel concentrations were lower for efavirenz users than non-efavirenz users at every time point; the geometric mean ratio for efavirenz users:non-efavirenz users ranged from 0.60 [90% confidence interval (CI) 0.46–0.79] at 1 month to 0.27 (90% CI 0.12–0.61) at 30 months after implant insertion. No pregnancies occurred over 60 woman-years of concomitant levonorgestrel implant and efavirenz use, although 11 women had levonorgestrel concentrations < 180 pg/mL (the previously suggested minimum threshold concentration for efficacy). Conclusions: Efavirenz users had lower levonorgestrel concentrations than non-efavirenz users, and one third of our concomitant efavirenz and levonorgestrel implant users had concentrations < 180 pg/mL. Continued evaluation of the contraceptive efficacy of the levonorgestrel implant may be needed for efavirenz users. Implications: Among 42 Malawian women using the levonorgestrel implant for contraception, women who were taking the antiretroviral efavirenz had lower serum levonorgestrel concentrations than women who were not taking efavirenz. However, none of the women who were taking efavirenz became pregnant over 60 women-years of follow-up. |
Factors associated with vaginal detection of prostate-specific antigen among participants in a clinical trial in Malawi
Zia Y , Davis N , Wiener J , Hobbs MM , Lapple D , Chinula L , Tegha G , Msika A , Tang J , Kourtis AP . Sex Transm Infect 2020 97 (1) 77 Self-report of sexual behaviours in clinical studies is often subject to misreporting due to recall or social desirability bias or misinterpretation of the study questionnaires.1 Use of biomarkers of semen exposure, such as the detection of prostate-specific antigen (PSA) in vaginal secretions, offers an additional means of assessing sexual behaviours and condom use that is not subject to reporting biases.2 In a secondary analysis of a clinical trial of hormonal contraception in Malawi,3 we examined associations of discordance between PSA detection and self-report of condomless sex over time with participant characteristics using log-binomial regression analyses with generalised estimating equations for repeated measures. All analyses were conducted using SAS V.9.3 (SAS Institute, Cary, North Carolina, USA). Testing for PSA was performed using the ABAcard p30 rapid immunochromatographic strip test (Abacus Diagnostics, West Hills, California, USA); samples containing ≥1.0 ng PSA/mL were considered positive for detection of semen, as previously described.4 Discordance between PSA detection and self-report was defined as detection of PSA in the vaginal samples, with report of condom use at last sex or no sex since last study visit. Given the rapid clearance of PSA, negative results for PSA were not considered in the definition of discordance or concordance, regardless of whether condomless sex was self-reported or not.4 |
Endogenous hormones and anitretroviral exposure in plasma, cervicovaginal fluid, and upper-layer packed cells of Malawian women living with HIV
Nicol M , Cottrell M , Corbett A , Chinula L , Tegha G , Stanczyk F , Hurst S , Kourtis AP , Tang JH . AIDS Res Hum Retroviruses 2020 36 (8) 641-646 BACKGROUND: Overlap in metabolism pathways of endogenous female sex hormones and antiretroviral drugs may lead to altered exposure to these compounds. METHODS: In a family planning clinic in Lilongwe, Malawi, blood, blood cell, and cervicovaginal fluid (CVF) samples from seventy-three HIV positive Malawian women taken in follicular and luteal menstrual phases were assessed for estradiol and progesterone by chemiluminescent immunoassay, and for antiretroviral concentration by liquid chromatography-mass spectrometry. RESULTS: In both follicular and luteal phases, estradiol concentrations were lower in women receiving efavirenz compared to women on non-efavirenz regimens or no antiretroviral therapy (p<0.01). Serum estradiol was moderately and negatively correlated with efavirenz plasma (r=-0.36, p<0.001) and CVF (r=-0.50, p<0.001) concentrations. Serum estradiol was a significant predictor of efavirenz CVF concentrations even after adjusting for efavirenz plasma concentrations (p=0.02). In upper-layer packed cells (ULPC), tenofovir diphosphate (TFVdp) concentrations were similar between follicular and luteal phases and were not correlated with estradiol or progesterone concentrations. Tenofovir concentrations in CVF were not associated with menstrual cycle or serum hormone concentrations. CONCLUSION: In CVF and plasma, efavirenz concentrations were negatively correlated with serum estradiol concentrations, suggesting a modulatory effect of estradiol on efavirenz metabolism and/or transport processes, and/or an effect of efavirenz on the metabolism of estradiol. Differences in CVF persisted even after adjusting for plasma concentrations, suggesting a mechanism specific to the female genital compartment separate from absorption or hepatic metabolism. In contrast, TFVdp concentrations in ULPC were not influenced by endogenous estradiol or progesterone concentrations. |
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