Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study.

BACKGROUND: Long-acting treatment for HIV has potential to improve adherence, provide durable viral suppression, and have long-term individual and public health benefits. We evaluated treatment with two antibodies that broadly and potently neutralise HIV (broadly neutralising antibodies; bNAbs), combined with lenacapavir, a long-acting capsid inhibitor, as a long-acting regimen. METHODS: This ongoing, randomised, blind, phase 1b proof-of-concept study conducted at 11 HIV treatment centres in the USA included adults with a plasma HIV-1 RNA concentration below 50 copies per mL who had at least 18 months on oral antiretroviral therapy (ART), CD4 counts of at least 500 cells per µL, and protocol-defined susceptibility to bNAbs teropavimab (3BNC117-LS) and zinlirvimab (10-1074-LS). Participants stopped oral ART and were randomly assigned (1:1) to one dose of 927 mg subcutaneous lenacapavir plus an oral loading dose, 30 mg/kg intravenous teropavimab, and 10 mg/kg or 30 mg/kg intravenous zinlirvimab on day 1. Investigational site personnel and participants were masked to treatment assignment throughout the randomised period. The primary endpoint was incidence of serious adverse events until week 26 in all randomly assigned participants who received one dose or more of any study drug. This study is registered with ClinicalTrials.gov, NCT04811040. FINDINGS: Between June 29 and Dec 8, 2021, 21 participants were randomly assigned, ten in each group received the complete study regimen and one withdrew before completing the regimen on day 1. 18 (86%) of 21 participants were male; participants ranged in age from 25 years to 61 years and had a median CD4 cell count of 909 (IQR 687-1270) cells per µL at study entry. No serious adverse events occurred. Two grade 3 adverse events occurred (lenacapavir injection-site erythaema and injection-site cellulitis), which had both resolved. The most common adverse events were symptoms of injection-site reactions, reported in 17 (85%) of 20 participants who received subcutaneous lenacapavir; 12 (60%) of 20 were grade 1. One (10%; 95% CI 0-45) participant had viral rebound (confirmed HIV-1 RNA concentration of ≥50 copies per mL) in the zinlirvimab 10 mg/kg group, which was resuppressed on ART, and one participant in the zinlirvimab 30 mg/kg group withdrew at week 12 with HIV RNA <50 copies per mL. INTERPRETATION: Lenacapavir with teropavimab and zinlirvimab 10 mg/kg or 30 mg/kg was generally well tolerated with no serious adverse events. HIV-1 suppression for at least 26 weeks is feasible with this regimen at either zinlirvimab dose in selected people with HIV-1. FUNDING: Gilead Sciences.

Relationship of Specific Bacteria in the Cervical and Vaginal Microbiotas With Cervicitis.

BACKGROUND: Cervicitis is an inflammatory condition of the cervix associated with upper genital tract infection and reproductive complications. Although cervicitis can be caused by several known pathogens, the etiology frequently remains obscure. Here we investigate vaginal bacteria associated with bacterial vaginosis as potential causes of cervicitis. METHODS: Associations between vaginal bacteria and cervicitis were assessed in a retrospective case-control study of women attending a Seattle sexually transmitted disease clinic. Individual bacterial species were detected using 2 molecular methods: quantitative polymerase chain reaction (qPCR) and broad-range 16S rRNA gene PCR with pyrosequencing. The primary finding from this initial study was evaluated using qPCR in a second cohort of Kenyan women. RESULTS: The presence of Mageeibacillus indolicus, formerly BVAB3, in the cervix was associated with cervicitis, whereas the presence of Lactobacillus jensenii was inversely associated. Quantities of these bacteria did not differ between cervicitis cases and controls, although in a model inclusive of presence and abundance, M. indolicus remained significantly associated with cervicitis after adjustment for other cervicitis-causing pathogens. M. indolicus was not associated with cervicitis in our study of Kenyan women, possibly due to differences in the clinical definition of cervicitis. CONCLUSIONS: Colonization of the endocervix with M. indolicus may contribute to the clinical manifestations of cervicitis, but further study is needed to determine whether this finding is repeatable and applicable to diverse groups of women. Colonization of the cervix with L. jensenii could be a marker of health, perhaps reducing inflammation or inhibiting pathogenic infection.

Sexual transmission of viral hepatitis.

Identification and vaccination of adults at risk for hepatitis B virus acquisition through sexual contact is a key strategy to reduce new hepatitis B virus infections among at-risk adults. Hepatitis C has emerged as a sexually transmitted infection among men with male sex partners (MSM). Several biological and behavioral factors have been linked to hepatitis C virus transmission among MSM, including human immunodeficiency virus coinfection; participation in sexual practices that result in mucosal damage or result in exposure to blood; presence of sexually transmitted diseases (STIs), particularly ulcerative STIs; multiple/casual sex partners; and unprotected anal intercourse.

Emerging Sexual Health Issues Among Women Who Have Sex with Women.

Women who have sex with women (WSW) comprise a diverse group of people who evidence a spectrum of sexual identity, sexual behaviors, sexual practices, and risk behaviors. WSW are at risk of acquiring a diversity of sexually transmitted infections (STIs) from current and prior partners, both male and female. Notably, human papillomavirus (HPV) is sexually transmitted between female partners, and Pap smear guidelines should be followed in this group. Bacterial vaginosis is common among WSW. WSW should not be presumed to be at low or no risk for STIs based on sexual orientation, and reporting of same sex behavior by women should not deter providers from considering and performing screening for STIs, including Chlamydia trachomatis, according to current guidelines. Effective delivery of sexual health services to WSW requires a comprehensive and open discussion of sexual and behavioral risks, beyond sexual identity, between care providers and their female clients.

Sexually transmitted infections among women who have sex with women.

Women who have sex with women (WSW) are a diverse group with variations in sexual identity, sexual behaviors, sexual practices, and risk behaviors. WSW are at risk of acquiring bacterial, viral, and protozoal sexually transmitted infections (STIs) from current and prior partners, both male and female. Bacterial vaginosis is common among women in general and even more so among women with female partners. WSW should not be presumed to be at low or no risk for STIs based on sexual orientation, and reporting of same-sex behavior by women should not deter providers from considering and performing screening for STIs, including chlamydia, in their clients according to current guidelines. Effective delivery of sexual health services to WSW requires a comprehensive and open discussion of sexual and behavioral risks, beyond sexual identity, between care providers and their female clients.

Gonorrhoea positivity among women aged 15-24 years in the USA, 2005-2007.

OBJECTIVE: To examine the epidemiology of young women screened for gonorrhoea in the USA. METHODS: Data on tests for gonorrhoea among women aged 15-24 years attending family planning clinics from 2005 to 2007 were obtained through the infertility prevention project. Clinics testing 90% or more of women for gonorrhoea and sending 50 or more gonorrhoea tests per year were included. Gonorrhoea positivity on a state and county level was calculated and compared by age and race/ethnicity. RESULTS: A total of 1,119,394 tests from 948 clinics was eligible for inclusion. Median state-specific gonorrhoea positivity was 1.3% (IQR 0.7-2.0%). Positivity was higher among women aged 15-19 years (1.4%, IQR 0.9-2.6%) than among those aged 20-24 years (1.1%, IQR 0.6-1.4%, p=0.03) and among non-Hispanic black women (3.8%, IQR 3.2-4.6%) than non-Hispanic white women (0.6%, IQR 0.4-0.8%, p<0.0001). Half of all gonorrhoea cases in these women originated from 57 of 753 counties. Among non-Hispanic white women, positivity was 2.0% or greater in 4% of counties, while 83% of counties had gonorrhoea positivity of less than 1.0%. Gonorrhoea positivity among non-Hispanic black women was 2.0% or greater in 58% of counties, and less than 1.0% in only one-third of counties. These disparities were present diffusely across the geographical areas included in this analysis. CONCLUSIONS: Gonorrhea positivity was consistently high for young non-Hispanic black women attending family planning clinics across multiple geographical regions. A large proportion of gonorrhoea morbidity was concentrated in a relatively small number of counties in the USA among this population of young women.

Chlamydia positivity in American Indian/Alaska Native women screened in family planning clinics, 1997-2004.

BACKGROUND: Previous studies demonstrated high levels of Chlamydia trachomatis (CT) infections within American Indian/Alaskan Native (AI/AN) populations but there are few analyses of CT prevalence in these populations over time. METHODS: We analyzed data from 7374 visits at which diagnostic tests for CT were collected in AI/AN women aged 15 to 24 years seen at family planning clinics associated with the Region X Infertility Prevention Project. Trends in population characteristics and test positivity were examined and compared with non-AI/AN women tested in the same setting and time period. Chlamydia positivity was adjusted for changes in diagnostic test type. Multivariable logistic regression was used to identify characteristics associated with infection. RESULTS: Adjusted CT positivity in AI/AN women rose from 7.8% to 11.0%, which was 1.5 to 2.2 times the non-AI/AN population levels over the study period (absolute difference 2.8%-6.6%). Differences persisted after correction for test type and age. Temporal changes in positivity among AI/AN women were associated with a rise in reported risk behaviors and decline in age of the population being tested. Risk factors associated with positivity among AI/AN women were younger age, > or =1 behavioral risks, > or =1 clinical findings, partner with chlamydia, chlamydia in past year, and pregnancy related visit. CONCLUSIONS: AI/AN women had consistently higher levels of chlamydia positivity than non-Native women, even after adjustment for age and diagnostic test. Further investigation of risks for chlamydia, related outcomes, access to screening, sexual networks, and enhanced surveillance would be beneficial for improving health in this vulnerable population.

Determinants of survival for Native American adults with HIV infection.

Few if any Native American/Alaska Native (NA/AN) people have been included in highly active antiretroviral therapy (HAART) treatment trials or epidemiologic studies, leaving little data on which to be assured of the efficacy of HAART in this unique population. This study aims to evaluate the impact of HAART and review determinants of survival in a cohort of NA/AN persons receiving treatment for HIV in a real life clinical setting. A retrospective chart review of 235 HIV-infected Native Americans receiving services at an urban medical center operated by the Indian Health Service from January 1, 1981 through June 30, 2004 was conducted, providing 782.7 person-years of follow-up. The main outcome measures were time from study entry and from incident AIDS diagnosis to death. Death rates fell from 18.4 (13.3-25.4) per 100 person-years in the period prior to 1998 to 6.4 (4.6-8.8) per 100 person-years in the years 1998-2004, (RR 0.35, p < 0.0001). Factors associated with the greatest reduction in risk of death from time of study entry were current use of HAART, HR 0.13 (0.06-0.30, p < 0.001), and CD4 count >/=200 at entry, HR 0.16 (0.08-0.35, p < 0.001). Current use of HAART was the strongest predictor of survival from time of AIDS diagnosis, HR 0.11 (0.05-0.25, p < 0.001). The use of HAART therapy and CD4 count were primary predictors of survival. Earlier diagnosis and access to effective medical treatment will be key factors in reducing disparities in health brought about by HIV infection in Native American/Alaska Native communities.