Title |
Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women
|
---|---|
Published in |
Nature Medicine, February 2018
|
DOI | 10.1038/nm.4506 |
Pubmed ID | |
Authors |
Lyle R McKinnon, Lenine J Liebenberg, Nonhlanhla Yende-Zuma, Derseree Archary, Sinaye Ngcapu, Aida Sivro, Nico Nagelkerke, Jose Gerardo Garcia Lerma, Angela D Kashuba, Lindi Masson, Leila E Mansoor, Quarraisha Abdool Karim, Salim S Abdool Karim, Jo-Ann S Passmore |
Abstract |
Several clinical trials have demonstrated that antiretroviral (ARV) drugs taken as pre-exposure prophylaxis (PrEP) can prevent HIV infection, with the magnitude of protection ranging from -49 to 86% (refs. ). Although these divergent outcomes are thought to be due primarily to differences in product adherence, biological factors likely contribute. Despite selective recruitment of higher-risk participants for prevention trials, HIV risk is heterogeneous even within higher-risk groups. To determine whether this heterogeneity could influence patient outcomes following PrEP, we undertook a post hoc prospective analysis of results from the CAPRISA 004 trial for 1% tenofovir gel (n = 774 patients), one of the first trials to demonstrate protection against HIV infection. Concentrations of nine proinflammatory cytokines were measured in cervicovaginal lavages at >2,000 visits, and a graduated cytokine score was used to define genital inflammation. In women without genital inflammation, tenofovir was 57% protective against HIV (95% confidence interval (CI): 7-80%) but was 3% protective (95% CI: -104-54%) if genital inflammation was present. Among women who highly adhered to the gel, tenofovir protection was 75% (95% CI: 25-92%) in women without inflammation compared to -10% (95% CI: -184-57%) in women with inflammation. Immunological predictors of HIV risk may modify the effectiveness of tools for HIV prevention; reducing genital inflammation in women may augment HIV prevention efforts. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 18 | 33% |
Canada | 6 | 11% |
South Africa | 4 | 7% |
Switzerland | 2 | 4% |
Australia | 2 | 4% |
Nigeria | 1 | 2% |
United Kingdom | 1 | 2% |
Philippines | 1 | 2% |
New Zealand | 1 | 2% |
Other | 3 | 6% |
Unknown | 15 | 28% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 33 | 61% |
Scientists | 13 | 24% |
Practitioners (doctors, other healthcare professionals) | 4 | 7% |
Science communicators (journalists, bloggers, editors) | 4 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 131 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 22 | 17% |
Researcher | 19 | 15% |
Student > Master | 15 | 11% |
Student > Postgraduate | 14 | 11% |
Student > Doctoral Student | 11 | 8% |
Other | 20 | 15% |
Unknown | 30 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 32 | 24% |
Medicine and Dentistry | 19 | 15% |
Agricultural and Biological Sciences | 15 | 11% |
Biochemistry, Genetics and Molecular Biology | 9 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 5% |
Other | 16 | 12% |
Unknown | 34 | 26% |