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Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness.
J Acquir Immune Defic Syndr. 2015 Jul 01; 69(3):264-9.JA

Abstract

OBJECTIVE

The CAPRISA 004 trial showed that coitally dosed tenofovir 1% gel reduced HIV acquisition by 39% overall and 54% when used consistently. The objective of this analysis was to ascertain its pharmacokinetic-pharmacodynamic relationship to protect against HIV acquisition.

DESIGN

Genital and systemic tenofovir concentrations in 34 women who acquired HIV (cases) were compared with 302 randomly selected women who remained HIV uninfected (controls) during the CAPRISA 004 trial. In total, 336 cervicovaginal fluid (CVF), 55 plasma, and 23 paired cervical and vaginal tissue samples were assayed by validated methods for tenofovir and tenofovir diphosphate (tenofovir-DP) detection.

RESULTS

Tenofovir was detected in the genital tract in 8 (23.5%) cases and 119 (39.4%) controls (P = 0.076). Among those with detectable genital tract tenofovir, the median CVF concentrations were 97% lower in cases compared with controls, 476 versus 13,821 ng/mL (P = 0.107). A total of 14.7% (5/34) of cases and 32.8% (99/302) of controls were found to have tenofovir CVF concentrations above 100 ng/mL [odds ratio (OR): 0.35, P = 0.037]. At a higher threshold, 8.8% (3/34) of cases and 26.2% (79/302) of controls were found to have tenofovir CVF concentrations above 1000 ng/mL (OR: 0.27, P = 0.036). Plasma tenofovir concentrations were <1 ng/mL in all women and were detected only in controls (16.7%) and not in cases (0%), (P = 0.031). Returned used tenofovir gel applicators and CVF concentrations were correlated (Spearman r = 0.22, P = 0.001).

CONCLUSIONS

A tenofovir concentration of ≥100 ng/mL in CVF was associated with 65% (95% CI: 6% to 87%) protection against HIV, whereas a ≥1000 ng/mL concentration correlated with 76% (95% CI: 8% to 92%) protection against HIV infection.

Authors+Show Affiliations

*Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC; †University of North Carolina Center for AIDS Research, Clinical Pharmacology and Analytical Chemistry Core, Eshelman School of Pharmacy, Chapel Hill, NC; ‡Centre for the AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa; and §Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

26181703

Citation

Kashuba, Angela D M., et al. "Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness." Journal of Acquired Immune Deficiency Syndromes (1999), vol. 69, no. 3, 2015, pp. 264-9.
Kashuba AD, Gengiah TN, Werner L, et al. Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness. J Acquir Immune Defic Syndr. 2015;69(3):264-9.
Kashuba, A. D., Gengiah, T. N., Werner, L., Yang, K. H., White, N. R., Karim, Q. A., & Abdool Karim, S. S. (2015). Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness. Journal of Acquired Immune Deficiency Syndromes (1999), 69(3), 264-9. https://doi.org/10.1097/QAI.0000000000000607
Kashuba AD, et al. Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness. J Acquir Immune Defic Syndr. 2015 Jul 1;69(3):264-9. PubMed PMID: 26181703.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genital Tenofovir Concentrations Correlate With Protection Against HIV Infection in the CAPRISA 004 Trial: Importance of Adherence for Microbicide Effectiveness. AU - Kashuba,Angela D M, AU - Gengiah,Tanuja N, AU - Werner,Lise, AU - Yang,Kuo-Hsiung, AU - White,Nicole R, AU - Karim,Quarraisha A, AU - Abdool Karim,Salim S, PY - 2015/7/17/entrez PY - 2015/7/17/pubmed PY - 2015/10/2/medline SP - 264 EP - 9 JF - Journal of acquired immune deficiency syndromes (1999) JO - J. Acquir. Immune Defic. Syndr. VL - 69 IS - 3 N2 - OBJECTIVE: The CAPRISA 004 trial showed that coitally dosed tenofovir 1% gel reduced HIV acquisition by 39% overall and 54% when used consistently. The objective of this analysis was to ascertain its pharmacokinetic-pharmacodynamic relationship to protect against HIV acquisition. DESIGN: Genital and systemic tenofovir concentrations in 34 women who acquired HIV (cases) were compared with 302 randomly selected women who remained HIV uninfected (controls) during the CAPRISA 004 trial. In total, 336 cervicovaginal fluid (CVF), 55 plasma, and 23 paired cervical and vaginal tissue samples were assayed by validated methods for tenofovir and tenofovir diphosphate (tenofovir-DP) detection. RESULTS: Tenofovir was detected in the genital tract in 8 (23.5%) cases and 119 (39.4%) controls (P = 0.076). Among those with detectable genital tract tenofovir, the median CVF concentrations were 97% lower in cases compared with controls, 476 versus 13,821 ng/mL (P = 0.107). A total of 14.7% (5/34) of cases and 32.8% (99/302) of controls were found to have tenofovir CVF concentrations above 100 ng/mL [odds ratio (OR): 0.35, P = 0.037]. At a higher threshold, 8.8% (3/34) of cases and 26.2% (79/302) of controls were found to have tenofovir CVF concentrations above 1000 ng/mL (OR: 0.27, P = 0.036). Plasma tenofovir concentrations were <1 ng/mL in all women and were detected only in controls (16.7%) and not in cases (0%), (P = 0.031). Returned used tenofovir gel applicators and CVF concentrations were correlated (Spearman r = 0.22, P = 0.001). CONCLUSIONS: A tenofovir concentration of ≥100 ng/mL in CVF was associated with 65% (95% CI: 6% to 87%) protection against HIV, whereas a ≥1000 ng/mL concentration correlated with 76% (95% CI: 8% to 92%) protection against HIV infection. SN - 1944-7884 UR - https://www.unboundmedicine.com/medline/citation/26181703/Genital_Tenofovir_Concentrations_Correlate_With_Protection_Against_HIV_Infection_in_the_CAPRISA_004_Trial:_Importance_of_Adherence_for_Microbicide_Effectiveness_ L2 - http://dx.doi.org/10.1097/QAI.0000000000000607 DB - PRIME DP - Unbound Medicine ER -