Journal: JAIDS Journal of Acquired Immune Deficiency Syndromes

Article Title: Antiviral Activity of Genital Tract Secretions After Oral or Topical Tenofovir Pre-exposure Prophylaxis for HIV-1

doi: 10.1097/qai.0000000000000110

Figure Lengend Snippet: FIGURE 1. Anti-HIV activity and TFV concentrations in CVL obtained after 6 weeks of oral TDF or topical 1% TFV vaginal gel. A, The percent inhibition of HIV infection by CVL samples from participants at baseline (enrollment, circles) and after 6 weeks of oral TDF (squares) or 6 weeks of daily vaginal TFV gel (triangles). The lines indicate the median and interquartile range for the group; values below zero indicate enhancement. B, The concentration of TFV detected in CVL. The line indicates median and interquartile range. C, Correlation of anti-HIV activity with TFV concentrations. The Spearman correlation coefficient after vaginal TFV gel is 0.64 (P , 0.001).

Article Snippet: Oral Truvada [combination of TFV disoproxil fumarate (TDF) and emtricitabine] and TDF were protective in HIV serodiscordant couples in the Partners PrEP Study,1 and Truvada significantly decreased HIV acquisition in TDF-2, a study among high-risk African men and women.1,2 In contrast, the oral TDF, Truvada, and vaginal TFV gel arms of the Vaginal and Oral Intervention to Control the Epidemic trial did not demonstrate efficacy.3 Another oral PrEP trial, FemPrEP, conducted in a population of young women similar to those enrolled in Vaginal and Oral Intervention to Control the Epidemic was stopped early after a planned interim analysis determined that Truvada was unlikely to demonstrate protection; subsequent analyses of drug levels in these trials suggest that poor adherence contributed to the negative outcomes.4 In contrast, partial efficacy was observed with pericoital intravaginal dosing of 1% TFV gel in CAPRISA 004, illustrating the potential to deliver safe and effective vaginal prevention products.5 A 39% (95% confidence interval: 6 to 61) and 54% (21%–70%) reduction in HIV-1 (herein designated HIV) and herpes simplex virus (HSV)-2 seroconversion, respectively, were observed in women who were randomized to apply 1% TFV vaginal gel before and after sex.5 Although adherence clearly plays a major role in modifying efficacy, biological factors that modulate the relationship between pharmacokinetics (PK) (drug levels), pharmacodynamics (drug activity), and host susceptibility to HIV may also contribute.

Techniques: Activity Assay, Inhibition, Infection, Concentration Assay

Journal: JAIDS Journal of Acquired Immune Deficiency Syndromes

Article Title: Antiviral Activity of Genital Tract Secretions After Oral or Topical Tenofovir Pre-exposure Prophylaxis for HIV-1

doi: 10.1097/qai.0000000000000110

Figure Lengend Snippet: FIGURE 2. Anti-HSV activity of CVL after 6 weeks of oral TDF or 6 weeks of TFV 1% vaginal gel. The percent inhibition of HSV-2 plaque formation using CVL obtained HIV from participants at baseline (circles) or after oral (squares) or vaginal (triangles) product use. The lines indicated median and interquartile range for the group; values below zero indicate enhancement.

Article Snippet: Oral Truvada [combination of TFV disoproxil fumarate (TDF) and emtricitabine] and TDF were protective in HIV serodiscordant couples in the Partners PrEP Study,1 and Truvada significantly decreased HIV acquisition in TDF-2, a study among high-risk African men and women.1,2 In contrast, the oral TDF, Truvada, and vaginal TFV gel arms of the Vaginal and Oral Intervention to Control the Epidemic trial did not demonstrate efficacy.3 Another oral PrEP trial, FemPrEP, conducted in a population of young women similar to those enrolled in Vaginal and Oral Intervention to Control the Epidemic was stopped early after a planned interim analysis determined that Truvada was unlikely to demonstrate protection; subsequent analyses of drug levels in these trials suggest that poor adherence contributed to the negative outcomes.4 In contrast, partial efficacy was observed with pericoital intravaginal dosing of 1% TFV gel in CAPRISA 004, illustrating the potential to deliver safe and effective vaginal prevention products.5 A 39% (95% confidence interval: 6 to 61) and 54% (21%–70%) reduction in HIV-1 (herein designated HIV) and herpes simplex virus (HSV)-2 seroconversion, respectively, were observed in women who were randomized to apply 1% TFV vaginal gel before and after sex.5 Although adherence clearly plays a major role in modifying efficacy, biological factors that modulate the relationship between pharmacokinetics (PK) (drug levels), pharmacodynamics (drug activity), and host susceptibility to HIV may also contribute.

Techniques: Activity Assay, Inhibition