The efficacy of once daily PrEP in preventing HIV-1 acquisition among uninfected heterosexuals in HIV-1 discordant partnerships, measured by calculating the HIV incidence per 100 person-years in each of three arms.

All randomized participants, less those who were found to ineligible (n=11), less those found to be infected at enrollment (n=14), and less those who did not return for any follow-up (n=25).

Safety of daily TDF or FTC/TDF among HIV-1 uninfected individuals randomized to TDF or FTC/TDF compared to those randomized to placebo measured as the number of participants with Serious Adverse Events (SAEs) during follow-up.

Randomized participants, less those found to be ineligible (n=11)

Adherence to study medication as assessed by pill count at follow-up visits. We assessed the total number of doses taken of the total dispensed doses.

Adherence to study drug measured as the percentage of visits when participants reported missing 1) any dose of study drug in the prior month and 2) 2 or more consecutive doses of study drug.

Participants with self-reported adherence.

HIV-1 resistance as measured by the number of seroconverters who had an HIV-1 reverse transcriptase mutation (K65R, K70E, M184I, or M184V) conferring resistance to TDF or FTC. These mutation types were pre-defined. Plasma samples for resistance testing were collected at the visit seroconversion was first detected and again at a visit within 1 month of seroconversion. Mutations detected at either of those visits are reported.

Both seroconverters found to have a resistance mutation had been HIV infected at enrollment (TDF arm: n=1; FTC-TDF arm: n=1).

Participants who seroconverted during the Partners PrEP trial, including those who were retrospectively found to be HIV infected at enrollment (TDF arm: n=5; FTC-TDF arm: n=3; placebo arm: n=6). For 4 of 96 HIV-1 seroconverters (TDF arm: n=2; FTC-TDF arm: n=1; placebo arm: n=1) HIV-1 RNA was unable to be amplified for HIV-1 resistance testing.

Prevalence of STIs measured as the number of participants with a positive test result for N. gonorrhoeae, C. trachomatis, or T. vaginalis during follow-up. Participants were tested for STIs at annual follow-up visits and at intervening visits at which the participant presented with symptoms of an STI. Assessment for symptomatic sexually transmitted infections was conducted quarterly.

N. gonorrhoeae and C. trachomatis testing were by APTIMA Combo 2 (Gen-Probe) or COBAS Amplicor (Roche Diagnostics). T. vaginalis testing was by APTIMA TV TMA (Gen-Probe) or In Pouch TV (Biomed Diagnostics).

Randomized participants, less those found to be ineligible (n=11)

Sexual risk behavior of participants, measured as the percentage of visits when participants reported having unprotected sex during follow-up.

All randomized participants, less those found to be ineligible (n=11).

Infant outcomes measured as the number of live-born infants born to female participants taking study drug that had any congenital anomalies.

Randomized female participants, less those found to be ineligible (n=7)

The slope of the linear model of the growth of infants (length) during the entirety of follow-up. The length of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.

Infants born to women taking study drug during follow-up

The slope of the linear model of the growth of infants (weight) during the entirety of follow-up. The weight of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.

Infants born to women taking study drug during follow-up

The slope of the linear model of the growth of infants (head circumference) during the entirety of follow-up. The head circumference of the infant was measured as a z-score, in terms of standard deviations from the age and gender specific median using the World Health Organization growth curve, accounting for skewness. The slope, representing the change over time of the z-score, was calculated using all available z-scores over 12 months and regressing against study month.

Infants born to women taking study drug during follow-up