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HIV at ICAAC PrEP 2103
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(Sept 10-13, Denver, CO)
Report written for NATAP by David H. Shepp, MD Associate Professor of Medicine Hofstra North Shore-LIJ School of Medicine North Shore University Hospital - Manhasset, NY
Pre-Exposure Prophlaxis (PrEP). Use of daily doses of tenfovir DF plus emtricitabine (TDF/FTC) by high-risk HIV-negative individuals has been shown in clinical trials to be effective in reducing rates of HIV acquisition. Efficacy of PrEP was first demonstrated in men having sex with men (MSM). Interim guidance from the CDC published in January 2011 suggested restricting use of PrEP to high risk MSM. Subsequent trials that included women have shown both positive and negative results, with negative results likely explained by low adherence. In 2012, updated guidance provided recommendations for use of PrEP in high-risk women. Little information has been available about how PrEP is currently being used in the US. Rawlings, et al [1] analyzed de-identified retail pharmacy records from January 2011- March 2013, using concurrent medications and diagnosis codes to identify TDF/FTC use in patients not being treated for HIV, HBV, or receiving post-exposure prophylaxis. One thousand seven hundred seventy four probable PrEP user were identified. Use increased markedly in 2012. Only 14% were under age 25. Surprisingly, 48% of PrEP users were women.
Nearly 2/3 of prescription were written by health care providers who did not have any use of TDF/FTC for HIV. The study is limited by the accuracy of pharmacy record data and diagnosis codes, but suggests that current PrEP use underrepresents individuals belonging to the highest risk groups (eg, young MSM), and that many PrEP prescribers are not experienced HIV clinicians. Further research is needed, but if these findings are confirmed, additional educational efforts may be needed to appropriately target PrEP to high risk individuals.
The efficacy of oral PrEP is highly dependent on high rates of adherence to daily use. Even in clinical trials, which may represent a "best case scenario", adherence among PrEP users has been suboptimal. Adherence, and therefore efficacy, in clinical practice may be even lower. Additionally, use of injectable hormonal contraception has been associated with an increased risk of HIV acquisition, and might reduce PrEP efficacy in women. To reduce the requirement for high level adherence, long-acting topical or parenteral antiviral preparations are being investigated. Smith et al [2] reported pre-clinical studies of a tenofovir DF-loaded intravaginal ring (IVR) for use in PrEP. Female pigtail macaques were chosen for study because they have cyclic menses similar to women. An IVR for these macaques was developed and shown to produce levels of tenofovir in cervico-vaginal fluid (CVF) over 28 days that exceeded 1,000 ng/mL, a level associated with protection in human studies of oral PrEP. Weekly high-dose intravaginal challenge with SHIV was administered to 6 macaques given an IVR and 6 control animals, starting 1 week after the placement of the IVR. IVRs were changed every 4 weeks. Six additional historical control macaques were included in the analysis. After 16 weeks, 11/12 controls and no IVR macaques became infected. In a second experiment, to study the effects of hormonal contraception on PrEP efficacy, depot medroxyprogesterone acetate (DMPA) was injected every 3 weeks starting 4 weeks before the first viral challenge. All six control animals but only 1 of 6 IVR animals became infected. The reason for the single IVR failure is being investigated, but it did not appear to be due to inadequate tenofovir levels in CVF.
These studies suggest that tenofovir DF loaded IVRs are a promising alternative for women to daily oral PrEP. Further investigations to understand the reason for the single failure seen with concurrent hormonal contraception may be helpful. Clinical trials of an IVR for use in women are expected to begin in the next few months.
1. Rawlings K, Mera R, Pechonkina A, et al. Status of Truvada (TVD) for HIV Pre-Exposure Prophylaxis (PrEP) in the United States: An Early Drug Utilization Analysis. 53rd ICAAC, Denver CO, Sept 10-13, 2013, Abstract H-663a.
2. Smith J, Srinivasan P, Rastogi R, et al. Pigtailed Macaques Under High Doses of Depot Medroxyprogesterone are Protected from Multiple SHIV Exposures with a Tenofovir Disoproxil Fumarate Intravaginal Ring. 53rd ICAAC, Denver CO, Sept 10-13, 2013, Abstract H-1532a.
ICAAC: Tenofovir Vaginal Ring Protects 5 of 6 Macaques From SHIV After High-Dose Depo-Provera - Written by Mark Mascolini - (09/18/13)
ICAAC: Status of Truvada (TVD) for HIV Pre-Exposure Prophylaxis (PrEP) in the United States: An Early Drug Utilization Analysis - (09/12/13)
53rd ICAAC Interscience Conference on Antimicrobial Agents and Chemotherapy
September 10-13
2013, Denver CO
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