Interim Guidance for Clinicians Considering the Use of Pre-Exposure Prophylaxis for the Prevention of HIV Infection in Heterosexually Active Adults

Study

Population

No. and sex of participants

Design

Total follow-up time (per participant median)

No. of incident HIV infections

Placebo

TDF/FTC

Total

iPrEx

MSM

2,499 (100% male)

RDBPCT

3,324 person-yrs (1.8 yrs)

64

36

100

Partners PrEP

Heterosexual HIV-discordant couples

4,758 couples (38% with female HIV+ partner)^†

RDBPCT

7,830 person-yrs (23 mos)

52

13

65^†

TDF2

Heterosexual men and women

1,216 (46% female)

RDBPCT

1,563 person-yrs (1.1 yrs)

24

9

33

FEM-PrEP

Heterosexual women

2,056 (100% female)

RDBPCT

1,407 person-yrs (NR)

35

33

68

Abbreviations: PrEP = pre-exposure prophylaxis; TDF/FTC = tenofovir disoproxil fumarate/emtricitabine; MSM = men who have sex with men; HIV = human immunodeficiency virus; RDBPCT = randomized, double-blind, placebo-controlled clinical trial; NR = not reported.

* Restricted to trials of oral TDF/FTC only; this guidance does not address use of other antiretroviral regimens.

^†For TDF/FTC and placebo groups only.

Study

Population

mITT^† % reduction in HIV incidence

(95% CI)

Combined self-report and pill-count medication adherence measures (95% CI)

Pill-count medication adherence measures (95% CI)

TDF blood detection^§ (95% CI)

iPrEx

MSM

44% (15%-63%)

>50%^¶ 50% (18%-70%)
>90%^¶ 73% (41%-88%)

NR

92%
(40%-99%)

All

Men

Women

Partners PrEP

Heterosexual HIV-discordant couples

75%
(55%-87%)

84%
(54%-95%)

66%
(28%-84%)

NR

100%**
(87%-100%)

90%
(58%-98%)

TDF2

Heterosexual men and women

62%
(22%-83%)

80%
(25%-97%)

49%
(-21%-81%, NS)

NR

NR

84%
(-62%-98%, NS)

FEM-PrEP

Heterosexual women

NS

NS

NS

NR

NR

NS

Abbreviations: PrEP = pre-exposure prophylaxis; TDF/FTC = tenofovir disoproxil fumarate/emtricitabine; mITT = modified intent to treat analysis; CI = confidence interval; MSM = men who have sex with men; HIV = human immunodeficiency virus; NR = not reported; NS = finding not statistically significant.

* Restricted to trials of oral TDF/FTC only; this guidance does not address use of other antiretroviral regimens.

† Excluded only those enrolled participants later found to be infected at randomization and those with no follow-up visit or HIV test.

§ The percentage of reduction in HIV incidence among persons with TDF detected in blood, compared with those without detectable TDF.

¶ The percentage reduction in HIV incidence, compared with the placebo group, is presented for two groups: those with 50% medication adherence and those with 90% adherence.

** In a substudy of participants who provided counts via home-based unannounced pill counts with supplementary adherence counseling if the counts were <80%.

Before initiating PrEP

Determine eligibility

• Document negative HIV antibody test immediately before starting PrEP medication.
• Test for acute HIV infection if patient has symptoms consistent with acute HIV infection or reports unprotected sex with an HIV-positive person in the preceding month.
• Determine if women are planning to become pregnant, are currently pregnant, or are breastfeeding.
• Confirm that patient is at ongoing, very high risk for acquiring HIV infection.
• If any sexual partner is known to be HIV-infected, determine whether receiving antiretroviral therapy; assist with linkage to care if not in care or not receiving antiretroviral therapy.
• Confirm that calculated creatinine clearance is ≥60 mL per minute (Cockcroft-Gault formula^†).

Other recommended actions

• Screen for hepatitis B infection; vaccinate against hepatitis B if susceptible, or treat if active infection exists, regardless of decision regarding prescribing PrEP.
• Screen and treat as needed for sexually transmitted infections (STIs).
• Disclose to women that safety for infants exposed during pregnancy is not fully assessed but no harm has been reported.
• Do not prescribe PrEP to women who are breastfeeding.

Beginning PrEP medication regimen

• Prescribe tenofovir disoproxil fumarate (TDF) 300 mg plus emtricitabine (FTC) 200 mg (i.e., one Truvada [Gilead Sciences] tablet) daily.
• In general, prescribe no more than a 90-day supply, renewable only after HIV testing confirms that patient remains HIV-uninfected. For women, ensure that pregnancy test is negative or, if pregnant, that the patient has been informed about use during pregnancy.
• If active hepatitis B infection is diagnosed, consider using TDF/FTC, which may serve as both treatment of active hepatitis B infection and HIV prevention.
• Provide risk-reduction and PrEP medication-adherence counseling and condoms.

Follow-up while PrEP medication is being taken

• Every 2-3 months, perform an HIV antibody test (or fourth generation antibody/antigen test) and document negative result.
• At each follow-up visit for women, conduct a pregnancy test and document results; if pregnant, discuss continued use of PrEP with patient and prenatal-care provider.
• Evaluate and support PrEP medication adherence at each follow-up visit, more often if inconsistent adherence is identified.
• Every 2-3 months, assess risk behaviors and provide risk-reduction counseling and condoms. Assess STI symptoms and, if present, test and treat for STIs as needed.
• Every 6 months, test for bacterial STIs, even if asymptomatic, and treat as needed.
• Three months after initiation, then every 6 months while on PrEP medication, check serum creatinine and calculate creatinine clearance.

On discontinuing PrEP (at patient request, for safety concerns, or if HIV infection is acquired)

• Perform HIV test(s) to confirm whether HIV infection has occurred.
• If HIV-positive, order and document results of resistance testing, establish linkage to HIV care.
• If HIV-negative, establish linkage to risk reduction support services as indicated.
• If active hepatitis B is diagnosed at initiation of PrEP, consider appropriate medication for continued treatment of hepatitis B infection.
• If pregnant, inform prenatal-care provider of TDF/FTC use in early pregnancy and coordinate care to maintain HIV prevention during pregnancy and breastfeeding.

* E.g., those with partners known to have HIV infection.

† Additional information available at Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41.