HIV 3

What were the clincal outcomes from the Bangkok Tenofovir Study?

- 48.9% reduction in HIV in tenofovir group vs placebo - 73.5% reduction in those with high adherence

Why use Truvada instead of tenofovir?

- Contains same dose of TDF - Emtricitabine very well-tolerated - PWID are also at risk for sexual HIV acquisition for which Truvada is indicated - Truvada has an approved label indication for PrEP to prevent sexual HIV acquisition in the United States

What bodily substances are not considered infectious if they are not visibly bloody?

- Feces - Nasal Secretions - Saliva - Sputum - Sweat - Tears - Urine - Vomitus

What was an interesting/concerning result of the VOICE study? What can this possibly be attributed to?

- Oral TDF arm and vaginal gel arm both stopped early for lack of efficacy - Daily oral Truvada arm continued to end, but still no efficacy as compared to placebo Low levels again

What is the risk of occupational HIV transmission for percutaneous exposure? Mucous membrane exposure?

- Percutaneous exposure 0.3% - Mucous membrane exposure 0.09%

What are considered high risk exposures that non-occupational (nPEP) should be started for?

- Receptive and insertive vaginal or anal intercourse - Needle sharing - Injuries with exposure to blood or other potentially infected HIV fluids

What factors may increase your risk of occupational HIV transmission?

- Visible contamination of device (such as needle) with patient's blood - Needle having been placed directly into vein or artery - Hollow-bore (vs solid) needle - Deep injury - Source patient with terminal illness - High viral load

When is post-exposure Prophylaxis (PEP) given?

-Given after exposure to prevent establishment of infection - Can be occupational (oPEP) or non-occupational (nPEP)

What were the three intervention arms of the PARTNERS study?

1 group tenofovir alone 1 group Truvada 1 group placebo

What are the indication for PrEP use by MSM?

1) Adult man 2) Without acute or established HIV infection 3) Any male sex partners in past 6 months (if female partners, also evaluate indications for PrEP use by heterosexual criteria) 4) Not in a monogamous partnership with a recently tested, HIV-negative man AND at least one of the following: - Any anal sex without condoms (receptive or insertive) in past 6 months - Any STI diagnosed or reported in past 6 months - Is in an ongoing sexual relationship with an HIV-positive male partner

What are the indication for PrEP use by PWID?

1) Adult person 2) Without acute or established HIV infection 3) Any injection of drugs not prescribed by a clinician in past 6 months AND at least one of the following.... - Any sharing of injection or drug preparation equipment in past 6 months - Been in a methadone, buprenorphine, or suboxone treatment program in past 6 months - Risk of sexual acquisition (evaluate for indications based on sexual behavior)

What are the indication for PrEP use by heterosexually active men and women?

1) Adult person 2) Without acute or established HIV infection 3) Any sex with opposite sex partners in past 6 months 4) Not in a monogamous partnership with a recently tested HIV-negative partner AND at least one of the following... - Is a man who has sex with both women and men (behaviorally bisexual) [also evaluate indications for PrEP use by MSM criteria] - Infrequently uses condoms during sex with 1 or more partners of unknown HIV status who are known to be at substantial risk of HIV infection (IVDU or bisexual male partner) - Is in an ongoing sexual relationship with an HIV-positive partner

For how long after nPEP initiation should patient be tested for HIV?

12 weeks (also test at baseline and week 4)

What was an interesting/concerning result of the FEM-PrEP study? What can this possibly be attributed to?

35 vs 33 new HIV infections in the placebo and Truvada arms TDF blood levels suggest that use was too low (< 40%) to assess efficacy. Also, ended up selecting for resistance mutations in patients that received Truvada

What is the ARV regimen for HIV ppx for an infant born from a non-suppressed mother? Describe timing as well

6-week course of zidovudine + 3 doses of nevirapine in the first week of life Should be started as soon as possible post-delivery - 1st dose at birth to 48 hours - 2nd dose 48 hours later - 3rd dose 96 hours after 2nd dose

What can be seen from both the FEM-PrEP and VOICE studies?

Adherence is a problem

Describe the typical nPEP regimen

All persons offered nPEP should be prescribed a 28-day course of a 3-drug antiretroviral regimen Truvada once daily plus either raltegravir 400 mg twice daily or dolutegravir 50 mg daily Alternative: Truvada QD + darunavir 800 mg and ritonavir 100 mg once daily

At what stages of pregnancy can HIV be transmitted?

Any stage

What are the preferred HIV regimens in pregnant women?

Atazanavir + ritonavir + Truvada or Epzicom Darunavir (BID) + ritonavir + Truvada or Epzicom Raltegravir (BID) + Truvada or Epzicom

What study looked at PrEP in persons who inject drugs (PWID)?

Bankgkok Tenofovir Study

What were the clinical implications of the PARTNERS study?

Both drug intervention arms were associated with reduction in HIV acquisition...placebo group stopped early by safety board Tenofovir had slightly higher rates, but not clinically signficant

Is the risk of occupational HIV transmission lower or higher than HBV and HCV?

Considerably lower

ARV in pregnant women should be continued for how long?

Continue ART on schedule during labor and before scheduled C-section

Describe the adminstration of zidovudine

Continuous IV infusion

What were the intervention arms in the VOICE study?

Daily oral TDF; daily oral Truvada; daily vaginal TFV 1% gel

What is a possible solution (for previously described problems) for females taking PrEP?

Dapivirine vaginal ring - 2nd generation NRTI

How was the IPGERGAY study different from the iPrEx study?

Different intervention in terms of Truvada dosing: 2 tablets with food 2 to 24 hours before sex, a 3rd tablet 24 hours after the first drug intake, and a 4th tablet 24 hours later

How often should patients taking PrEP be tested for HIV?

Every 3 months

Is PrEP recommended only for MSM and transgender women?

FALSE; PrEP for heterosexual serodiscordant couples as well

When is pre-exposure Prophylaxis (PrEP) given?

Given prior to exposure to prevent establishment of infection

Describe the follow-up testing for the exposed occupational patient

HIV testing at baseline, 6 weeks, 12 weeks, and 4 months

If source patient has known history of resistance mutations, what should be done?

May use their current regimen

Is IV zidovudine required for HIV-positive women before delivery?

No Give IV ZDV until delivery to women with VL ≥1,000 copies/mL (or unknown VL) near delivery, regardless of antenatal regimen or mode of delivery IV ZDV not required for women receiving combination ARV regimens who have VL ≤1,000 copies/ mL consistently during late pregnancy and near delivery and no concerns regarding adherence to the regimen

What major studies looked at PrEP for heterosexual serodiscordant couples?

PARTNERS and TDF2

Even if fully adherent, what are other issues in females that prevent proper PrEP treatment?

PK/PD in lower GI and female genital tracts - Takes 2 doses of Truvada per week in male population (MSM) to achieve desired concentration in lower GI tract (receptive anal intercourse); why on-demand dosing worked in IPERGAY study. Dose concentration also last longer than in females - Takes 7 doses of Truvada per week (perfect adherence) to achieve desired concentration in female genital tract

HIV ppx is usually primary or secondary?

Primary

What is the preferred oPEP regimen?

Raltegravir 400 mg po BID + Truvada 1 tablet PO daily

What was a problem with the TDF2 study?

Reduction in HIV acquisition with Truvada observed in both men and women but study underpowered to demonstrate sex-based differences in outcomes

When should the patient be initially reevaluated after oPEP initiation?

Reevaluate at 72 hours post-exposure regardless of oPEP initiation

When is nPEP not recommended?

Reported exposure presents no substantial risk of HIV transmission OR Care is sought > 72 hours after potential exposure

What were the clinical implications from the IPERGAY study?

Significant (86%) relative reduction in new HIV infections with patients taking Truvada; also that adherence is issue

When is nPEP recommended?

Source of the body fluids is known to be HIV-positive AND Reported exposure presents a substantial risk for transmission

When should the zidovudine be started in infants?

Start as close to the time of birth as possible (within 6-12 hours of delivery)

What is the alternative regimen for infant HIV ppx if mother has history of zidovudine resistance?

Start regardless of maternal zidovudine resistance history

Why is non-occupational HIV exposure harder to develop a treatment plan for?

Testing the donor may be harder (less info)

What were the clinical implications from the iPrEx study?

Truvada may be effective in preventing transmission in the high risk MSM and transgender women populations

What are the adverse effects of Truvada?

Uncommon and consist mostly of HA, nausea, and flatulence (mostly in 1st month of therapy)

Should infants born from a virally suppressed mother receive ARV ppx?

Yes 4-week zidovudine 4 mg/kg po q12h chemoprophylaxis advised for all HIV-exposed neonates

Should HIV-infected pregnant women be treated with an ARV regimen?

Yes; all HIV-infected pregnant women should receive a potent combination ARV regimen to reduce the risk of perinatal transmission

When should occupational PEP (oPEP) be started? How long should the regimen be for?

oPEP should be started as soon as possible after the exposure, less effective as time progresses especially after 72 hours Optimal duration unknown - 4 weeks appeared protective in occupational and animal studies