Preexposure Prophylaxis (PrEP) Using Antiretroviral Therapy to Prevent Human Immunodeficiency Virus (HIV) Infection

The Centers for Medicare & Medicaid Services (CMS) has determined that Pre-Exposure Prophylaxis (PrEP) using antiretroviral drugs to prevent Human Immunodeficiency Virus (HIV) is covered as an additional preventive service under §1861(ddd)(1) of the Social Security Act (the Act).  Specifically, CMS has determined that PrEP using antiretroviral drugs to prevent HIV is reasonable and necessary for the prevention of an illness or disability; is recommended with a grade of A by the United States Preventive Services Task Force (USPSTF); and is appropriate for individuals entitled to Medicare benefits under Part A or enrolled under Part B.

After considering the public comments, CMS is expanding coverage from our proposed decision and will cover PrEP using antiretroviral drugs approved by the U.S. Food and Drug Administration (FDA) to prevent HIV in individuals at increased risk of HIV acquisition.  The determination of whether an individual is at increased risk for HIV is made by the physician or health care practitioner who assesses the individual’s history.  CMS also covers furnishing HIV PrEP using antiretroviral drugs, including the supplying or dispensing of these drugs and the administration of injectable PrEP.

For individuals being assessed for or using PrEP to prevent HIV, CMS covers all the following as an additional preventive service:

a)  Up to eight individual counseling visits every 12 months, that include HIV risk assessment (initial or continued assessment of risk), HIV risk reduction, and medication adherence.  Counseling must be furnished by a physician or other health care practitioner.  Individuals must be competent and alert at the time that counseling is provided.

b)  Up to eight HIV screening tests every 12 months.

c) A single screening for hepatitis B virus (HBV).

These screening tests are covered when the appropriate FDA-approved laboratory tests and point of care tests are used consistent with FDA-approved labeling and in compliance with the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations.

See Appendix B for the draft National Coverage Determinations manual language.

TO:       Administrative File:  CAG-00464N

FROM:       Coverage and Analysis Group

SUBJECT:       Final National Coverage Determination for Pre-Exposure Prophylaxis (PrEP) for Human Immunodeficiency Virus (HIV) Prevention

DATE:       September 30, 2024

I. Decision

The Centers for Medicare & Medicaid Services (CMS) has determined that Pre-Exposure Prophylaxis (PrEP) using antiretroviral drugs to prevent Human Immunodeficiency Virus (HIV) is covered as an additional preventive service under §1861(ddd)(1) of the Social Security Act (the Act).  Specifically, CMS has determined that PrEP using antiretroviral drugs to prevent HIV is reasonable and necessary for the prevention of an illness or disability; is recommended with a grade of A by the United States Preventive Services Task Force (USPSTF); and is appropriate for individuals entitled to Medicare benefits under Part A or enrolled under Part B.

After considering the public comments, CMS is expanding coverage from our proposed decision and will cover PrEP using antiretroviral drugs approved by the U.S. Food and Drug Administration (FDA) to prevent HIV in individuals at increased risk of HIV acquisition.  The determination of whether an individual is at increased risk for HIV is made by the physician or health care practitioner who assesses the individual’s history.  CMS also covers furnishing HIV PrEP using antiretroviral drugs, including the supplying or dispensing of these drugs and the administration of injectable PrEP.

For individuals being assessed for or using PrEP to prevent HIV, CMS covers all the following as an additional preventive service:

a)  Up to eight individual counseling visits every 12 months, that include HIV risk assessment (initial or continued assessment of risk), HIV risk reduction, and medication adherence.  Counseling must be furnished by a physician or other health care practitioner.  Individuals must be competent and alert at the time that counseling is provided.

b)  Up to eight HIV screening tests every 12 months.

c) A single screening for hepatitis B virus (HBV).

These screening tests are covered when the appropriate FDA-approved laboratory tests and point of care tests are used consistent with FDA-approved labeling and in compliance with the Clinical Laboratory Improvement Amendments of 1988 (CLIA) regulations.

See Appendix B for the draft National Coverage Determinations manual language.

II. Background

Throughout this document we use numerous acronyms, some of which are not defined as they are presented in direct quotations.  Please find below a list of these acronyms and corresponding full terminology:

AIDS – Acquired immunodeficiency syndrome
AAHIVS - American Academy of HIV Medicine Specialists
APHL – Association of Public Health Laboratories
ART – Antiretroviral therapy
CAB – Cabotegravir
CDC – Centers for Disease Control and Prevention
CMS – Centers for Medicare & Medicaid Services
CD4+ – cluster of differentiation 4+ T helper cells or CD4 count
FDA – US Food and Drug Administration
HBV – Hepatitis B Virus
HHS – Department of Health and Human Services
HIBC – High-intensity behavioral counseling
HIV – Human Immunodeficiency Virus Infection
IDU – Intravenous drug use
kg – kilogram
MSM – Men who have sex with men
mg – milligram
mL – milliliter
NASTAD - National Alliance of State and Territorial AIDS Directors
NCA – National Coverage Analysis
NCD – National Coverage Determination
NDRN – National Disability Rights Network  
NIA – National Institute on Aging
NIAID – National Institute of Allergy & Infectious Disease
NIH – National Institutes of Health
NLM – National Library of Medicine
OI – Opportunistic infection
PEP – Post-exposure prophylaxis
PWID – people who inject drugs
PrEP – Pre-Exposure Prophylaxis
RCT – Randomized controlled trial
RNA – Ribonucleic acid
STD – sexually transmitted disease
STI – sexually transmitted infection
TAF-FTC – emtricitabine in combination with tenofovir alafenamide
TDF-FTC – emtricitabine in combination with tenofovir disoproxil fumarate
TGW – transgender women  
US – United States
USPSTF – United States Preventive Services Task Force
U=U – Undetectable=Untransmittable
WHO – World Health Organization

Epidemiology

There were approximately 39 million people across the globe with HIV in 2022 (United States (US) Department of Health and Human Services (HHS), 2023a).  In the US, the condition continues to be a serious public health issue.  In 2022, an estimated 1.2 million people aged 13 and older had HIV in the US, and for every 100 people with HIV, 87 people knew their HIV status (Centers for Disease Control & Prevention (CDC), 2023a). An estimated 1.3 million individuals worldwide acquired HIV in 2022, marking a 38% decline in new HIV infections since 2010 (HHS, 2023a).  New HIV infections, or HIV incidence, refers to the estimated number of people who newly acquired HIV during a given period such as a year, which is different from the total number of people who already have been diagnosed (new and pre-existing cases) with HIV during a year, or HIV prevalence.

Due to continuing medical advances, earlier initiation, and expanded access to medications, HIV is now considered a chronic condition rather than a terminal illness (World Health Organization (WHO), 2023).  Antiretroviral therapy (ART) is known to reduce HIV-related morbidity and mortality.  The WHO recognizes that people living with HIV are now surviving, aging, and requiring lifelong care and treatment (WHO, 2023).  People living with HIV are at risk of developing chronic complications and comorbidities, such as noncommunicable diseases and mental health disorders, which may be pre-existing, HIV-associated, or due to aging.  Over 53% of the people in the US diagnosed with HIV are aged 50 and older (HHS, 2023b).  Additionally, HIV is newly diagnosed in thousands of people aged 50 and older every year.

From 2015 through 2019 in the US and 6 dependent areas, the largest percentage increase (48%) in the rate of persons living with diagnosed HIV was among persons aged ≥65 years (from 145.5 in 2015 to 216.0 in 2019; rates are per 100,000 population) (CDC, 2021b).  At year-end 2019, persons aged 55–59 years made up the largest percentage of persons living with diagnosed HIV (15% of 1,061,482 total).  The highest rate (741.1 per 100,000 of the US population) was among persons aged 50–54 years, followed by those aged 55–59 years (737.7 per 100,000 US population) and those aged 45–49 years (577.2 per 100,000 US population).

HIV disproportionately impacts identifiable racial and ethnic groups.  African Americans, more than any other racial/ethnic group, bear the most severe burden of HIV in the US followed by those who are Hispanic (CDC, 2021b).  In 2021, of the estimated number of persons living with diagnosed or undiagnosed HIV, 40% were Black/African American, 68% of whom were male.  The prevalence rate for Black/African American persons was 7 times the rate for White persons (CDC, 2021a; HHS, 2023c).  Of the estimated number of persons living with diagnosed or undiagnosed HIV, 25% were Hispanic/Latino, of whom 83% were male. The prevalence rate for Hispanic/Latino persons (625.8) was 3 times the rate for White persons.  This disproportionate impact is related to these racial/ethnic groups having higher rates of HIV in their communities (HHS, 2023c).  In addition, a range of social, economic, and demographic factors, such as stigma, discrimination, income, education, and geographic region can affect people’s risk for HIV as well as their HIV-related outcomes.

Risk

HIV is spread through contact with the blood, semen, pre-seminal fluid, rectal fluids, vaginal fluids, or breast milk of a person with HIV.  Anyone can get HIV, but certain groups have a higher risk of acquiring HIV, including people who have another sexually transmitted infection (STI), people who inject drugs with shared needles, gay and bisexual men, especially those who are Black/African American or Hispanic/Latino American, and people who engage in risky sexual behaviors, such as not using condoms (National Library of Medicine (NLM), 2021).  In the US, HIV is spread mainly by having anal or vaginal sex or sharing injection drug equipment, such as syringes or needles, with a person who has HIV.  In the US in 2022, men who had sex with men (MSM) accounted for 67% of all new HIV infections (CDC, 2023b).  Heterosexual sex accounted for 22% and persons with injection drug use constituted about 7% of new HIV diagnoses.

HIV/Acquired immunodeficiency syndrome (AIDS)

HIV is a virus that attacks the body’s immune system by destroying cluster of differentiation 4+ or CD4+ T helper cells (referred to as CD4 count), a type of white blood cell that is vital to fighting off infection (National Institute of Allergy & Infectious Disease (NIAID), 2020; CDC, 2024).  The first signs of HIV infection may be flu-like symptoms, including fever, chills, rash, night sweats, muscle aches, sore throat, fatigue, swollen lymph nodes, and mouth ulcers (NLM, 2021).  These symptoms may come and go within two to four weeks.  This stage is called acute HIV infection.  If the infection is not treated, it becomes chronic HIV infection.  Without taking HIV medicine, this period may last a decade or longer, but some may progress faster.  Often, there are no symptoms during this stage.  If it is not treated, eventually the virus will weaken the body's immune system.  As the disease progresses, the amount of HIV in the blood (called viral load) goes up and the number of CD4 cells goes down. The person may have symptoms as the virus levels increase in the body.  Then the infection will progress to AIDS.  This is the late stage of HIV infection.  With AIDS, the immune system is badly damaged causing increasingly severe infections, known as opportunistic infections (OIs), such as pneumonia, salmonella infection, candidiasis, toxoplasmosis, and tuberculosis.  AIDS is defined by a CD4 count of 200 cells/mm³ or one or more AIDS-defining neoplastic conditions or opportunistic infections.  Thus, a person may be living with HIV for years before the condition is suspected.  So, the only way to know for sure whether a person has HIV is to get HIV screening.[1] 

Treatment

The treatment for HIV is called antiretroviral therapy (ART) and involves taking a combination of HIV medicines (called an HIV treatment regimen) every day (NIH, 2021).  ART is recommended as a life-long treatment for everyone who has HIV and also reduces the risk of HIV transmission.  These medications prevent HIV from multiplying or making copies of itself, which reduces the amount of HIV in the body (called the viral load).  Having less HIV in the body gives the immune system a chance to recover and produce more CD4 cells.  Even though there is still some HIV in the body, the immune system is strong enough to fight off infections and certain HIV-related cancers.  By reducing the amount of HIV in the body, HIV medicines also reduce the risk of HIV transmission.  A main goal of HIV treatment is to reduce a person’s viral load to an undetectable level.  An undetectable viral load means that the level of HIV in the blood is too low to be detected by a viral load test.  People with HIV who maintain an undetectable viral load have effectively no risk of transmitting HIV to their HIV-negative partners through sex, a concept known as Undetectable=Untransmittable, or U=U. 

Preventive Options

Pre-exposure prophylaxis (PrEP) involves the use of ART on an ongoing basis (e.g., daily or every two months) or before and after HIV exposure events (“on-demand” or “event-driven” PrEP) to decrease the risk of acquiring HIV from sex or injection drug use (CDC, 2022).  When taken as prescribed, PrEP is effective for preventing HIV.  PrEP can be an oral medication or an injection.  As of the date of this publication, the FDA has approved three medications for use as PrEP:  emtricitabine (FTC) 200 mg in combination with tenofovir disoproxil fumarate (TDF) 300 mg (TDF-FTC – brand name Truvada® or generic equivalent); emtricitabine (FTC) 200 mg in combination with tenofovir alafenamide (TAF) 25 mg (TAF-FTC – brand name Descovy®); and cabotegravir (CAB) 600 mg injection (brand name Apretude®).  Truvada® is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection.  The FDA approval for TAF-FTC or Descovy® excluded persons at risk from receptive vaginal sex because the efficacy of Descovy® to reduce the risk of HIV-1 infection from vaginal exposures was not evaluated.  Apretude® is prescribed for people at risk of acquiring HIV through sex who weigh at least 77 pounds (lbs) (35 kilograms (kg)). 

Tenofovir, a nucleotide/nucleoside reverse transcriptase inhibitor of HIV, inhibits viral replication in cells (HHS, 2023d).  Although tenofovir alafenamide and tenofovir disoproxil fumarate are both prodrugs of tenofovir, tenofovir alafenamide transports the active metabolite, tenofovir diphosphate, more rapidly into peripheral blood mononuclear cells (PBMCs) than tenofovir disoproxil fumarate with at least four times higher concentrations resulting in increased antiviral activity.[2] Cabotegravir (Apretude®) is an extended-release injectable integrase strand transferase inhibitor.  Cabotegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration that is essential for the HIV replication cycle.

Scientific evidence demonstrates that PrEP is a safe and effective tool that can help reduce new cases of HIV, when taken as prescribed, yet PrEP usage remains limited (CDC, 2021c).  In 2019, the CDC estimated that approximately 285,000 of 1.2 million (or 23%) eligible individuals for PrEP received it, an increase from about 20% in 2015.  Chou et al. (2023) notes that a number of clinician and patient barriers to wider use of PrEP have been identified, including lack of knowledge or awareness of PrEP (particularly among primary care providers), perception of HIV risk, stigma, distrust of healthcare providers and systems, access to PrEP and costs, and concerns about harms. 

Factors that may affect the balance of benefits and harms in persons prescribed PrEP include adverse effects, such as possible injection site reactions and reduced kidney function, the potential for antiretroviral resistance in persons who unknowingly acquire HIV while taking PrEP, and the potential for behavioral risk compensation (Chou et al., 2023).  Behavioral risk compensation refers to an increase in behaviors associated with HIV transmission (e.g., sex without a condom or multiple sexual partners).  Because PrEP does not protect against other sexually transmitted infections (STIs), such as syphilis, chlamydia, and gonorrhea, behavioral risk compensation could increase the rate of STIs, in addition to reducing HIV prevention benefits.  (See analysis section of this decision memo for more details regarding benefits and harms of PrEP using ART to prevent HIV.) 

United States Preventive Services Task Force (USPSTF)

The USPSTF recommends that clinicians prescribe PrEP using effective ART to persons who are at increased risk of HIV acquisition to decrease the risk of acquiring HIV (USPSTF Grade A Recommendation, 2023).  The recommendation was based on convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at increased risk of HIV acquisition and adequate evidence of small harms, including kidney and gastrointestinal adverse effects, resulting in high certainty of substantial net benefit (Barry et al., 2023; Owens et al., 2019).  The USPSTF also found convincing evidence that the effectiveness of PrEP is highly correlated with adherence.  (See Analysis section for discussion on benefits and harms.)

The USPSTF assigns one of five letter grades to each of its recommendations (A, B, C, D, I). The following tables from the USPSTF website provides the current grade definitions and descriptions of levels of certainty (https://www.uspreventiveservicestaskforce.org/uspstf/about-uspstf/methods-and-processes/grade-definitions).

Grade Definitions

Levels of Certainty Regarding Net Benefit

* The USPSTF defines certainty as "likelihood that the USPSTF assessment of the net benefit of a preventive service is correct." The net benefit is defined as benefit minus harm of the preventive service as implemented in a general, primary care population. The USPSTF assigns a certainty level based on the nature of the overall evidence available to assess the net benefit of a preventive service.

III. History of Medicare Coverage

CMS may add coverage of "additional preventive services" under Part B if the statutory requirements set forth at section 1861(ddd)(1)-(2) of the Act are met. Our regulations provide:

A.  Current Request

CMS received a complete, formal request to consider a National Coverage Determination (NCD) for provider-administered PrEP for HIV prevention from ViiV Healthcare, asking CMS to review new scientific evidence and to adopt the USPSTF’s evidence-based recommendation.

The request letter is available at: https://www.cms.gov/Medicare/Coverage/DeterminationProcess/downloads/id310.pdf

B.  Benefit Category

Medicare is a defined benefit program. For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in the Act. PrEP using antiretroviral drugs for the prevention of HIV may be considered an “additional preventive service” that falls within the benefit category under §1861(s)(2)(BB). CMS is authorized to cover "additional preventive services" if certain statutory requirements are met as provided under §1861(ddd) of the Act.

IV. Timeline of Recent Activities 

V.  Food and Drug Administration (FDA) Status

In July 2012, the FDA approved an indication for the use of daily oral TDF-FTC (Truvada®) “in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk” (FDA, 2013). In May 2018, the approval for TDF-FTC was extended to adolescents weighing at least 35 kg (77 lbs) based on safety trials in adolescents and young adults.  As of April 2024, the FDA label states that “Truvada® is indicated in at-risk adults and adolescents weighing at least 35 kg for [PrEP] to reduce the risk of sexually acquired HIV-1 infection.”  The label also states:

Prior to or when initiating Truvada®, test for hepatitis B virus infection; prior to initiation and during use of Truvada®, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all individuals; in individuals with chronic kidney disease, also assess serum phosphorus; screen all individuals for HIV-1 immediately prior to initiating Truvada® for HIV-1 PrEP and at least once every 3 months while taking Truvada®, and upon diagnosis of any other sexually transmitted infections (STIs); use as part of a comprehensive prevention strategy including other prevention measures; strictly adhere to dosing schedule; counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use, knowledge of partner(s)’ HIV-1 status, including viral suppression status, regular testing for STIs that can facilitate HIV-1 transmission); inform uninfected individuals about and support their efforts in reducing sexual risk behavior. 

In addition, the Truvada® label states:

Published studies indicate an increased risk of HIV-1 infection during pregnancy and an increased risk of mother to child transmission during acute HIV-1 infection. In women at risk of acquiring HIV-1, consideration should be given to methods to prevent acquisition of HIV, including continuing or initiating Truvada® for HIV-1 PrEP, during pregnancy…. Truvada® is not recommended in HIV-uninfected individuals if creatinine clearance is below 60 mL/min.

In October 2019, the FDA approved daily oral TAF-FTC (Descovy®) for PrEP in at-risk adults and adolescents weighing at least 35 kg to reduce the risk of HIV-1 infection from sexual acquisition, excluding persons at risk from receptive vaginal sex (FDA, 2022). The latter population was specifically excluded from the Descovy® approval because the efficacy of Descovy® to reduce the risk of HIV-1 infection from vaginal exposures was not evaluated. The FDA label for Descovy® reflects the same testing/screening and counseling guidance as Truvada®; Descovy® may be used in adults and adolescents weighing at least 35 kg and with a creatinine clearance greater than or equal to 30 mL per minute.

In December 2021, the injectable integrase strand transferase inhibitor extended-release cabotegravir (Apretude®) was FDA-approved for PrEP, which can be administered every 8 weeks, after 2 loading doses given 4 weeks apart (FDA, 2023).  The FDA label states:

Apretude® is indicated in at-risk adults and adolescents weighing at least 35 kg for PrEP to reduce the risk of sexually acquired HIV-1 infection; screen for HIV-1 immediately prior to initiating and prior to each injection; clinical and laboratory monitoring should be considered for hepatotoxicity; counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use, knowledge of partner(s)’ HIV-1 status, including viral suppression status, regular testing for STIs that can facilitate HIV-1 transmission); inform uninfected individuals about and support their efforts in reducing sexual risk behavior; discuss the benefit-risk of using Apretude® with individuals of childbearing potential or during pregnancy.

The Truvada®, Descovy® and Apretude® labels state that risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including but not limited to condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network (FDA, 2020; 2022; 2023).

VI.  General Methodological Principles

When making NCDs concerning additional preventive services, CMS applies the statutory criteria in § 1861(ddd)(1) of the Act and regulations at 42 CFR § 410.64, and evaluates relevant clinical evidence to determine whether or not the service is reasonable and necessary for the prevention or early detection of illness or disability, is recommended with a grade of A or B by the USPSTF, and is appropriate for individuals entitled to benefits under Part A or enrolled under Part B of the Medicare program.

VII. Evidence

A.  Introduction
The evidence summarized in this section includes the peer-reviewed, published medical literature on pertinent clinical trials of PrEP using ART for persons at increased risk of HIV acquisition. Our assessment focuses on the key evidence questions below.

B.  Discussion of Evidence

1. Evidence Questions[3]

Question 1: Is the evidence sufficient to determine that the USPSTF recommends that clinicians prescribe PrEP using effective ART to persons at high risk ³ of HIV acquisition with a grade of A or B recommendation?

Question 2: Is the evidence sufficient to determine that prescribing PrEP with effective antiretroviral drugs for persons at high risk³ of HIV acquisition is reasonable and necessary for the prevention or early detection of illness or disability under §1861(ddd)(1) of the Act?

Question 3: Is the evidence sufficient to determine that prescribing PrEP with effective antiretroviral drugs for persons at high risk³ of HIV acquisition is appropriate for Medicare beneficiaries under Part A or Part B?

The USPSTF 2019 recommendation used the term “high risk,” but the USPSTF 2023 final recommendation uses “increased risk” and language in the Evidence Questions reflected the USPSTF 2019 decision. We adopt in this decision the modified language in the 2023 USPSTF recommendation.  However, we did not change our evidence questions from the proposed decision memorandum to the final decision memorandum to maintain consistency of documentation.  We note the USPSTF (2023) states that the 2023 USPSTF recommendation concerning the identification of persons to be considered for HIV PrEP is consistent with their 2019 recommendation.

2.  External Technology Assessments

CMS did not request an external technology assessment (TA) on this issue.

3.  Internal Technology Assessment

The reviewed evidence was gathered from articles submitted by the requester, resources suggested by public commenters, two systematic reviews performed by AHRQ for the USPSTF (Chou et al., 2019; Chou et al., 2023), and from a literature search of PubMed performed by CMS staff. Keywords for the search included, “preexposure prophylaxis or prep or tenofovir or truvada or descovy or cabotegravir and Anti-HIV Agents or hiv or human immunodeficiency virus.”  Publications that presented original human clinical data on PrEP regimens approved by the FDA were considered. Abstracts, meeting presentations, reviews, animal studies, and non-English language publications were excluded. Studies examining on-demand dosing, oral TDF monotherapy, oral maraviroc, tenofovir vaginal gel, injectable rilpivirine, and dapivirine vaginal ring were excluded.  One study focusing on the risk factor of people who inject drugs (PWID) and oral TDF monotherapy was included because it was the only clinical trial focusing on this population.

4.  Medicare Evidence Development & Coverage Advisory Committee (MEDCAC)

A MEDCAC meeting was not convened on this issue.

5.  Evidence Tables

Below are two evidence tables.  Table 1 contains summary descriptive information about the key clinical trials of PrEP.  Table 2 contains summary results from the key clinical trials of PrEP.  The full citation for the publication can be found in the bibliography of this decision memorandum. 

Table 1.  Study characteristics of key clinical trials of PrEP (adapted from Chou et al., 2019; Chou et al., 2023) 

Table 2.  HIV Pre-Exposure Prophylaxis Key Clinical Trials: Results (adapted from USPSTF 2019 and 2023) 

Evidence-based Guidelines

The CDC/United States Public Health Service guideline, “PrEP for the Prevention of HIV Infection in the United States – 2021 Update: A Clinical Practice Guideline” (CDC, 2021d), encourages healthcare providers to increase awareness of PrEP and offer PrEP as a core primary care service in order to reduce missed opportunities for providing PrEP.  The CDC recommends taking a brief, targeted sexual history of all adult and adolescent patients as part of ongoing primary care and PrEP to be offered to sexually active adults and adolescents at substantial risk of HIV acquisition.  The guideline criteria for identifying patients at substantial risk of acquiring HIV follow the inclusion criteria of the major randomized trials of PrEP.  The criteria include:  sexually-active adults who have had anal or vaginal sex in the past six months and any of the following:  HIV-positive sexual partner (especially if partner has an unknown or detectable viral load); or a bacterial STI in the past six months; or a history of inconsistent or no condom use with sexual partner(s).  The CDC states that most persons who inject drugs are sexually active and report sexual behaviors that confer risk of HIV acquisition.  The guideline states that PWID are likely to benefit from PrEP with any FDA-approved medication with or without an identified sexual behavior risk of HIV acquisition.  PWID who have a HIV-positive injecting partner or sharing injection equipment are at substantial risk of acquiring HIV.  The CDC guideline also includes various recommendations regarding baseline and follow-up visit timing of laboratory tests for patients receiving daily oral PrEP (see table 3 below) and cabotegravir (see table 4 below). 

Table 3. CDC Guideline daily oral PrEP timing of laboratory tests (CDC, 2021e)

Table 4. CDC Guideline Cabotegravir injection PrEP timing of laboratory tests (CDC, 2021e)

The World Health Organization (WHO) recommends oral PrEP containing TDF, dapivirine vaginal ring (for individuals assigned female at birth), and cabotegravir as additional prevention choices for people at substantial risk of HIV as part of combination HIV prevention approaches (WHO, 2022).  The WHO notes that risk of HIV acquisition varies greatly within populations and geographical locations.

Population-level HIV incidence is an important determinant of individual-level risk of HIV acquisition. However, when considering who could benefit from PrEP, it is important to consider the characteristics and behaviors of individuals and their partners that could lead to HIV exposure. Even in locations with a low overall HIV incidence, there may be individuals at substantial risk who could benefit from PrEP services. Individuals requesting PrEP should be given priority to be offered PrEP since requesting PrEP indicates that there is likely to be a risk of acquiring HIV (WHO, 2022, p. 11).

To note, the dapivirine vaginal ring has been withdrawn by its manufacturer from FDA review related to the manufacturer’s assessment that there is little chance of obtaining approval (Gollub & Vaughan, 2022).

Professional Society Recommendations

The International Antiviral Society – USA Panel updated their recommendations for ART for treatment and prevention of HIV in December 2022 (Gandhi et al., 2023).  The society recommends discussing PrEP with all sexually active adolescents and adults and anyone who injects nonprescription drugs or who has a substance use disorder, without specific criteria for risk behaviors or screening tools.

Populations with disproportionately high HIV incidence rates should be particularly encouraged to consider PrEP as part of their HIV prevention plans; these include cisgender men and transgender individuals who have sex with men; young adults and adolescents; people whose sexual partners are from regions of generalized HIV epidemic; persons who use nonprescription drugs and alcohol; individuals who exchange sex for money, goods, or services; partners of incarcerated individuals; and anyone with a recent bacterial STI (p. 72).  

Daily oral TAF/FTC is preferred over TDF/FTC for individuals with creatinine clearance between 30 and 60 mL/min or when there is known osteopenia or osteoporosis.  (Bone density scans are not necessary before starting TDF/FTC).  Further, TAF/FTC use should be limited to cisgender men of any sexual orientation and anyone whose risks do not include receptive vaginal sex (including neovaginal sex) or those whose risk is exclusively posed by injection drug use.  Data on efficacy of TAF/FTC for preventing HIV acquisition through receptive vaginal sex are not available.  Long acting injectable cabotegravir is recommended for prevention of sexual transmission of HIV across populations (p.72).

VIII. Public Comment

Public comments sometimes cite published clinical evidence and give CMS useful information. Public comments that give information on unpublished evidence, such as the results of individual practitioners or patients, are less rigorous and therefore less useful for making a coverage determination. Public comments that contain personal health information will be redacted or not be made available to the public.

CMS uses the initial public comments to inform its proposed decision. CMS responds in detail to the public comments on a proposed decision when issuing the final decision memorandum. All comments that were submitted without personal health information may be viewed in their entirety by using the following link: PrEP to prevent HIV NCA initial public comments.

Initial Public Comment Period: 01/12/2023 – 02/11/2023

During the 30-day comment period following the release of the tracking sheet, CMS received 37 comments.  The majority of commenters supported Medicare coverage of PrEP to prevent HIV and to align with the USPSTF grade A recommendation.  Commenters noted the safety and efficacy of PrEP as an essential tool to ending the HIV epidemic.  They emphasized the need to improve PrEP uptake, adherence, and access.  Numerous comments focused on access to the newest PrEP drug, the injectable cabotegravir or Apretude®.  Two commenters were not in support of Medicare coverage of PrEP using ART to prevent HIV.  One of these commenters did not agree with the FDA approval of these drugs, disagreed with the outcome measure in the trials, and stated that the PrEP antiretroviral drugs are not appropriate for the Medicare population due to adverse effects to the kidneys and the need for longer term studies.  The second comment did not support PrEP to prevent HIV and stated that Medicare coverage would negatively impact users of the 340B drug pricing program.

CMS received comments from community health centers, patient advocacy organizations, pharmaceutical companies, institutions of higher education, health systems and medical centers, physicians and other health care professionals, attorneys, and individuals. 

Ten comments were provided by professional associations/organizations, including the American Academy of HIV Medicine Specialists (AAHIVS), Gerontological Society of America, Association of Nurses in AIDS Care, HIV Medicine Association, International Association of Providers of AIDS Care, HealthHIV, National Alliance of State and Territorial AIDS Directors (NASTAD), National Coalition of STD Directors, National Disability Rights Network (NDRN), and National Association of Social Workers. 

Second Public Comment Period:  07/12/2023 – 08/11/2023

During the second 30-day comment period following the release of the proposed NCD and decision memorandum, CMS received 81 comments.  One comment was omitted from publication on the CMS website because it included extensive personal health information that could not be effectively redacted.  One comment did not provide a stance on the proposed decision.  The majority of commenters supported Medicare coverage of PrEP to prevent HIV and to align with the USPSTF grade A recommendation, but several commenters recommended changes to the proposed screening services. Commenters in support of the NCD highlighted that Medicare coverage of PrEP as a preventive service with no cost to beneficiaries would enhance access to PrEP medications and services for underserved and underrepresented communities.  Some commenters asked for coverage of PrEP medications without barriers such as prior authorizations or step therapy, based on the decisions made between the provider and patient.  Five commenters, along with eight additional co-signers, did not support our proposal to cover the PrEP medications under Part B and requested to require coverage of PrEP medications under Medicare Part D without beneficiary cost sharing.  These same commenters supported PrEP related services to be covered by Part A/B, including screening services and the counseling visits.  Other commenters supported transitioning PrEP coverage from Medicare Part D to Part B, but raised implementation concerns and recommended a transition period to prevent disruptions in access and an educational and outreach campaign for providers, pharmacies, and pharmacists.  Commenters requested that pharmacists be considered as eligible Medicare providers of PrEP administration and related services.  Detailed summaries with CMS responses are included below. 

Many comments were provided by physicians and other healthcare professionals (26) and advocacy organizations.  Thirteen comments did not identify an affiliation or profession.  We received one comment which included 32 undersigned organizations and one comment undersigned by nine organizations.  CMS received a comment cosigned by a United States Representative and United States Senator in support of this NCD.  There were 12 comments from professional associations/societies, including the American Academy of HIV Medicine (AAHIVM), American Clinical Laboratory Association (ACLA), California Society of Health-System Pharmacists (CSHP) Foundation for Research Education, American Society of Consultant Pharmacists (ASCP), National Network of Sexually Transmitted Diseases Clinical Prevention Training Centers (NNPTC), America’s Health Insurance Plans (AHIP), Infectious Diseases Society of America (IDSA), HIV Medicine Association (HIVMA), American Academy of Family Physicians (AAFP), American Pharmacists Association (APhA), National Community Pharmacists Association (NCPA), and National Coalition of STD Directors (NCSD).  Comments were received from community health centers (6) and health care systems (3).  There were seven comments provided by pharmaceutical and healthcare companies, including Johnson & Johnson, ViiV Healthcare, Gilead Sciences, Merck, OptiMed Pharmacy, Quest Diagnostics and CVS Health. 

Several commenters provided references for our deliberation of this NCD.  We appreciate this information.  All such references were assessed for inclusion in our evidence review.   

Comment:  Many commenters supported the proposed coverage of PrEP as an additional preventive service under Part B with no cost-sharing for Medicare beneficiaries and suggested that this approach would enhance access to PrEP medications and services.  Commenters said that coverage of PrEP with no cost-sharing is an important step to improve access to lifesaving preventive care.  Commenters said that the proposed coverage of PrEP with no cost-sharing, as well as related screening and counseling services, will help reduce disparities in access, uptake, and adherence for affected populations.  Commenters also said that the NCD supports national efforts towards the goal of ending the HIV epidemic in the United States.  

Response: We thank the commenters for their support.

Comment:  Commenters suggested that we include language in this NCD that ensures coverage of future PrEP products to encourage ongoing innovation and reduce future administrative burden on CMS.

Response:  The NCD states that Medicare will cover PrEP using antiretroviral drugs approved by the FDA to prevent HIV in individuals at increased risk of HIV acquisition (please see Appendix B).  This language in the final NCD applies to any drug approved by the FDA for this indication.  New drugs approved by the FDA with this indication are also subject to this NCD.

Comment:  Commenters asked CMS to align our NCD language with the draft USPSTF (2022) recommendation regarding assessment of risk for HIV acquisition. Specifically, commenters noted that, while the 2022 draft USPSTF recommendation was consistent with the 2019 final USPSTF recommendation, the 2022 draft described the recommended population as at “increased risk,” rather than “high risk.” In addition, commenters said that this revised language is more consistent with current consensus about appropriate terminology.  Several commenters pointed out that using language like “high risk” can be stigmatizing and misleading.  Several commenters noted that many people who may benefit from PrEP may not perceive themselves to be at “high risk” and may not pursue the preventive service.  

Response:  We are changing the “high risk” reference to “increased risk” in this final decision memorandum and in Appendix B. We thank commenters for their comments on this matter. We appreciate commenters’ concerns about potential stigmatization associated with the term “high risk” and CMS seeks to align the NCD with the final 2023 USPSTF recommendation.

Comment:  Several commenters requested that CMS adopt CDC’s guidelines, which specify that all sexually active adults and adolescents should receive information about PrEP and that PrEP should be provided to any patient who requests it, including those that do not report HIV risk factors.  One commenter said that CMS should empower physicians wishing to facilitate access to PrEP to a broader range of patients who could benefit from that intervention by adopting the CDC’s framework.  Other commenters recommended that CMS avoid both “high risk” and “increased risk,” and instead use “at risk.” The commenters explain that this would not only avoid stigmatizing language, but also mirror the FDA-approved labeling for PrEP drugs.

Response:  Although we are not adopting the specific language from the CDC guidelines, CMS is covering individual counseling visits for individuals being assessed for or taking HIV PrEP and this counseling includes HIV risk assessment (initial or continued assessment of risk), HIV risk reduction, and medication adherence.  The determination of whether an individual is at increased risk for HIV is made by the physician or health care practitioner who assesses the individual’s history.

Comment: Commenters asked CMS to revise certain other phrases used in the proposed decision to avoid stigmatizing language. For example, one commenter suggested that we rephrase “a person may be infected with HIV for years before the condition is suspected” to state that, “a person may be living with HIV for years before the condition is suspected.”

Response: We thank the commenters for their suggestions. We have implemented several revisions throughout to replace potentially stigmatizing language with person-centered language. We agree with commenters that language choice is important. 

Comment: Some commenters raised implementation and access concerns for the oral PrEP drugs, including administrative and monetary costs for pharmacy enrollment in Medicare Part B and complexities of Medicare Part B billing in comparison to Part D.  The commenters stated that a transition to coverage of the oral PrEP drugs from Medicare Part D to Part B would require careful implementation and guidance from CMS to ensure that patients, pharmacies, plans, and providers have clarity during a potentially confusing transition.  They stated that any pharmacy may bill Part D, yet not all pharmacies are enrolled in Part B and if they choose not to enroll, it could affect thousands of PrEP patients’ coverage.

Response:  We appreciate commenters sharing these concerns.  We have taken additional steps to prepare pharmacies, Medicare health and drug plans, and providers for this transition to coverage of the oral PrEP drugs from Medicare Part D to Part B.  CMS published a website containing several additional resources, hosted office hours and encouraged pharmacies and other affected parties to prepare for this transition.  The website is available at https://www.cms.gov/medicare/coverage/prep.  CMS shared this information to encourage pharmacies and other interested parties to prepare for this NCD to avoid any possible disruptions for beneficiaries.  The Fact Sheet recommended that pharmacies not already enrolled as a durable medical equipment, prosthetics, orthotics, and supplies (DMEPOS) supplier should enroll as a Part B Pharmacy as soon as possible in preparation for this final NCD. Enrolling as a Part B Pharmacy has a lower level of burden and cost, is different than enrolling as a DMEPOS supplier, and they have different forms for enrollment - CMS-855S for DMEPOS suppliers versus form CMS-855B for Part B Pharmacy suppliers.  The fact sheet is available through the website.  CMS then released a Technical Frequently Asked Questions for Pharmacies to provide more technical information for submitting future Medicare Part B claims for PrEP for HIV in advance of the final NCD.  CMS also issued a memo to communicate the transition to coverage of the oral PrEP drugs from Medicare Part D to Part B to the Medicare Advantage Organizations and Part D Plan Sponsors.  All of this information is available through the website.  Furthermore, CMS engaged and coordinated outreach efforts with the Medicare Administrative Contractors for this change.

Comment:  One commenter stated that CMS does not have authority to change coverage of drugs that are self-administered and covered under Medicare Part D to coverage under Medicare Part B.  The commenter also stated that such a transition could create additional out-of-pocket costs for beneficiaries and cause disruptions to distribution and access to drugs.

Response:  CMS is authorized per section 1861(ddd)(1) of the Act and implementing regulations at 42 CFR § 410.64 to add coverage of “additional preventive services” under Part B.  As noted above, the Secretary must determine through the NCD process whether the service is recommended with a grade A or B by the USPSTF and meets certain other requirements. There is no cost-sharing under Part B for Medicare beneficiaries for the items and services that are covered under this authority. Thus, for individuals who receive PrEP under this NCD, there will be no Medicare Part B cost-sharing.

CMS is also finalizing through this NCD coverage of counseling visits, certain additional screening tests, the supplying or dispensing fee of HIV PrEP drugs and the administration of PrEP injectable drugs.  Those additional preventive services will also not be subject to Part B cost sharing.  Per 42 CFR § 422.100(k), Medicare Advantage plans may not charge deductibles, copayments, or coinsurance for in-network Medicare-covered preventive services (as defined in § 410.152(l)); additional preventive services identified for coverage through the NCD process are listed at § 410.150(l)(11) and are therefore required to be covered by Medicare Advantage plans without cost-sharing.  The additional preventive services adopted by this NCD include the HIV PrEP drugs; the furnishing of HIV PrEP, including the supplying of HIV PrEP drugs (similar to the fee that is paid for other oral drugs currently covered under Part B) and the administration of the injectable HIV PrEP drug; and the other covered additional preventive services related to PrEP for HIV, which include the counseling services, laboratory and point of care screening tests.

While cost sharing has been eliminated under Part B, we appreciate the commenter’s concerns about possible disruptions as Medicare beneficiaries with drug coverage under Part D and the pharmacies they use to fill current PrEP prescriptions may not be immediately familiar with this shift to Medicare Part B.  CMS hosted office hours, released a dedicated PrEP for HIV informational website, a Fact Sheet and a Technical Frequently Asked Questions before publishing this final NCD.  CMS shared this information to encourage pharmacies and other interested parties to prepare for this NCD to avoid any possible disruptions for beneficiaries. These documents include information on coding and claims processing for pharmacies, physicians, and health care practitioners to bill the Medicare program for the HIV PrEP drugs; the furnishing of HIV PrEP, including the supplying of HIV PrEP drugs (similar to the fee that is paid for other oral drugs currently covered under Part B) and the administration of injectable HIV PrEP drugs; and the other covered additional preventive services related to PrEP for HIV, which include the counseling services, laboratory and point of care screening tests.  The website is available at https://www.cms.gov/medicare/coverage/prep where both the fact sheet and technical FAQ are also available. 

Comment:  Commenters were concerned that if coverage of PrEP is moved to Part A/B, there might be concerns about where and how patients receive their medications, especially if there is an implication that they need to get them in a clinical setting.

Response:  Thank you for this comment offering concerns regarding access.  In the case of PrEP drugs, pharmacies enrolled in the Medicare program will be able to dispense PrEP drugs and submit a claim to Medicare for reimbursement. 

Comment:  Commenters stated that all FDA approved PrEP medications need to be covered without barriers such as prior authorizations or step therapy, based on the decisions made between the provider and patient.  Commenters asked that CMS include language in the final NCD affirming that prior authorization or other utilization management is not permissible for PrEP medications.  Furthermore, commenters asked that CMS prohibit prior authorizations for the purpose of assessing HIV risk.

Response:  Medicare Advantage plans must follow this National Coverage Determination, including providing PrEP drugs for HIV with no cost sharing at in-network providers beginning on September 30, 2024, the date this NCD was issued. Payment for PrEP drugs and services under this NCD for a Medicare enrollee should be billed to the enrollee’s Medicare Advantage plan, not Original Medicare. Please see the August 1, 2024, HPMS memo for additional information about billing and contact the Medicare Advantage plan for further information.

Comment:  Commenters asked whether the significant cost threshold would be met for this NCD.  Commenters asked about the effective date of the new coverage requirements for the PrEP antiretroviral drugs and related preventive services for Medicare Advantage plans.  The commenters asked that the effective date not be earlier than the first plan year after the NCD is finalized, so that the Medicare Advantage plans have an opportunity to consider the additional costs of these new preventive services.  The commenters also stated that this same time frame apply for Part D sponsors so that they can make the necessary operational changes and communications to pharmacies regarding any changes in Part D coverage for the PrEP antiretroviral drugs because of the finalization of the NCD.

Response:  CMS has determined that this NCD does not meet the significant cost threshold. Therefore, Medicare Advantage plans are required to assume the costs and cover the drugs and services in this NCD beginning on September 30, 2024.

Comment:  Commenters had various implementation concerns, including pharmacy enrollment in Medicare Part B, complexities of Medicare Part B billing in comparison to Part D, how pharmacies will know whether to bill Part D or Part B for antiretroviral drugs (for purposes of prevention versus the treatment of HIV), and related claims processing concerns.

Response:  CMS has provided and will continue to provide outreach and education to providers, pharmacies, health plans, and individuals regarding these preventive antiretroviral drugs.  We will utilize various tools available to us, including the Medicare Learning Network, partner outreach resources, CMS Open Doors forums, and communications with the MACs.  CMS coordinated efforts with other Health and Human Services agencies as well.  While numerous pharmacies are already enrolled to bill Medicare, we encouraged those that are not enrolled to begin the process of enrollment if they would like to dispense PrEP drugs and receive Medicare reimbursement (see previous discussions on the PrEP for HIV informational website, Fact Sheet, technical FAQ, and HPMS memo).

Comment: Commenters noted difficulties that individuals may face when obtaining drugs covered under the Medicare Part B benefit, including the commenters’ perceptions that Part B medications must be picked up within a day after prescriptions are billed, may only be available as 30-day prescription fills, and may be difficult to obtain through telehealth visits and mail order shipments.

Response:  There is no 30-day prescription fill limit on the PrEP drugs under Medicare Part B.  Pharmacies can bill Medicare once the medication is picked up.  Mail order pharmacies may enroll in Medicare as a durable medical equipment supplier if they meet all regulatory requirements in 42 CFR § 424 Subpart P. Mail order pharmacies may contact their Medicare Administrative Contractor if they have questions about enrolling as a Part B pharmacy.  Lastly, CMS has no face-to-face requirement for this preventive service. Current regulations and opportunities for telehealth visits are applicable.

Comment:  A few commenters recommended CMS cover PrEP related services without cost-sharing under Medicare Parts A & B and require coverage of PrEP medications under Medicare Part D drug coverage without beneficiary cost sharing.

Response:  CMS is authorized to add coverage of "additional preventive services" under Part B if the Secretary determines using the NCD process that the service is recommended with a grade A or B by the USPSTF and meets certain other requirements, including whether the services are appropriate for individuals entitled to benefits under Part A or enrolled under Part B.  Additional preventive services are only covered under Part B by statute. Medicare does not have the authority under this provision to eliminate cost-sharing under Part A or D.

Comment:  Several commenters noted that they consider pharmacists to have a significant role in making PrEP available and recommended that CMS expand coverage to include payment for services of pharmacists, including initiating PrEP, administering PrEP and related services, such as office visits and counseling, according to their state’s pharmacist scope of practice laws.  Also, commenters asked CMS to explicitly include pharmacists as one of the health care practitioners mentioned in the NCD text.

Response:  Currently, pharmacists are not recognized Medicare providers or suppliers and are not eligible to be paid directly for furnished services.  Pharmacists may provide, when all conditions are met, services as auxiliary personnel “incident to” a physician’s or other practitioner’s service in certain settings.  The incident to regulations requires supervision by a physician or other practitioner.  For further details regarding “incident to” services, we recommend that interested parties consult 42 CFR §§ 410.26 and 410.27.

Comment:  One commenter gave CMS several administrative pathway recommendations to cover pharmacists’ services under Medicare part B, including updating regulations and allowing pharmacists to enroll as ‘other qualified nonphysician practitioners’ or using a waiver under section 1135 of the Act or using enforcement discretion.

Response:  This comment is outside the scope of this NCD analysis.

Comment:  Comments were received from federally qualified health centers (FQHCs) and several Ryan White HIV/AIDS Program clinics.  The commenters believe that PrEP drugs should be continued to be covered by Medicare Part D due to the financial constraints of how Part B drugs are covered/reimbursed under the FQHC Prospective Payment System (PPS). 

Response:  Medicare does not have the authority under this provision to eliminate cost-sharing under Part D.  CMS is using its authority to add Part B coverage of these additional preventive services.  Since these drugs would be covered as a type of preventive service, they would be paid at 100 percent of reasonable costs in FQHCs and therefore they would not be paid under the FQHC PPS, per § 405.2449, § 405.2410(b), and § 410.152(l).

Comment:  A couple of commenters stated that coverage needed to include provider parity for non-physician practitioners, such as nurse practitioners, physician assistants, and pharmacists.

Response:  These comments are beyond the scope of this NCD analysis.  Payment and coding issues will be addressed in the implementing instructions given to Medicare contractors.

Comment:  A couple of commenters requested ‘consistent, transparent, fair, and sustainable’ reimbursement rates for the PrEP medications and for the dispensing of the medications.

Response:  Reimbursement rates and coding are beyond the scope of this NCD analysis.  However, CMS established pharmacy supplying fees to be paid to the supplier of HIV PrEP drugs (similar to the fee that is paid for other oral drugs currently covered under Part B).

Comment:  One commenter requested CMS issue guidance to state Medicaid programs encouraging submission of State Plan Amendments (SPAs) to add pharmacists as other licensed practitioners, allowing Medicaid reimbursement of services within pharmacists’ state scope of practice laws.

Response:  This NCD applies to the Medicare program.  Addressing comments regarding Medicaid is beyond the scope of this NCD.

Comment: Commenters asked CMS to extend coverage to include copays for doctor’s visits and lab fees, which they stated can be cost-prohibitive for some patients.

Response:  There is no cost-sharing for Medicare preventive services that are included in this NCD under Part B.  The covered services are FDA approved PrEP using antiretroviral drugs, specified counseling visits, specified laboratory tests, administration of the injectable PrEP drug, supplying or dispensing oral PrEP, and labs, when such services are appropriate for the individual.

Comment:  One commenter recommended that CMS allow coverage of laboratory developed tests performed in Clinical Laboratory Improvement Amendments of 1988 (CLIA)-certified laboratories, in addition to FDA-approved lab tests.  The commenter stated that CMS did not present evidence to support the requirement that lab tests be FDA-approved or that such a requirement would improve screening accuracy and reduce harm.  The commenter stated that CLIA-certified labs provide evidence of a laboratory developed test’s validity and should be included in coverage.

Response:  CMS will require that Medicare-covered HIV screening tests are FDA-approved laboratory tests or FDA-approved point of care tests, used consistent with FDA-approved labeling and in compliance with the CLIA regulations.  Such requirements were previously established in the Screening for HIV Infection NCD (210.7) and will be maintained in this final decision. 

Comment:  Commenters asked that CMS ensure coverage of nucleic acid or HIV-1 RNA tests, in addition to appropriate HIV antigen/antibody tests, for the screening of HIV, as recommended by the CDC, USPSTF, and as included on the FDA drug label for cabotegravir.  One commenter also stated that more frequent HIV screening than what was proposed by CMS may be needed in certain scenarios. 

Response:  We appreciate these comments. We are increasing the number of counseling visits and HIV screenings to eight for the final decision.  CMS proposed seven individual counseling visits and HIV screenings based on the clinical trial that provided evidence on cabotegravir (Landovitz et al., 2021).  We understand that injectable cabotegravir may include an oral lead-in with oral cabotegravir for approximately one month to assess the tolerability of cabotegravir, and that HIV screening and counseling may be needed eight times within the 12-month period.  A total of eight (each HIV screening and counseling visits) accounts for the lead-in period which we did not account for in the proposed decision.  As described in Landovitz et al. (2021), FDA approved rapid (point of care) tests and antigen-antibody tests were used at study sites.  HIV RNA tests were used as diagnostic tests, which is beyond the scope of this NCD.  As noted above, CMS will also continue to cover HIV screening according to requirements established in NCD 210.7.

Comment:  Several commenters noted that the CDC guideline is cited within the USPSTF’s grade A recommendation for PrEP to prevent HIV and that CMS’ coverage of STI screening (Screening for Sexually Transmitted Infections (STIs) and High-Intensity Behavioral Counseling (HIBC) to Prevent STIs (NCD 210.10)) for those being considered for or those who are on PrEP does not align with the CDC’s recommendations.

Response:  We appreciate these comments.  CMS did not propose the inclusion of STI screening as part of this NCD.  While we acknowledge the importance of STI screening, we are not including additional coverage for STI screening in the context of this NCD.  Coverage is available under our existing NCD. (see STI Screening and HIBC to Prevent STIs (NCD 210.10), https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=352&ncdver=1). 

Comment: Commenters asked that CMS clearly state that kidney function, pregnancy, and lipid testing is covered for persons being considered for or taking PrEP to prevent HIV. 

Response:  CMS did not propose to include these tests as part of coverage for PrEP as part of the “additional preventive services” benefit.  Kidney function, pregnancy, and lipid testing may be covered by Medicare when considered reasonable and necessary under section 1862(a)(1)(A) for specific patients. 

Comment:  Commenters asked that CMS include coverage of hepatitis C virus screening in this NCD.

Response:  CMS did not propose the inclusion of hepatitis C virus screening as part of this NCD.  The USPSTF (2023) recommendation and the FDA drug labels for the injectable and oral PrEP antiretroviral drugs do not mention hepatitis C virus screening of individuals taking PrEP. While we acknowledge the importance of hepatitis C virus screening based on risk in the primary health care setting, we are not including screening for hepatitis C virus in the context of this NCD.  Medicare coverage for Screening for Hepatitis C Virus in Adults is provided in our existing NCD.  See (NCD 210.13), https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=361&ncdver=1#:~:text=A%20screening%20test%20is%20covered,blood%20transfusion%20prior%20to%201992).

IX. CMS Analysis

Introduction

National coverage determinations (NCDs) are determinations by the Secretary with respect to whether or not a particular item or service is covered nationally under title XVIII of the Act (§ 1869(f)(1)(B)). In order to be covered by Medicare, an item or service must fall within one or more benefit categories contained within Part A or Part B, and must not be otherwise excluded from coverage. CMS is authorized to cover "additional preventive services" if certain statutory requirements are met as provided under § 1861(ddd)(1) of the Act.

Regulations at 42 CFR § 410.64 provide:

When making NCDs, it is important to consider whether the evidence is relevant to the Medicare beneficiary population. In considering the generalizability of the results of the body of evidence to the Medicare population, it is necessary to consider at least the age, race, and gender of the study participants.

Evidence Review Summary

Question 1:  Is the evidence sufficient to determine that the USPSTF recommends that clinicians prescribe PrEP using effective ART to persons who are at high risk of HIV acquisition with a grade of A recommendation by the United States Preventive Services Task Force?

The USPSTF (August 2023) recommended (Barry et al., 2023):

https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/prevention-of-human-immunodeficiency-virus-hiv-infection-pre-exposure-prophylaxis

The USPSTF also found:

Convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV in persons at increased risk of HIV acquisition.  The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with a small magnitude of harms, which include kidney and gastrointestinal adverse effects, weight gain, and injection site reactions, depending on the specific PrEP formulation used. The USPSTF concludes with high certainty that there is substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV in persons at increased risk of acquiring HIV. 

CMS concludes that the evidence is sufficient to determine that the USPSTF recommends that clinicians prescribe PrEP using effective antiretroviral therapy to persons who are at increased risk of HIV acquisition to decrease the risk of acquiring HIV with a grade of A.

Question 2: Is the evidence sufficient to determine that prescribing PrEP with effective antiretroviral drugs for persons at high risk of HIV acquisition is reasonable and necessary for the prevention or early detection of illness or disability under §1861(ddd)(1) of the Act?

Our reviewed evidence is limited to FDA approved PrEP using ART to prevent HIV and does not include studies examining the dapivirine vaginal ring, oral TDF monotherapy, alternative (non-daily) oral dosing schedules (e.g., event-driven [on-demand] or intermittent dosing), and other PrEP regimens (e.g., oral maraviroc, tenofovir vaginal gel, or injectable rilpivirine).  

Quality and strength of evidence

The evidence base for this decision is mainly derived from two recent systematic reviews, which were prepared for the USPSTF recommendation that clinicians prescribe PrEP using effective antiretroviral therapy to persons who are at increased risk of HIV acquisition to decrease the risk of acquiring HIV (Chou et al., 2019; Chou et al., 2023).  CMS agrees with the USPSTF that the evidence demonstrates benefits and small harms for PrEP with ART, when used as prescribed, in reducing the risk of HIV in persons at increased risk of HIV acquisition. The evidence demonstrated efficacy and safety of PrEP; in addition to the beneficial effects of repeated condom provision, sexual risk-reduction counseling, and the diagnosis and treatment of sexually transmitted infections (STIs), all of which were provided to clinical trial participants.  The evidence demonstrating small harms for PrEP with ART reveals the need for ongoing risk assessment, counseling, and monitoring for safety, such as HIV screening, during the administration of PrEP with ART. 

Benefits

Chou et al. (2019; 2023) reviewed 11 randomized controlled trials (RCTs) that evaluated the effect of daily oral TDF-FTC PrEP (Truvada®) on the risk of HIV acquisition:

Agot K, Taylor D, Corneli AL, et al. Accuracy of self-report and pill-count measures of adherence in the FEM-PrEP clinical trial: implications for future HIV-prevention trials. AIDS Behav. 2015 May;19(5):743-51. doi: 10.1007/s10461-014-0859-z. PMID: 25100053.

Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, Tappero JW, Bukusi EA, Cohen CR, Katabira E, Ronald A, Tumwesigye E, Were E, Fife KH, Kiarie J, Farquhar C, John-Stewart G, Kakia A, Odoyo J, Mucunguzi A, Nakku-Joloba E, Twesigye R, Ngure K, Apaka C, Tamooh H, Gabona F, Mujugira A, Panteleeff D, Thomas KK, Kidoguchi L, Krows M, Revall J, Morrison S, Haugen H, Emmanuel-Ogier M, Ondrejcek L, Coombs RW, Frenkel L, Hendrix C, Bumpus NN, Bangsberg D, Haberer JE, Stevens WS, Lingappa JR, Celum C; Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2;367(5):399-410. doi: 10.1056/NEJMoa1108524. Epub 2012 Jul 11. PMID: 22784037; PMCID: PMC3770474.

Bekker LG, Roux S, Sebastien E, et al. Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town trial): a randomised, open-label, phase 2 trial. Lancet HIV. 2018 02;5(2):e68-e78. doi: 10.1016/S2352-3018(17)30156-X. PMID: 28986029.

CDC, 2021a. ;Estimated HIV incidence and prevalence in the United States 2015–2019. HIV ;Surveillance Supplemental Report ;2021;26(1).  Retrieved from https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-supplemental-report-vol-26-1.pdf.

CDC, 2021b. Centers for Disease Control and Prevention. HIV Surveillance Report, 2019; vol. 32. https://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-report-2018-updated-vol-32.pdf

CDC, 2021c. Monitoring selected national HIV prevention and care objectives by using HIV surveillance data—United States and 6 dependent areas, 2019. ;HIV Surveillance Supplemental Report ;2021;26(No.2). ;https://stacks.cdc.gov/view/cdc/160192. ;Published May 2021. Accessed ;January 26, 2023.

CDC, 2021d.  Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2021 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf. Published December 2021.

 CDC, 2022.  Preventing HIV with PrEP. Retrieved from https://www.cdc.gov/hiv/prevention/prep.html?CDC_AAref_Val=https://www.cdc.gov/hiv/basics/prep/about-prep.html.

CDC, 2023a.  Estimated HIV incidence and prevalence in the United States, 2018–2022. ; HIV Surveillance Supplemental Report, 2024; 29 (No.1). ;https://stacks.cdc.gov/view/cdc/156513.  Accessed 05/28/2024.

CDC, 2023b. ; Diagnoses of HIV Infection in the United States and Dependent Areas, 2022.  HIV Surveillance Report, 2022; vol. 35. https://stacks.cdc.gov/view/cdc/156509. ; Accessed 05/28/2024.

CDC, 2023c.  Core indicators for monitoring the Ending the HIV Epidemic initiative (preliminary data): National HIV Surveillance System data reported through June 2023; and preexposure prophylaxis (PrEP) data reported through March 2023. HIV Surveillance Data Tables 2023;4(3). https://stacks.cdc.gov/view/cdc/136159. Accessed 05/28/2024.

CDC, 2024. About HIV. Available at https://www.cdc.gov/hiv/about/?CDC_AAref_Val=https://www.cdc.gov/hiv/basics/whatishiv.html.  Published January 2024.  Accessed 05/15/2024. 

Centers for Disease Control and Prevention (CDC) and Association of Public Health Laboratories. Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. Available at http://stacks.cdc.gov/view/cdc/23447.  Published June 27, 2014. Accessed May 2, 2023.

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