Human Immunodeficiency Virus

Care: A Primary Care Provider’s Guide

a, b
Santina Wheat, MD, MPH, AAHIVS *, Evan Wittke, MD

KEYWORDS

HIV
Primary care
LGBTQ1 health
Treatment as prevention
PrEP
PEP

KEY POINTS

Lesbian, gay, bisexual, transgender and queer1 persons, particularly those from commu-
nities of color are at increased risk of human immunodeficiency virus (HIV) infection.

Multiple prevention strategies exist to drastically reduce risk of HIV acquisition.

HIV diagnosis depends on HIV antibody, antigen, and viral load testing algorithms, with
fourth-generation testing providing results within 2 weeks of infection.

Recommended initial HIV treatment for most patients includes an integrase inhibitor and 2
nucleoside reverse transcriptase inhibitors.

Patients living with HIV continue to require primary care interventions.

INTRODUCTION

In the early 1980s, various opportunistic infections (OIs) and rare immunodeficiency-
related cancers were diagnosed in gay American men. These cases were the early
beginning of the AIDS epidemic in America. As human immunodeficiency virus (HIV)
was identified as the causative agent for these AIDS cases, the shift of HIV/AIDS
care quickly went from primary care clinicians, who were first identifying these unusual
presentations, to infectious disease (ID) specialists.
As HIV management has advanced to the point that patients living with HIV are living
relatively normal lifespans, the shift of care has begun to revert to primary care. HIV is
no longer the death sentence seen in the early AIDS crisis; it now represents an oppor-
tunity for primary care clinicians to care for patients living with HIV in the context of
their comprehensive health. Consequently, it is important that primary care clinicians
embrace their expanding role by familiarizing themselves with general HIV primary
care and using the expertise of ID colleagues when appropriate.

a
Northwestern McGaw Family Medicine Residency Program Humboldt Park, Lending Hands
for Life at Erie Family Health Centers, 2750 West North Avenue, Chicago, IL 60647, USA;
b
Northwestern McGaw Family Medicine Residency Program Humboldt Park, 2750 West North
Avenue, Chicago, IL 60647, USA
* Corresponding author.
E-mail address: swheat@eriefamilyhealth.org

Prim Care Clin Office Pract 48 (2021) 311–328

https://doi.org/10.1016/j.pop.2021.02.011 primarycare.theclinics.com
0095-4543/21/ª 2021 Elsevier Inc. All rights reserved.
312 Wheat & Wittke

Primary care clinicians have an opportunity to provide holistic, thoughtful care to

their patients living with HIV and those at risk of HIV infection. It is only through these
efforts that we will help put an end to the HIV epidemic.

US HUMAN IMMUNODEFICIENCY VIRUS EPIDEMIOLOGY

HIV is spread through contact with blood, semen, preseminal fluid, rectal fluids,
vaginal fluids, or breast milk of a person with HIV. In the United States, HIV is spread
mainly by having anal or vaginal sex or sharing injection drug equipment, such as nee-
dles, with a person who has HIV. According to an end-of-year 2018 analysis, the Cen-
ters for Disease Control and Prevention (CDC) estimates that approximately 1.2 million
people, older than 13 years of age, in the 50 US states and 6 territories are living with
HIV; in addition, an estimated 161,800 individuals live with undiagnosed HIV infection.1
In 2018, 37,968 people living in the United States and dependent areas received a new
HIV diagnosis. During 2018, the United States experienced 15,820 HIV-related deaths.
Given that new infections outweigh HIV deaths in the United States, the prevalence of
HIV is increasing. Consequently, it is imperative that the US medical workforce be
bolstered in order to care for this population and that more be done to prevent the
spread of HIV.
In the United States, there is marked disparity in subpopulations that acquire HIV.
Various social determinants of health interplay with the HIV epidemic. New diagnoses
of AIDS are highest in men who have sex with men (MSM) (Fig. 1). In addition, rates of
HIV diagnosis are highest in African American and Hispanic/Latino MSM (Fig. 2).
Young black MSM are disproportionately affected by HIV infection.
Given the prevalence of HIV in the MSM community, the lack of awareness of HIV
status is one of the greatest barriers to reducing new HIV infections overall, but also
in reducing racial and geographic disparities. To help address this, per CDC guide-
lines, MSM who are high risk for HIV acquisition should be screened at least annually.2

Fig. 1. AIDS classifications among adults and adolescents with diagnosed HIV infection, by
transmission category and year of classification, 1985 to 2017, United States and 6 depen-
dent areas. (From Centers for Disease Control and Prevention (CDC) National Center for
HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention. Epidemi-
ology of HIV Infection 2018 (preliminary). Available at https://www.cdc.gov/hiv/pdf/library/
slidesets/cdc-hiv-surveillance-epidemiology-2018.pdf. Accessed August 1, 2020.)
 HIV Care 313

Fig. 2. Diagnoses of HIV infection by MSM aged 13 years by race/ethnicity, 2010 to 2018—
United States. (From Centers for Disease Control and Prevention (CDC) National Center for
HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of HIV/AIDS Prevention. Estimated
HIV Incidence and Prevalence in the United States, 2010-2018. Available at https://www.cdc.
gov/hiv/pdf/library/slidesets/cdc-hiv-linley-HIV-Incidence-Prevalence-2010-2018.pdf. Ac-
cessed August 1, 2020.)

Transgender individuals represent another population at high risk of HIV infection. In

a 2015 study, transgender women are at highest risk of HIV infection compared with
gay, bisexual, and MSM.3 Transgender men who have sex with cisgender men also
demonstrated higher rates of HIV infection. Even though the CDC has recommended
yearly HIV screening for patients at higher risk of contracting HIV, transgender individ-
uals have lower rates of HIV testing compared with their cisgender counterparts. In
addition, there have not been formalized recommendations to include transgender
people in the annual HIV screening recommendation.
Transgender people face multiple barriers that hinder their ability to prevent and di-
agnose HIV infections early. Namely, transgender people are at higher risk of discrim-
ination and societal stigma, which oftentimes prevent them from accessing medical
services. Furthermore, some transgender people have risk factors, including commer-
cial sex work, intravenous (IV) drug use, mental health issues, homelessness, and
incarceration, to name a few. The situation is not helped when swathes of the
geographic medical coverage in the United States demonstrate limited to no
transgender-affirming medical providers and/or services.

HUMAN IMMUNODEFICIENCY VIRUS PREVENTION

Abstinence and condom use are the most known methods of HIV prevention. As dis-
cussed previously, HIV preexposure prophylaxis (PrEP) is currently available as 2 reg-
imens. The first regimen is a daily oral fixed-dose combination of tenofovir disoproxil
fumarate (TDF) 300 mg and emtricitabine (FTC) 200 mg, that has been shown to be
safe and effective in reducing the risk of sexual HIV acquisition in adults. The second
option is a daily oral fixed-dose combination of tenofovir alafenamide (TAF) 25 mg and
FTC 200 mg; this option is not currently indicated for persons assigned female at birth
because its efficacy has not been fully studied in this group, although efforts are
ongoing. In addition, PrEP is recommended as a prevention option in the case of sero-
discordant couples and, as such, should be discussed with patients living with HIV
and their partners, patients who have multiple sexual partners of uncertain HIV status
314 Wheat & Wittke

and share needles or other equipment to inject drugs.4 Alternative regimens of PrEP
are currently under investigation.
In addition to PrEP, 2 more medication-based prevention strategies exist. The first
option, known as postexposure prophylaxis (PEP), involves the administration of a 3-
drug regimen within 72 hours of possible HIV exposure. The patient should undergo
rapid HIV antigen/antibody testing and/or source, if known and amenable, testing at
time of presentation. If appropriate, the patient continues to take PEP for approxi-
mately 28 days. However, if source testing has been done and the source is HIV nega-
tive, it is acceptable to discontinue PEP if there is no concern for acute HIV infection in
the source. If the source is HIV positive, but virally suppressed, then the odds that the
exposed patient will contract HIV without PEP is low. Some exposed patients may
prefer to continue the 28-day regimen of PEP, even if a source has viral suppression.5
The final medication-related strategy for HIV prevention is known as treatment as
prevention (TasP). TasP effectively means that people living with HIV who take HIV
medicine as prescribed and get and keep an undetectable viral load (or stay virally
suppressed) have effectively no risk of transmitting HIV to their HIV-negative sexual
partners.6

HUMAN IMMUNODEFICIENCY VIRUS PRESENTATIONS

Identification of HIV can present a complicated diagnostic scenario for clinicians.

Acute HIV infection commonly manifests symptoms within 2 to 4 weeks of HIV expo-
sure. Symptoms are oftentimes described as “flulike” and can include fevers, chills,
rash, night sweats, muscle aches, sore throat, fatigue, swollen lymph nodes, diarrhea,
unintentional weight loss, headaches, and mouth ulcers. In the early acute phase of
HIV infection, the virus multiplies inside the body and is transmissible to others. It is
in this early stage of infection that third-generation serologic testing can produce
negative or indeterminate results for HIV, because antibodies may take 3 to 4 weeks
postinfection to be measured; this period is commonly referred to as “the window
period.” The now recommended fourth-generation HIV testing is more sensitive in
early acute HIV infection and can detect HIV within 2 weeks of infection.7
Following acute HIV infection, patients may enter a prolonged period of minimal to
no symptoms, which underlies the insidious nature of HIV. Patients often dismiss their
initial symptoms as related to a “cold or flu,” giving the virus time to multiply and dam-
age the immune system. However, some patients with chronic HIV infection may
develop unusual symptoms, including oral ulcers, oral candidiasis, unexplained
weight loss, recurrent fevers, chronic diarrhea, persistent night sweats, lymphadenop-
athy, chronic fatigue, or chronic or persistent herpes simplex or herpes zoster
infections.
As HIV progresses, it continues to use CD41 T cells to proliferate. Over time, HIV
causes the CD4 count to decrease, whereas the viral load climbs and/or develops
moderate persistent viremia. The timing and degree to which the HIV causes the
CD4 count to decrease are variable; however, once a patient develops a CD4 count
of less than 200 cells/mm3, they have developed significant immunodeficiency.

OPPORTUNISTIC INFECTIONS

Historically, OIs were the first clinical presentation of AIDS. Without treatment, OIs
typically present 7 to 10 years after infection with HIV. OIs have been defined as infec-
tions that are more severe or more frequent because of the immunosuppression
caused by untreated HIV. Before effective medical treatment, OIs were a poor prog-
nostic indicator, with patients only surviving 1 to 2 years after OI presentation.
 HIV Care 315

Fortunately, since the 1990s, treatment has improved and significantly decreased the
morbidity and mortality related to OIs. Although there are others, the hallmarks of OIs
include pneumocystis pneumonia (PCP), toxoplasma encephalitis, cytomegalovirus
retinitis, cryptococcal meningitis, tuberculosis, disseminated Mycobacterium avium
complex (MAC), pneumococcal respiratory disease, and certain cancers, such as
Kaposi sarcoma and central nervous system lymphoma.
Although there are now a variety of safe and effective antiretroviral regimens, the
CDC estimates indicate that more than 40% of Americans living with HIV are not virally
suppressed. In addition, although viral suppression eliminates most OIs, some, such
as tuberculosis, pneumococcal disease, and dermatomal zoster, continue to occur at
higher incidence in persons with HIV.8 When certain OIs, such as tuberculosis and
syphilis, occur, they increase HIV viral and therefore can accelerate HIV progression
and increase the risk of transmission. As such, clinicians must still be able to identify
and treat OIs, as they continue to contribute to preventable morbidity and mortality.
In addition, for some OIs, the provider must carefully consider timing of the initiation
of antiretroviral therapy (ART) and treatment of the OI, as there may be a possibility of
immune reconstitution inflammatory syndrome (IRIS). IRIS is an exaggerated inflam-
matory response that is either an unmasking of a previously undiagnosed OI or the
worsening of a previously treated OI upon introduction of ART. IRIS ranges from
mild disease to being life threatening.9
Some of the more common OIs are presented in Table 1. More extensive updated
OI guidelines are available as part of the Health and Human Services AIDS guidelines
and are regularly updated at https://aidsinfo.nih.gov/guidelines/.10

DIAGNOSIS/TESTING RECOMMENDATIONS

The US Preventive Services Task Force (USPSTF) provides a grade A recommenda-

tion that clinicians screen for HIV infection in adolescents and adults aged 15 to 65. In
addition, those at increased risk under the age of 15 and over the age of 65 should be
screened as well. Increased risk includes those with new partners, having sex without
a condom with a partner whose HIV status is unknown, transactional sex, presence of
another sexually transmitted infection (STI) or partner with an STI, and having a partner
who is living with HIV or at high risk for HIV.
There is no clear guidance on optimal timing for repeat screening. In addition, the
USPSTF provides a grade A recommendation for screening of all pregnant patients,
including those presenting in labor with an unknown HIV status.11
The testing algorithm for the diagnosis of HIV infection in adults and children greater
than 24 months of age was updated in 2014, with the advent of the fourth-generation
testing assay. This assay detects immunoglobulin M and immunoglobulin G (IgG) an-
tibodies along with the p24 antigen. When a specimen is reactive, it then reflexively
has supplemental testing distinguishing between HIV-1 and HIV-2. As such, when
reactive on this assay, it is both the screening and the confirmatory test. This testing
algorithm replaced the previous gold-standard algorithm of a positive antibody test
followed by a western blot test.
Testing algorithms are based on the detection windows of the different components
of the HIV virus. As demonstrated in Fig. 3, approximately 10 days after infection
acquisition, the HIV virus may be detectable by nucleic amplification test in the
plasma.12 The p24 antigen is intermittently detectable 4 to 10 days after infection.
IgG antibodies are detectable 18 to 38 days after the detection of the virus.
As Fig. 4 illustrates, the first step of testing begins with a combination immunoassay
that detects both HIV-1 and HIV-2 antibodies, as well as HIV-1 p24 antigen. When
 316
Wheat & Wittke
Table 1
Selected common opportunistic infections in acquired immunodeficiency syndrome

Clinical
OI Presentation Diagnosis Prevention Treatment Secondary Prophylaxis
Human Mostly Depends on cytologic and Chemoprophylaxis Chemotherapy, in combination Suppression of HIV
herpesvirus-8 asymptomatic immunologic cell markers, as not recommended with ART, should be replication to
(Kaposi nontender, well as histology. Clinical administered to patients prevent
sarcoma– hyperpigmented, diagnosis alone is not with visceral involvement recurrence
associated macular, or sufficient
herpesvirus) nodular skin
lesions
Mycobacterium Symptoms may Compatible clinical signs and Chemoprophylaxis At least 2 drugs as initial Restart secondary
avium complex include fever, symptoms coupled with the if CD4 <50 cells/ therapy to prevent or delay prophylaxis
night sweats, isolation of MAC from mm3 and not emergence of resistance when CD4 <
weight loss, cultures of blood, lymph virally Clarithromycin 500 mg po 100 cells/mm3
fatigue, diarrhea, node, bone marrow, or other suppressed twice daily plus ethambutol
and abdominal normally sterile tissue or on ART with 15 mg/kg po daily,
pain body fluids azithromycin or
Hepatomegaly, or clarithromycin Azithromycin 500–600 mg plus
splenomegaly, ethambutol 15 mg/kg po
or lymphade- daily when drug interactions
nopathy or intolerance precludes the
use of clarithromycin
Testing of susceptibility to
clarithromycin or
azithromycin is
recommended
Chronic therapy at least 12 mo
 Pneumocystis Subacute onset Histopathologic or CD4 counts < 21 d Secondary prophylaxis
pneumonia of progressive cytopathologic 200 cells/ TMP-SMX: (TMP 15–20 mg and should be started
dyspnea, fever, demonstration of organisms mm3 or CD4 < SMX 75–100 mg)/kg/d IV immediately after
nonproductive in tissue, bronchoalveolar 14% should given every 6 or 8 h, may treatment and
cough, and lavage fluid, or induced receive switch to po formulations discontinued when
chest discomfort sputum samples is required chemoprophylaxis after clinical improvement CD4 counts have
that worsens for a definitive diagnosis of against PCP increased from <
within days PCP Trimethoprim- 200 cells/
to week sulfamethoxazole mm3 to >
(TMP-SMX) 200 cells/
One double- mm3 for >3 mo
strength as a result of ART
TMP-SMX
tablet daily
is the preferred
regimen

From US DHHS-NIH/AIDS Info. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Available at https://
clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/whats-new-guidelines. Accessed August 20, 2020.

HIV Care
317
318 Wheat & Wittke

Fig. 3. Sequence of appearance of laboratory markers for HIV-1 infection. (From Centers for
Disease Control and Prevention (CDC). Laboratory Testing for the Diagnosis of HIV Infection:
Updated Recommendations. Available at http://stacks.cdc.gov/view/cdc/23447. Accessed
August 1, 2020.)

specimens are reactive on this assay, it then undergoes additional supplemental

testing with an immunoassay that differentiates HIV-1 from HIV-2 antibodies. Speci-
mens reactive on the initial immunoassay and nonreactive or indeterminate on the
antibody differentiation assay proceed to HIV-1 nucleic acid testing for resolution.13
The fourth-generation testing algorithm has several advantages over previous rec-
ommendations, including increased accuracy of acute HIV-1 infection and therefore

Fig. 4. Recommended laboratory HIV testing algorithm for serum or plasma specimens.
(From Centers for Disease Control and Prevention (CDC). 2018 Quick reference guide: Rec-
ommended laboratory HIV testing algorithm for serum or plasma specimens. Available at
https://stacks.cdc.gov/view/cdc/50872. Accessed August 1, 2020.)
 HIV Care 319

earlier diagnosis, increased accuracy of diagnosis of HIV-2 infection, equally accurate

diagnosis of established HIV-1 infection, and fewer indeterminate results. Fourth-
generation testing can be done with both serum and rapid testing options and is pos-
itive within 2 weeks of infection. The testing algorithm is updated at least every 5 years
because of anticipated improvement in laboratory testing.

ANTIRETROVIRAL THERAPY

Before the advent of expanded antiretroviral therapies, the treatment of patients with
HIV was largely centered on patient CD4 counts. However, there is a large body of ev-
idence that suggests that early initiation of ART is associated with decreased
morbidity and mortality. Barring significant barriers to patient medication adherence,
under current US Department of Health and Human Services guidelines, ART initiation
is indicated in all people living with HIV, regardless of CD4 count.13
In the current ART repertoire, there are several classes of medications that work to
combat HIV and are outlined in Table 2.14
Box 1 demonstrates the current recommended HIV ART regimens for most
patients.15
The regimens in Box 1 represent the currently recommended initial therapies for
most patients; however, various factors influence how patients receive their medica-
tions. For example, pill burden can be a hurdle to patient medication adherence and
should be discussed with patients regularly in order to optimize their care. Many med-
ications can represent high-cost burdens to patients; however, ART regimens can be
covered by various insurance plans and by federal, state, and local organizations to
cover medication cost.
In addition, medication side effects, drug-drug interactions, and regimen interac-
tions with patient comorbidities are important factors to consider while treating pa-
tients with HIV.

LABORATORY MONITORING

Like many conditions, HIV requires regular laboratory monitoring in order to assess
patient progress and control HIV. Table 3 demonstrates recommended laboratory
monitoring strategies.16
In general, the goals of ART include reducing HIV viral load to undetectable levels
and increasing CD4 count. Patient clinical responses may differ in terms of CD4 recov-
ery depending on various factors. However, as viral load reaches levels less than 200
copies/mL on standard testing, a patient has reached a key goal in their HIV treatment.
The viral load is the most important marker to follow, as it helps influence treatment
decisions, aids patients and clinicians in ART adherence counseling, and assists in
troubleshooting of general health maintenance.

PRIMARY CARE AND HUMAN IMMUNODEFICIENCY VIRUS

Although effective ART exists for persons living with HIV, there are 3 main reasons it
continues to be challenging to achieve and maintain durable viral suppression. First,
not all persons with HIV have received a diagnosis, and despite effective testing,
once diagnosed, many have already developed immunosuppression. Second, once
diagnosed, not all persons have linkage with continuous care. Last, even when linked
with care, barriers to adherence, pharmacokinetic barriers, and unknown biologic fac-
tors may impact the ability of viral suppression. Achieving viral suppression and
ensuring that a patient has an effective ART regimen through direct provision or
 320
Table 2
Human immunodeficiency virus antiretroviral therapies

Wheat & Wittke

Drug Class Generic Name (Other Names and Acronyms) Brand Name
Nucleoside reverse transcriptase inhibitors (NRTIs)
NRTIs block reverse transcriptase, an enzyme HIV needs to Abacavir (abacavir sulfate, ABC) Ziagen
make copies of itself Emtricitabine (FTC) Emtriva
Lamivudine (3TC) Epivir
Tenofovir disoproxil fumarate (tenofovir DF, TDF) Viread
Zidovudine (azidothymidine, AZT, ZDV) Retrovir
NNRTIs bind to and later alter reverse transcriptase, an Doravirine (DOR) Pifeltro
enzyme HIV needs to make copies of itself Efavirenz (EFV) Sustiva
Etravirine (ETR) Intelence
Nevirapine (extended-release nevirapine, NVP) Viramune
Viramune XR (extended release)
Rilpivirine (rilpivirine hydrochloride, RPV) Edurant
PIs block HIV protease, an enzyme HIV needs to make Atazanavir (atazanavir sulfate, ATV) Reyataz
copies of itself Darunavir (darunavir ethanolate, DRV) Prezista
Fosamprenavir (fosamprenavir calcium, FOS-APV, FPV) Lexiva
Ritonavir (RTV) Norvir
*Although ritonavir is a PI, it is generally used as a
pharmacokinetic enhancer as recommended in the
Guidelines for the Use of Antiretroviral Agents in Adults
and Adolescents with HIV and the Guidelines for the Use
of Antiretroviral Agents in Pediatric HIV Infection.
Saquinavir (saquinavir mesylate, SQV) Invirase
Tipranavir (TPV) Aptivus
Fusion inhibitors block HIV from entering the CD4 cells of Enfuvirtide (T-20) Fuzeon
the immune system
CCR5 antagonists block CCR5 coreceptors on the surface of Maraviroc (MVC) Selzentry
certain immune cells that HIV needs to enter the cells
Integrase inhibitors block HIV integrase, an enzyme HIV Dolutegravir (dolutegravir sodium, DTG) Tivicay
needs to make copies of itself Raltegravir (raltegravir potassium, RAL) Isentress
Isentress HD
Attachment inhibitors bind to the gp120 protein on the Fostemsavir (fostemsavir tromethamine, FTR) Rukobia
outer surface of HIV, preventing HIV from entering CD4
cells
Postattachment inhibitors block CD4 receptors on the
surface of certain immune cells that HIV needs to enter
the cells
Pharmacokinetic enhancers are used in HIV treatment to
increase the effectiveness of an HIV medicine included in
an HIV regimen
Combination HIV medicines contain 2 or more HIV
medicines from 1 or more drug classes
Ibalizumab-uiyk (Hu5A8, IBA, Ibalizumab, TMB-355, TNX- Trogarzo
355)
Cobicistat (COBI, c) Tybost
Abacavir and lamivudine (abacavir sulfate/lamivudine, Epzicom
ABC/3TC)
Abacavir, dolutegravir, and lamivudine (abacavir sulfate/ Triumeq
dolutegravir sodium/lamivudine, ABC/DTG/3TC)
Abacavir, lamivudine, and zidovudine (abacavir sulfate/ Trizivir
lamivudine/zidovudine, ABC/3TC/ZDV)
Atazanavir and cobicistat (atazanavir sulfate/cobicistat, Evotaz
ATV/COBI)
Bictegravir, emtricitabine, and tenofovir alafenamide Biktarvy
(bictegravir sodium/emtricitabine/tenofovir alafenamide
fumarate, BIC/FTC/TAF)
Darunavir and cobicistat (darunavir ethanolate/cobicistat, Prezcobix
DRV/COBI)
Darunavir, cobicistat, emtricitabine, and tenofovir Symtuza
alafenamide (darunavir ethanolate/cobicistat/
emtricitabine/tenofovir AF, darunavir ethanolate/
cobicistat/emtricitabine/tenofovir alafenamide,
darunavir/cobicistat/emtricitabine/tenofovir AF,
darunavir/cobicistat/emtricitabine/tenofovir
alafenamide fumarate, DRV/COBI/FTC/TAF)
Dolutegravir and lamivudine (dolutegravir sodium/ Dovato
lamivudine, DTG/3TC)
Dolutegravir and rilpivirine (dolutegravir sodium/ Juluca
rilpivirine hydrochloride, DTG/RPV)
Doravirine, lamivudine, and tenofovir disoproxil fumarate Delstrigo
(doravirine/lamivudine/TDF, doravirine/lamivudine/
HIV Care
tenofovir DF, DOR/3TC/TDF)
Efavirenz, emtricitabine, and tenofovir disoproxil fumarate Atripla
(efavirenz/emtricitabine/tenofovir DF, EFV/FTC/TDF)
(continued on next page)
321
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Table 2

Wheat & Wittke

(continued )
Drug Class Generic Name (Other Names and Acronyms) Brand Name
Efavirenz, lamivudine, and tenofovir disoproxil fumarate Symfi
(EFV/3TC/TDF)
Efavirenz, lamivudine, and tenofovir disoproxil fumarate Symfi Lo
(EFV/3TC/TDF)
Elvitegravir, cobicistat, emtricitabine, and tenofovir Genvoya
alafenamide (elvitegravir/cobicistat/emtricitabine/
tenofovir alafenamide fumarate, EVG/COBI/FTC/TAF)
Elvitegravir, cobicistat, emtricitabine, and tenofovir Stribild
disoproxil fumarate (QUAD, EVG/COBI/FTC/TDF)
Emtricitabine, rilpivirine, and tenofovir alafenamide Odefsey
(emtricitabine/rilpivirine/tenofovir AF, emtricitabine/
rilpivirine/tenofovir alafenamide fumarate,
emtricitabine/rilpivirine hydrochloride/tenofovir AF,
emtricitabine/rilpivirine hydrochloride/tenofovir
alafenamide, emtricitabine/rilpivirine hydrochloride/
tenofovir alafenamide fumarate, FTC/RPV/TAF)
Emtricitabine, rilpivirine, and tenofovir disoproxil Complera
fumarate (emtricitabine/rilpivirine hydrochloride/
tenofovir disoproxil fumarate, emtricitabine/rilpivirine/
tenofovir, FTC/RPV/TDF)
Emtricitabine and tenofovir alafenamide (emtricitabine/ Descovy
tenofovir AF, emtricitabine/tenofovir alafenamide
fumarate, FTC/TAF)
Emtricitabine and tenofovir disoproxil fumarate Truvada
(emtricitabine/tenofovir DF, FTC/TDF)
Lamivudine and tenofovir disoproxil fumarate (Temixys, Cimduo
3TC/TDF)
Lamivudine and zidovudine (3TC/ZDV) Combivir
Lopinavir and ritonavir (ritonavir-boosted lopinavir, LPV/r, Kaletra
LPV/RTV)

From US DHHS-NIH/AIDS Info. FDA-Approved HIV Medicines. Available at https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/58/fda-approved-hiv-

medicines. Accessed August 20, 2020.
 HIV Care 323

Box 1
Recommended antiretroviral regimens for initial therapy

Recommended initial regimens for most people with HIV

Recommended regimens are those with demonstrated durable virologic efficacy, favorable
tolerability and toxicity profiles, and ease of use.
INSTI plus 2 NRTIs:

BIC/TAF/FTC (AI)

DTG/ABC/3TC (AI)—if HLA-B*5701 negative

DTG plus (TAF or TDF)a plus (FTC or 3TC) (AI)

RAL plus (TAF or TDF)a plus (FTC or 3TC) (BI for TDF/[FTC or 3TC], BII for TAF/FTC)
INSTI plus 1 NRTI:

DTG/3TC (AI), except for individuals with HIV RNA greater than 500,000 copies/mL, HBV
coinfection, or in whom ART is to be started before the results of HIV genotypic
resistance testing for reverse transcriptase or HBV testing are available
Recommended initial regimens in certain clinical situations
These regimens are effective and tolerable but have some disadvantages when compared with
the regimens listed above or have less supporting data from randomized clinical trials.
However, in certain clinical situations, one of these regimens may be preferred.
INSTI plus 2 NRTIs:
Note: For individuals of childbearing potential, see perinatal recommendations before
prescribing one of these regimens.

EVG/c/(TAF or TDF)a/FTC (BI)
Boosted PI plus 2 NRTIs:

In general, boosted DRV is preferred over boosted ATV

(DRV/c or DRV/r) plus (TAF or TDF)a plus (FTC or 3TC) (AI)

(ATV/c or ATV/r) plus (TAF or TDF)a plus (FTC or 3TC) (BI)

(DRV/c or DRV/r) plus ABC/3TC—if HLA-B*5701 negative (BII)
NNRTI plus 2 NRTIs:

DOR/TDFa/3TC (BI) or DOR plus TAFa/FTC (BIII)

EFV plus (TAF or TDF)a plus (FTC or 3TC)
 EFV 600 mg plus TDF plus (FTC or 3TC) (BI)
 EFV 400 mg/TDF/3TC (BI)
 EFV 600 mg plus TAF/FTC (BII)

RPV/(TAF or TDF)/FTC (BI)—if HIV RNA less than 100,000 copies/mL and CD4 count greater
than 200 cells/mm3
Regimens to consider when ABC, TAF, and TDF cannot be used or are not optimal:

DTG/3TC (AI), except for individuals with HIV RNA greater than 500,000 copies/mL, HBV
coinfection, or in whom ART is to be started before the results of HIV genotypic resistance
testing for reverse transcriptase or HBV testing are available

DRV/r plus RAL twice a day (CI)—if HIV RNA less than 100,000 copies/mL and CD4 count
greater than 200 cells/mm3

DRV/r once daily plus 3TCa (CI)
a
TAF and TDF are 2 forms of TFV approved by FDA. TAF has fewer bone and kidney toxicities
than TDF, whereas TDF is associated with lower lipid levels. Safety, cost, and access are among
the factors to consider when choosing between these drugs.
Note: The following are available as coformulated drugs: ABC/3TC, ATV/c, BIC/TAF/FTC, DOR/
TDF/3TC, DRV/c, DRV/c/TAF/FTC, DTG/3TC, DTG/ABC/3TC, EFV (400 mg or 600 mg)/TDF/3TC,
EFV/TDF/FTC, EVG/c/TAF/FTC, EVG/c/TDF/FTC, RPV/TAF/FTC, RPV/TDF/FTC, TAF/FTC, TDF/3TC,
and TDF/FTC.
Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ARV, antiretroviral;
ATV, atazanavir; ATV/c, atazanavir/cobicistat; ATV/r, atazanavir/ritonavir; BIC, bictegravir; CD4,
CD4 T lymphocyte; DOR, doravirine; DRV, darunavir; DRV/c, darunavir/cobicistat; DRV/r, daruna-
vir/ritonavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; EVG/c, elvitegravir/cobicistat;
324 Wheat & Wittke

FDA, Food and Drug Administration; FTC, emtricitabine; INSTI, integrase strand transfer inhib-
itor; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcrip-
tase inhibitor; PI, protease inhibitor; RAL, raltegravir; RPV, rilpivirine; STR, single-tablet
regimen; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; TFV, tenofovir.

From US DHHS-NIH/AIDS Info. Guidelines for the Use of Antiretroviral Agents in Adults and
Adolesecents Living with HIV. Available at https://aidsinfo.nih.gov/guidelines/html/1/adult-
and-adolescent-arv/11/what-to-start. Accessed August 20, 2020.

linkage to care, is the most important aspect of preventive care. Once viral suppres-
sion has been achieved, many aspects of preventive care are the same as for those
not living with HIV.

Cervical Cancer Screening

The Pap test should be used for cervical cancer screening for those less than 30 years
of age. Screening should begin within 1 year of the onset of sexual activity, regardless
of mode of HIV transmission, but no later than age 21. For those aged 21 to 29, a Pap
test should be done at the time of initial diagnosis with HIV. Provided the initial Pap test
is normal, the next Pap test should be in 12 months. If 3 consecutive Pap tests are
normal, follow-up Pap tests should be every 3 years. After the age of 30, either Pap
testing only or Pap testing and HPV co-testing is acceptable for screening. Patients
who have both a negative HPV and a negative Pap test can have their next cervical
cancer screening in 3 years. If screening is abnormal, clinicians may follow the
same diagnostic guidelines for patients without HIV.17

Anal Cancer Screening

Clear guidelines do not exist for screening for anal cancer. A randomized controlled
trial is currently being conducted to determine if treatment of AIN2-AIN3 reduces
the incidence of anal cancer. It is expected that guidelines will be developed following
completion of this study. Currently, some experts recommend cytologic screening for
persons living with HIV only when high-resolution anoscopy is available. Abnormal
cytology should be followed by high-resolution anoscopy with the biopsy of abnormal
lesions to rule out invasive cancer.18

Reproductive Health
Clinicians should provide education and reproductive health counseling and pre-
scribe or refer for contraceptive services to patients who desire to prevent or delay
any future pregnancy. For patients desiring to prevent pregnancy, contraceptive
methods should be chosen with respect to the interaction of the ART. In the absence
of drug-drug interaction, most contraceptive methods are acceptable if reasonable
to the patient.19
Patients desiring pregnancy should be counseled on ART as a method to prevent
sexual and perinatal transmission and should be offered referral to someone skilled
in reproductive health for persons with HIV.20
Screening for STIs should primarily be conducted based on the sexual practices of
the patients and any partners they may have and therefore may be more frequent than
the following recommendations. In addition to age-based STI screening guidelines for
all persons, the following are HIV-specific recommendations. Female patients living
with HIV should have trichomonas screening upon diagnosis of HIV and annually
thereafter. All patients should have testing for gonorrhea, chlamydia, and syphilis
upon diagnosis and at least annually thereafter. All patients living with HIV should
 Table 3
Laboratory testing schedule for monitoring people with human immunodeficiency virus before and after initiation of antiretroviral therapy

Frequency of Testing
ART Initiation 2–8 w after ART
Laboratory Test Entry Into Care or Changes Initiation or Changes Every 3–6 mo Every 6 mo Every 12 mo Treatment Failure
HIV serology U
CD4 cell count U U U U U
HIV viral load U U U U U U
Resistance testing U U U
HLA-B*5701 testing U
Tropism testing U U
Hepatitis B serologies U U U
Hepatitis C serology U U
Basic chemistry U U U U
ALT, AST, total bilirubin U U U U
CBC with differential U U U U
Random or fasting lipid profile U U U
Random or fasting glucose U U U
Urinalysis U U U U
Pregnancy test U U

Adapted from US DHHS-NIH/AIDS Info. Laboratory Testing Schedule for Monitoring People with HIV Before and After Initiation of Antiretrovrial Therapy. Avail-
able at https://clinicalinfo.hiv.gov/en/table/table-3-laboratory-testing-schedule-monitoring-people-hiv-and-after-initiation-antiretroviral. Accessed August 20,
2020.

HIV Care
325
326 Wheat & Wittke

also receive screening for hepatitis B and hepatitis C on diagnosis. Patients living with
HIV, who are MSM, should have hepatitis C testing annually.21
Immunizations
Most immunizations for patients living with HIV are the same as those not living with
HIV. However, there are a few additions and a few contraindications. Live vaccina-
tions, such as MMR, Varicella, and live intranasal influenza, are not recommen-
ded/contraindicated for patients with CD4 counts less than 200 cells/mm.3 The
HPV vaccination 3-dose series may be given to those living with HIV, even if not
received during the recommended age interval. Menactra should be given to pa-
tients living with HIV as a 2-dose series at least 8 weeks apart, with revaccination
every 5 years. When diagnosed with HIV before the age of 65, patients require mul-
tiple doses of pneumococcal vaccines: 1 dose of PCV13 followed by 1 dose of
PPSV23 at least 8 weeks later, then another dose of PPSV23 at least 5 years after
previous PPSV23; at age 65 years or older, administer 1 dose of PPSV23 at least
5 years after most recent PPSV23. Currently, no clear recommendation exists for
zoster vaccination.22
Age-Based Screenings
Most cancer screenings, such as colon cancer, breast cancer, prostate cancer, and
lung cancer, except for those mentioned above, follow age and exposure guidelines
similarly to those not living with HIV. The risk of osteoporosis is greater in patients
living with HIV because of the virus and certain medications. As such, in addition
to postmenopausal women, male patients older than 50 may benefit from DEXA
scan.23
Comorbidities
As previously stated, effective ART has made the treatment of HIV/AIDS a chronic dis-
ease. As such, once virally suppressed, the PCP should focus on control of other
comorbidities. The PCP can follow standard guidelines for screening and treatment
of non-HIV-related diseases. However, certain medications have increased risk of
drug-drug interactions. Medication interactions are important for the PCP to consider
when recommending new medications. Medication interactions can be reviewed with
the use of the free interaction checker provided through the University of Liverpool
(https://www.hiv-druginteractions.org/). The PCP is well positioned to provide quality
HIV care of their patients living with HIV.

CLINICS CARE POINTS

People living with human immunodeficiency virus (HIV) who take HIV medicine as prescribed
and have a suppressed viral load have effectively no risk of transmitting HIV to their HIV-
negative sexual partners.

Fourth-generation HIV testing can be done with both serum and rapid testing options and is
positive within 2 weeks of infection.

Barring significant barriers to patients taking medication, antiretroviral therapy (ART)
initiation is indicated in all people living with HIV.

Achieving viral suppression and ensuring patients have an effective ART regimen through
provision or linkage to care is the most important aspect of preventive care.
 HIV Care 327

DISCLOSURE

The authors have nothing to disclose.

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