REVIEW

CURRENT
OPINION HIV treatment and prevention 2019: current
standards of care
Nittaya Phanuphak a and Roy M. Gulick b

Purpose of review
The purpose of this review is to summarize the current standards of care for both HIV treatment and HIV
prevention in 2019.
Recent findings
Current HIV treatment is started as soon as feasible in a person with HIV infection and consists of a three-
drug oral daily antiretroviral regimen, consisting of two nucleoside analogue reverse transcriptase inhibitors
combined with a third drug, either an integrase inhibitor, a non-nucleoside reverse transcriptase inhibitor,
or a protease inhibitor. Present treatment regimens are potent, convenient, generally well tolerated and
durable, and lead to a normal life expectancy. Present antiretroviral-based HIV prevention strategies focus
on treating people with HIV infection with antiretrovirals as soon as feasible to reduce their risk of
transmitting to others, and providing two-drug pre-exposure prophylaxis (PrEP) and three-drug post-exposure
prophylaxis (PEP) to those HIV-uninfected individuals who are at risk for HIV infection. PrEP is highly
effective when used correctly. Further data on early antiretroviral therapy and PrEP are needed to
demonstrate any impact on HIV epidemic control.
Summary
HIV treatment and HIV prevention have improved markedly in recent years due to the development of oral
antiretrovirals that are potent, convenient, and generally well tolerated, and lead to virologic suppression
and decreased HIV transmission.
Keywords
antiretroviral therapy, HIV prevention, HIV treatment, pre-exposure prophylaxis

HIV TREATMENT – CURRENT STANDARD WHEN TO START?

OF CARE
Introduction
The current standard of care is to treat people with
HIV infection with antiretroviral therapy (ART) as
soon as feasible, both to improve their own health
and to reduce their risk of HIV transmission to
others. Standard initial treatment today consists
of a three-drug oral daily regimen composed of
two nucleoside analogue reverse transcriptase inhib-
itors (NRTIs) in combination with a third drug,
either an integrase inhibitor, a non-nucleoside
reverse transcriptase inhibitor or a protease inhibi-
tor. Over 23 million people, at present, are taking
ART worldwide. Effective antiretroviral treatment of
HIV infection changes the natural history of the
infection, allowing an essentially normal life expec-
tancy for those who can take and are adherent to
therapy both in developed [1,2] and developing
countries [3].
On the basis of randomized clinical trials demon-
strating significant clinical benefits in the START [4]
and TEMPRANO studies [5] with an approximately
50% reduction in morbidity and mortality, present
global HIV treatment guidelines recommend start-
ing ART as soon as feasible in an individual with HIV
&& &&
infection [6 ,7,8 ,9]. Not only does antiretroviral
treatment benefit the person with HIV infection,
but it reduces the risk of sexual transmission to
a
Chief of PREVENTION, Thai Red Cross AIDS Research Centre,
Pathumwan, Bangkok, Thailand and bRochelle Belfer Professor of Medi-
cine, Division of Infectious Diseases, Weill Cornell Medicine, New York,
New York, USA
Correspondence to Roy M. Gulick, Rochelle Belfer Professor of Medi-
cine, Chief, Division of Infectious Diseases, Weill Cornell Medicine, Box
125, 1300 York Avenue, New York, NY, USA. Tel: +1 212 746 6320;
e-mail: rgulick@med.cornell.edu
Curr Opin HIV AIDS 2020, 15:4–12
DOI:10.1097/COH.0000000000000588

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KEY POINTS
 Present HIV treatment is started as soon as feasible and
consists of a three-drug oral daily
antiretroviral regimen.
 Effective HIV treatment controls viral replication,
enhances or maintains immune function, decreases
morbidity and mortality, and supports a normal
life expectancy.
 Present antiretroviral-based HIV prevention consists of
two-drug oral pre-exposure prophylaxis (PrEP) and
three-drug oral post-exposure prophylaxis (PEP) to
individuals at risk of HIV infection.
others by over 90% [10]. On the basis of randomized
clinical trials and pilot studies that demonstrated
improvements in viral suppression rates [11–13],
there is an increasing interest in starting ART the
same day that HIV is first diagnosed – the ‘test and
treat’ strategy.
WHAT TO START?
At present, there are 32 antiretroviral drugs
approved by the US Food and Drug Administration
(FDA) for the treatment of HIV infection (Table 1).
Antiretroviral drugs fall into seven mechanistic clas-
ses targeting individual steps in the life cycle of HIV
(Fig. 1):
(1) CD4 post-attachment entry inhibitors
(2) CCR5 receptor antagonists
(3) Fusion inhibitors
(4) NRTIs
(5) Non-nucleoside reverse transcriptase inhibitors
(NNRTI)
(6) Integrase strand transfer inhibitors (INSTIs)
(7) Protease inhibitors
The present standard of care for initial treatment
of HIV infection, based on clinical trials demonstrat-
ing clinical, virologic and immunologic benefits,
is a three-drug oral daily regimen consisting of
two NRTIs in combination with a third drug (either
&& && &&
an INSTI, NNRTI, or PI) [6 ,7,8 ,14 ]. One-pill,
once-daily, fixed-dose combination antiretroviral
regimens, first approved in 2006, are popular with
providers and patients, and include at least nine
present three-drug formulations (Table 2). On the
basis of viral potency, tolerability and convenience,
present guidelines recommend most commonly a
regimen of the two-NRTI combination of tenofovir
[either the older disoproxil fumarate (TDF)
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HIV treatment and prevention 2019 Phanuphak and Gulick
formulation or the newer alafenamide (TAF) formu-
lation], lamivudine or emtricitabine, and an inte-
grase inhibitor that does not require pharmacologic
boosting: bictegravir, dolutegravir or raltegravir
&& &&
[6 ,7,8 ].
The alternative NRTI combination of abacavir/
lamivudine is used less commonly and requires
screening for a genetic marker HLA-B5701 that is
associated with a hypersensitivity reaction that can
be life-threatening [15]; zidovudine/lamivudine is
used uncommonly today because of side effects and
toxicity. Alternative third drugs include the NNRTIs
doravirine, efavirenz and rilpivirine; the pharmaco-
logically boosted PIs atazanavir and darunavir; and
the pharmacologically enhanced ‘boosted’ INSTI
&& &&
elvitegravir [6 ,7,8 ]. In addition to initial oral
three-drug regimens, alternative strategies include
two-drug oral regimens of dolutegravir/lamivudine
&&
[16 ,17], and pharmacologically boosted darunavir
in combination with lamivudine, emtricitabine or
an integrase inhibitor (dolutegravir or raltegravir)
[18,19]. Recent clinical trials of present first-line
regimens demonstrate virologic suppression rates
of near 90% at 48 weeks [20,21]. In clinical practice,
current initial treatment regimens generally result
in virologic suppression rates of 80% or greater
throughout the world, both in developed and
developing countries.
SWITCHING ANTIRETROVIRAL THERAPY
REGIMENS: VIROLOGIC SUPPRESSION
Despite the success of initial antiretroviral regimens,
patients may need to change their regimens either in
the setting of virologic suppression (for convenience,
tolerability, drug–drug interactions, pregnancy, etc.)
or for virologic failure. With virologic suppression,
the fundamental principle when switching is to
maintain virologic suppression. Recommendations
are to review the antiretroviral history, including
prior drug-related toxicities and drug resistance test-
&&
ing results [6 ]. If there is no pre-existing drug resis-
tance, within-class or between-class changes usually
will maintain virologic suppression. The best studied
regimens in this clinical setting are the novel two-
drug oral co-formulated regimen of dolutegravir/ril-
&&
pivirine [22 ] and the two-drug combination of
a pharmacologically enhanced ‘boosted’ protease
inhibitor, either atazanavir or darunavir, with lam-
ivudine (or emtricitabine) [23–25]; both treatment
strategies showed non-inferiority compared to con-
tinuing standard three-drug regimens. Emerging
maintenance regimens include a boosted protease
inhibitor with an integrase inhibitor (e.g. boosted
&&
darunavir and dolutegravir) [26,27 ] or dolutegra-
vir/lamivudine [28,29,30 ].
&&
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Long acting art for treatment and prevention

Table 1. Currently approved antiretroviral drugs

Trade Year of US
Drug class Generic name Abbreviation(S) name FDA approval

Nucleoside analogue reverse zidovudine ZDV, AZT Retrovir 1987

transcriptase inhibitors (NRTIs)
didanosine ddI Videx 1991
a
zalcitabine ddC Hivid 1992
stavudine d4T Zerit 1994
lamivudine 3TC Epivir 1995
abacavir ABC Ziagen 1998
tenofovir disoproxil fumarate TDF Viread 2001
emtricitabine FTC Emtriva 2003
tenofovir alafenamide TAF Descovyb 2015
Non-nucleoside analogue reverse nevirapine NVP Viramune 1994
transcriptase inhibitors (NNRTIs)
delavirdine DLV Rescriptor 1997
efavirenz EFV Sustiva 1998
etravirine ETR Intelence 2008
rilpivirine RPV Edurant 2011
doravirine DOR Pifeltro 2018
Protease inhibitors (PIs) saquinavir SQV Invirase 1995
ritonavir RTV Norvir 1996
indinavir IDV Crixivan 1996
nelfinavir NFV Viracept 1997
amprenavir APV Agenerasea 1999
lopinavir/ritonavir LPV/r Kaletra 2000
atazanavir ATV Reyataz 2003
fosamprenavir FPV Lexiva 2003
tipranavir TPV Aptivus 2005
darunavir DRV Prezista 2006
Entry inhibitors (EIs)
Fusion inhibitor enfuvirtide ENF, T-20 Fuzeon 2003
CCR5 antagonist maraviroc MVC Selzentry 2007
CD4 post-attachment inhibitor ibalizumab IBA Trogarzo 2018
Integrase strand transfer inhibitors raltegravir RAL Isentress 2007
(INSTIs)
elvitegravir EVG Vitekta 2012
dolutegravir DTG Tivicay 2013
bictegravir BIC Biktarvyc 2018

a
Withdrawn from market.
b
Fixed-dose combination of TAF with emtricitabine.
c
Fixed-dose combination of TAF, emtricitabine and bictegravir.

VIROLOGIC FAILURE assessing adherence, tolerability, and the potential

Virologic failure may be defined as the repeated
detection of HIV RNA (typically >200 copies/ml)
&&
in a person on antiretroviral drugs [6 ]. The most
likely cause of virologic failure is suboptimal adher-
ence, although other factors, such as baseline or
acquired drug resistance, or drug–drug interactions,
may also play a role. In the setting of virologic failure,
the goal is to re-establish virologic suppression. This is
done by reviewing the antiretroviral history,
for drug–drug interactions, and then performing
resistance testing (genotype for first or second regi-
men failure, both genotype and phenotype for sub-
&&
sequent regimens failures) [6 ]. This information
should be reviewed, and susceptible drugs or drug
classes should be identified with the ultimate goal of
designing a new regimen with two (or preferably
three) fully active agents. Newer drugs with distinct
mechanisms of action (e.g. HIV entry inhibitors) or

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FIGURE 1. Life cycle of HIV and mechanistic antiretroviral classes.
investigational agents in newer drug classes (e.g. HIV
maturation inhibitors, HIV capsid inhibitors) should
provide full virologic activity, even in the presence of
drug resistance to conventional drug classes.
SIDE EFFECTS AND TOXICITY
Antiretroviral drugs, like all drugs, can be associated
with side effects and toxicities. As a class, the most
common side effect for antiretroviral drugs is likely
gastrointestinal (nausea, vomiting, diarrhea),
although this is less common with recommended
drugs available at present. The most serious toxicities
of antiretroviral drugs can be life-threatening, includ-
ing hypersensitivity reactions with a rash and
Table 2. One-pill, once-daily, three-drug oral HIV
treatment regimens (trade name; year of US FDA approval)
TDF/FTC/EFV (Atripla; 2006)
TDF/FTC/RPV (Complera; 2011)
TDF/FTC/EVG/cobicistat (Stribild; 2012)
ABC/3TC/DTG (Triumeq; 2014)
TAF/FTC/EVG/cobicistat (Genvoya; 2015)
TAF/FTC/RPV (Odefsey; 2016)
TAF/FTC/BIC (Biktarvy; 2018)
TAF/FTC/DRV/cobicistat (Symtuza; 2018)
TDF/3TC/DOR (Delstrigo; 2018)
3TC, lamivudine; ABC, abacavir; BIC, bictegravir; DOR, doravirine; DRV,
darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; FTC,
emtricitabine; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir
disoproxil fumarate.
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HIV treatment and prevention 2019 Phanuphak and Gulick
constitutional symptoms caused by abacavir or less
commonly with some NNRTIs including etravirine,
and drug-related hepatitis associated with NNRTIs and
protease inhibitors. Although teratogenicity was orig-
inally linked to the use of efavirenz (US FDA pregnancy
category D), more recent data do not suggest a link
[31], and the drug is recommended as an alternative
&&
choice in current perinatal guidelines [32 ].
With the present need for life-long ART, long-
term and chronic toxicities are of concern. Metabolic
and morphologic changes were common in the past,
but generally are not associated with current regi-
mens. The original formulation of tenofovir [diso-
proxil fumarate (TDF)] is associated with renal and
bone toxicity, although this is reduced with the
newer formulation, tenofovir alafenamide (TAF)
[33]. Efavirenz is associated with central nervous
system side effects, most commonly vivid dreams,
in up to 50% of people, and rarely, with increased
suicidality [34]. Increased cardiovascular events are
associated with some of the protease inhibitors [35].
Integrase inhibitors are generally well tolerated,
although there have been some links to central ner-
vous system side effects [36] and to weight gain [37].
ANTIRETROVIRAL-BASED HIV PREVENTION:
CURRENT STANDARD OF CARE
Introduction
Use of antiretroviral drugs for HIV prevention
started more than two decades ago with prevention
www.co-hivandaids.com 7
Long acting art for treatment and prevention
of mother-to-child transmission of HIV (PMTCT).
Since then, a large amount of data accumulated to
demonstrate the effect of antiretroviral drugs to
prevent HIV transmission by reducing HIV RNA in
people living with HIV to undetectable levels [treat-
ment as prevention (TasP)], and also their effects on
preventing HIV-uninfected persons from acquiring
HIV infection before exposure [pre-exposure pro-
phylaxis (PrEP)] or immediately after exposure
[post-exposure prophylaxis (PEP)].
Prevention of mother-to-child transmission
of HIV
Prevention of mother-to-child transmission com-
prises TasP given to HIV-infected pregnant women,
PrEP given via pregnant women to babies around
the time of delivery, and PEP given to babies after
exposure to risk during delivery. Current PMTCT
regimens use similar combinations of antiretroviral
drugs used for HIV treatment in adults precluding
the ones which do not have adequate safety data for
use in pregnancy. In May 2018, the Tsepamo study
in Botswana reported a neural tube defect rate of
0.9% among 426 women taking dolutegravir-based
regimens at conception, which was higher than
&&
0.1% seen with other regimens [38 ,39]. Expanded
surveillance with 1683 deliveries from mothers tak-
ing dolutegravir at conception identified a neural
tube defect rate of 0.3%, which, although lower than
the 2018 data, remained significantly higher than
women taking non-dolutegravir regimens at con-
& ners while plasma HIV RNA was detectable during
ception [40 ]. On the basis of these data, the WHO
now recommends that dolutegravir should be acces-
sible for women of childbearing potential, while
continued surveillance is needed [41].
Over the past decade, perinatally acquired HIV
infections in settings where overall transmission rates
are below 2% have mainly occurred from mothers
with limited or no antenatal care and antiretroviral
treatment [42]. Integrase inhibitors such as raltegra-
vir and dolutegravir, which have the ability to rapidly
reduce maternal plasma HIV RNA and cross the pla-
centa to act as PrEP in babies, are recommended as the
third drug or additional fourth drug in PMTCT regi-
mens for late-presenting pregnant women [43–45]. A
raltegravir-based regimen started after 20 weeks of
gestation led to faster HIV RNA reduction and a
greater proportion with viral suppression at delivery,
compared with efavirenz-based regimens [46]. Ralte-
gravir used to intensify PMTCT regimens in pregnant
women after 28 weeks of gestation also proved to be
well tolerated and feasible in a nation-wide PMTCT
programme in Thailand [43].
Once-daily nevirapine is recommended as PEP
for breastfed babies for 6 weeks. For formula-fed
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
babies, once-daily nevirapine or twice-daily zidovu-
dine is recommended from birth until 4–6 weeks of
age [9]. Breastfeeding is not recommended where
safe formula feeding is widely accessible as trans-
missions from mothers with suppressed HIV RNA
were reported [47,48].
Treatment as prevention
Data from the HPTN 052, PARTNER and Opposites
Attract studies confirmed that ART-induced viro-
logic suppression virtually eliminates sexual trans-
mission of HIV among HIV-serodiscordant couples:
HPTN 052 and PARTNER1 demonstrated no linked
sexual transmission within mainly heterosexual
couples when HIV-infected partners had undetect-
able plasma HIV RNA [10,49]. The PARTNER2 and
Opposites Attract studies subsequently revealed that
there was no linked sexual transmission among
male-to-male serodiscordant couples with almost
70 000 condomless sex acts when plasma HIV
& &
RNA levels were undetectable [50 ,51 ]. These study
data endorsed the ‘Undetectable equals Untransmit-
table’ (or ‘U¼U’) campaign which aimed to reduce
stigma related to infectiousness of people living
with HIV, and also to advocate for early access to
HIV testing and treatment [52]. All seroconversion
events in these studies occurred from outside sexual
partners, highlighting high potential of HIV acqui-
sition from concurrent partners in both heterosex-
ual and male-to-male stable relationships. A few
transmissions also occurred from seropositive part-
the very early phase of treatment or virologic failure
[10]. Therefore, other HIV prevention modalities are
needed to fill these transmission gaps not covered by
treatment as prevention.
Pre-exposure prophylaxis
Pre-exposure prophylaxis is generally recommended
to HIV-uninfected persons with substantial risks of
HIV infection such as being in a serodiscordant
relationship, using condoms inconsistently, having
bacterial sexually transmitted infections or sharing
injection equipment use. Most guidelines recom-
mend PrEP in serodiscordant relationship only if
the partner with HIV is not on effective therapy
&&
[8 ,53–55]. Some guidelines also recommend PrEP
for individuals with multiple sex partners [52], PEP
&&
users [53], methamphetamine users [56 ] or with
&&
sustained or ongoing risks [56 ].
Oral daily and event-driven PrEP using TDF-based
regimens demonstrated HIV preventive efficacy in
heterosexual men and women, men who have sex
with men (MSM) and people who inject drugs
(Table 3). HIV preventive efficacy of daily PrEP is very
Volume 15  Number 1  January 2020

Table 3. Studies of oral pre-exposure prophylaxis (PrEP)
Study
Study population(s) PrEP regimen
iPrEX [57] MSM Daily TDF/emtricitabine
Partners PrEP [58] Heterosexual men Daily TDF/emtricitabine
and women Daily TDF
TDF2 [59] Heterosexual men Daily TDF/emtricitabine
and women
Bangkok TDF [60] People who Daily TDF
inject drugs
PROUD [61] MSM Daily TDF/emtricitabine
IPERGAY [62,63] MSM Event-driven TDF/
emtricitabine
TDF, tenofovir disoproxil fumarate.
high but also highly correlated with the degree of
&&
adherence [56 ]. Six cases of HIV seroconversion,
despite high adherence to PrEP and adequate drug
levels, have been reported to date, pointing to the fact
that PrEP failure when used consistently is very rare,
&&
although not impossible [64 ].
Efficacy data of PrEP in transgender women are
limited, with no HIV acquisition seen when PrEP
was taken with adequate drug levels, but with too
small numbers of transgender women in studies
to demonstrate significant benefit [65,66]. Recent
pharmacokinetic data among Thai transgender
women on daily oral TDF/emtricitabine with daily
oral feminizing hormones showed reduced plasma
tenofovir levels by 12% with no changes in plasma
&&
estrogen and testosterone levels [67 ]. Another
study conducted in US transgender women on daily
TDF/emtricitabine and various feminizing hormone
regimens also revealed reduced level of rectal tissue
tenofovir diphosphate level with no effect on estro-
gen and testosterone plasma levels [68]. This
highlighted the need to purposefully enrol trans-
gender women in future HIV prevention studies.
With available data on PrEP efficacy and drug levels,
general recommendations for PrEP use for MSM may
not be applicable to transgender women.
Oral PrEP containing TDF/emtricitabine when
taken two tablets within 2–24 h before sex followed
by daily dosing until 2 days after the last sex act,
known as event-driven or on-demand PrEP, also
proved to be highly protective against HIV transmis-
sion among MSM regardless of sex frequency in the
IPERGAY (Intervention Préventive de l’Exposition
aux Risques avec et pour les hommes Gays) study
[62,63]. The AmPrEP (Amsterdam PrEP) study in
Amsterdam and Prevenir study in Paris demon-
strated no HIV seroconversions among event-driven
PrEP users who used it correctly [69,70]. Europen
AIDS Clinical Society and British HIV Association
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HIV treatment and prevention 2019 Phanuphak and Gulick
Overall efficacy in Efficacy in participants with
reducing HIV acquisition detectable plasma tenofovir levels
44% 92%
75% 90%
67% 86%
63% 78%
49% 74%
86% Not applicable
86% Not applicable
recommend event-driven PrEP since 2018 for MSM
&&
[8 ,54] and WHO updated its recommendation on
oral PrEP to include event-driven PrEP for MSM in
&&
July 2019 [71 ].
The DISCOVER study recently showed the
non-inferiority of TAF/emtricitabine to TDF/emtri-
citabine in reducing HIV infection in MSM and
transgender women [72]. Although transgender
women made up only 1.4% of study participants,
the US FDA’s Advisory Committee voted in favour of
TAF/emtricitabine efficacy for PrEP in MSM and
transgender women, but not cis-gender women,
in August 2019 [73].
Rapid and targeted PrEP roll-outs have
demonstrated impact on HIV epidemic control
&&
[74 ,75,76]. PrEP demedicalization through key
population-led [77], nurse-led [78,79], pharmacist-
led [80] or even self-led [81] models have high
potential to enhance uptake among individuals
who will benefit most from PrEP, but are often
marginalized due to discrimination and criminali-
zation towards same-sex relationship, sex work and/
or substance use.
Post-exposure prophylaxis
Initiation of PEP is recommended as soon as possible
after exposure, but can be offered up to 72 h. Major
guidelines currently recommend three-drug oral
PEP regimens with TDF/emtricitabine (or lamivu-
dine), and dolutegravir or raltegravir, whereas
boosted darunavir and boosted lopinavir are recom-
&& &&
mended as alternative third drugs [8 ,14 ,82,83].
Use of rilpivirine as the third drug in PEP regimens is
recommended by a few country guidelines, includ-
ing Thailand and Australia [45,84]. These drugs
are recommended based on considerations of toler-
ability and completion rates, and also cost and
availability.
www.co-hivandaids.com 9
Long acting art for treatment and prevention
CONCLUSION
Present antiretroviral treatment of HIV infection
controls viral replication, enhances and maintains
immunologic function, and decreases clinical mor-
bidity and mortality, providing a normal life expec-
tancy to people living with HIV who take their
therapy. In addition, suppression of viral replication
dramatically reduces the risk of HIV transmission to
others. The current standard of care is a three-drug
daily oral antiretroviral regimen with two NRTIs and
a third drug – these regimens are potent, convenient
and generally well tolerated. Current antiretroviral-
based HIV prevention employs PrEP with two-drug
or PEP with three-drug oral regimens. These strate-
gies are highly effective when used correctly. The
impact on HIV epidemic control has been demon-
strated when these HIV treatment and prevention
strategies are scaled up.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
Phanuphak and Gulick: none.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
& of special interest
&& of outstanding interest
1. Samji H, Cescon A, Hogg RS, et al. Closing the gap: increases in life
expectancy among treated HIV-positive individuals in the United States
and Canada. PLoS One 2013; 8:e81355.
2. Lohse N, Obel N. Update of survival for persons with HIV infection in Denmark.
Ann Intern Med 2016; 165:749–750.
3. Johnson LF, Mossong J, Dorrington RE, et al. Life expectancies of South
African adults starting antiretroviral treatment: collaborative analysis of cohort
studies. PLoS Med 2013; 10:e1001418.
4. INSIGHT START Study Group. Lundgren JD, Babiker AG, Gordin F, et al.
Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J
Med 2015; 373:795–807.
5. TEMPRANO ANRS 12136 Study Group. Danel C, Moh R, Gabillard D, et al.
A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J
Med 2015; 373:808–822.
6. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for
&& the use of antiretroviral agents in HIV-1 infected adults and adolescents.
Department of Health and Human Services (7/10/19). https://aidsinfo.nih.-
gov/guidelines/html/1/adult-and-adolescent-arv/0. [Accessed 19 July 2019]
Current US antiretroviral treatment guidelines that are comprehensive and
up-to-date.
7. Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral drugs for treatment and
prevention of HIV infection in adults: 2018 recommendations of the Interna-
tional Antiviral Society-USA Panel. JAMA 2018; 320:379–396.
8. European AIDS Clinical Society (EACS). European Guidelines for treatment
&& of HIV-positive adults in Europe; 2018, version 9.1. http://www.eacsocie-
ty.org/files/2018_guidelines-9.1-english.pdf. [Accessed 19 July 2019]
Current European antiretroviral guidelines that are user-friendly and up-to-date.
9. World Health Organization. Consolidated Guidelines on the use of antire-
troviral drugs for treatment and preventing HIV infection, 2nd ed.; 2016.
https://www.who.int/hiv/pub/arv/arv-2016/en/ [Accessed 19 July 2019]
10 www.co-hivandaids.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
10. Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the
prevention of HIV-1 transmission. N Engl J Med 2016; 375:830–839.
11. Rosen S, Maskew M, Fox MP, et al. Initiating antiretroviral therapy for HIV at a
patient’s first clinic visit: the RapIT randomized controlled trial. PLoS Med
2016; 13:e1002015.
12. Koenig SP, Dorvil N, Devieux JG, et al. Same-day HIV testing with initiation of
antiretroviral therapy versus standard care for persons living with HIV: a
randomized unblinded trial. PLoS Med 2017; 14:e1002357.
13. Pilcher CD, Ospina-Norvell C, Dasgupta A, et al. The effect of same-day
observed initiation of antiretroviral therapy on HIV viral load and treatment
outcomes in a US public health setting. J Acquir Immune Defic Syndr 2017;
74:44–51.
14. World Health Organization. Updated recommendations on first-line and
&& second-line antiretroviral regimens and postexposure prophylaxis and recom-
mendations on early infant diagnosis of HIV – Interim Guidance; 2018.
https://www.who.int/hiv/pub/guidelines/ARV2018update/en/. [Accessed
19 July 2019]
Current WHO antiretroviral guidelines for low and middle-income countries.
15. Mallal S, Phillips E, Carosi G, et al. HLA-B5701 screening for hypersensitivity
to abacavir. N Engl J Med 2008; 358:568–579.
16. Cahn P, Madero JS, Arribas JR, et al. Dolutegravir plus lamivudine versus
&& dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretro-
viral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48
results from two multicentre, double-blind, randomised, noninferiority, phase 3
trials. Lancet 2019; 393:143–155.
Large randomized study of two-drug vs. three-drug ART for initial treatment of HIV
infection.
17. Cahn P, Sierra Madero J, Arribas J, et al. Durable efficacy of dolutegravir
(DTG) plus lamivudine (3TC) in antiretroviral treatment-naive adults with HIV-1
infection: 96-week results from the GEMINI studies. 10th IAS Conference
on HIV Science (IAS 2019), 21–24 July 2019, Mexico City [abstract
#WEAB0404LB].
18. Figueroa MI, Sued OG, Gun AM, et al. DRV/R/3TC for HIV-1 treatment naı̈ve
patients: week 48 results of the ANDES study. Conference on Retroviruses
and Opportunistic Infections (CROI), 4–7 March 2018, Boston, Massachu-
setts [abstract #489].
19. Raffi F, Babiker AG, Richert L, et al. Ritonavir-boosted darunavir combined
with raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults infected
with HIV-1: 96 week results from the NEAT001/ANRS143 randomised
noninferiority trial. Lancet 2014; 384:1942–1951.
20. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and
tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial
treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre,
phase 3, randomised controlled noninferiority trial. Lancet 2017; 390:
2063–2072.
21. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine,
and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir
alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a
randomised, double-blind, multicentre, phase 3, noninferiority trial. Lancet
2017; 390:2073–2082.
22. Aboud M, Orkin C, Podzamczer D, et al. Efficacy and safety of dolutegravir-
&& rilpivirine for maintenance of virological suppression in adults with HIV-1: 100-
week data from the randomised, open-label, phase 3 SWORD-1 and
SWORD-2 studies. Lancet HIV 2019 (e-published 12 July).
Two-year data for two-drug antiretroviral maintenance regimen.
23. Perez-Molina JA, Rubio R, Rivero A, et al. Simplification to dual therapy
(atazanavir/ritonavir þ lamivudine) versus standard triple therapy [atazana-
vir/ritonavir þ two nucleos(t)ides] in virologically stable patients on antire-
troviral therapy: 96 week results from an open-label, noninferiority, randomized
clinical trial (SALT study). J Antimicrob Chemother 2017; 72:246–253.
24. Fabbiani M, Gagliardini R, Ciccarelli N, et al. Atazanavir/ritonavir with lami-
vudine as maintenance therapy in virologically suppressed HIV-infected
patients: 96 week outcomes of a randomized trial. J Antimicrob Chemother
2018; 73:1955–1964.
25. Pulido F, Ribera E, Lagarde M, et al. Dual therapy with darunavir and ritonavir
plus lamivudine vs triple therapy with darunavir and ritonavir plus tenofovir
disoproxil fumarate and emtricitabine or abacavir and lamivudine for main-
tenance of human immunodeficiency virus type 1 viral suppression: rando-
mized, open-label, noninferiority DUAL-GESIDA 8014-RIS-EST45 trial. Clin
Infect Dis 2017; 65:2112–2118.
26. Capetti AF, De Socio GV, Cossu MV, et al. Durability of dolutegravir plus
boosted darunavir as salvage or simplification of salvage regimens in HIV-1
infected, highly treatment-experienced subjects. HIV Clin Trials 2018;
19:242–248.
27. Spinner C, K€ ummerle T, Schneider J, et al. A switch to dolutegravir in
&& combination with boosted darunavir is safe and effective in suppressed
patients with HIV: a subanalysis of the Dualis study. 10th IAS Conference
on HIV Science (IAS 2019), 21–24 July 2019, Mexico 15 City [abstract
#MOPEB269].
First randomized study of novel two-drug maintenance regimen.
28. Taiwo BO, Marconi VC, Berzins B, et al. Dolutegravir Plus lamivudine
maintains human immunodeficiency virus-1 suppression through week 48
in a pilot randomized trial. Clin Infect Dis 2018; 66:1794–1797.
Volume 15  Number 1  January 2020

29. Joly V, Burdet C, Landman R, et al. Dolutegravir and lamivudine maintenance
therapy in HIV-1 virologically suppressed patients: results of the ANRS 167
trial (LAMIDOL). J Antimicrob Chemother 2019; 74:739–745.
30. van Wyk J, Ajana F, Bisshop F, et al. Switching to DTGþ3TC fixed dose
&& combination (FDC) is noninferior to continuing a TAF-based regimen (TBR) in
maintaining virologic suppression through 24 weeks (TANGO Study). 10th
IAS Conference on HIV Science (IAS 2019), 21–24 July 2019, Mexico City
[abstract #WEAB0403LB].
Randomized study of two-drug vs. three-drug maintenance antiretroviral regimens.
31. Ford N, Mofenson L, Shubber Z, et al. Safety of efavirenz in the first trimester of
pregnancy: an updated systematic review and meta-analysis. AIDS 2014;
28(Suppl 2):S123–131.
32. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of
&& Perinatal Trnasmission. Recommendations for use of antiretroviral drugs in
pregnant HIV-1-infected women for maternal health an interventions to reduce
perinatal HIV transmission in the United States; 7 December; 2018. https://
aidsinfo.nih.gov/guidelines/html/3/perinatal/0. [Accessed 19 July 19]
Current US perinatal antiretroviral guidelines.
33. Wang H, Lu X, Yang X, Xu N. The efficacy and safety of tenofovir alafenamide
versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1
therapy: meta-analysis. Medicine 2016; 95:e5146.
34. Mollan KR, Smurzynski M, Eron JJ, et al. Association between efavirenz as initial
therapy for HIV-1 infection and increased risk for suicidal ideation or attempted
or completed suicide: an analysis of trial data. Ann Intern Med 2014; 161:1–10.
35. Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of
contemporary protease inhibitors: the D:A:D international prospective multi-
cohort study. Lancet HIV 2018; 5:e291–e300.
36. Hoffmann C, Llibre JM. Neuropsychiatric adverse events with dolutegravir and
other integrase strand transfer inhibitors. AIDS Rev 2019; 21:4–10.
37. Bourgi K, Rebeiro PF, Turner M, et al. Greater weight gain in treatment naı̈ve
persons starting dolutegravir-based antiretroviral therapy. Clin Infect Dis
2019; doi: 10.1093/cid/ciz407 [Epub ahead of print]
38. Zash R, Makhema J, Shapiro RL. Neural-tube defects with dolutegravir
&& treatment from the time of conception. N Engl J Med 2018; 379:979–981.
First study of dolutegravir-associated neural tube defects in large study from
Botswana.
39. World Health Organization. Potential safety issue affecting women living with
HIV using dolutegravir at the time of conception. http://www.who.int/medi-
cines/publications/drugalerts/Statement_on_DTG_18May_2018final.pd-
f?ua=1. [Accessed 29 July 2019]
40. Zash R, Holmes L, Diseko M, et al. Neural-tube defects and antiretroviral
& treatment regimens in Botswana. N Engl J Med 2019 (Epub 22 July 19).
A follow-up study from Botswana showing lower neural tube defects than 2018
data which remained higher than in women taking non-dolutegravir regimens.
41. World Health Organization. Policy Brief: Update of recommendations on first-
line and second-line antiretroviral regimens; July 2019. https://apps.who.int/
iris/bitstream/handle/10665/325892/WHO-CDS-HIV-19.15-en-
g.pdf?ua=1. [Accessed 29 July 2019]
42. Taylor AW, Nesheim SR, Zhang X, et al. Estimated perinatal HIV infection
among infants born in the United States. JAMA Pediatr 2017; 171:435–442.
43. Puthanakit T, Thepnarong N, Chaithongwongwatthana S, et al. Intensification
of antiretroviral treatment with raltegravir for pregnant women living with HIV at
high risk of vertical transmission. J Virus Erad 2018; 4:61–65.
44. British HIV Association. British HIV Association guidelines for the manage-
ment of HIV in pregnancy and postpartum 2018 (2019 interim update).
https://www.bhiva.org/file/5bfd30be95deb/BHIVA-guidelines-for-the-man-
agement-of-HIV-in-pregnancy.pdf. [Accessed 29 July 2019]
45. Department of Disease Control, Thailand Ministry of Public Health.
Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017.
http://www.thaiaidssociety.org/images/PDF/hiv_thai_guideline_2560.pdf.
[Accessed 29 July 2019]
46. Mirochnick M, Shapiro DE, Morrison L, et al. Randomized trial of raltegravir-
ART vs efavirenz-ART when initiated during pregnancy. Conference of Retro-
viruses and Opportunistic Infections, 4–7 March 2019, Seattle, Washington
[abstract number 39].
47. Shapiro RL, Hughes MD, Ogwu A, et al. Antiretroviral regimens in pregnancy
and breast-feeding in Botswana. N Engl J Med 2010; 362:2282–2294.
48. Palombi L, Pirillo MF, Andreotti M, et al. Antiretroviral prophylaxis for breast-
feeding transmission in Malawi: drug concentrations, virological efficacy and
safety. Antivir Ther 2012; 17:1511–1519.
49. Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and
risk of HIV transmission in serodifferent couples when the HIV-positive partner
is using suppressive antiretroviral therapy. JAMA 2016; 316:171–181.
50. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through
& condomless sex in serodifferent gay couples with the HIV-positive partner
taking suppressive antiretroviral therapy (PARTNER): final results of a multi-
centre, prospective, observational study. Lancet 2019; 393:2428–2438.
A landmark study to confirm the treatment as prevention concept among male-male
serodiscordant couples.
51. Bavinton BR, Pinto AN, Phanuphak N, et al. Viral suppression and HIV
& transmission in serodiscordant male couples: an international, prospective,
observational, cohort study. Lancet HIV 2018; 5:e438–e447.
Another landmark study to confirm the treatment as prevention concept among
male-male serodiscordant couples.
1746-630X Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
HIV treatment and prevention 2019 Phanuphak and Gulick
52. UNAIDS. Undetectable ¼ Untransmittable: Public health and HIV viral load
suppression, UNAIDS Explainer. https://www.unaids.org/sites/default/files/
media_asset/undetectable-untransmittable_en.pdf. [Accessed 29 July 2019]
53. World Health Organization. WHO implementation tool for preexposure
prophylaxis (PrEP) of HIV infeciton, Module 1 Clinical; July 2017. https://
apps.who.int/iris/bitstream/handle/10665/255889/WHO-HIV-2017.17-eng.
pdf?sequence=1. [Accessed 29 July 2019]
54. British HIV Association. BHIVA/BASHH guidelines on the use of HIV pre-
exposure prophylaxis (PrEP); 2018. https://www.bhiva.org/PrEP-guidelines.
[Accessed 29 July 2019]
55. Ministry of Health, New South Wales. Pre-Exposure Prophylaxis of HIV with
Antiretroviral Medications; April 2016. https://www1.health.nsw.gov.au/pds/
ActivePDSDocuments/GL2016_011.pdf. [Accessed 29 July 2019]
56. Riddell JT, Amico KR, Mayer KH, et al. HIV pre-exposure prophylaxis: a review.
&& JAMA 2018; 319:1261–1268.
This is a concise review on PrEP efficacy, implementation challenges and sexually
transmitted and drug resistance concerns related to PrEP.
57. Molina JM, Capitant C, Spire B, et al. On-demand pre-exposure prophylaxis in
men at high risk for HIV-1 infection. N Engl J Med 2015; 373:2237–2246.
58. Molina JM, Charreau I, Spire B, et al. Efficacy, safety, and effect on sexual
behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex
with men: an observational cohort study. Lancet HIV 2017; 4:e402–e410.
59. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for
HIV prevention in men who have sex with men. N Engl J Med 2010;
363:2587–2599.
60. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV
prevention in heterosexual men and women. N Engl J Med 2012; 367:
399–410.
61. Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure
prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med
2012; 367:423–434.
62. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for
HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok
Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3
trial. Lancet 2013; 381:2083–2090.
63. McCormack S, Dunn DT, Desai M, et al. Preexposure prophylaxis to prevent the
acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot
phase of a pragmatic open-label randomised trial. Lancet 2016; 387:53–60.
64. Cohen SE, Sachdev D, Lee SA, et al. Acquisition of tenofovir-susceptible,
&& emtricitabine-resistant HIV despite high adherence to daily preexposure
prophylaxis: a case report. Lancet HIV 2018. http://dx.doi.org/10.1016/
S2352-3018(18)30288-1.
This study summarized PrEP breakthrough cases despite high adherence with
details on time of acquisition, resistance patterns and likely causes of PrEP failure.
65. Grant RM, Anderson PL, McMahan V, et al. Uptake of preexposure prophy-
laxis, sexual practices, and HIV incidence in men and transgender women who
have sex with men: a cohort study. Lancet Infect Dis 2014; 14:820–829.
66. Deutsch MB, Glidden DV, Sevelius J, et al. HIV pre-exposure prophylaxis in
transgender women: a subgroup analysis of the iPrEx trial. Lancet HIV 2015;
2:e512–e519.
67. Hiransuthikul A, Janamnuaysook R, Himmad K, et al. Drug-drug interactions
&& between feminizing hormone therapy and preexposure prophylaxis among
transgender women: the iFACT study. J Int AIDS Soc 2019; 22:e25338.
This is the first study with strong pharmacokinetic study design to demonstrate
potential interactions between PrEP and feminizing hormones used by HIV-unin-
fected transgender women.
68. Shieh E, Marzinke M, Fuchs E, et al. Transgender women on estrogen have
significantly lower tenofovir/emtricitabine concentrations during directly ob-
served dosing when compared to cis men. HIV Research for Prevention
conference (HIVR4P), 21–25 October 2018, Madrid [abstract number
OA23.03].
69. Hoornenborg E, Coyer L, Achterbergh RCA, et al. Sexual behaviour and
incidence of HIV and sexually transmitted infections among men who have sex
with men using daily and event-driven preexposure prophylaxis in AMPrEP:
2 year results from a demonstration study. Lancet HIV 2019; 6:e447–e455.
70. Molina JM, Ghosn J, Algarte-Genin M, et al. Incidence of HIV-infection with
daily or on-demand PrEP with TDF/FTC in Paris area. Update from the ANRS
Prevenir Study. 10th IAS Conference on HIV Science, 21–24 July, 2019,
Mexico City [abstract number TUAC0202].
71. World Health Organization. What’s the 2þ1þ1? Event-driven oral preexpo-
&& sure prophylaxis to prevent HIV for men who have sex with men: update to
WHO’s recommendation on oral PrEP; July 2019. https://apps.who.int/iris/
bitstream/handle/10665/325955/WHO-CDS-HIV-19.8-eng.pdf?ua=1. [Ac-
cessed 29 July 2019]
This WHO recommendation provides good update on the efficacy and safety of
event-driven PrEP in MSM, along with useful implementing algorithms.
72. Hare CB, Coll J, Ruane P, et al. The phase 3 DISCOVER Study: daily F/TAF or
F/TDF for HIV preexposure prophylaxis. Conference of Retroviruses and
Opportunistic Infections, 4–7 March 2019, Seattle, Washington [abstract
number 104].
73. Maddipatla M. FDA panel backs Gilead’s HIV prevention drug Descovy,
except in women. https://www.reuters.com/article/us-gilead-sciences-fda/
fda-panel-backs-gileads-hiv-prevention-drug-descovy-except-in-women-
idUSKCN1UX2DD. [Accessed 11 August 2019]
www.co-hivandaids.com 11
Long acting art for treatment and prevention
74. Grulich AE, Guy R, Amin J, et al. Population-level effectiveness of rapid,
&& targeted, high-coverage roll-out of HIV preexposure prophylaxis in men who
have sex with men: the EPIC-NSW prospective cohort study. Lancet HIV
2018; 5:e629–e637.
Landmark study which demonstrated clearly that PrEP roll-out needs to reach high
coverage rapidly among targeted population in order to achieve an impact on the
reduction of new HIV infections at a population level.
75. Public Health England. Progress towards ending the HIV epidemic in the
United Kingdom: 2018 report. http://assets.publishing.service.gov.uk/gov-
ernment/uploads/system/uploads/attachment_data/file/759408/HIV_an-
nual_report_2018.pdf. [Accessed 29 July 2019]
76. San Francisco Department of Public Health. HIV Epidemiology Annual Report
2017. San Francisco, CA: San Francisco Department of Public Health; 2017.
https://www.sfdph.org/dph/files/reports/RptsHIVAIDS/AnnualReport2017-
Green-20180904-Web.pdf. [Accessed 29 July 2019]
77. Phanuphak N, Sungsing T, Jantarapakde J, et al. Princess PrEP program:
the first key population-led model to deliver pre-exposure prophylaxis
to key populations by key populations in Thailand. Sex Health 2018;
15:542–555.
78. Schmidt HA, McIver R, Houghton R, et al. Nurse-led preexposure prophylaxis:
a nontraditional model to provide HIV prevention in a resource-constrained,
pragmatic clinical trial. Sex Health 2018; 15:595–597.
12 www.co-hivandaids.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
79. Girometti N, McCormack S, Devitt E, et al. Evolution of a pre-exposure
prophylaxis (PrEP) service in a community-located sexual health clinic: con-
cise report of the PrEPxpress. Sex Health 2018; 15:598–600.
80. Tung EL, Thomas A, Eichner A, Shalit P. Implementation of a community
pharmacy-based pre-exposure prophylaxis service: a novel model for pre-
exposure prophylaxis care. Sex Health 2018; 15:556–561.
81. Sullivan PS, Siegler AJ. Getting pre-exposure prophylaxis (PrEP) to the
people: opportunities, challenges and emerging models of PrEP implementa-
tion. Sex Health 2018; 15:522–527.
82. British Association of Sexual Health and HIV. UK guideline for the use of HIV
postexposure prophylaxis following sexual exposure (PEPSE); 2015. https://
www.bhiva.org/PEPSE-guidelines. [Accessed 29 July 2019]
83. Centers for Disease Control and Prevention, U.S. Department of Health and
Human Services. Updated Guidelines for Antiretroviral Postexposure Pro-
phylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure
to HIV, United States; 2016. https://www.cdc.gov/hiv/pdf/programre-
sources/cdc-hiv-npep-guidelines.pdf. [Accessed 29 July 2019]
84. Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine.
Postexposure prophylaxis after nonoccupational and occupational exposure
to HIV, Australasian National Guidelines (Second Edition). http://www.pep.-
guidelines.org.au/index.php/prescribing-pep/recommended-pep-regimens.
[Accessed 29 July 2019]
Volume 15  Number 1  January 2020