HIV Treatment and Prevention 2019: Current Standards of Care
HIV Treatment and Prevention 2019: Current Standards of Care
HIV Treatment and Prevention 2019: Current Standards of Care
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
improvements in viral suppression rates [11–13], [16 ,17], and pharmacologically boosted darunavir
there is an increasing interest in starting ART the in combination with lamivudine, emtricitabine or
same day that HIV is first diagnosed – the ‘test and an integrase inhibitor (dolutegravir or raltegravir)
treat’ strategy. [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,
WHAT TO START? current initial treatment regimens generally result
At present, there are 32 antiretroviral drugs in virologic suppression rates of 80% or greater
approved by the US Food and Drug Administration throughout the world, both in developed and
(FDA) for the treatment of HIV infection (Table 1). developing countries.
Antiretroviral drugs fall into seven mechanistic clas-
ses targeting individual steps in the life cycle of HIV
(Fig. 1): SWITCHING ANTIRETROVIRAL THERAPY
REGIMENS: VIROLOGIC SUPPRESSION
(1) CD4 post-attachment entry inhibitors Despite the success of initial antiretroviral regimens,
(2) CCR5 receptor antagonists patients may need to change their regimens either in
(3) Fusion inhibitors the setting of virologic suppression (for convenience,
(4) NRTIs tolerability, drug–drug interactions, pregnancy, etc.)
(5) Non-nucleoside reverse transcriptase inhibitors or for virologic failure. With virologic suppression,
(NNRTI) the fundamental principle when switching is to
(6) Integrase strand transfer inhibitors (INSTIs) maintain virologic suppression. Recommendations
(7) Protease inhibitors 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-
The present standard of care for initial treatment tance, within-class or between-class changes usually
of HIV infection, based on clinical trials demonstrat- will maintain virologic suppression. The best studied
ing clinical, virologic and immunologic benefits, regimens in this clinical setting are the novel two-
is a three-drug oral daily regimen consisting of drug oral co-formulated regimen of dolutegravir/ril-
two NRTIs in combination with a third drug (either &&
pivirine [22 ] and the two-drug combination of
&& && &&
an INSTI, NNRTI, or PI) [6 ,7,8 ,14 ]. One-pill, a pharmacologically enhanced ‘boosted’ protease
once-daily, fixed-dose combination antiretroviral inhibitor, either atazanavir or darunavir, with lam-
regimens, first approved in 2006, are popular with ivudine (or emtricitabine) [23–25]; both treatment
providers and patients, and include at least nine strategies showed non-inferiority compared to con-
present three-drug formulations (Table 2). On the tinuing standard three-drug regimens. Emerging
basis of viral potency, tolerability and convenience, maintenance regimens include a boosted protease
present guidelines recommend most commonly a inhibitor with an integrase inhibitor (e.g. boosted
regimen of the two-NRTI combination of tenofovir &&
darunavir and dolutegravir) [26,27 ] or dolutegra-
[either the older disoproxil fumarate (TDF) vir/lamivudine [28,29,30 ].
&&
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Trade Year of US
Drug class Generic name Abbreviation(S) name FDA approval
a
Withdrawn from market.
b
Fixed-dose combination of TAF with emtricitabine.
c
Fixed-dose combination of TAF, emtricitabine and bictegravir.
investigational agents in newer drug classes (e.g. HIV constitutional symptoms caused by abacavir or less
maturation inhibitors, HIV capsid inhibitors) should commonly with some NNRTIs including etravirine,
provide full virologic activity, even in the presence of and drug-related hepatitis associated with NNRTIs and
drug resistance to conventional drug classes. 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
SIDE EFFECTS AND TOXICITY [31], and the drug is recommended as an alternative
&&
Antiretroviral drugs, like all drugs, can be associated choice in current perinatal guidelines [32 ].
with side effects and toxicities. As a class, the most With the present need for life-long ART, long-
common side effect for antiretroviral drugs is likely term and chronic toxicities are of concern. Metabolic
gastrointestinal (nausea, vomiting, diarrhea), and morphologic changes were common in the past,
although this is less common with recommended but generally are not associated with current regi-
drugs available at present. The most serious toxicities mens. The original formulation of tenofovir [diso-
of antiretroviral drugs can be life-threatening, includ- proxil fumarate (TDF)] is associated with renal and
ing hypersensitivity reactions with a rash and bone toxicity, although this is reduced with the
newer formulation, tenofovir alafenamide (TAF)
Table 2. One-pill, once-daily, three-drug oral HIV [33]. Efavirenz is associated with central nervous
treatment regimens (trade name; year of US FDA approval) system side effects, most commonly vivid dreams,
TDF/FTC/EFV (Atripla; 2006)
in up to 50% of people, and rarely, with increased
suicidality [34]. Increased cardiovascular events are
TDF/FTC/RPV (Complera; 2011)
associated with some of the protease inhibitors [35].
TDF/FTC/EVG/cobicistat (Stribild; 2012)
Integrase inhibitors are generally well tolerated,
ABC/3TC/DTG (Triumeq; 2014)
although there have been some links to central ner-
TAF/FTC/EVG/cobicistat (Genvoya; 2015) vous system side effects [36] and to weight gain [37].
TAF/FTC/RPV (Odefsey; 2016)
TAF/FTC/BIC (Biktarvy; 2018)
TAF/FTC/DRV/cobicistat (Symtuza; 2018) ANTIRETROVIRAL-BASED HIV PREVENTION:
TDF/3TC/DOR (Delstrigo; 2018) CURRENT STANDARD OF CARE
3TC, lamivudine; ABC, abacavir; BIC, bictegravir; DOR, doravirine; DRV, Introduction
darunavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; FTC,
emtricitabine; RPV, rilpivirine; TAF, tenofovir alafenamide; TDF, tenofovir
Use of antiretroviral drugs for HIV prevention
disoproxil fumarate. started more than two decades ago with prevention
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high but also highly correlated with the degree of recommend event-driven PrEP since 2018 for MSM
&& &&
adherence [56 ]. Six cases of HIV seroconversion, [8 ,54] and WHO updated its recommendation on
despite high adherence to PrEP and adequate drug oral PrEP to include event-driven PrEP for MSM in
&&
levels, have been reported to date, pointing to the fact July 2019 [71 ].
that PrEP failure when used consistently is very rare, The DISCOVER study recently showed the
&&
although not impossible [64 ]. non-inferiority of TAF/emtricitabine to TDF/emtri-
Efficacy data of PrEP in transgender women are citabine in reducing HIV infection in MSM and
limited, with no HIV acquisition seen when PrEP transgender women [72]. Although transgender
was taken with adequate drug levels, but with too women made up only 1.4% of study participants,
small numbers of transgender women in studies the US FDA’s Advisory Committee voted in favour of
to demonstrate significant benefit [65,66]. Recent TAF/emtricitabine efficacy for PrEP in MSM and
pharmacokinetic data among Thai transgender transgender women, but not cis-gender women,
women on daily oral TDF/emtricitabine with daily in August 2019 [73].
oral feminizing hormones showed reduced plasma Rapid and targeted PrEP roll-outs have
tenofovir levels by 12% with no changes in plasma demonstrated impact on HIV epidemic control
&& &&
estrogen and testosterone levels [67 ]. Another [74 ,75,76]. PrEP demedicalization through key
study conducted in US transgender women on daily population-led [77], nurse-led [78,79], pharmacist-
TDF/emtricitabine and various feminizing hormone led [80] or even self-led [81] models have high
regimens also revealed reduced level of rectal tissue potential to enhance uptake among individuals
tenofovir diphosphate level with no effect on estro- who will benefit most from PrEP, but are often
gen and testosterone plasma levels [68]. This marginalized due to discrimination and criminali-
highlighted the need to purposefully enrol trans- zation towards same-sex relationship, sex work and/
gender women in future HIV prevention studies. or substance use.
With available data on PrEP efficacy and drug levels,
general recommendations for PrEP use for MSM may
not be applicable to transgender women. Post-exposure prophylaxis
Oral PrEP containing TDF/emtricitabine when Initiation of PEP is recommended as soon as possible
taken two tablets within 2–24 h before sex followed after exposure, but can be offered up to 72 h. Major
by daily dosing until 2 days after the last sex act, guidelines currently recommend three-drug oral
known as event-driven or on-demand PrEP, also PEP regimens with TDF/emtricitabine (or lamivu-
proved to be highly protective against HIV transmis- dine), and dolutegravir or raltegravir, whereas
sion among MSM regardless of sex frequency in the boosted darunavir and boosted lopinavir are recom-
&& &&
IPERGAY (Intervention Préventive de l’Exposition mended as alternative third drugs [8 ,14 ,82,83].
aux Risques avec et pour les hommes Gays) study Use of rilpivirine as the third drug in PEP regimens is
[62,63]. The AmPrEP (Amsterdam PrEP) study in recommended by a few country guidelines, includ-
Amsterdam and Prevenir study in Paris demon- ing Thailand and Australia [45,84]. These drugs
strated no HIV seroconversions among event-driven are recommended based on considerations of toler-
PrEP users who used it correctly [69,70]. Europen ability and completion rates, and also cost and
AIDS Clinical Society and British HIV Association availability.
1746-630X Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-hivandaids.com 9
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