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Introduction
Currently, no high-e cacy vaccine against HIV exists; therefore,
a range of other preventive measures, behavioral and biological,
are the subjects of intense scrutiny.
Among prevention options, the use of antiretroviral (ARV)
therapy has attracted considerable attention. ARV therapy is
the mainstay of management for patients with established HIV
infection. ese drugs, by blocking critical steps in viral replication,
prevent immune destruction and opportunistic infections. e
same medications have now been considered for additional roles
in preventing the transmission of the virus to people following
(predominantly) sexual exposures.
Antibiotics and antiparasitic agents have long been used as
part of preventative disease control, for example, in tuberculosis
and malaria. Infection with HIV poses special problems, however,
and even a er 25 years since the discovery of the virus we have
little understanding of the initial events in its natural history.
Development and e cacy testing of large number of potential
microbicides and other preventive strategies, such as ARV pre- and
post-exposure prophylaxis, have been hampered by the lack of
simple animal models. Until recently, the only surrogate animal
models used to study intravaginal or rectal HIV transmission
were macaques infected with simian immunode ciency virus
(SIV) or SIV/HIV (SHIV) chimeric viruses, an expensive
option. However, in the last few years, researchers have developed
“humanized bone marrow-liver-thymus” mice that are susceptible
to HIV infection; these models will be referred to later.
In this chapter, we review the uses of ARV for prevention,
in the approximate chronological order that they have been
investigated:
Post-exposure prophylaxis following occupational exposure
to HIV (PEP)
Post-exposure prophylaxis following nonoccupational (sexu-
al) exposure to HIV (nPEP)
Pre-exposure prophylaxis for women with topical microbi-
cides containing ARV
Pre-exposure prophylaxis of HIV with oral ARV (PrEP)
E ective treatment of infected persons to reduce HIV trans-
mission to their partners
Reduction of the HIV epidemic by widespread use of e ec-
tive ARV in infected individuals (Test and Treat strategy)
HIV Post-Exposure Prophylaxis
Post-exposure prophylaxis (PEP) is the use of ARV drugs to
prevent HIV infection a er high-risk exposure to HIV. Despite
the widespread use of PEP in developed countries, the level of
medical evidence for PEP remains relatively low. is section
gives a general overview of the underlying principles surrounding
PEP usage; practitioners should be familiar with national and
local guidelines when prescribing PEP.
e rationale for PEP comes from a combination of animal
models and retrospective case–control studies in health care
workers and studies on mother-to-child HIV transmission. In
the US, a nationwide, prospective, placebo-controlled trial of
prophylaxis with zidovudine (AZT) a er percutaneous exposure
to HIV among health care workers had to be discontinued when
only 84 subjects had enrolled a er 1 year, since thousands would
be needed to assess reduction of a 0.3% risk of transmission.1
erefore, there is no randomized clinical trial evidence attesting
to the e ectiveness or not of PEP.
Tenofovir given within 24 hours to macaques inoculated with
simian immunode ciency virus prevented infection in all animals
but the failure rate reached 50% when given later. is animal
model supports recommendations that PEP should be given
as soon as possible and not later than 72 hours a er exposure,
preferably within 24 hours.2 Animal models further support a
28-day course of treatment.2–4 ese early animal studies were
imperfect because the HIV challenge was intravenous inoculation.
Evidence that PEP can prevent transmission of HIV in humans
has been limited to a single case-control study of needle-stick injury
(not sexual transmission) conducted by Cardo and colleagues.5 Fr om
reports to national surveillance systems in the US, Italy, France, and
the United Kingdom, 33 cases of HIV acquisition from 712 needle-
stick exposures were retrospectively identi ed. is study showed that
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persons who received AZT were 81% less likely to be infected with
HIV than non-treated controls [95% CI, 48–94%].5 e probability
of HIV infection increased when blood was visible on the device,
or a needle used in an artery or vein, a er deep injuries, and the
use of a large bore hollow needle. An AIDS-de ning illness within
the source was an additional risk of infection, probably re ecting
the high viral load in advanced stages of HIV infection.5 On the
basis of this study, the Centers for Disease Control and Prevention
(CDC) published guidelines in 1998 for PEP a er occupational
exposure; although, recommendations for non-occupational exposure
(nPEP) were not published until 2005, due to paucity of evidence.
An important factor o en overlooked when transposing the Cardo
study to non-occupational settings was that the majority of health
care workers received PEP within 4 hours of their exposure.
Evidence that the prescription of ARV drugs may prevent
human-to-human HIV transmission also came from studies
investigating mother-to-child transmission. A number of studies
proved that AZT when given to mothers during pregnancy
and newborns for six weeks a er birth reduces the risk of HIV
transmission by 67%. is reduction is further improved if
lamivudine (3TC) is used in addition to AZT. Furthermore, even
if mothers were not treated but AZT was given to newborns, the
risk of HIV transmission was 9% compared with 27% when no
treatment was given (see other chapters).
From these studies, there is a crude estimate of approximately
70% reduction in HIV transmission risk by using a single ARV
drug, a suggestion of a further 90–95% risk reduction if two
drugs are used, and an estimate of the time frame (within 24
hours but still some e ect out to 72 hours) within which any
protective bene t might be achieved.
Nonetheless, it should be noted that PEP failures have been
reported a er occupational and sexual exposure even when PEP
was initiated within the recommended time frame.6,7
However, there are still a number of critical areas where
evidence is lacking:
Duration: PEP courses shorter than 28 days have not been
studied.
Number of drugs used: Studies to date have looked at only one
or two drug therapies. ere is no evidence of any additional
protection by using three-drug combinations.
Choice of drugs: To date, only AZT, 3TC, tenofovir, and
nevirapine have been studied. Nevirapine is no longer
recommended because of the risk of allergic reactions and
hepatotoxicity. e use of reverse transcription inhibitors has
theoretical appeal as they inhibit the generation of pro-viral
DNA. On the other hand, protease inhibitors, which are active
only a er viral integration has occurred, do not prevent cellular
infection and would be considered illogical choices for PEP.
PEP FOR OCCUPATIONAL EXPOSURE
Accidental injuries with HIV-contaminated sharps in health
care workers pose signi cant risk for HIV transmission; thus
all cases should be taken seriously and treated as an emergency.
Usually the HIV status of source is known thus additional
information about source viral load, current ARV treatment,
and history of drug resistance may assist in determining an
optimal PEP regimen. While high HIV RNA plasma viral load
increases risk of infection it should be noted that undetectable
viral load does not eliminate risk of infection.8 ere are many
factors which may in uence HIV transmission including di erent
phenotypes and strain virulence. Every health care facility should
have established procedures for needlestick injury reporting and
emergency response. e PEP initiation starter packs should be
available to ensure that PEP, if indicated, is commenced without
delays. Baseline HIV, Hepatitis B, and C serology should be
obtained and appropriate follow-up arranged at week 4–6, month
3, and month 6.
PEP AND COMMUNITY ‘‘STREET’
NEEDLE-STICK INJURY
ere are considerable media and community fears regarding
risk of HIV infection a er accidental percutaneus injury with
injecting equipment discarded in public places, e.g., streets, parks,
beaches, or children’s playgrounds. Despite common beliefs, the
risk of HIV infection from this type of exposure is very low. HIV
survival in discarded needles depends on temperature, humidity,
viral load, and other factors. ere have been no published
reports about HIV acquired through “street” needlestick injuries.
Estimation of risk of transmission is based on HIV prevalence in
intravenous drug use (IDU) which varies among communities.
For instance, in Australia, prevalence of HIV among IDU is
low (1% = 0.01) and PEP is not prescribed for community
needle-stick injury (risk = 1/300 × 0.01 = 1/30,000). It should
be noted that Hepatitis C and B are more prevalent and easier
to transmit through community needle-stick injuries than HIV.
Patients should be given Hepatitis B and tetanus immunization
if not immune.
PEP FOR NON-OCCUPATIONAL EXPOSURE (nPEP)
Unprotected vaginal and/or anal intercourse is the main reason
for prescribing nPEP in non-occupational settings. Contrary to
occupational settings, the HIV status of the source (partner)
serostatus is o en unknown, nor the exact time of exposure.
erefore, in clinical practice, it is necessary to estimate the risk
of HIV transmission. Various epidemiological studies give an
estimate of transmission risk associated with certain activities
(Table 71.1).
Where nPEP guidelines have been produced, most recommend
using nPEP for high-risk exposures (usually greater than 0.0001,
or 0.000067 [otherwise expressed as 1/10,000 or 1/15,000]).
To estimate the risk, the following need to be determined:
Route of exposure (vaginal/anal/oral, insertive/receptive)
Knowledge of risk carried by route of exposure (Table 71.1)
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Risk of a source being HIV positive (calculated as prevalence
of HIV in social group to which a source belongs (e.g., het-
erosexual, men who have sex with men [MSM], sex worker,
or IDU). Practitioners should be familiar with local serop-
revalence data. Country-speci c data for general population
and some sub-groups is also available through the UNAIDS/
WHO Global HIV/AIDS online database at www.who.int/
globalatlas/pgrms/HIV.
e presence of genital ulcerations or other sexually transmit-
ted diseases which increase risk of HIV transmission
Risk of HIV Transmission = Risk carried by route of exposure x
risk of source being HIV+
Example 1: Heterosexual male presents for nPEP following
unprotected vaginal intercourse with a female sex worker while
on holiday in Bali (Indonesia)
Risk = 0.0001 (or 1/1000) (risk of the single exposure via
insertive vaginal intercourse) X 0.01 9 or 1/10) (10% prevalence
of HIV in female sex workers in Indonesia) = 0.000001 (or
1/10, 000); whether nPEP is recommended would be equivocal
in this instance.
Example 2: Patient is a gay male who had unprotected receptive
anal intercourse with a casual male partner in Sydney, Australia
Risk = 0.008 (or 1/120) X 0.01 (or 1/10) (10% prevalence of
HIV in gay males in Sydney) = 0.0008 (or 1/1200); therefore,
nPEP would be unequivocally recommended
e following general guidelines should be considered when
prescribing PEP, or nPEP:
e usual duration of treatment is 28 days
PEP is usually indicated within 72 hours of exposure
Commonly used two-drug regimens include
AZT + lamivudine (Combivir): Some patients ex-
perience gastrointestinal (GI) side effects, thus often
antiemetic, e.g., metoclopramide, is added.
— Advantages: Lower cost.
— Disadvantages: Twice a day, GI side e ects are common.
Tenofovir + emtricitabine (Truvada)
— Advantages: Once a day, less side e ects.
— Disadvantages: Higher cost
Some guidelines recommend a 3-drug regimen, when a pro-
tease inhibitor is added, e.g., lopinavir/ritonavir (Kaletra).
e rationale is that a 3-drug regimen more e cacious than
a 2-drug regimen for controlling HIV replication in chroni-
cally HIV infected patients, especially when the prevalence
of drug resistance in the source patient population is high.13
Despite this, there is no evidence that a 3-drug regimen is su-
perior to a 2-drug regimen
Avoid abacavir (potential life-threatening hypersensitivity)
and nevirapine (fulminant liver failure requiring liver trans-
plant has been recorded in a US health care worker).14
e patient should be informed that ARV drugs are not li-
censed for PEP use and do not guarantee 100% protection
Baseline HIV screening test at PEP presentation and follow-
up visits at month 1, 3, and 6 should be arranged to detect
those already infected with HIV or those who are serocon-
verting. nPEP recipients should be further screened for other
sexually transmitted infections (STIs), including syphilis,
Hepatitis B and C.
ARV drugs used for PEP/nPEP have signi cant toxicities. e
most common are GI symptoms (nausea, vomiting), which
result in almost half of PEP recipients prematurely terminating
treatment due to unacceptable side e ects.
nPEP should only be considered as one of the several methods
of HIV prevention. From a public health perspective nPEP has
been shown to have a limited contribution to the numbers of
new HIV infections averted. An Australian retrospective study
of 1552 nPEP recipients estimated that the number of new HIV
infections prevented ranged between 0.9 and 9.2.15 In the same
six-year period there were 1,138 new infections reported in the
geographical area covered by the study. A French study with
8958 individuals showed similar estimations (7.7 new infections
prevented over a 4-year period).16
Several studies have found that nPEP is cost-e ective when
prescribed in high-risk settings (unprotected receptive anal
intercourse with source being HIV+) as well as occupational
exposures.16–18 However, these studies assumed that provision
of nPEP prevented lifetime costs associated with HIV infection.
Such an assumption is true only if there are no ongoing exposure
risks. Unfortunately, it has been shown that receipt of nPEP
among the MSM population in Sydney was associated with a
three-fold increased risk of subsequent HIV seroconversion due
to continuing risk behaviors.19
Table 71.1: Exposure and Transmission Risk Per Single
Exposure
Type of exposure with
known HIV+ source
Estimated risk of HIV
transmission per single
exposure(9–12)
Receptive anal intercourse 1/120 (0.008)
Receptive vaginal intercourse 1/1000† (0.001)
Insertive anal or vaginal intercourse 1/1000† (0.001)
Receptive fellatio with/without ejaculation Not measurable‡
Insertive fellatio Not measurable‡
Cunnilingus Not measurable‡
Sharing/use contaminated injecting
equipment
1/150 (0.0067)
Occupational needle stick injury 1/333 (0.003)
Community needlestick injury Not measurable‡
Bites, etc. Not measurable‡
Other trauma Not measurable‡
Non-occupational exposure of intact
mucous membrane§ and skin
Not measurable‡
*These estimates are based on prospective studies, not cross-sectional data or
fi gures derived from modeling.
†This estimate has been rounded down from 1/909 to 1/1,000.
‡Although there have been case reports of transmission, the risk associated with the
exposure is so low that it is not measurable.
§Conjunctiva, oral, or nasal mucosa.
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ere are some controversies around enhanced safe-sex
messages, counseling, and health promotion to minimize risk
of seroconversion when a patient presents for nPEP. In addition,
there is uncertainty of how ARV therapy use within the source
should a ect the risk assessment. In HIV+ patients who are
on therapy, those with an undetectable plasma viral load range
from 75% in the U.S. to 95% in Australia.20,21 Plasma viral load
is certainly one of the strongest correlates of HIV transmission
among serodiscordant couples. People with an undetectable
plasma viral load have usually an undetectable viral load in
semen.22,23 eoretically, if the source is known to be on ARV
therapy (ART) with an undetectable viral load, then their risk
of transmission would be negligible and nPEP would not be
warranted. However, this situation has not been addressed with
nPEP guidelines.
Keynotes:
Inform patients that evidence that PEP prevents HIV infec-
tion is limited;
Calculate risk of HIV transmission before prescribing PEP;
Prescribe PEP for high-risk exposures (usually greater than
0.000067 [or1/15,000]);
ere is no evidence that a two- or three-drug regimen is bet-
ter than one drug; and
ARV drugs with the best evidence are: AZT and tenofovir.
PEP Guidelines (Online)
WHO: www.who.int/hiv/pub/guidelines/PEP/en/
UK: www.dh.gov.uk/en/Publicationsandstatistics/Publications/
PublicationsPolicyAndGuidance/DH_088185
USA: www.cdc.gov/mmwr/preview/mmwrhtml/rr5409a1.htm
Australia: www.ashm.org.au/default2.asp?active_page_id=251
Pre-exposure Prophylaxis for Women with
Topical Microbicides Containing ARV
HIV prevention strategies that women can use and control remain
a pressing priority. Microbicides are products that can be applied
to the vagina (or rectum) with the intention of reducing the
acquisition of STIs, including HIV. ey are reviewed elsewhere
in this volume (see Microbicides for prevention of sexually
transmitted infections, by GP Talwar and Kavita B Garg).
However, three “ rst-generation” microbicides have already failed
e cacy trials, and two-cellulose sulfate and nonoxynol-9 actually
increased women’s risk of infection.
Nevertheless, Abdool Karim at the Centre for the AIDS
Program of Research in South Africa (CAPRISA), Durban, and
her colleagues tested a 1% vaginal gel formulation of the ARV
drug tenofovir between 2007 and 2009.24
e CAPRISA 004 trial assessed e ectiveness and safety of a
1% vaginal gel formulation of tenofovir, a nucleotide transverse
transcriptase inhibitor, for the prevention of HIV acquisition
in women. A double-blind, randomized controlled trial was
conducted comparing tenofovir gel (n = 445) with placebo gel
(n = 444) in sexually active, HIV uninfected 18- to 40-year-old
women in urban and rural KwaZulu-Natal, South Africa. HIV
serostatus, safety, sexual behavior, gel, and condom use were
assessed at monthly follow-up visits for 30 months. HIV incidence
in the tenofovir gel arm was 5.6 per 100 women-years, i.e., person
time of study observation, (38/680.6 women-years) compared
with 9.1 per 100 women-years (60/660.7 women years) in the
placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high
adherers (gel adherence > 80%), HIV incidence was 54% lower (P
= 0.025) in the tenofovir gel arm. In intermediate adherers (gel
adherence 50 to 80%) and low adherers (gel adherence < 50%)
the HIV incidence reduction was 38% and 28%, respectively.
Tenofovir gel reduced HIV acquisition by an estimated 39%
overall, and by 54% in women with high gel adherence. No
increase in overall adverse event rates was observed. ere were
no changes in viral load and no tenofovir resistance in HIV
seroconvertors. A coitally related dosing strategy was selected
to achieve high adherence, based on in-depth consultations with
the communities involved. Sexual behavior data showed that
women in the key study population had infrequent high-risk
sex with migrant partners. Monkey challenge data and perinatal
transmission studies informed the timing of doses in relation to
sex. e “before and a er” sex doses were modeled on the timing
of nevirapine in its proven strategy for preventing mother-to-
child HIV transmission. Women were requested to insert one
dose of gel within 12 hours before sex and a second dose of gel
as soon as possible within 12 hours a er sex and no more than
two doses of gel in a 24-hour period. Hence, the dosing strategy
was referred to as“BAT24.” e latter restriction was imposed due
to the lack of human safety data on more than two doses of gel
per day. In addition, in CAPRISA, use of tenofovir gel reduced
herpes simplex virus-2 incidence by 51% versus placebo, i.e., a
“dual e ect,” likely to be very important (unpublished data).
It is not possible to derive from this study any conclusions on
the safety and e ectiveness of tenofovir gel for anal sex. Similarly,
it is not possible to make any conclusions on the e ectiveness of
tenofovir gel in relation to the timing of gel applications because
when the gel was applied, BAT 24 was usually followed.
Another study, VOICE, which began enrolment in August
2009, will compare the safety, acceptability, and e ectiveness of
daily oral versus topical PrEP strategies in 5,000 women in South
Africa, Uganda, Zimbabwe, and Zambia (NCT00705679). It will
also be the rst to provide comparative data on the 2 methods
of administration.
Pre-exposure Prophylaxis of HIV with Oral ARV
e earlier animal models2–4 assessed e cacy of PEP a er
intravenous challenge with virus in macaques. In sexual
transmission, HIV rst replicates at a low level at the mucosal
point of entry in the new host.25 It is therefore possible that
e ective PrEP can exploit this brief period of virus vulnerability,
if founder populations of infected cells do not expand su ciently
to establish a self-propagating infection.
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Recently researchers have created “humanized bone marrow-
liver-thymus mice,” and shown that their female reproductive
tract is not only susceptible to intravaginal infection by HIV-1,
but can also be completely protected by PrEP with emtricitabine
(FTC)/tenofovir (TDF).26
In addition, oral or subcutaneous PrEP with FTC, TDF, or
both, has been shown to protect against rectal SHIV transmission
in a rhesus macaque model that closely resembles human
transmission.27,28
In humans, three clinical studies of oral PrEP have been
completed to date. e rst study 29 was conducted among
women in Ghana, Nigeria, and Cameroon, and was intended
as an e cacy study of oral tenofovir. Although the study was
terminated early for political reasons, the data supported the
safety of daily tenofovir. Another placebo-controlled safety study
of once-daily oral tenofovir has recently been completed by CDC
in 400 MSM, with a favorable result.30
Recently, Grant and colleagues,31 reported that the
combination of emtricitabine and tenofovir disoproxil fumarate
(FTC-TDF) (Truvada), administered orally on a daily basis by
men and transgender women (born male) who have sex with
men, provides partial protection from HIV infection. e trial,
called the Pre-exposure Prophylaxis Initiative (iPrEx) study, was
a placebo-controlled, double-blind, randomized trial involving
2,499 subjects in the Americas, South Africa, and ailand. Of
the 100 incident infections, 64 occurred in the placebo group
and 36 in the FTC-TDF group, for an estimated e cacy of 44%
with a 95% con dence interval of 15 to 63. In the FTC-TDF
group, the study drug was pharmacologically detected in 51% of
subjects who remained free of HIV infection but in only 9% of
those who became infected. us, exposure to FTC-TDF was
associated with a reduction in HIV acquisition, which supports
the biologic plausibility of the primary result. In fact, a small
substudy found that risk of infection plummeted by 92% in
people who had measurable drug levels in their blood.
e results of the Pre-exposure Prophylaxis Initiative study
also reveal real challenges and raised many concerns.32,33 First,
the association between self-reported drug adherence and
pharmacological detection of the study drug was very poor, which
underscores the need for better reporting tools to predict drug
adherence. Second, although renal insu ciency and decreases in
bone mineral density were seen in a relatively small fraction of
subjects and was reversible on drug discontinuation, this nding
raises both safety and monitoring concerns regarding possibly
cumulative toxic e ects associated with large-scale exposure of
at-risk persons to daily FTC-TDF therapy for an extended period.
e side e ect pro le for FTC-TDF was probably diluted, given
the reported medication-compliance issues, and thus would
probably be more substantial with full compliance. e study
also raises cost-e ectiveness concerns, in that 1,220 subjects
were prescribed medication for up to 2.8 years in order to
prevent an estimated 28 infections, or expressed another way;
treating 43 people to stop one infection. Furthermore, the fact
that FTC-TDF (Truvada) is patent-protected, and therefore an
expensive medication, raises questions as to whether its use as
a preventative measure should be funded by the government,
private health industry, or by the individual. It should be noted
that this study was conducted in highly supportive environment
when speci c high-risk groups had access to counselling (safe
sex) and health-promotion activities (condom use) which may
be not a case in real-world settings, di erent populations and
geographical locations. ere is concern that the widespread use
of PrEP might lead people to take more risks than they would
otherwise, o setting the bene t of the intervention. ere is
always a risk for evolution of multi-drug resistant HIV strains.
Other studies of PrEP are ongoing, in IDU (Bangkok), women
in Africa (VOICE-see earlier section on microbicides), and
FEMPrEP, (a phase III trial to evaluate the safety and e ectiveness
of daily oral TDF/FTC), all of whose results should further guide
recommendations in this eld.
ere are currently no guidelines for prescribing PrEP,
although, CDC has published interim guidance.34
Effective Treatment of Infected Persons to
Reduce HIV Transmission to Their Partners
Viral load is the major determinant governing the risk of sexual
transmission in HIV-1 discordant couples,35 and therefore,
e ective ARV should dramatically reduce transmission rates.
In a meta-analysis of data from ve studies, some of which were
unpublished, investigators reported only ve cases of HIV-1
transmission from patients receiving ART to sexual partners
during 1098 person-years of follow-up, which is consistent with
an infection rate of 0.19–1.09 per 100 person years.36
In 2010, Donnell and colleagues (the Partners in Prevention
HSV/HIV Transmission study team)37,38 reported the results of a
study nested within a placebo-controlled trial, which showed no
e ect of Herpes simplex virus-2 treatment on HIV transmission
in nearly 3,400 African serodiscordant heterosexual couples.
As one in 10 participants started on ARV during the trial, the
investigators were able to compare HIV transmission before
and a er starting treatment. HIV incidence was 2.24 per 100
person-years before starting ARV (102 transmission events) and
0.37 per 100 person-years a er starting treatment (one event
which probably occurred before full suppression of viral load in
the index partner), yielding an adjusted incidence rate ratio of
0.08, a 12-fold reduction in transmission.
Investigators in Switzerland also reviewed transmission rates
among discordant couples in their country, concluding that
in a monogamous relationship, with no concurrent sexually
transmitted infections, the risk of HIV transmission was
“negligible.”39 Another observational cohort study from Uganda
reported similar data. Free ARV programs were initiated in 2004,
and the rates of HIV-1 transmission before and a er the programs
began, in the Rakai district, were measured.40 Two hundred and
y HIV-1 discordant couples were followed between 2004 and
2009 and 32 HIV-1-positive partners initiated ART. Forty-two
HIV-1 transmissions occurred over 459.4 person-years prior
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to ART initiation, incidence 9.2/100 person-years (95% CI,
6.59–12.36). In 32 couples in which the HIV-1 index partners
started ART, no HIV-1 transmissions occurred during 53.6
person-years. e 95% con dence interval for the incidence rate
di erence was -11.91 to -6.38 (P < 0.0097). Couples reported
more consistent condom use during ART, but there was no
signi cant di erence in the number of sexual partners or other
risk behaviors. Although there was a signi cant increase in
consistent condom use following ART initiation, the reduction
in risk was most likely due to the direct reduction in HIV-1 viral
load in the HIV-1-positive partners on ART. ese ndings add
to the growing body of evidence supporting the use of ART for
HIV-1 prevention.
Ongoing studies such as the HIV-1 Prevention Trials Network
052 study (by NIAID) will test the hypothesis that ART can
prevent HIV-1 transmission among HIV-1 discordant couples
by randomizing couples in whom the infected partner has a
CD4 cell count of 250–550 cells per microliter to either start
ARVs immediately, or wait until the CD4 count drops below
250 cells per microliter41; results are expected in 2014. is
trial will provide useful data on long-term measures of e cacy
of ART among discordant couples, adherence when ARV are
initiated earlier, incidence of drug resistance, and potential risk
compensation.
Reduction of the HIV Epidemic by
Widespread Use of Effective
ARV in Infected Individuals
e “treatment as prevention” strategy aims to reduce community
viral load and assumes that this will reduce HIV transmission.
Indeed, lower rates of HIV diagnosis in San Francisco and
British Columbia have accompanied lower viral loads in HIV-
infected people undergoing viral tests,42,43 and in Taiwan, rapid
expansion of ARV was associated with a 50% reduction in new
HIV diagnoses.44 Granich and colleagues45 have developed a
statistical model predicting that universal testing of all sexually
active adults and immediate ARV therapy (regardless of CD4
count) could have a major e ect on generalized epidemics.
However, Hosein and Wilson46 make pertinent comments
on the situation among MSM in France, with continuing high
incidence,47 despite high uptake of highly active antiretroviral
therapy, and where 92% of treated patients achieve an undetectable
viral load. Similar situations pertains among MSM in Sydney19,48
and in Amsterdam.49 ey suggest that the preventative role
of treatment may be di erent in MSM to heterosexuals and
IDU, because of higher biological transmission rates, and the
sexual milieu of MSMs. As mentioned in the French study,
such circumstances include a high HIV prevalence, increased
rates of unprotected anal sex with more partners, and increased
prevalence of STIs.
us, merely intensifying a treatment uptake as prevention
strategy for MSM without addressing other co-existing issues at the
individual or community level may not lead to sustained changes
in some HIV epidemics. As the majority of HIV transmissions
worldwide occur within the heterosexual community, selective
use of ARV medications may have di ering outcomes on HIV
transmission in di erent populations, e.g., in countries where
transmitted drug resistance is common, where sub-optimal rst-
line ARV use has created a pool of resistance to these agents, or
where ARV roll-out has not reached the majority of infected
people.
Conclusions
ARV drugs alone, while having a dramatic impact at the
individual level, are unlikely to have a signi cant impact on
HIV transmission at the population level unless accompanied
by a range of additional strategies, such as, universal access to
testing and treatment, education on risk behaviors, and removing
barriers to condom use and needle/syringe exchange programs.
All of these strategies unfortunately highlight de ciencies in the
way health and HIV is managed globally. e greatest challenge
in reducing HIV transmission rates is not necessarily achieved
through biological interventions such as ARV alone but the more
di cult task of changing human behavior.
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Authors Queries
AQ-1 Author: Note that IDU has been expanded to Intravenous Drug Use. Please verify.
AQ-2 Author: Citation for footnote explanation indicated by asterisk is missing; kindly cite the same.
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