Prevention of HIV-1 Infection with Antiretroviral Therapy

The authors discuss the efficacy of ART for HIV-1 prevention in persons who have unprotected sex. They recommend condoms to all couples at every visit in the HIV Prevention Trials Network (HPTN) 052 clinical trial (NCT00074581), and subjects in the early-therapy and delayed-therapy groups of the trial reported similar condom usage, both at baseline and during follow-up.

n engl j med 365;20nejm.org november 17, 20111934
T h en e w e ngl a nd j o u r na lo f m e dic i n e
c o r r e s p on de nc e
Prevention of HIV-1 Infection with Antiretroviral Th
To the Editor: To recommend antiretroviral
therapy (ART) as a policy to prevent transmission
of the human immunodeficiency virus type 1
(HIV-1), it is critical to understand the risk of
transmission through sex without condom use
when the plasma viral load in patients receiving
ART is fully suppressed. In addition to data re-
ported by Cohen et al. (Aug. 11 issue),1 a 2009
meta-analysis2 showed no transmissions in 291
person-years, and the Partners in Prevention
Study (ClinicalTrials.gov number, NCT00194519)3
showed one transmission in 273 person-years,
but some couples used condoms. Accounting for
the proportions of couples having sex without
the use of condoms (approximately 4%,1 75%,2
and 4%3 in these three studies, respectively), only
approximately 292 person-years of sex without
the use of condoms with viral-load suppression
have been observed over all studies combined.
Even with no transmissions, these findings are
associated with an upper 95% confidence limit
for the transmission rate of 1.3 per 100 person-
years. We think this is too high a rate on which to
base a public health prevention policy. Further,
there remain no data on men who have sex with
men, among whom transmission rates for anal sex
are likely to be different than rates for vaginal sex.
Alison Rodger, M.D.
Andrew Phillips, Ph.D.
University College London
London, United Kingdom
[e-mail]
Jens Lundgren, Ph.D.
University of Copenhagen
Copenhagen, Denmark
No potential conflict of interest relevant to this letter was re-
ported.
1. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1
infection with early antiretroviral therapy. N Engl J Med 2011;
365:493-505.
2. Attia S, Egger M, Müller M, Zwahlen M, Low N. Sexual trans-
mission of HIV according to viral load and antiretroviral therapy:
systematic review and meta-analysis. AIDS 2009;23:1397-404.
3. Donnell D, Baeten JM, Kiarie J, et al. Heterosexual HIV-1
transmission after initiation of antiretroviral therapy: a prospec-
tive cohort analysis. Lancet 2010;375:2092-8.
To the Editor: Cohen et al. compared the ef-
fects of early and delayed therapy for HIV-1–
infected subjects among serodiscordant couples
and found that the first regimen more signifi-
cantly reduced the rates of sexual transmission
and the incidence of clinical events of HIV-1.
However, a comprehensive survey should be per-
formed to assess the changes in sexual behavior
among the subjects in response to ART. During
the study, although interviews regarding sexual
behavior were conducted at each visit, the chang-
es in sexual behavior before and after ART were
not compared. Reynolds et al.1 found that HIV-1
transmission was reduced among HIV-1–discor-
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correspondence
n engl j med 365;20nejm.org november 17, 2011 1935
dant couples after initiation of ART because of
the reduced HIV-1 viral load and the increased
consistency of condom use. Nonetheless, the data
indicate that ART increases risk-taking sexual
behavior.2 Furthermore, the high prevalence of
HIV-1 drug resistance in persons who did not
receive ART in other studies3,4 suggests that
drug-resistance testing is necessary for the selec-
tion of the initial ART regimen and helpful in
discussing the possible reasons for HIV-1 trans-
mission among serodiscordant couples.
Xiaohua Tao, M.D.
Dan Shao, Ph.D.
Wei Xue, M.D.
Dermatology Hospital of Jiangxi Province
Nanchang, China
[e-mail]
No potential conflict of interest relevant to this letter was re-
ported.
1. Reynolds SJ, Makumbi F, Nakigozi G, et al. HIV-1 transmis-
sion among HIV-1 discordant couples before and after the intro-
duction of antiretroviral therapy. AIDS 2011;25:473-7.
2. Shafer LA, Nsubuga RN, White R, et al. Antiretroviral ther-
apy and sexual behavior in Uganda: a cohort study. AIDS 2011;
25:671-8.
3. Hamers RL, Siwale M, Wallis CL, et al. HIV-1 drug resistance
mutations are present in six percent of persons initiating anti-
retroviral therapy in Lusaka, Zambia. J Acquir Immune Defic
Syndr 2010;55:95-101.
4. Ross L, Lim ML, Liao Q, et al. Prevalence of antiretroviral
drug resistance and resistance-associated mutations in antiret-
roviral therapy-naïve HIV-infected individuals from 40 United
States cities. HIV Clin Trials 2007;8:1-8.
The Authors Reply: Rodger and colleagues
rightly note that we do not know the benefits of
ART in persons who have unprotected sex (sex
without the use of condoms). We recommended
condoms to all couples at every visit in the HIV
Prevention Trials Network (HPTN) 052 clinical
trial (NCT00074581), and subjects in the early-
therapy and delayed-therapy groups of the trial
reported similar condom usage, both at baseline
and during follow-up. Subjects who reported 100%
condom use were less likely to have an HIV-1
transmission event. However, the acquisition of
sexually transmitted diseases and the frequent
occurrence of pregnancy during the study indi-
cate that self-reported condom use was mislead-
ing, or that condoms performed imperfectly. To
fully understand the efficacy of ART for HIV-1
prevention in persons who have unprotected sex
requires a clinical trial that excludes the use of
condoms, but such a trial would be unethical.
Our article did not offer a public health recom-
mendation; rather, we noted the considerable
public health potential of ART under the condi-
tions we used. Finally, the degree to which the
results we observed in heterosexual couples can
be extrapolated to men who have sex with men is
simply unknown.
Tao and colleagues comment on the potential
for increased risk-taking sexual behavior after
the initiation of ART, citing self-reported behav-
ior; this has been a source of intense study for
many years, with variable results.1 An increase in
risky sexual behavior is unlikely to substantially
alter the prevention benefit of ART.2 However,
the unlinked transmission of HIV-1 in partners
of treated subjects in our study and other stud-
ies3 warrants special attention. Transmitted drug
resistance has been recognized worldwide4 and
can compromise treatment of HIV-1. In our study,
all subjects were treated with effective ART
regimens, and these regimens were switched
in participants with virologic failure. ART can
reduce HIV-1 transmission only with durable
suppression of HIV-1. The durability of HIV-1
suppression and longer-term transmission risks
will be studied during continuation of the HPTN
052 trial.
Myron S. Cohen, M.D.
University of North Carolina at Chapel Hill
Chapel Hill, NC
[e-mail]
Ying Q. Chen, Ph.D.
Fred Hutchinson Cancer Research Center
Seattle, WA
Thomas R. Fleming, Ph.D.
University of Washington
Seattle, WA
for the HPTN 052 Study Team
Since publication of their article, the authors report no fur-
ther potential conflict of interest.
1. Crepaz N, Hart TA, Marks G. Highly active antiretroviral
therapy and sexual risk behavior: a meta-analytic view. JAMA
2004;292:324-36.
2. Cohen MS, Gay C, Kashuba AD, Blower S, Paxton L. Narra-
tive review: antiretroviral therapy to prevent the sexual trans-
mission of HIV-1. Ann Intern Med 2007;146:591-601.
3. Celum C, Wald A, Lingappa JR, et al. Acyclovir and transmis-
sion of HIV-1 from persons infected with HIV-1 and HSV-2. N Engl
J Med 2010;362:427-39.
4. Hamers RL, Wallis CL, Kityo C, et al. HIV-1 drug resistance
in antiretroviral-naive individuals in sub-Saharan Africa after
rollout of antiretroviral therapy: a multicentre observational
study. Lancet Infect Dis 2011;11:750-9.
The New England Journal of Medicine
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Copyright © 2011 Massachusetts Medical Society. All rights reserved.