Introduction
According to the 2012 Joint United Nations Programme on HIV/AIDS (UNAIDS) Report on
the global AIDS epidemic [1], sub-Saharan Africa continues to bear a disproportionate
share of the global HIV burden. The regions of eastern and southern Africa remain
the areas most heavily affected by HIV/AIDS. In particular, South Africa, with an
estimated 5.6 (5.3–5.9) million HIV-infected people in 2011, continues to have the
world's largest epidemic. The vast majority of newly HIV-infected individuals from
sub-Saharan Africa acquire the virus during unprotected heterosexual intercourse.
In this context, preventing the heterosexual transmission of HIV among adults, especially
young adults, is a public health priority. From the beginning of the HIV/AIDS epidemic,
several randomized controlled trials (RCTs) were conducted to test a number of behavioral
and biomedical prevention strategies. The efficacy of voluntary medical adult male
circumcision (VMMC) in reducing male HIV acquisition by 50% to 60% in sub-Saharan
African populations has been demonstrated in three RCTs published in 2005 [2] and
in 2007 [3],[4]. VMMC is to date one of the most promising interventions to curb the
spread of HIV in these regions, demonstrated to be acceptable in traditionally non-circumcising
African communities [5], and expected to be significantly life- and cost-saving in
terms of averted HIV infections and related medical costs [6]–[10]. Since 2007, it
is recommended by UNAIDS and the World Health Organization (WHO) as an important,
complementary strategy to fight HIV in these settings.
However, to our knowledge, the effectiveness of VMMC roll-out in reducing the spread
of HIV among adults has not yet been published in scientific journals. Such evidence
is of major public health importance because it will mobilize the international community
in support of VMMC roll-out programs in sub-Saharan Africa. This demonstration can
be achieved by demonstrating that the overall reduction in HIV prevalence and incidence
rates among all adult men attributable to a VMMC campaign is sizeable. The a priori
conditions being that VMMC uptake is substantial and that its protective effect on
HIV acquisition is not compensated by an increase in risky sexual behavior.
The primary objectives of this study were to assess the association of VMMC roll-out
in a South African community with (a) VMMC uptake, (b) risky sexual behavior, and
(c) the levels of HIV prevalence and incidence rates among adult men.
Methods
Ethics Committee Approval
Ethical clearance for both surveys was granted by the Human Research Ethics Committee
(Medical) of the University of the Witwatersrand on May 8, 2007 (protocol study number
M070367).
Study Setting
The study was conducted in the township of Orange Farm, located in Gauteng province,
South Africa. The township has an estimated population of 110,000 adults. The HIV
epidemic in the province is among the most severe in the world, with a prevalence
rate estimated at 0.30 among antenatal women in 2010 [11].
ANRS Project
The ANRS (French Agency for AIDS and Viral Hepatitis Research) project consists of
an RCT and a community roll-out. The RCT (ANRS 1265) was the first study to test the
effect of VMMC on HIV acquisition and was conducted in this community in 2002–2005
[2]. About 2,700 VMMCs were performed among volunteers aged 18 to 24 y in that period.
The roll-out, also known as the “Bophelo Pele” ANRS-12126 project, was implemented
in early 2008. This roll-out is a comprehensive community-based HIV prevention intervention
offering free VMMC services to all men aged 15 and older living in Orange Farm. Through
the roll-out, about 18 000 adult VMMCs were performed between 2008 and 2010. This
ongoing roll-out has been described elsewhere in detail [12]. In brief, project activities
include community mobilization and outreach, using communication approaches aimed
at both men and women, and incorporating broader HIV prevention strategies. Free VMMC
is offered at the project's main center, which has been designed for low-income settings
according to UNAIDS/WHO operational guidelines [13]. Prior to surgery, participants
receive group education on VMMC, individual HIV risk reduction counseling, treatment
of symptomatic sexually transmitted infections (STI), and they are offered HIV testing.
Baseline Survey
A cross-sectional survey was conducted at baseline among a random sample of 1,998
men between November 2007 and April 2008, after the RCT, and before the roll-out became
fully operational, to collect baseline data. This survey was used to assess MC prevalence
before the VMMC roll-out. A first random sample of households was selected from Statistics
South Africa Enumerator Area aerial photographs. All men aged 15 to 49 y, who had
slept in the selected households the night before the investigative team's visit,
were eligible for inclusion. A second random sample of households was selected and
volunteers underwent the same procedures, except that only men aged 16 to 29 were
included. Voluntary, written informed consent was obtained, in addition to parental
consent for those aged under 18. Each participant was interviewed at the study site
using an anonymous structured standardized questionnaire adapted from an instrument
designed by UNAIDS [14]. The following background characteristics were collected:
age group, ethnic group, religion, having at least one child, occupation, alcohol
consumption, education level, having ever been married, and, if relevant, date and
place of MC. The sexual behavior characteristics collected were: age at first sexual
intercourse, number of lifetime sexual partners, self-reported consistent condom use
with non-spousal partners in the last 12 months, and number of non-spousal partners
in the last 12 months. In addition to variables listed above, intention to become
circumcised was collected among uncircumcised men. Each interview was followed by
an individual HIV and STI counseling session during which confidential HIV testing
was offered using rapid tests. Participants underwent a clinical examination performed
by a trained male nurse during which their clinical MC status (presence or absence
of foreskin) was assessed. Participants with symptomatic STIs were treated free of
charge at the study site or at local health facilities according to the national STI
syndromic management treatment guidelines. Individuals testing HIV positive were offered
an immediate CD4 count at the study site. Antiretroviral (ARV) treatment was arranged,
in collaboration with the health facilities in the community as per national guidelines.
The household response rate was 3,258/3,390 (96.1%), the individual response was 2,000/2,383
(83.9%), and the combined response rate was 80.7%.
Follow-up Survey
This survey, designed to evaluate the Bophelo Pele project, was conducted between
October 2010 and June 2011, independently from the baseline survey, 3 y after the
beginning of the roll-out. For this survey, a first random sample of households was
selected from Statistics South Africa Enumerator Area aerial photographs. All men
aged 15 to 49, who had slept in the selected households the night before the investigative
team's visit, were eligible for inclusion. Voluntary, written informed consent was
required, in addition to parental consent for those aged under 18. Each participant
was interviewed at the study site using an anonymous structured standardized questionnaire
adapted from an instrument designed by UNAIDS [14]. Participants were encouraged to
undergo HIV testing, which was provided at the study site using rapid tests. Participants
with symptomatic STIs were treated free of charge at the study site or at local health
facilities according to the national STI syndromic management treatment guidelines.
Individuals testing HIV positive were offered an immediate CD4 count at the study
site. ARV treatment was arranged, in collaboration with the health facilities in the
community as per national guidelines. A second random sample of households was selected
and volunteers underwent the same procedures, except that only men aged 18 to 33 were
included. A total of 3,338 volunteers aged 15 to 49 were recruited. The household
response rate was 7,701/8,022 (96.0%), the individual response was 3,334/4,021 (82.9%),
and the combined response rate was 79.6%.
Laboratory Procedures
Each participant was invited to supply a venous blood sample (8 ml) for HIV testing.
Samples were collected in plasma preparation tubes and centrifuged. Samples were tested
within 6 months following collection. A screening test (GenscreenTM HIV1/2 version
2, Bio-Rad) was performed on all plasma samples. For reactive samples, a confirmatory
test was run (VironostikaTM HIV Uni- Form II plus O, bioMérieux, Boxtel). If the sample
reacted positively for both assays, a second confirmatory test was conducted (Murex
HIV-1.2.O, Murex Biotech Ltd.). Plasma samples testing positive for HIV were also
tested for the presence of ARV drugs currently in use in South Africa (lamivudine,
stavudine, zidovudine, nevirapine, efavirenz, ritonavir, lopinavir, atazanavir, emtricitabine,
tenofovir) using Ultra Performance Liquid Chromatography coupled with Tandem Mass
Spectrometry according to a slightly modified previously published method [15].
In addition, plasma samples testing positive for HIV were also tested using the BED
HIV incidence assay (HIV-1 Calypte Incidence BED EIA [BED]; Calypte Biomedical Corporation).
Since the first detuned enzyme immunoassay to detect recent HIV seroconversion was
described in 1,998 [16], there has been great interest in the application of laboratory
methods to measure HIV incidence rates from cross-sectional samples [17]. Currently,
the most widely used incidence assay is the BED HIV-1 Capture EIA (BED) assay [18].
The BED assay detects levels of anti-HIV IgG relative to total IgG and is based on
the observation that the ratio of anti-HIV IgG to total IgG increases with time after
HIV infection. If a confirmed HIV-1 positive specimen is reactive on the standard
sensitive EIA and has a normalized optical density lower than a given cut-off value
of the BED assay, it is considered recently infected. However, two of the current
challenges in using HIV incidence assays to characterize HIV incidence rates are (a)
knowledge of the BED window period, defined as the time interval following HIV infection
during which individuals are characterized by the assay as recently infected, that
is, the optical density is lower than the pre-set cut-off value, and (b) misclassifications.
The main source of misclassifications is the number of HIV-infected persons falsely
identified as recent seroconverters, which depends on the proportion of HIV-positive
participants whose infection duration exceeds the BED window period. Different cut-off
values and correction methods were used. See Text S1.
Outcomes
We assessed six outcomes of interest. From the clinical examination data, we calculated
the adult MC prevalence rate. From the questionnaire data, we calculated two sexual
behavior outcomes that could potentially change among those having undergone MC surgery:
prevalence rate of men consistently using condoms with non-spousal partners in the
last 12 months, and prevalence rate of men having two or more non-spousal partners
in the last 12 months. From the serological data, we calculated the prevalence rate
of ARV detection, the HIV prevalence rate, and the BED HIV incidence rate. The level
of HIV among men was investigated by comparing these two latter rates between circumcised
and uncircumcised men, and by calculating the increase in HIV prevalence rate that
would have been expected without the VMMCs performed by the ANRS project.
Statistical Analyses
Covariates and standardization
The basic covariates were the following: age group in deciles, ethnic group (Sotho,
Zulu, other), religion (Christian, no religion, other), having at least one child
(yes, no), occupation (employed, unemployed, other), age at first sexual intercourse
(age 15 or older, before age 15), alcohol consumption (less than once a week, once
a week or more), education level (not at school and grade 12 not completed, at school
and grade 12 not completed, grade 12 completed), and ever having been married (yes,
no). Other sexual behavior covariates were number of lifetime partners, coded as a
continuous variable and as a discrete variable (less than 5, 5 or more), number of
non-spousal partnerships in the past 12 months (less than 2, 2 or more), consistent
condom use with non-spousal partners in the last 12 months (yes, no). Results were
standardized on the age-structure observed in 2010 using weighting coefficients calculated
for each age group.
Baseline MC prevalence rate
In the baseline survey, circumcised men were either circumcised during the RCT or
in another context. We calculated the MC prevalence rate which would have been expected
in 2007–2008 if the men who were circumcised during the RCT had remained uncircumcised.
We called this rate the baseline MC prevalence rate. We assumed that this proportion
would have remained constant over time in the period 2008–2011 without the ANRS project.
MC uptake
We defined MC uptake as the proportion of the population that was circumcised at the
time of the follow-up survey when excluding the proportion that were not circumcised
in the ANRS project context (baseline MC prevalence rate).
BED HIV incidence rates
To calculate BED HIV incidence rates, we used the follow-up survey data and cut-off
values of 0.80 and 1.51, which correspond in this population to BED window periods
of about 6 and 12 months, respectively [19], with and without correction for misclassifications.
Two correction methods were used [20],[21]. In these calculations, we excluded those
testing positive for at least one ARV, because they were not likely to have been infected
with HIV within the preceding 12 months.
Risk factor analysis of MC status
Using the follow-up survey data, we analyzed the association of background and sexual
behavior characteristics with MC status by estimating prevalence rate ratios (PRR)
using bivariate and multivariate general linear models (log-binomial and Poisson regression).
Comparison of outcomes between circumcised and uncircumcised men
To compare HIV prevalence and incidence rates between circumcised and uncircumcised
men, we calculated HIV PRR and HIV incidence rate ratios (IRR) using general linear
models and the follow-up survey data. As participants were not randomized, we observed
that men accepting the intervention had different risk profiles than those who remained
uncircumcised. To take into account this selection bias, these regressions were weighted
by the inverse of the estimation of the propensity score [22] to obtain weighted PRR
(wPRR) and IRR (wIRR). Each circumcised participant was weighted by the inverse of
the propensity score, and each uncircumcised participant was weighted by the inverse
of one minus the propensity score. This score is the probability of being circumcised
and was estimated using a logistic regression from the following set of basic covariates:
background characteristics and age at first sexual intercourse younger than 15 y.
These basic covariates are not altered by the intervention and are potentially associated
with MC status as well as HIV prevalence and incidence rates. To assess the association
of possible sexual behavior changes with the intervention, we added the other sexual
behavior characteristics to the regression model.
Association of VMMC roll-out with HIV levels
Using the follow-up survey data, we estimated what would have been the HIV prevalence
rate among circumcised men if they had not been circumcised, by calculating the HIV
prevalence rate among uncircumcised men after weighing each uncircumcised man by p/(1−p),
with p being his propensity score [23]. This allowed us to calculate what the HIV
prevalence and incidence rates would have been, averaged on all men in 2010–2011,
assuming that the MC prevalence rate had remained at its baseline level.
Other details on the statistical analyses are provided in Text S1. Statistical analyses
were performed using R version 2.14.1. All the confidence intervals are 95% intervals
and were estimated along with p-values by bootstrap based on at least 2,000 replications.
Results
Baseline Data and MC Prevalence Rate
The baseline survey participants' background characteristics are described in Table
1. During the baseline survey, MC prevalence rate was 0.17 (95% CI 0.15–0.19). The
baseline MC prevalence rate, corresponding, as described in the methods, to the MC
prevalence rate expected if the men who were circumcised during the RCT had remained
uncircumcised, was estimated to be 0.12 (95% CI 0.10–0.14).
10.1371/journal.pmed.1001509.t001
Table 1
Characteristics of the sample surveyed in 2007–2008 (baseline survey).
Sample Sizen (%) n = 1,988
Circumcisedn (%; 95% CI)
Background Characteristics
Age group
15–19
773 (38.9%)
70 (9.1%; 7.2%–11.2%)
20–24
668 (33.6%)
128 (19.2%; 16.3%–22.2%)
25–29
310 (15.6%)
97 (31.3%; 26.3%–36.6%)
30–34
97 (4.9%)
17 (17.5%; 10.9%–25.8%)
35–39
62 (3.1%)
4 (6.5%; 2.0%–14.4%)
40–49
78 (3.9%)
13 (16.7%; 9.6%–25.9%)
Ethnic group
Sotho
674 (33.9%)
93 (13.8%; 11.3%–16.5%)
Zulu
897 (45.1%)
126 (14.0%; 11.9%–16.4%)
Other
417 (21.0%)
110 (26.4%; 22.3%–30.7%)
Religion
Christian
783 (39.4%)
118 (15.1%; 12.7%–17.7%)
No religion
893 (44.9%)
165 (18.5%; 16.0%–21.1%)
Other
312 (15.7%)
46 (14.7%; 11.1%–19.0%)
Alcohol consumption
Less than once a week
1,421 (71.5%)
212 (14.9%; 13.1%–16.8%)
Once a week or more
567 (28.5%)
117 (20.6%; 17.4%–24.0%)
Education
Not at school and grade 12 not completed
806 (40.5%)
168 (20.8%; 18.1%–23.7%)
At school and grade 12 not completed
749 (37.7%)
62 (8.3%; 6.4%–10.4%)
Grade12 completed
433 (21.8%)
99 (22.9%; 19.1%–27.0%)
Occupation
Employed
684 (34.4%)
151 (22.1%; 19.1%–25.3%)
Unemployed
383 (19.3%)
77 (20.1%; 16.3%–24.3%)
Other
921 (46.3%)
101 (11.0%; 9.1%–13.1%)
Ever married
No
1,726 (86.8%)
270 (15.6%; 14.0%–17.4%)
Yes
262 (13.2%)
59 (22.5%; 17.8%–27.8%)
Has at least one child
No
1,497 (75.3%)
219 (14.6%; 12.9%–16.5%)
Yes
491 (24.7%)
110 (22.4%; 18.9%–26.2%)
Sexual behavior characteristics
Age at first sexual intercourse
Age 15 or older
1,488 (74.8%)
239 (16.1%; 14.3%–18.0%)
Before age 15
500 (25.2%)
90 (18.0%; 14.8%–21.5%)
Number of lifetime partners
Less than 5
969 (48.7%)
120 (12.4%; 10.4%–14.6%)
5 or more
1,019 (51.3%)
209 (20.5%; 18.1%–23.1%)
Number non-spousal partners in the past 12 months
Less than 2
1,070 (53.8%)
156 (14.6%; 12.6%–16.8%)
2 or more
918 (46.2%)
173 (18.8%; 16.4%–21.5%)
Consistent condom usea
No
817 (41.1%)
169 (20.7%; 18.0%–23.6%)
Yes
657 (33.0%)
103 (15.7%; 13.0%–18.6%)
a
Self-reported, with non-spousal partners in the last 12 months.
MC Prevalence Rate
In 2010–2011, at the time of the follow-up survey, MC prevalence rate was 1,771/3,338
(0.53; 95% CI 0.51–0.55) among adults. In the 15- to 29-y age group, MC prevalence
rate was 1,630/2,810 (0.58; 95% CI 0.56–0.60). Among men who had been circumcised
during the roll-out, 817/892 (91.5%; 95% CI 89.8%–93.3%) reported having been circumcised
by the ANRS-12126 project.
VMMC Uptake
In 2007–2008, baseline MC prevalence rate was 237/1,988 (0.12; 95% CI 0.10–0.14).
From this estimate, we calculated that following the VMMCs performed during the ANRS
project, the adult VMMC uptake among uncircumcised men was 46.7% (95% CI 44.3%–49.0%).
VMMC uptake was 52.6% (95% CI 50.3%–54.7%) in the 15- to 24-y age group. Figure 1
represents the MC prevalence rate by age group before and after the ANRS project.
10.1371/journal.pmed.1001509.g001
Figure 1
Male circumcision prevalence rates by age group before and after the ANRS project
in the community of Orange Farm (South Africa).
The error bars represent the 95% confidence intervals.
Description of the Follow-up Survey Sample and Comparison by MC Status
The follow-up survey participants' background characteristics are described in Table
2. Among them, 169/3,338 (5.1%) had participated in the baseline survey. The age distribution
of the Orange Farm male population is reported in Figure S1. We compared 1,848 circumcised
men with 1,490 uncircumcised men. Circumcised men (mean age in years = 24.5; 95% CI
24.0–25.0) were younger (p<0.001) than uncircumcised men (mean age in years = 27.3;
95% CI 26.7–28.0). Their comparison in terms of background and sexual behavior characteristics
is reported in Table 2. When controlling for age, circumcised men were less likely
to be Zulu (a traditionally non-circumcising group), more likely to be in school,
more educated, and less likely to be married. In the multivariate analysis, the same
factors, apart from marital status, remained statistically significant.
10.1371/journal.pmed.1001509.t002
Table 2
Characteristics of the sample surveyed in 2010–11 (follow-up survey) and association
with male circumcision status.
Sample Sizen (%) n = 3,338
Circumcisedn (%; 95% CI)
PRR Adjusted on Age Group
Multivariate PRRa
Background Characteristics
Age group
15–19
806 (24.1%)
481 (59.7%; 56.2%–62.9%)
1 p<0.001*
1 p<0.001*
20–24
1,287 (38.6%)
762 (59.2%; 56.6%–61.9%)
0.99 (0.92–1.07) p = 0.856
1.03 (0.95–1.13) p = 0.526
25–29
717 (21.5%)
380 (53.0%; 49.4%–56.6%)
0.89 (0.81–0.97) p = 0.004
0.96 (0.85–1.08) p = 0.520
30–34
323 (9.7%)
152 (47.1%; 41.9%–52.5%)
0.79 (0.69–0.89) p = 0.000
0.90 (0.77–1.06) p = 0.196
35–39
89 (2.7%)
33 (37.1%; 27.3%–42.7%)
0.62 (0.46–0.81) p = 0.000
0.74 (0.52–0.96) p = 0.026
40–49
116 (3.5%)
40 (34.5%; 26.5%–42.7%)
0.58 (0.44–0.72) p = 0.000
0.72 (0.53–0.95) p = 0.010
Ethnic group
Sotho
1,123 (33.6%)
649 (55.8%; 52.5%–59.1%)
1
1
Zulu
1,599 (47.9%)
841 (50.2%; 47.4%–52.6%)
0.91 (0.84–0.98) p = 0.028
0.91 (0.84–0.98) p = 0.020
Other
616 (18.5%)
358 (55.4%; 51.0%–60.0%)
1.03 (0.93–1.14) p = 0.538
1.03 (0.93–1.13) p = 0.572
Religion
Christian
1,602 (48.0%)
896 (53.9%; 51.0%–56.8%)
1
1
No religion
1,332 (39.9%)
732 (53.2%; 50.2%–56.0%)
0.96 (0.90–1.03) p = 0.284
0.97 (0.91–1.05) p = 0.512
Other
404 (12.1%)
220 (49.5%; 44.2%–55.5%)
0.92 (0.83–1.02) p = 0.148
0.95 (0.85–1.07) p = 0.402
Alcohol consumption
Less than once a week
2,384 (71.4%)
1.325 (53.4%; 51.0%–55.4%)
1
1
Once a week or more
954 (28.6%)
523 (52.2%; 49.1%–56.0%)
1.02 (0.94–1.10) p = 0.684
1.01 (0.93–1.09) p = 0.878
Education
Not at school and grade 12 not completed
1,430 (42.8%)
687 (44.7%; 41.6%–47.6%)
1
1
At school and grade 12 not completed
668 (20.0%)
410 (61.3%; 57.3%–64.9%)
1.22 (1.10–1.37) p = 0.000
1.19 (1.03–1.37) p = 0.016
Grade12 completed
1,240 (37.1%)
751 (59.2%; 56.1%–62.4%)
1.23 (1.14–1.34) p = 0.000
1.22 (1.12–1.33) p = 0.000
Occupation
Employed
1,214 (36.4%)
632 (48.9%; 45.4%–52.0%)
1
1
Unemployed
1,131 (33.9%)
605 (51.2%; 48.3%–54.5%)
0.95 (0.87–1.04) p = 0.262
0.93 (0.86–1.02) p = 0.134
Other
993 (29.7%)
611 (60.4%; 57.3%–63.3%)
1.08 (0.98–1.18) p = 0.130
0.99 (0.88–1.11) p = 0.876
Ever married
No
2,535 (75.9%)
1.483 (57.9%; 55.7%–60.0%)
1
1
Yes
803 (24.1%)
365 (41.9%; 37.8%–45.7%)
0.87 (0.78–0.97) p = 0.020
0.91 (0.81–1.00) p = 0.068
Has at least one child
No
2,279 (68.3%)
1.330 (57.9%; 55.6%–59.9%)
1
1
Yes
1,059 (31.7%)
518 (45.1%; 41.8%–48.5%)
0.97 (0.89–1.05) p = 0.472
1.00 (0.92–1.10) p = 0.886
Sexual behavior characteristics
Age at first sexual intercourse
Age 15 or older
2,603 (78.0%)
1.425 (52.2%; 50.1%–54.4%)
1
1
Before age 15
735 (22.0%)
423 (56.6%; 52.7%–60.2%)
1.04 (0.96–1.12) p = 0.364
1.05 (0.96–1.13) p = 0.250
Number of lifetime partners
Less than 5
1,293 (38.7%)
729 (55.6%; 52.5%–58.9%)
1
1
5 or more
2,045 (61.3%)
1.119 (51.5%; 48.8%–53.9%)
1.00 (0.92–1.07) p = 0.998
0.97 (0.89–1.06) p = 0.538
1.00 (0.99–1.01) p = 0.17*
1.00 (0.99–1.01) p = 0.54*
Number of non-spousal partners in the past 12 months
Less than 2
1,608 (48.2%)
862 (50.1%; 47.2%–52.7%)
1
1
2 or more
1,730 (51.8%)
986 (56.3%; 54.0%–59.0%)
1.05 (0.98–1.12) p = 0.168
1.01 (0.93–1.09) p = 0.870
Consistent condom useb
No
1,517 (56.6%)
873 (56.3%; 53.7%–59.4%)
1
1
Yes
1,161 (43.4%)
658 (54.9%; 51.8%–58.1%)
0.95 (0.89–1.03) p = 0.120
0.94 (0.87–1.01) p = 0.120
PRR obtained using log-binomial regression.
a
Adjusted on all the covariates in the table.
b
Self-reported, with non-spousal partners in the last 12 months.
*
Linear trend.
Sexual Behavior and MC Status
No significant association between MC status and sexual behavior characteristics was
identified after weighting. Among circumcised and uncircumcised men, the proportion
consistently using condoms with non-spousal partners in the past 12 months was 615/1,399
(44.0%; 95% CI 41.7%–46.5%) versus 505/1,113 (45.4%; 95% CI 42.2%–48.6%) with wPRR = 0.94
(95% CI 0.85–1.03). The proportion having two or more non-spousal partners was 893/1,771
(50.4%; 95% CI 47.9%–52.9%) versus 692/1,567 (44.2%; 95% CI 41.3%–46.9%) with wPRR = 1.03
(95% CI 0.95–1.10). The details are provided in Table 3.
10.1371/journal.pmed.1001509.t003
Table 3
Variations among men of key outcomes between the baseline and the follow-up survey,
and by circumcision status in the follow-up survey.
Outcome
Baseline Valuea(95% CI)
Follow-up Survey Valuea(95% CI)
aPRR (95% CI)
ARV prevalence rate
Among all men
38/1,988 (1.9%; 1.1%–2.9%)
109/3,388 (3.2%; 2.4%–4.1%)
1.72 (1.07–3.13)
Among HIV positive men
38/288 (13.4%; 7.9%–19.0%)
109/412 (26.4%; 20.2%–32.4%)
1.96 (1.28–3.36)
Consistent condom use prevalence rateb
Among circumcised men
95/270 (35.2%; 29.7%–41.1%)
615/1,399 (44.0%; 41.7%–46.5%)
1.05 (0.88–1.27)
Among uncircumcised men
496/1,163 (42.6%; 39.7%–45.6%)
505/1,113 (45.4%; 42.2%–48.6%)
1.05 (0.94–1.16)
Weighted prevalence rate ratioc
NA
0.94 (0.85–1.03)
NA
All
591/1,433 (41.2%; 38.5%–43.9%)
1,120/2,512 (44.6%; 42.6%–46.6%)
1.03 (0.95–1.12)
Prevalence rate of those having two or more non-spousal partnersd
Among circumcised men
172/339 (50.8%; 44.9%–56.5%)
893/1,771 (50.4%; 47.9%–52.9%)
1.08 (0.96–1.24)
Among uncircumcised men
704/1,649 (42.7%; 40.1%–45.5%)
692/1,567 (44.2%; 41.3%–46.9%)
1.11 (1.03–1.20)
Weighted prevalence rate ratioc
NA
1.03 (0.95–1.10)
NA
All
876/1,988 (44.1%; 41.7%–46.6%)
1,585/3,338 (47.5%; 45.7%–49.3%)
1.12 (1.05–1.19)
HIV prevalence rate
Among men aged 15–49
288/1,988 (14.5%; 12.5%–16.6%)
412/3,338 (12.3%; 10.9%–13.7%)
0.87 (0.73–1.02)
Among men aged 15–29
96/1,450 (6.6%; 5.5%–8.0%)
122/2,436 (5.0%; 4.2%–5.8%)
0.70 (0.56–0.89)
Among men not receiving ARV and aged 15–49
249/1,949 (12.8%; 10.7%–14.3%)
303/3,229 (9.4%; 8.1%–10.6%)
0.77 (0.63–0.94)
Among men not receiving ARV and aged 15–29
91/1,445 (6.3%; 5.0%–7.4%)
101/2,414 (4.2%; 3.4%–4.9%)
0.64 (0.49–0.83)
a
Standardized on the 2010 age-structure.
b
Proportion (%) consistently using condoms with non-spousal partners in the last 12
months.
c
The weights are the inverse of the propensity score, which was estimated from the
basic covariates using logistic regression.
d
Proportion (%) having had two or more non-spousal partners in the last 12 months.
aPRR, prevalence rate ratio obtained using general linear models adjusted on basic
covariates (age group, ethnic group, religion, having at least a child, occupation,
age at first sexual intercourse, alcohol consumption, education level, and having
ever been married); NA, not applicable.
HIV and ARV Prevalence Rate by MC Status at Follow-up
Overall HIV prevalence rate was 412/3,338 (0.12; 95% CI 0.11–0.14). ARV prevalence
rate was 109/3,388 (0.032; 95% CI 0.024–0.041) and reached 109/412 (0.26; 95% CI 0.20–0.32)
among those tested positive for HIV. The proportion of HIV positive men taking ARVs
among circumcised and uncircumcised men was similar: 31/117 (26.8%) versus 77/295
(26.2%) with PRR adjusted on age = 1.08 95% CI 0.63–1.68; p = 0.74. Figure 2 illustrates
HIV prevalence rate by age in 5-y age-group increments. HIV prevalence rate was 295/1,567
(0.19; 95% CI 0.16–0.21) among uncircumcised men and 117/1,771 (0.066; 95% CI 0.053–0.081)
among circumcised men. As indicated in Table 4, a propensity analysis showed that
HIV prevalence rate was lower among circumcised men, with wPRR = 0.52 (95% CI 0.41–0.67),
corresponding to a reduction of 48% (95% CI 33%–59%). When controlling for the additional
sexual behavior covariates, the wPRR was similar: 0.50 (95% CI 0.39–0.64).
10.1371/journal.pmed.1001509.g002
Figure 2
HIV prevalence rates by age group and circumcision status (n = 3,338).
The error bars represent the 95% confidence intervals.
10.1371/journal.pmed.1001509.t004
Table 4
HIV prevalence among circumcised and uncircumcised men in the follow-up survey.
Male Circumcision Status
HIV Prevalence Rate (95% CI)
PRR Adjusted on Age Group (95% CI)
wHIV Prevalence Rate (95% CI)
wPRR (95% CI)
Uncircumcised
295/1,567 (0.19; 0.16–0.21)
1
146/1,848 (0.079; 0.067–0.092)
1
Circumcised
117/1,771 (0.066; 0.053–0.081)
0.49 (0.38–0.62)
228/1,490 (0.15; 0.14–0.17)
0.52 (0.41–0.67)
wHIV prevalence rate, weighted HIV prevalence rate; wPRR, weighted prevalence rate
ratio using a propensity weighting score, which was estimated from the basic covariates
(age group, ethnic group, religion, having at least a child, occupation, age at first
sexual intercourse, alcohol consumption, education level, and ever having been married)
using logistic regression.
HIV Prevalence Rate by Intention to Become Circumcised at Baseline
Using the baseline data, among uncircumcised men, when controlling for basic covariates,
we could not detect a difference in HIV prevalence rate among those intending to become
circumcised in comparison to other men (adjusted PRR = 1.01; 95% CI 0.74–1.40).
Association of the ANRS Project VMMCs with HIV Prevalence Rate at Follow-up
Without the VMMCs performed during the ANRS project, HIV prevalence rate would have
been 0.147 (95% CI 0.129–0.164) at the time of the follow-up survey instead of 0.123
(95% CI 0.109–0.138). It follows that without these VMMCs, HIV prevalence rate in
2010–2011 would have been 19% higher (95% CI 12%–26%) among men aged 15 to 49 y. It
would have been 28% higher (95% CI 16%–42%) among men aged 15 to 29 y. Among men not
receiving ARV, the relative increases would have been 22.0% (95% CI 13.9%–30.7%) for
the 15 to 49 age group and 28.5% (95% CI 15.1%–43.0%) for the 15 to 29 age group.
BED HIV Incidence Rate at Follow-up
The results obtained when using the BED HIV incidence assay are provided in Table
5. This table shows that the estimations of wIRR between circumcised and uncircumcised
men remained fairly stable when varying cut-off values and corrections methods, with
estimated wIRRs ranging from 0.39 to 0.43, and 95% CI from a minimum lower boundary
of 0.15 to a maximum upper boundary of 0.82. These values correspond to a reduction
of BED HIV incidence rate ranging from 57%–61% with 95% confidence intervals of 29%
to 76% and 14% to 83%, respectively. As shown in Table 5, these results were similar
when controlling for sexual behavior characteristics. Other results are provided in
Text S1.
10.1371/journal.pmed.1001509.t005
Table 5
HIV incidence rates and rate ratios obtained in 2010–2011 with the BED incidence assay
for selected cut-off values, with and without corrections for misclassifications.
Cut-off
HIV-Negative
HIV-Positive
Recently Infected
Correction for Misclassifications
BED HIV Incidence Ratea (per 100 person years; 95% CI)
wIRR (95% CI)
Adjustedb wIRR 95% CI)
Circumcised Men
Uncircumcised Men
0.8
3,020
247
63
None
1.2 (0.5–1.9)
3.9 (2.1–5.7)
0.39 (0.15–0.82)
0.37 (0.13–0.80)
0.8
3,020
247
63
Correction-1
1.0 (0.4–1.7)
3.2 (1.4–5.6)
0.40 (0.19–0.78)
0.37 (0.18–0.72)
0.8
3,020
247
63
Correction-2
0.8 (0.3–1.4)
2.8 (1.2–4.6)
0.40 (0.21–0.76)
0.37 (0.197–0.76)
1.51
3,020
247
31
None
1.3 (0.8–1.9)
4.1 (2.8–5.7)
0.43 (0.22–0.72)
0.41 (0.22–0.73)
1.51
3,020
247
31
Correction-1
1.2 (0.7–1.8)
3.9 (2.4–5.6)
0.43 (0.25–0.69)
0.41 (0.23–0.70)
1.51
3,020
247
31
Correction-2
1.0 (0.6–1.6)
3.3 (2.1–4.8)
0.43 (0.24–0.63)
0.41 (0.24–0.68)
The details of corrections-1 and -2 are provided in Text S1.
a
Standardized on the 2010 age-structure.
b
Adjusted on the following self reported sexual behavior covariates: lifetime number
of sexual partners, consistent condom use with non-spousal partners in the last 12
months, and number of non-spousal partners in the last 12 months.
wIRR, weighted IRR using a propensity weighting score, which was estimated from the
basic covariates (age group, ethnic group, religion, having at least a child, occupation,
age at first sexual intercourse, alcohol consumption, education level, and ever having
been married) using logistic regression.
Variation over Time
Table 3 indicates that ARV prevalence rate increased over time. This table also indicates
that no variation in consistent condom use with non-spousal partners was detected.
In contrast, we detected a small increase over time of the number of non-spousal partners
in the last 12 months. This table shows an overall decrease in HIV prevalence rate
when excluding men on ARV, and among men aged 15 to 29.
Discussion
This study has shown that the roll-out of free VMMC can lead to a substantial uptake
in just a few years, especially among young men, in an African community where MC
is not a social norm. Furthermore, we could not detect any evidence of sexual behavior
differences between circumcised and uncircumcised men. Lastly, the roll-out of VMMC
in this community was associated with a reduction in the prevalence and incidence
of HIV among circumcised men in comparison with uncircumcised men, and we estimated
that without the project, HIV prevalence averaged on all adult men would have been
significantly higher.
This effectiveness study has some limitations. Firstly, this study used a quasi-experimental
design. It was not randomized and cannot prove a causal association. Secondly, HIV
incidence was not measured in the context of a cohort study, which is the gold standard.
We chose another design in order to be able to extrapolate HIV incidence among a random,
cross sectional sample of men to the entire male population of the community. The
possible selection bias associated with cohort studies followed up for many years
may undermine extrapolating results from the sample analysis. Thirdly, we used an
incidence assay to estimate IRRs, which has limitations, as described below. Lastly,
the propensity score methods used can only reduce the selection bias associated with
the observed covariates. We cannot exclude the possibility that there were also some
unobserved confounding factors. However, the fact that those intending to become circumcised
are not more aware of their HIV status [24] and not more infected with HIV, as found
here, is reassuring. One additional limitation is that this study was conducted without
the support of a national adult VMMC campaign. As a result, the VMMC uptake obtained
may have been lower than what would have been observed if such campaign was in effect,
since it would likely have reinforced our local communication campaign and encouraged
VMMC uptake in the community.
Observing a lower HIV prevalence rate among circumcised men in comparison with uncircumcised
men is not surprising. It is the natural consequence of (a) the established causal
relationship between adult VMMC and the reduction of male HIV acquisition demonstrated
in the three RCTs [2]–[4] and (b) the absence of differences in sexual behavior between
circumcised and uncircumcised men, which could have reduced, if not annulled, the
protective effect of MC. The reduced HIV incidence rate among circumcised men caused
a reduction in HIV prevalence rate.
The absence of a statistical association between MC status and sexual behavior is
encouraging and suggests that the so-called “risk compensation” or “behavioral disinhibition”
(i.e., increased risky sexual behavior following adult MC) is either too small to
be detectable even in large samples, or simply does not exist. The association of
MC with no or minor sexual behavior changes had already been suggested but only in
the context of the three MC RCTs and post-trial follow-up studies [2],[25],[26] and
is consistent with the findings of a study conducted in the Orange Farm community,
which showed that willingness to become circumcised was not associated with sexual
behavior characteristics [24].
The BED assay provides more or less precise estimations of HIV incidence rates because
it is nearly impossible to know precisely the factor by which the assay overestimates
or underestimates HIV incidence rates. However, estimations of HIV IRRs are likely
to be more precise, especially when calculating ratios of incidence rates measured
at the same time among subgroups of the same population having the same gender and
of approximately the same age [19]. This was clearly observed in our study with a
rather stable estimation of HIV IRRs obtained when varying cut-off values and types
of correction. It is therefore not surprising that we found an association of MC with
HIV incidence rates similar to what was observed in the RCT conducted in the same
community and elsewhere.
Six years after the international recommendation to include adult VMMC as a complementary
HIV prevention method among adults in sub-Saharan Africa, about three million adult
VMMCs have been performed. This represents less than 10% of the 35 million adult VMMC
that are needed to effectively reduce the spread of the epidemic [10]. Our experience
in Orange Farm shows that an uptake of about 50% can be obtained in about 3 y. However,
this is contingent upon the implementation of an intensive promotion campaign incorporating
broader HIV prevention methods, community involvement and support, a dedicated project
staff, and the availability of quality adult MC surgeries optimizing cost, time, and
personnel to increase accessibility. The current campaign in Orange Farm has been
conducted while funded by private institutions. The success of this intervention,
and the fact that VMMC roll-out among adults is a short-term task, shows that the
involvement of private structures should be encouraged.
This study pleads for the changing of norms and practices regarding MC in southern
and eastern Africa, where some ethnic groups, such as the Zulus, were circumcised
in the past and have only recently (at the beginning of the 19th century) abandoned
this cultural practice for military reasons under the leadership of Dingiswayo [27].
One possibility to promote this change is to encourage neonatal MC, similarly to countries
where MC is the norm, and where the procedure is performed at an early age, usually
before puberty.
Because adult VMMC has been shown to reduce the acquisition not only of HIV but also
of herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) [28]–[30], the next
step should be to confirm that these results are reproduced in similar phase 4 studies.
It will also be important to demonstrate that women, as expected, do indirectly benefit
from the roll-out of adult VMMC through the reduction of their exposure to HIV, because
of the overall reduction in HIV prevalence rate among men. This finding is especially
important because there is a potential increase of male-to-female HIV transmission
during the healing period following MC surgery if the abstinence period is not observed
[31], even if it is unlikely that this effect will undermine the benefits of adult
VMMC roll-out [32].
This study suggests that the roll-out of adult VMMC is associated with a reduction
in HIV in a sub-Saharan community where MC is not a social norm. Along with studies
demonstrating the acceptability of adult VMMC in traditionally non-circumcising communities
in sub-Saharan Africa [5], it gives hope that the epidemic can be reduced in settings
where most men are uncircumcised. However, the demonstration that VMMC roll-out can
indirectly lead to a reduction of HIV acquisition among women and uncircumcised men
needs to be undertaken. The main implication of this study is that the current roll-out
of adult VMMC—endorsed by UNAIDS and WHO, and supported by international agencies
such as PEPFAR, the Global Fund, and by donors like the Bill and Melinda Gates Foundation—should
be accelerated.
Supporting Information
Figure S1
Age distribution of the Orange Farm male population obtained in 2010 from a random
sample of 1,195 men.
(PDF)
Click here for additional data file.
Figure S2
Boxplots of estimated propensity scores by circumcision status: minimum, first decile,
lower quartile, median, upper quartile, ninth decile, and maximum.
(PDF)
Click here for additional data file.
Table S1
Comparison of the results given by a log-binomial and a Poisson regression for weighted
HIV prevalence and incidence rate ratios between circumcised and uncircumcised men.
(PDF)
Click here for additional data file.
Text S1
Supplemental methods and results.
(PDF)
Click here for additional data file.