Review Article - Cohort Study

Download as pdf or txt
Download as pdf or txt
You are on page 1of 8

Colombe et al.

BMC Infectious Diseases (2019) 19:518


https://doi.org/10.1186/s12879-019-4151-8

RESEARCH ARTICLE Open Access

HIV-seroconversion among HIV-1


serodiscordant married couples in
Tanzania: a cohort study
Soledad Colombe1* , James Beard2, Baltazar Mtenga3, Peter Lutonja3, Julius Mngara3, Claudia J. de Dood4,
Govert J. van Dam5, Paul L. A. M. Corstjens4, Samuel Kalluvya6, Mark Urassa3, Jim Todd2,3 and Jennifer A. Downs1,6

Abstract
Background: Heterosexual transmission is the main driver of the HIV epidemic in Tanzania. Only one estimate of the
incidence rate of intra-marital HIV seroconversion in Tanzania has been reported and was derived from data collected
between 1991 and 1995. Moreover, little is known about the specific risk factors for intra-marital seroconversion in
Tanzania. Improved evidence around factors that increase the risk of HIV transmission to a serodiscordant spouse is
needed to develop and improve evidence-based interventions. We sought to investigate the rate of intra-marital HIV
seroconversion among HIV sero-discordant couples in Tanzania as well as its associated risk factors.
Methods: We identified all HIV positive individuals in the TAZAMA HIV-serosurvey cohort and followed up their
serodiscordant spouse from 2006 to 2016. The rate of seroconversion was analyzed by survival analysis using non-
parametric regressions with exponential distribution.
Results: We found 105 serodiscordant couples, 14 of which had a seroconverting spouse. The overall HIV-1 incidence
rate among spouses of people with HIV-1 infection was 38.0 per 1000 person/years [22.5–64.1]. Notably, the HIV-1
incidence rate among HIV-1 seronegative male spouses was 6.7[0.9–47.5] per 1000 person/years, compared to 59.3
[34.4–102.1] per 1000 person/years among female spouses. Sex of the serodiscordant spouse was the only significant
variable, even after adjusting for other variables (Hazard rate = 8.86[1.16–67.70], p = 0.036).
Conclusions: Our study suggests that rates of HIV-1 seroconversion of sero-discordant partners are much higher
within marriage than in the general population in Tanzania. The major risk factor for HIV-1 seroconversion is sex of the
serodiscordant spouse, with female spouses being at very high risk of acquiring HIV infection. This suggests that future
programs that target serodiscordant couples could be a novel and effective means of preventing HIV-1 transmission in
Tanzania.
Keywords: HIV, Modes of transmission, Heterosexual behavior

Background co-infection [3–5], low condom use, numerous sexual


An estimated 790,000 new HIV infections occurred in partners, and lack of male circumcision [6].
Southern and Eastern Africa in 2016. Of these, 55,000 In 2011, the Tanzania HIV/AIDS and Malaria indicator
happened in Tanzania, where the prevalence of HIV is survey showed that women and men who were married
twice as high in women as in men [1]. Heterosexual were more likely to be HIV infected compared to men
transmission is the main driver of the HIV epidemic in and women that were never married [6]. Within mar-
Tanzania [2], with typical risk factors including presence riage, additional factors associated with increased risk of
of sexually transmitted infections (STI), Schistosoma spp. HIV acquisition from a seropositive spouse include use
of hormonal contraception [7], concurrent sexual part-
* Correspondence: [email protected]
nerships [8], alcohol use [8], age discordancy [9], genital
1
Center for Global Health, Department of Medicine, Weill Cornell Medicine, inflammation and discharge [10], non-antiretroviral
402 East 67th Street, 2nd Floor, New York, NY 10065, USA
Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Colombe et al. BMC Infectious Diseases (2019) 19:518 Page 2 of 8

(ART) use by the HIV-positive partner [11] and aware- HIV-1 positive at an HIV testing clinic within the
ness of the partner’s status [12]. TAZAMA cohort between 2006 and 2013. Throughout
In addition, women in either long-term relationships the rest of the methods we will refer to these individuals
or marriage are more at risk of acquiring HIV than men, as “baseline individuals” for clarity and brevity.
likely due to an array of cultural, social, economic, and
biological reasons [13]. In particular, male-to-female Identification of serodiscordant spouse and relationship
HIV transmission occurs with higher frequency than time period
female-to-male transmission [14] and condoms are Through the DSS we identified all spouses of baseline
rarely used in intimate relationships in Tanzania [15]. In- individuals and obtained their HIV-1 test results from
timate partner violence and gender-based violence can both the sero-surveys and from HIV tests at other
also prevent women from protecting themselves against clinics. We excluded couples that were never serodiscor-
HIV [13] and women who experience intimate partner dant from the analysis, and couples for which the spouse
violence are as much as 1.5 times more likely to acquire had HIV-1 seroconverted more than 6 months after ei-
HIV [13]. ther partner reported the end of the relationship. For
Only one estimate of the incidence rate of intra- each couple, we determined the at-risk dates for HIV-1
marital HIV seroconversion in Tanzania has been re- seroconversion during which they reported being in a
ported and was derived from data collected between sexual relationship with a partner who was HIV-1 posi-
1991 and 1995 [16]. Moreover, little is known about the tive. We collected demographic and sexual behavior data
specific risk factors for intra-marital seroconversion in from the first DSS or sero-survey following the start of
Tanzania. Improved evidence around factors that in- the serodiscordant relationship. Sexual behavior data in-
crease the risk of HIV seroconversion within serodiscor- cluded the number of extra-marital partners, having sex
dant spouses is needed to develop and improve with sex workers, and traveling men.
evidence-based interventions. We used data from all sero-surveys until the last sero-
We sought to investigate the rate of intra-marital HIV- survey with questions pertaining to the relationship time
seroconversion within serodiscordant couples in Tanzania period. Seroconverters were defined as individuals who
as well as its associated risk factors. We hypothesized that had been HIV-1 seronegative in one sero-survey and
the rate of intra-marital HIV-seroconversion would be who were found to be HIV-1 seropositive in a subse-
more than twice as high as the rate of HIV-seroconversion quent sero-survey. All DBS available until the date of
in the general population and that women would have the spouse potential seroconversion were tested for
higher rates of acquiring HIV than men. Schistosoma circulating anodic antigen for both the
baseline individual and his or her spouse.
Methods
Identification of HIV-1 infected individuals
Our study was conducted within the ongoing TAZAMA Follow-up
project, a community-based longitudinal open HIV- The follow-up period started either from the start of the
testing cohort in Kisesa, northwest Tanzania, which doc- relationship or from the first positive HIV result for the
uments detailed demographic, sexual, and behavioral baseline individual. The follow-up period ended either at
data and collects dried blood spots (DBS) approximately the spouse’s seroconversion date, or at the end of the re-
every 3 years from a population of ~ 30,000 individuals. lationship, or at the last sero-survey for which a spouse
Those wishing to know their HIV status may undergo had an available HIV-1 test result and remained HIV-
voluntary HIV testing and counseling on the same day seronegative. The seroconversion date was approximated
as collection of the DBS, and if tested positive, are re- as the mid-point between the last negative DBS and the
ferred to a treatment clinic. The HIV testing (sero-sur- first positive test, either at a sero-survey or at another
vey) is nested within a Demographic Surveillance System clinic.
(DSS) which visits every household in the catchment
area approximately every 9 months to document house- Laboratory testing
hold members and relationships. Additional details have Dried blood spots
been previously described [17]. Details collected from DBS were collected by finger prick onto a Whatman
both the DSS and sero-surveys included the start and Protein Saver 903 card (GE Healthcare Bio-Sciences,
end dates of sexual relationships with both the spouse Pittsburgh, PA). DBS cards were dried out of direct sun-
with whom they lived and with external sexual partners light and sealed in a gas-impermeable zip bag with desic-
and the frequency of sexual intercourse. cant and humidity indicator. Cards were stored at the
For this project, we identified all individuals whose National Institute for Medical Research (NIMR) labora-
DBS tested positive for HIV-1 or who were found to be tory in Mwanza at − 20 °C.
Colombe et al. BMC Infectious Diseases (2019) 19:518 Page 3 of 8

HIV-1 testing males versus females. A parametric survival model with


Diagnosis of HIV-1 infection was confirmed using a exponential distribution, adjusted for all significantly dif-
screening and subsequent confirmatory test, as recom- ferent baseline factors as well as biologically sound vari-
mended by national HIV guidelines, at each time point. ables, was used to assess endpoint incidence difference
These were: Uniform II Category III Ab test followed by by schistosome infection status. Time-dependent vari-
Enzygnost test (sero-surveys 5 and 6), Uniform II Cat- ables characterized at each sero-survey (such as number
egory IV Ab+Ag test followed by Enzygnost test (sero- of extra-marital sex partners, frequency of sex, etc) were
survey 7), and Determine test followed by Unigold test defined as representative of the time period following
(sero-survey 8). Samples that were negative at the the sero-survey and are called “survey-dependent vari-
screening test were reported as negative. Samples that ables” for the rest of the manuscript.
were positive at the screening test were tested with the Variables that were associated with failure at 10% sig-
confirmatory test. If the confirmatory test was negative, nificance were individually included into the model and
the final result was reported as negative. If the confirma- model goodness-of-fit assessed through step-wise ana-
tory test was positive, the final result was reported as lysis. Based on the results of the analysis, a second ana-
positive. lysis was performed after stratifying by sex of the
serodiscordant spouse. All analyses were performed in
Schistosoma sp. testing STATA 14.1 (College Station, TX, USA). All results were
DBS were tested for schistosome for both HIV seronega- expressed with 95% confidence intervals (CIs) and statis-
tive and seropositive individuals by Circulating Anodic tical significance was set at P < 0.05 (two-tailed).
Antigen (CAA) at Leiden University Medical Center by We conducted a sensitivity analysis in which survey-
eluting whole blood from banked DBS collected during dependent variables were defined as representative of
the sero-surveys and then concentrating the sample as the time period preceding the sero-survey results. Finally
previously described [18]. The CAA test is a genus- we conducted a second sensitivity analysis in which we
specific assay that detects a gut-associated antigen se- excluded all couples for which the baseline individual
creted into the host bloodstream by adult schistosome was on ART.
worms. The test does not differentiate between the
Schistosoma mansoni and haematobium species present Ethics, consent and permissions
in the Kisesa area of Tanzania. A lower limit threshold Ethical approval for retrospective and prospective ana-
of 2 pg CAA per mL of eluted blood was used for the lysis of these data was obtained from Bugando Medical
assay. Thirty-five individuals had stored serum samples Centre in Mwanza (BREC/001/04/2011), the National
but no DBS samples available for testing and underwent Institute for Medical Research in Dar es Salaam (NIMR/
serum CAA testing at NIMR with a lower limit thresh- HQ/R.8a/Vol.IX/2446), and Weill Cornell Medicine in
old of 30 pg CAA per mL [19]. Samples scoring values New York (1108011883). Study participants provided
above the threshold were designated positive for Schisto- written informed consent during enrollment into the co-
soma infection, and a person with schistosome positivity hort study as per the approved procedures of the
at any point in the time during the relationship was de- TAZAMA project, which included consent for future
fined as having the infection. testing of DBS samples [17].

Statistical analysis Results


Analysis included all couples as described above. Binary We identified 1439 baseline individuals who were found
variables were described as proportions and continuous to be HIV-1 seropositive at a sero-survey between 2006
variables were described using median and interquartile and 2013. Of these 554 had at least one spouse regis-
range. We assessed differences in baseline characteristics tered in the DSS after the time of the baseline individ-
using Chi-square or Fisher’s exact test for proportions ual’s first positive test. Among the 554, 289 had at least
and the nonparametric equality test for medians. one spouse who had HIV-1 test results and 105/289
A survival analysis was conducted to investigate the were serodiscordant couples between 2006 and 2016
difference in HIV-1 seroconversion rates between spouse who met criteria for inclusion in this analysis. From
of a baseline individual by sex. The event of interest was these serodiscordant couples, this yielded 368.8 years of
defined as HIV-1 seroconversion. Data was censored at total analysis time at risk and under observation.
the end of the relationship or for loss to follow-up, de- 63.8% (67/105) of couples had a male baseline individ-
fined as the last negative sero-survey at which the ual and a female serodiscordant spouse. An overwhelm-
spouse provided a DBS. The Kaplan-Meyer method was ing proportion of baseline individuals and spouses were
used to compare time to seroconversion between the of Sukuma ethnicity (97.1% (102/105) and 92.4% (97/
HIV-serodiscordant spouses of baseline individuals for 105), respectively), Christian (83.8% (88/105) and 92.4%
Colombe et al. BMC Infectious Diseases (2019) 19:518 Page 4 of 8

(87/105), respectively), and reported having only one After stepwise multivariable analysis, sex of the sero-
spouse (87.6% (92/105) and 90.5% (95/105), respectively) discordant partner was the only variable that yielded a
. 52.2% (48/92) of the baseline individuals were schisto- best of fit model. Female spouses thus had a rate of sero-
some positive. 54.5% (55/101) of the serodiscordant conversion 8.77[1.15–67.04] times higher than male
spouses were schistosome positive. All couples were het- spouses (p = 0.036). The Kaplan-Meyer survival curves
erosexual. The demographics of the population are pre- by spouse sex are presented in Fig. 1.
sented in Table 1 as a comparison between the 14 After running the sensitivity analyses, when survey-
people who HIV-seroconverted during follow-up and dependent variables were defined as representative of
the 91 people who did not. Serosurvey-dependent vari- the time period preceding the sero-survey results, the
ables are presented in Table 2. hazard ratio for female spouses was 8.86[1.16–67.70],
14/105 (13.3%) partners HIV-1 seroconverted, and 13 of p = 0.036. When excluding all couples on ART from the
these were women. The overall HIV-1 incidence rate analysis, the hazard ratio for female spouses was still
among spouses of people with HIV-1 infection was 38.0 8.89[1.16–67.92], p = 0.035. Finally, when stratifying by
per 1000 person/years [22.5–64.1]. Notably, the HIV-1 in- sex, none of the variables were significantly associated
cidence rate among HIV-1 seronegative male spouse was with seroconversion.
6.7[0.9–47.5] per 1000 person/years, compared to 59.3
[34.4–102.1] per 1000 person/years among female spouse. Discussion
After univariable analysis, sex of the serodiscordant In this in-depth study of a community of approximately
partner was the only variable that was significantly asso- 30,000 individuals, the intra-marriage HIV-incidence in
ciated with HIV-1 seroconversion. HIV-1 uninfected our study population was overall 19 times the general
female spouses of HIV-1 infected male baseline individ- national HIV-incidence [1]. This effect was largely due
uals were found to have higher incidence rates of sero- to women being highly susceptible to incident HIV in-
conversion than HIV-1 uninfected male spouses of HIV- fection, yielding an incidence of 60 seroconversions per
1 infected female baseline individuals (Hazard ratio 1000 person-years in women and only 7 per 1000
(HR) = 8.77, p = 0.036). None of the spouses of baseline person-years in men. This is a greater than eight-fold in-
individuals on ART or with formal education serocon- crease in HIV acquisition in women as compared to
verted. None of the serodiscordant spouses in a polyg- men, and suggests that intra-marriage seroconversion in
amous marriage or with reported extra-marital partners serodiscordant couples deserves more attention in
acquired HIV. Results of the univariable analyses are Tanzania, and that disproportionate transmission from
presented in Table 2. men to women, particularly in the absence of female-

Table 1 Characteristics of the spouse, baseline individual and couple by spouse seroconversion status
Variable Non-seroconverters Seroconverters p-value
N = 91 N = 14
Variables concerning the baseline individual
Sex (Female) 40.7% (37/91) 7.1% (1/14) 0.016
Education (Received at least 1 year of formal schooling) 24.4% (22/90) 0.0% (0/14) 0.037
ART intake 12.1% (11/91) 0% (0/14) 0.353
Marital status (Polygamy) 13.2% (12/91) 7.1% (1/14) 1
Age in years at the start of the time period of interest 39[33–45] 44[37–53] 0.125
Schistosome CAA positivity 51.3% (41/80) 58.3% (7/12) 0.647
Variables concerning the serodiscordant spouse
Sex (Female) 59.3% (54/91) 92.9% (13/14) 0.016
Education (Received at least 1 year of formal schooling) 42.9% (39/91) 21.4% (3/14) 0.037
Marital status (Polygamy) 12.1% (11/91) 0% (0/14) 0.353
Age in years at the start of the time period of interest 37[31–46] 35.5[32–46] 0.828
Male and circumcised 46.4% (13/28) – –
Schistosome CAA positivity 54.0% (47/87) 57.1% (8/14) 0.828
Variables concerning the couple
Age difference between the baseline individual and his/her spouse -3[−9;4] −5[−8;-4] 0.246
Length of the time period of interest (in days) 1029 [691–1882] 1093.5[571–1150.5] 0.228
Colombe et al. BMC Infectious Diseases (2019) 19:518 Page 5 of 8

Table 2 Results of the univariable analysis for factors associated with HIV-1 seroconversion
Variable Person-time Number of Hazard ratio p-value
(in years) events [95%CI]
Variables concerning the baseline individual
Sex Male 221.50 13 0.11[0.015–0.87] 0.036
Female 149.43 1
Education Never attended school 294.91 14 0[0]a 0.992
Ever attended school 71.01 0
ART intake No 318.72 14 0[0]a 0.992
Yes 50.06 0
Ln(CAA)d – – – 1.18[0.93–1.49] 0.177
STI symptoms No 291.31 11 1.03[0.29–3.68] 0.969
Yes 77.46 3
Schistosome CAA positivity Negative 167.80 5 1.35[0.43–4.24] 0.611
Positive 172.27 7
Variables concerning the serodiscordant spouse
Sex Male 149.43 1 8.77[1.15–67.04] 0.036
Female 221.50 13
Education Never attended school 234.99 11 0.48[0.13–1.72] 0.258
Ever attended school 135.94 3
Other risks for HIVbd No 297.77 14 0[0]a 0.994
Yes 71.00 0
Risky sex behaviorc,d No 66.43 4 0[0]a 0.994
Yes 19.15 0
Ln(CAA) d – – – 1.11[0.85–1.44] 0.453
Number of extramarital partnersd None 303.95 14 0[0]a 0.994
One or more 66.97 0
STI Symptomsd No 285.8 12 0.57[0.13–2.57] 0.468
Yes 82.94 2
Schistosome CAA positivity Negative 152.33 6 1.03[0.36–2.98] 0.953
Positive 196.75 8
Variables concerning the couple
Age difference between the baseline – – – 1.00[0.9991–1.001] 0.734
individual and his/her spouse in years
Sex frequencyd Less than once a month 37.22 1
Between once a month and 134.64 6 1.66[0.20–13.78] 0.639
once a week
More than once a week 166.50 5 1.12[0.13–9.57] 0.919
a
No convergence of the model due to presence of zeros. No conclusion on the association between the variable and seroconversion can be made due to short
person-time available. ART was still included in the final model stepwise analysis
b
Other risks for HIV include incisions and transfusions
c
Risky sex behaviors include having sex with women at bars or with traveling men
d
Survey-dependent variables

controlled HIV-prevention measures, may continue to 1991 and 1995, with the rate of seroconversion for
push the HIV epidemic towards female predominance. women only being twice as high as the rate of sero-
Only one other estimate of the intra-marriage HIV- conversion for men [16]. The difference between the
incidence in Tanzania has been published, reporting a prior and current findings reflects the large decrease
rate of HIV seroconversion among serodiscordant in HIV incidence in Tanzania over the past 30 years
couples of 75(28–163) per 1000 person-years between as well as changes in drivers of the epidemic, such as
Colombe et al. BMC Infectious Diseases (2019) 19:518 Page 6 of 8

factors may be less important. Our results are con-


sistent with the well-described finding that, per sex
act, women are indeed more at risk of HIV-1 infec-
tion than men [25], likely due to a larger surface area
of the vagina and the ability of the virus to pass eas-
ily through the cells of the vaginal lining. Too few
partners were on ART to assess the role of ART on
seroconversion in our study, although the finding that
no partners of baseline individuals on ART serocon-
verted is consistent with other studies that showed
lower incidence of HIV when HIV positive partner
was on ART.
Our study supports findings of a large independent
serodiscordant couples’ study in Zambia. Our estimate
Fig. 1 Kaplan-Meier survival estimates for seroconversion by sex of
of the role of schistosome infection in the transmit-
the spouse. The curve represents the risk of seroconverting over
time by sex of the serodiscordant spouse ting partner on HIV-1 incidence (HR = 1.35, p = 0.6) is
of similar magnitude of that found in the much larger
Zambia study [4] (adjusted HR between 1.4 and 1.8,
changes in sexual behavior and women’s susceptibility. p < 0.005) and shows a directional trend towards an
In other countries in Sub-Saharan Africa, reported increased transmission of HIV-1 from baseline indi-
HIV incidence in HIV-serodiscordant couples concord viduals infected with Schistosoma spp.. Schistosome
with our results, although varies widely (from 20 to infection could lead to genital inflammation and ex-
118 per 1000 person-years) [20–22]. Of note, these posure to blood or higher genital tract HIV-1 RNA
studies reported rates in serodiscordant negative fe- viral loads [26, 27]. Schistosoma spp. leads to higher
males less than twice as high as rates in serodiscor- HIV-1 RNA plasma viral load as well [5], which is
dant negative males [20]. highly predictive of transmission to sexual partners
Although uptake of ART among HIV-serodiscordant [28]. Even though our project was located in a com-
couples has been recommended where feasible [23], it munity cohort of 30,000 people, our sample size of
does not remove the need for behavioral interventions discordant couples provided only enough power (80%)
to reduce HIV acquisition from outside partners [12]. to detect significance for a hazard ratio of 3.7 or
Serodiscordance within a couple may lead to in- above, far higher than the hazard ratio estimates ob-
creased outside-partnership sex and increased risk of tained by this or the Zambia study. Our study simi-
outside transmission [12]. Tanzania has not focused larly may have lacked power to document an effect of
its efforts on serodiscordant couples yet and these re- schistosome status on HIV acquisition in the receiving
sults suggest that future programs that target serodis- partner, which has previously been documented in
cordant couples may be an effective way to prevent other studies [5, 29].
HIV-1 transmission in Tanzania. Couples’ voluntary Our results are to be interpreted in light of some
HIV counseling and testing significantly reduces HIV limitations. We were unable to test for viral loads, or
transmission in discordant couples and has been additional immunologic markers that might provide
shown to increase a couple’s knowledge about HIV insight into the reasons for our observations, due to
serodiscordance and prevention behaviors [21]. In the insufficient quantity of blood in DBS. We were also
light of the shift to test-and-treat strategies, couples’ unable to perform phylogenetic analyses that would
targeted-strategies for increasing uptake of ART could have permitted determination of whether the HIV-
be a key tool to achieve the goal of eliminating HIV seroconverting partner had been infected from a part-
transmission, and this should include specific HIV ner outside of the marriage. Partners might also
prevention messages to the HIV negative partner. under or overestimate the number of extra-marital
Surprisingly, the usual risk factors for HIV-1 sero- sexual partners based on their gender [30]. Further
conversion within marriage, such as sex frequency, studies with larger numbers of seroconverters should
count of extra-marital sex partners and age difference be undertaken, which should include better assess-
with the spouse, were not significant within our co- ment of loss to follow up among the HIV negative
hort [24]. It is possible that this was due to the marital partners of PLHIV. Despite those limitations,
higher age of our study participants than has been our finding that all sensitivity analyses gave the same
observed in most other serodiscordant couple studies results strengthens confidence in the quality and ac-
[4, 16]. In these older adults, traditional HIV risk curacy of our analysis.
Colombe et al. BMC Infectious Diseases (2019) 19:518 Page 7 of 8

Conclusions Author details


1
In conclusion, our study suggests that rates of HIV-1 Center for Global Health, Department of Medicine, Weill Cornell Medicine,
402 East 67th Street, 2nd Floor, New York, NY 10065, USA. 2Department of
seroconversion are much higher within marriage than in Population Health, London School of Hygiene and Tropical Medicine,
the general population in Tanzania. The major risk fac- London, UK. 3National Institute for Medical Research, Mwanza Research
tor for HIV-1 seroconversion is sex of the serodiscordant Centre, Mwanza, Tanzania. 4Department of Cell and Chemical Biology, Leiden
University Medical Center, Leiden, Netherlands. 5Department of Parasitology,
spouse, with female spouses being at very high risk of Leiden University Medical Center, Leiden, Netherlands. 6Department of
HIV-seroconverting. Medicine, Bugando Medical Centre, Mwanza, Tanzania.
This suggests that future programs that target serodis-
Received: 18 February 2019 Accepted: 31 May 2019
cordant couples, regardless of source of infection, could
be a novel and effective means of preventing HIV-1
transmission in Tanzania. In addition, future studies References
should explore the source of HIV acquisition in order to 1. UNAIDS. http://aidsinfo.unaids.org/. Published 2018. Accessed 6 June 2018.
focus HIV prevention efforts on specific risk groups. 2. The United Republic of Tanzania. Ministry of Health and social welfare.
National Guidelines for the management of HIV and AIDS. 5th ed: National
AIDS control Programme; 2015.
Abbreviations 3. Secor WE. The effects of schistosomiasis on HIV/AIDS infection, progression
AIDS: Acquired Immune Deficiency Syndrome; ART: Antiretroviral Therapy; and transmission. Curr Opin HIV AIDS. 2012;7(3):254–9.
CAA: Circulating Anodic Antigen; DBS: Dried Blood Spot; DSS: Demographic 4. Wall KM, Kilembe W, Vwalika B, Dinh C, Livingston P, Lee YM, et al.
Surveillance System; HIV: Human Immunodeficiency Virus; HR: Hazard Ratio; Schistosomiasis is associated with incident HIV transmission and death in
NIMR: National Institute for Medical Research; RNA: Ribonucleic acid; Zambia. PLoS Negl Trop Dis. 2018;12(12):e0006902.
STI: Sexually Transmitted Infection 5. Downs JA, Dupnik KM, van Dam GJ, Urassa M, Lutonja P, Kornelis D, et al.
Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral
Acknowledgments load at HIV-1 seroconversion: a nested case-control study. PLoS Negl Trop
We thank the TAZAMA study team and health care workers for the excellent Dis. 2017;11:e0005968. https://doi.org/10.1371/journal.pntd.0005968.
data they have continued to collect for the past 24 years, as well as the 6. Ministry of Health Zanzibar, National Bureau of Statistics Dar es Salaam, Office
Kisesa community members for their participation. of Chief Government Statitician Zanzibar, ICF, USAID, UNICEF, UNFPA. Tanzania
Demographic and Health Survey and Malaria Indicator Survey (TDHS-MIS)
2011–12. Dar es Salaam; 2012. https://doi.org/10.1017/CBO9781107415324.004.
Authors’ contributions 7. Haddad LB, Polis CB, Sheth AN, Brown J, Kourtis AP, King C, et al. Contraceptive
SC designed the study, cleaned and analysed the data, interpreted the methods and risk of HIV acquisition or female-to-male transmission. Curr HIV/
results and wrote the original manuscript. JB and BM contributed the data, AIDS Rep. 2014. https://doi.org/10.1007/s11904-014-0236-6.
cleaned the data, interpreted the results and revised the manuscript. PL, JM, 8. Seeley J, Nakiyingi-Miiro J, Kamali A, Mpendo J, Asiki G, Abaasa A, et al. High
CJdD, GJvD and PLAMC contributed to the laboratory testing, supplied HIV incidence and socio-behavioral risk patterns in fishing communities on
reagents, and revised the manuscript. SK, MU and JT designed and the shores of Lake Victoria, Uganda. Sex Transm Dis. 2012. https://doi.org/
supervised the study and revised the manuscript. JAD designed and 10.1097/OLQ.0b013e318251555d.
supervised the study, interpreted the results and wrote the original 9. Harling G, Newell M, Tanser F, Kawachi I, Subramanian S, Bärnighausen T. Do
manuscript. All authors have contributed to writing this manuscript and age-disparate relationships drive HIV incidence in young women ? Evidence
agreed to the final version. from a population cohort in rural KwaZulu-Natal, South Africa. J Acquir
Immune Defic Syndr. 2014. https://doi.org/10.1097/QAI.0000000000000198.
Funding 10. Wall KM, Kilembe W, Vwalika B, Haddad LB, Hunter E, Lakhi S, et al. Risk of
This work was supported by a Kellen Junior Faculty Fellowship from Weill heterosexual HIV transmission attributable to sexually transmitted infections
Cornell Medicine and the National Institutes of Health (K23 AI 110238 to and non-specific genital inflammation in Zambian discordant couples,
J.A.D.). The funder had no role in the design, data collection, analysis and 1994–2012. Int J Epidemiol. 2017. https://doi.org/10.1093/ije/dyx045.
interpretation of results in this study. 11. Biraro S, Ruzagira E, Kamali A, Whitworth J, Grosskurth H, Weiss HA. HIV-1
transmission within marriage in rural Uganda: a longitudinal study. PLoS
One. 2013. https://doi.org/10.1371/journal.pone.0055060.
Availability of data and materials 12. Ndase P, Celum C, Thomas K, Donnell D, Fife KH, Bukusi E, et al. Outside
Data are available to researchers who meet the criteria for access to sexual partnerships and risk of HIV acquisition for HIV uninfected partners in
confidential data from the TAZAMA project, upon request. The TAZAMA data African HIV serodiscordant partnerships. J Acquir Immune Defic Syndr. 2012.
follow the INDEPTH Policies, which requires information and signatures https://doi.org/10.1097/QAI.0b013e318237b864.
before obtaining the data. Interested researchers should contact John 13. UNAIDS. Ending Aids Progress Towards the 90-90-90 Targets. Global Aids
Changalucha at [email protected]. Update. 2017; UNAIDS/JC2900E.
14. Nicolosi A, Leite MLC, Musicco M, Arid C, Gavazzeni G, Lazzarin A, et al. The
Ethics approval and consent to participate efficiency of male-to-female and female-to-male sexual transmission of the
Ethical approval for retrospective and prospective analysis of these data was human immunodeficiency virus: a study of 730 stable couples.
obtained from Bugando Medical Centre in Mwanza (BREC/001/04/2011), the Epidemiology. 1994. https://doi.org/10.1097/00001648-199411000-00003.
National Institute for Medical Research in Dar es Salaam (NIMR/HQ/R.8a/ 15. Exavery A, Kanté AM, Jackson E, Noronha J, Sikustahili G, Tani K, et al. Role
Vol.IX/2446), and Weill Cornell Medicine in New York (1108011883). Study of condom negotiation on condom use among women of reproductive
participants provided informed written consent during enrollment into the age in three districts in Tanzania. BMC Public Health. 2012. https://doi.org/
cohort study as per the approved procedures of the TAZAMA project, which 10.1186/1471-2458-12-1097.
included consent for future testing of DBS samples [15]. 16. Hugonnet S, Mosha F, Todd J, Mugeye K, Klokke A, Ndeki L, et al. Incidence
of HIV infection in stable sexual partnerships: a retrospective cohort study of
1802 couples in Mwanza region, Tanzania. J Acquir Immune Defic Syndr.
Consent for publication
2002. https://doi.org/10.1097/00042560-200205010-00010.
Not applicable.
17. Mwaluko G, Urassa M, Isingo R, Zaba B, Boerma JT. Trends in HIV and
sexual behaviour in a longitudinal study in a rural population in
Competing interests Tanzania, 1994-2000. Aids. 2003;17(18):2645–51. https://doi.org/10.1097/
The authors declare that they have no competing interest. 01.aids.0000088225.55968.9d.
Colombe et al. BMC Infectious Diseases (2019) 19:518 Page 8 of 8

18. Downs JA, Corstjens PLAM, Mngara J, Lutonja P, Isingo R, Urassa M, et al.
Correlation of serum and dried blood spot results for quantitation of
Schistosoma circulating anodic antigen: a proof of principle. Acta Trop.
2015. https://doi.org/10.1016/j.actatropica.2015.06.026.
19. Corstjens PLAM, De Dood CJ, Kornelis D, Tjon Kon Fat EM, Wilson RA,
Kariuki TM, et al. Tools for diagnosis, monitoring and screening of
Schistosoma infections utilizing lateral-flow based assays and
upconverting phosphor labels. Parasitology. 2014. https://doi.org/10.
1017/S0031182014000626.
20. Kamali A, Price MA, Lakhi S, Karita E, Inambao M, Sanders EJ, et al. Creating
an African HIV clinical research and prevention trials network: HIV
prevalence, incidence and transmission. PLoS One. 2015. https://doi.org/10.
1371/journal.pone.0116100.
21. Chemaitelly H, Awad SF, Shelton JD, Abu-Raddad LJ. Sources of HIV
incidence among stable couples in sub-Saharan Africa. J Int AIDS Soc. 2014.
https://doi.org/10.7448/IAS.17.1.18765.
22. Chemaitelly H, Awad SF, Abu-Raddad LJ. The risk of HIV transmission within
HIV-1 sero-discordant couples appears to vary across sub-Saharan Africa.
Epidemics. 2014;6:1–9. https://doi.org/10.1016/j.epidem.2013.11.001.
23. World Health Organization. Consolidated guidelines on the use of
antiretroviral drugs for treating and preventing HIV infection:
recommendations for a public health approach. World Heal Organ. 2016.
https://doi.org/10.1016/j.jped.2014.04.007.
24. Harling G, Newell M-L, Tanser F, Bärnighausen T. Partner age-disparity and
HIV incidence risk for older women in rural South Africa. AIDS Behav. 2015.
https://doi.org/10.1007/s10461-014-0952-3.
25. Griesbeck M, Scully E, Altfeld M. Sex and gender differences in HIV-1
infection. Clin Sci. 2016. https://doi.org/10.1042/CS20160112.
26. Kjetland EF, Leutscher PDC, Ndhlovu PD. A review of female genital
schistosomiasis. Trends Parasitol. 2012. https://doi.org/10.1016/j.pt.2011.10.008.
27. Leutscher PDC, Pedersen M, Raharisolo C, Jensen JS, Hoffmann S, Lisse I, et
al. Increased prevalence of leukocytes and elevated cytokine levels in
semen from Schistosoma haematobium-infected individuals. J Infect Dis.
2005. https://doi.org/10.1086/429334.
28. Fraser C, Hollingsworth TD, Chapman R, de Wolf F, Hanage WP. Variation in
HIV-1 set-point viral load: epidemiological analysis and an evolutionary
hypothesis. Proc Natl Acad Sci. 2007. https://doi.org/10.1073/pnas.0708559104.
29. Mazigo HD, Nuwaha F, Wilson S, Kinung’hi SM, Morona D, Waihenya R, et al.
Epidemiology and interactions of human immunodeficiency virus - 1 and
Schistosoma mansoni in sub-Saharan Africa. Infect Dis Poverty. 2013;2(1):2.
https://doi.org/10.1186/2049-9957-2-2.
30. Nnko S, Boerma JT, Urassa M, Mwaluko G, Zaba B. Secretive females or
swaggering males? An assessment of the quality of sexual partnership
reporting in rural Tanzania. Soc Sci Med. 2004. https://doi.org/10.1016/j.
socscimed.2003.10.031.

Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.

You might also like