Review Article - Cohort Study
Review Article - Cohort Study
Review Article - Cohort Study
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
© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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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
(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
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