LETTER TO THE EDITOR
In sub-Saharan Africa, stable, heterosexual HIV-1 serodiscordant couples (i.e., one member is HIV-1 infected and the other uninfected) account for a substantial proportion of new infections and are a priority population for novel prevention interventions (1). Serodiscordant couples frequently have high pregnancy incidence and intentionally risk HIV-1 transmission in order to conceive (2, 3). Earlier antiretroviral therapy (ART) initiation (i.e., at CD4 counts >350 cells/μL) substantially reduces the risk of HIV-1 transmission within HIV-1 serodiscordant couples (4). Early ART may reduce peri-conception HIV-1 transmission risk due to decreased HIV-1 viral load and infectiousness (5, 6). We investigated fertility intentions and interest in early ART for HIV-1 prevention among East African HIV-1 infected individuals in serodiscordant partnerships.
Between July and December 2011, we conducted a cross-sectional study among Kenyan and Ugandan heterosexual HIV-1 serodiscordant couples participating in the Partners PrEP Study, a phase III, multisite, randomized, placebo-controlled trial of oral pre-exposure prophylaxis (PrEP) for HIV-1 prevention (7). During the trial, participants received standard HIV-1 prevention services including regular HIV-1 risk-reduction counseling and free condoms. They were informed and counseled about the results of clinical trials of new interventions for HIV-1 prevention, including HPTN 052 and the clinical and prevention benefits of early ART (4, 8). In July 2011, the independent data and safety monitoring board recommended that the placebo arm of the trial be discontinued due to clear demonstration of PrEP efficacy for HIV-1 prevention (8). Unblinding visits were conducted at which the results of the study were conveyed. HIV-1 uninfected partners in the placebo arm were thereafter offered active PrEP. Standardized questionnaires were administered regarding partnership status, willingness to have the HIV-1 infected partner start ART at CD4 counts >350 cells/μL if it would lower risk of transmitting HIV-1 to their partner, perceived benefits and concerns about early ART, and the number and timing of additional children.
For this analysis, data were analyzed from couples in which the HIV-1 infected participants had CD4 counts >350 cells/μL and did not have WHO stage 3 or 4 HIV-1 disease (i.e., did not meet criteria for initiation of ART under WHO guidelines at the time), were not already on ART, and whose serodiscordant partnership was intact. We used descriptive analytical methods and multivariate logistic regression models to evaluate the association between fertility intentions and interest in early ART after adjusting for a priori confounders (age, sex, education, partnership duration, number of children, coital frequency, unprotected sex and contraception). Data were analyzed using Stata 12.1 (StataCorp, College Station, TX). The University of Washington Human Subjects Review Committee and ethics review committees at collaborating institutions at each of the study sites approved the study procedures. All participants provided written informed consent.
A total of 571 HIV-1 serodiscordant couples completed the questionnaire and were included in the analysis, of which 368 (64%) were couples in which the HIV-1 infected partner was female. For HIV-1 infected partners, the median age was 34 years (interquartile range [IQR] 28, 40), and the median CD4 cell count was 586 cells/μL (IQR 461, 765). Couples had a median duration of partnership of 8.3 years (IQR 3.6, 14.8), and a median of 2 children (IQR 1, 4).
Fertility intentions were common, expressed by 36% of HIV-1 infected women and 28% of HIV-1 infected men. For the majority of couples (76%), HIV-1 uninfected partners were in agreement with the fertility intentions of their HIV-1 infected partners: for 314 couples (55%), both members did not want more children, whereas for 121 couples (21%), both members desired additional children. One hundred thirty-six couples (24%) had discordant fertility intentions, the majority of which (74%) were couples in which the HIV-1 uninfected male partner desired additional children but their HIV-1 infected female partner did not.
A majority of the 571 HIV-1 infected participants with CD4>350 cells/μL indicated willingness to start early ART for HIV-1 prevention: 76% and 71% of men and women. HIV-1 infected partners with fertility intentions were significantly more likely to express interest in early ART for HIV-1 prevention (adjusted odds ratio [aOR] 1.83, 95% confidence interval [CI], 1.12-2.99, p=0.02) than those without fertility intentions. Younger age (<25 years), male sex, lack of children with their partner, and unprotected sex in the prior month were also associated with fertility intentions among the HIV-1 infected partners (Table 1).
Table 1.
Correlates of Fertility Intentions Among East African HIV-1 Infected Women and Men (N=571)
| Factor | Fertility Intentions | Risk Estimates | ||
|---|---|---|---|---|
| Yes (N=190) | No (N=381) | Adjusted OR (95% CI) | p-value | |
| Interest in early ARTa | ||||
| No | 45 (29) | 108 (71) | Ref | |
| Yes | 145 (35) | 273 (65) | 1.83 (1.12, 2.99) | 0.02 |
| Age | ||||
| ≥45 | 8 (12) | 58 (88) | Ref | |
| 35-44 | 33 (19) | 144 (81) | 1.68 (0.67, 4.22) | 0.3 |
| 25-34 | 88 (39) | 137 (61) | 4.97 (1.96, 12.63) | 0.001 |
| 18-24 | 61 (59) | 42 (41) | 10.63 (3.68, 30.70) | <0.001 |
| Sex | ||||
| Women | 134 (36) | 234 (64) | Ref | |
| Men | 56 (28) | 147 (72) | 1.65 (1.00, 2.73) | 0.05 |
| Education (years) | ||||
| None | 18 (31) | 40 (69) | Ref | |
| Primary | 120 (32) | 251 (68) | 0.87 (0.43, 1.76) | 0.7 |
| Secondary | 52 (37) | 90 (63) | 0.98 (0.45, 2.14) | 0.9 |
| Partnership duration (years) | ||||
| ≤5 | 97 (50) | 97 (50) | Ref | |
| 6-10 | 47 (35) | 89 (65) | 0.76 (0.43, 1.76) | 0.3 |
| 11-37 | 42 (18) | 181 (81) | 0.67 (0.45, 2.14) | 0.2 |
| Children with partner | ||||
| Any | 136 (29) | 338 (71) | Ref | |
| None | 54 (56) | 43 (44) | 2.54 (1.42, 4.53) | 0.002 |
| Unprotected sex, prior month | ||||
| None | 126 (32) | 272 (68) | Ref | |
| Any | 46 (46) | 54 (54) | 1.67 (1.00, 2.77) | 0.05 |
ART = antiretroviral therapy
In summary, fertility intentions were common and interest in early ART for HIV-1 prevention was high among East African HIV-1 infected individuals in heterosexual, mutually-disclosed serodiscordant partnerships. All couples had received counseling about the efficacy of ART for HIV-1 prevention, and those who desired to have children were nearly twice as likely to express interest in early ART as those without fertility intentions.
Our finding that HIV-1 infected individuals with fertility intentions were more likely to report unprotected sex is consistent with other studies from sub-Saharan Africa (2, 9), and reflects the need for safer conception counseling and services for HIV-1 serodiscordant couples. Our findings suggest that both men and women in HIV-1 serodiscordant partnerships desire children, with somewhat higher interest for men, possibly reflecting desire to have biologic children with a current partner, the perception of fertility as proof of virility, or sociocultural pressures (10, 11).
The World Health Organization (WHO) has recently recommended early ART for HIV-1 infected members of serodiscordant couples to reduce risk of HIV-1 transmission to uninfected partners (12). Our results emphasize that a majority of HIV-1 infected persons with higher CD4 counts may be interested in early ART, particularly those who desire to conceive. Future studies should explore the feasibility and acceptability of implementing early ART for HIV-1 prevention in African HIV-1 serodiscordant couples desiring children.
Partners PrEP Study Team:
University of Washington Coordinating Center and Central Laboratories, Seattle, USA: Connie Celum (principal investigator, protocol co-chair), Jared M. Baeten (medical director, protocol co-chair), Deborah Donnell (protocol statistician), Robert W. Coombs, Jairam Lingappa, M. Juliana McElrath.
Study sites and site principal investigators:
Eldoret, Kenya (Moi University, Indiana University): Kenneth Fife, Edwin Were; Kabwohe, Uganda (Kabwohe Clinical Research Center): Elioda Tumwesigye; Jinja, Uganda (Makerere University, University of Washington): Patrick Ndase, Elly Katabira; Kampala, Uganda (Makerere University): Elly Katabira, Allan Ronald; Kisumu, Kenya (Kenya Medical Research Institute, University of California San Francisco): Elizabeth Bukusi, Craig Cohen; Mbale, Uganda (The AIDS Support Organization, CDC-Uganda): Jonathan Wangisi, James Campbell, Jordan Tappero; Nairobi, Kenya (University of Nairobi, University of Washington): James Kiarie, Carey Farquhar, Grace John-Stewart; Thika, Kenya (University of Nairobi, University of Washington): Nelly Rwamba Mugo; Tororo, Uganda (CDC-Uganda, The AIDS Support Organization): James Campbell, Jordan Tappero, Jonathan Wangisi.
Data management was provided by DF/Net Research, Inc. (Seattle, USA) and site laboratory oversight was provided by Contract Laboratory Services (University of the Witwatersrand, Johannesburg, South Africa).
Acknowledgements
We are grateful to the study participants for their participation and dedication. We thank the study team members at the research sites and at the University of Washington for their contributions to data collection.
Funding source: This study was supported through research grants from the US National Institutes of Health (R01 MH095507) and the Bill & Melinda Gates Foundation (grant ID # 47674). AM was funded by training grant # D43 TW000007 funded by the Fogarty International Center of the National Institutes of Health.
Role of the funding source: The authors designed and executed the study, had full access to the raw data, performed all analyses, wrote the manuscript, and had final responsibility for the decision to submit for publication. The funder had no role in design, data collection, analysis, interpretation, or writing of the report.
Footnotes
Author contributions
AM and JMB designed the study and wrote the first draft of the manuscript. AM performed the statistical analyses. All authors contributed to data collection, interpretation of the results and the writing of the manuscript, and all approved the final draft.
Competing interests
The authors report no competing interests.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
References
- 1.Coburn BJ, Gerberry DJ, Blower S. Quantification of the role of discordant couples in driving incidence of HIV in sub-Saharan Africa. Lancet Infect Dis. 2011 Apr;11(4):263–4. doi: 10.1016/S1473-3099(11)70080-9. [DOI] [PubMed] [Google Scholar]
- 2.Ngure K, Mugo N, Celum C, Baeten JM, Morris M, Olungah O, et al. A qualitative study of barriers to consistent condom use among HIV-1 serodiscordant couples in Kenya. AIDS Care. 2012;24(4):509–16. doi: 10.1080/09540121.2011.613911. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Mugo NR, Heffron R, Donnell D, Wald A, Were EO, Rees H, et al. Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples. AIDS. 2011 Sep 24;25(15):1887–95. doi: 10.1097/QAD.0b013e32834a9338. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493–505. doi: 10.1056/NEJMoa1105243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Mastro TD, Cohen MS, Rees H. Antiretrovirals for safer conception for HIV-negative women and their HIV-1-infected male partners: how safe and how available? AIDS. 2011 Oct 23;25(16):2049–51. doi: 10.1097/QAD.0b013e32834c4c62. [DOI] [PubMed] [Google Scholar]
- 6.Vernazza PL, Graf I, Sonnenberg-Schwan U, Geit M, Meurer A. Preexposure prophylaxis and timed intercourse for HIV-discordant couples willing to conceive a child. AIDS. 2011 Oct 23;25(16):2005–8. doi: 10.1097/QAD.0b013e32834a36d0. [DOI] [PubMed] [Google Scholar]
- 7.Mujugira A, Baeten JM, Donnell D, Ndase P, Mugo NR, Barnes L, et al. Characteristics of HIV-1 Serodiscordant Couples Enrolled in a Clinical Trial of Antiretroviral Pre-Exposure Prophylaxis for HIV-1 Prevention. PLoS One. 2011;6(10):e25828. doi: 10.1371/journal.pone.0025828. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Baeten JM, Donnell D, Ndase P, Mugo NR, Campbell JD, Wangisi J, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2;367(5):399–410. doi: 10.1056/NEJMoa1108524. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Bunnell R, Opio A, Musinguzi J, Kirungi W, Ekwaru P, Mishra V, et al. HIV transmission risk behavior among HIV-infected adults in Uganda: results of a nationally representative survey. AIDS. 2008 Mar 12;22(5):617–24. doi: 10.1097/QAD.0b013e3282f56b53. [DOI] [PubMed] [Google Scholar]
- 10.Cooper D, Moodley J, Zweigenthal V, Bekker LG, Shah I, Myer L. Fertility intentions and reproductive health care needs of people living with HIV in Cape Town, South Africa: implications for integrating reproductive health and HIV care services. AIDS Behav. 2009 Jun;13(Suppl 1):38–46. doi: 10.1007/s10461-009-9550-1. [DOI] [PubMed] [Google Scholar]
- 11.Cooper D, Harries J, Myer L, Orner P, Bracken H, Zweigenthal V. “Life is still going on”: reproductive intentions among HIV-positive women and men in South Africa. Soc Sci Med. 2007 Jul;65(2):274–83. doi: 10.1016/j.socscimed.2007.03.019. [DOI] [PubMed] [Google Scholar]
- 12.WHO [2012 August 16];Guidance on couples HIV testing and counselling, including antiretroviral therapy for treatment and prevention in serodiscordant couples: Recommendations for a public health approach. 2012 Available from: http://www.who.int/hiv/pub/guidelines/9789241501972/en/index.html. [PubMed]