Morrison CS, Wang J, Van Der Pol B, Padian N, Salata RA, Richardson BA. Pregnancy and the risk of HIV-1 acquisition among women in Uganda and Zimbabwe. AIDS 2007 May 11;21(8):1027-1034.
To assess the effect of pregnancy on the risk of HIV-1 acquisition.
A multi-center prospective cohort study of women seeking reproductive and general healthcare services in Uganda and Zimbabwe.
Women were recruited and followed at three sites in Kampala (Uganda), and four sites in Harare and Chitungwiza (Zimbabwe).
Between November 1999 and January 2004, 4,531 women were enrolled in the study. The inclusion criteria were: 1. age 18-35 years; 2. uninfected with HIV; 3. sexually active, but not pregnant or intending to become pregnant in the next year; and 4. either using no hormonal method (non-HC), or combined oral contraceptive pills (COC; low-dose pills containing 30 µg ethinylestradiol) and 150 µg levonorgestrel or depot medroxyprogesterone (DMPA; 150 µg administered every 12 weeks) for at least three months, with intent to continue use for the following year. Women were ineligible if they had a hysterectomy, had used an intrauterine device, or had a spontaneous or induced abortion in the previous month. A smaller group of "high-risk referral" women with sexually transmitted infections (STI) or STI symptoms were recruited in Uganda because of low initial HIV-1 incidence at that study site. After excluding 92 women because of no follow-up or the exclusive use of non-study contraceptive methods, and an additional 24 women because of missing pregnancy data, 4,415 women were studied. The median age of study participants was 25 years, median education was 10 years, and most participants lived with a partner. Study participants had a median of two lifetime pregnancies and 28% breastfed at enrollment. At baseline, 34.7% of participants used COC, 34.2% used DMPA, and 31.1% did not use a hormonal method. Few participants reported multiple sex partners, commercial sex, or sex while using alcohol or drugs, and fewer than half reported recent condom use.
Women were followed quarterly for 15-24 months. Study visits included a physical examination; pregnancy, HIV-1, and STI testing; and administration of a standardized questionnaire to collect demographic, sexual behavior, reproductive heath, and contraceptive history data. Pregnancy testing was performed using a urine test for human chorionic gonadotropin (hCG). Clinicians also recorded clinical impressions concerning possible pregnancy on the physical examination form. In the event of discordant results between the pregnancy test and the clinical impression item, the latter variable was used. This situation occurred primarily when a pregnancy was recently completed and the hCG test remained positive. Women also received pretest HIV counseling and provided blood for testing for HIV, syphilis, and herpes simplex virus 2 (HSV-2). HIV-infected women were counseled and referred for ongoing medical and social support. To confirm incident HIV-1 infections, HIV-1-DNA polymerase chain reaction (PCR) was performed retrospectively on serial visit specimens to identify more precisely the timing of infection. The date of HIV-1 acquisition was defined as the date of the first positive PCR result. PCR testing for gonorrhea and chlamydia was conducted on endocervical specimens. Serum was tested for HSV-2 antibodies utilizing an enzyme-linked immunosorbent assay. Trichomonas and yeast infection were diagnosed by microscope, and bacterial vaginosis was diagnosed according to Amsel criteria.
The outcome was the number of days from the baseline visit to the earlier date of the first positive HIV-1 result or the last study contact.
The 24-month retention rate was 92% and the mean follow-up was 21.9 months. Among the 31,106 visit segments included in the analysis, women were pregnant in 2,867 visit segments (9.2%); not currently pregnant but lactating (NP/L) in 4,699 segments (15.1%); not pregnant and not lactating (NP/NL), but using hormonal contraception in 17,668 segments (56.8%); and NP/NL and not using hormonal contraception in 5,872 segments (18.9%). Ugandan women contributed more pregnancy segments than Zimbabwean women (61% and 39%, respectively). Pregnancy was more common among younger women (18-24 years), women living with a partner, and women with less than three lifetime pregnancies at study enrollment. No important difference was seen in pregnancy occurrence by educational level. During follow-up, pregnant women were less likely to have multiple partners, to have a new sex partner, or to use alcohol or drugs during sex compared with the NP/NL and no hormonal contraception-use group. However, pregnant women were much more likely to report some unprotected sex during visit intervals (82.0%) than were women in the NP/NL and no contraception-use group (37.8%). There were 211 incident HIV-1 infections, giving an incidence rate of 2.73 per 100 woman years (wy) (4.05 per 100 wy in Zimbabwe and 1.53 per 100 wy in Uganda). Thirteen incident HIV-1 infections occurred among pregnant women (1.64 per 100 wy) and 33 (2.72 per 100 wy), 126 (2.94 per 100 wy), and 39 (2.70 per 100 wy) incident HIV-1 infections occurred among NP/L women, NP/NL women using hormonal contraception, and NP/NL women not using hormonal contraception, respectively. Neither pregnancy nor lactation was significantly associated with the risk of HIV-1 acquisition in either or multivariate analyses. Covariates significantly associated with increased HIV-1 acquisition included Zimbabwe site and Uganda high-risk referral group, not living with a partner, young age, high participant behavioral risk, high primary partner risk, and recent alcohol use. When adjusting for covariates, both site (p=0.010) and age (p=0.003) were found to be statistically significant. Sensitivity analyses did not alter the primary results of the study.
The authors conclude that neither pregnancy nor lactation placed women at increased risk of HIV-1 acquisition, providing reassurance for women desiring to become pregnant (and who would subsequently breastfeed) in areas with high HIV-1 prevalence.
Based on the Newcastle-Ottawa assessment scale for cohort studies, this study received an average rating. Randomization was not possible and selection and confounding biases could not be ruled out. Also, at the point of enrollment, study participants were not pregnant and did not desire to become pregnant during the following year, limiting generalizability to other groups of women. In addition, the authors were unable to precisely measure the onset of pregnancy, as participants were only assessed every 12 weeks, and the measurement of sexual risk behaviors was self-reported and the accuracy of such data is unknown.
Results from this study differ from previous studies, which suggested that pregnancy is associated with an increased risk of HIV-1 acquisition.(1,2,3) In addition, a national HIV survey conducted in South Africa identified pregnancy as a risk factor for HIV acquisition.(4) However, only one of these previous studies was prospective and adjusted for demographic, reproductive health, and sexual risk behaviors,(3) and none of the previous studies adjusted for hormonal contraceptive use. Another possibility for the differences in the results may be due to the varying study populations with associated differences in pregnancy rates, behavioral and STI co-factors, and HIV-1 exposure risk. For example, although the results for Zimbabwean women in this study were quite different from those from Rakai,(3) the results for the Ugandan general population group (the group most closely resembling the Rakai population) were more similar. If the latter possibility is true, the generalizability of the findings in this study may be limited.
Because regions with high HIV-1 prevalence are also areas with high levels of fertility, the potential role of pregnancy in HIV-1 acquisition is considerable. The lack of an increase in the risk of HIV-1 acquisition during pregnancy and lactation should provide reassurance for women desiring to become pregnant in areas with a high prevalence of HIV-1. This information is important in contraceptive counseling and in planning interventions to reduce HIV-1 acquisition among women.
- Taha TE, Hoover DR, Dallabetta GA, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998 Sep 10;12(13):1699-706.
- Gray RH, Wabwire-Mangen F, Kigozi G, et al. Randomized trial of presumptive sexually transmitted disease therapy during pregnancy in Rakai, Uganda. Am J Obstet Gynecol 2001 Nov;185(5):1209-17.
- Gray RH, Li X, Kigozi G, Serwadda D, et al. Increased risk of incident HIV during pregnancy in Rakai, Uganda: a prospective study. Lancet 2005 Oct 1;366(9492):1182-8.
- Shisana O, Rehle T, Simbayi LC, Parker W, et al. South African national HIV prevalence, HIV incidence, behavior and communication survey, 2005. Cape Town, South Africa: HSRC Press; 2005. (No abstract available.)