1. Relative time to pregnancy among HIV-infected and uninfected women in the Women’s Interagency HIV Study (WIHS),
Beth S. Linas, MHS; Howard Minkoff, MD; Mardge H. Cohen, MD; Roksana Karim, PhD; Deborah Cohan, MD, MPH; Rodney Wright, MD; Mary Young, MD; D. Heather Watts, MD; Elizabeth T. Golub, PhD, MPH
Department of Epidemiology
Johns Hopkins School of Public Health
138th Annual Meeting
American Public Health Association
November 9, 2010
© 2009, Johns Hopkins University. All rights reserved.

2. Presenter Disclosures
Beth S. Linas
The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:
No relationships to disclose

3. Background Literature suggests that HIV infection may impair fertility
HIV-infected women are more likely than uninfected women to avoid pregnancy, both via contraception and abstinence [Massad et al. AIDS 2004]
HIV-infected women are less likely than uninfected women to report heterosexual activity in the previous six months (65% vs. 76% respectively) [Wilson et al. AIDS 1999]
We hypothesized that the rate of pregnancy would be lower among HIV-infected women than among uninfected women
The availability of HAART has accompanied an increase in live births among HIV-infected women in some cohorts

4. Women’s Interagency HIV Study (WIHS)
Largest NIH-funded ongoing multicenter prospective cohort study of the natural and treated history of HIV infection and related outcomes
3,766 women enrolled ( ; )
6 sites: Bronx NY, Brooklyn NY, Washington DC, Los Angeles CA, San Francisco CA, and Chicago IL
Data Management and Analysis Center located in Baltimore, MD
Semiannual visits
Interviews include questions concerning demographics, medical history, behaviors and medications
Physical and gynecologic examinations
Provision of biologic samples: blood, saliva, cervicovaginal lavage fluid
975 HIV negative have been enrolled, 22 seroconverted

5. Eligibility Criteria N = 1,412 Women eligible for current analysis
Total WIHS Cohort
-Participants were age ≤45
-No hysterectomy, tubal ligation or oophorectomy
-Sexually Active with male partners/Report pregnancy outcome within last year
-At least 2 WIHS Study visits between April 1, 2002 and March 31, 2009
N = 1,412
Women eligible for current analysis
(9,039 person-yrs)
HIV-infected
N = 941
HIV-uninfected
N = 471
Women reporting both hormonal and non-hormonal contraceptive use were included as pregnancies occurred among these groups

6. Ascertainment of Exposures and Outcomes
Main exposure: HIV status
Other exposures assessed semiannually:
CD4+ lymphocyte count
Plasma HIV viral load
Age
Behavioral factors
Prior births
Main outcome assessed via self-report:
“Have you been pregnant since your last visit?”

7. Statistical Analyses
Incidence rates of pregnancy calculated for overall sample and stratified by HIV status
Poisson regression conducted to compare pregnancy rates and predictors thereof
Kaplan-Meïer curves constructed to examine time to pregnancy between HIV-infected and uninfected women
Generalized gamma survival analysis conducted (parametric model) to examine relative time to first pregnancy between
All statistical analyses completed in SAS 9.2

8. Results
Total N = 1,412
HIV+
941
HIV-
471

9. Table 1: Baseline Visit Demographics and Characteristics N = 1,412
Characteristic N (%)
HIV+
N=941
HIV-
N=471
P-value
Age: Median (IQR)
34 (29-39)
30 (23-37)
<0.001
Race
White Non-Hispanic
109 (12)
61(13)
0.865
Black Non-Hispanic
523 (56)
253 (54)
Hispanic
266 (28)
136 (29)
Other
43(5)
21 (4)
Never Married
371 (41)
232 (52)
Exchanged sex
22 (2)
37 (8)
Current drug user
209 (23)
178 (39)
Alcohol (≥3 drinks/week)
132 (14)
120 (26)
Use of any contraceptives in past 6 months
768 (84)
359 (79)
0.018
Male sex partners in past 6 months
73 (8)
26 (6) 1
730 (80)
243 (53) ≥2
112(12)
188(41)
Trying to get pregnant in last year
49 (5)
32 (8)
0.457
Parity (prior births)
209(23)
159(35)
1-2
436 (47)
187 (41) ≥3
112(24)
275(30)
Baseline visit= first visit for eligible women between
HIV negative women had more partners in the past 6 months
HIV positive women reported having parity 1-2 more than HIV uninfected women
*Women who used marijuana, crack/cocaine, heroin, methamphetamines and injection drug users

10. Pregnancy Incidence Rates, 2002-2009
Total pregnancies: N= 766
HIV+: 404 pregnancies among 396 women
HIV-: 362 pregnancies among 354 women
Overall pregnancy rate: 1.2/100 person-years
(95% CI: )
HIV+
0.95/100 person-years
(95% CI: )
HIV-
1.7/100 person-years
(95% CI: )
The raw data suggests there is a statistically different rate of pregnancy between HIV infected and uninfected women
Specifically that HIV infected women have lower rates of pregnancy

11. -this is shown here in the kaplan meier curve
Proportion Pregnancy Free
-this is shown here in the kaplan meier curve
Statistically significant log rank test

12. Final Generalized Gamma Model* Incident Rate Ratio (95% CI)
Table 2: Incidence Rate Ratio and Relative Time to First Pregnancy,
Final Poisson Model*
Final Generalized Gamma Model*
Incident Rate Ratio (95% CI)
Relative Time (95% CI)
HIV+
0.60 (0.46,0.78)
1.73 (1.35,2.36)
Age (per year increase)
0.86 (0.85,0.88)
1.3 (1.13,1.70)
Exchanged sex since last visit
0.67 (0.34,1.32)
1.10 (0.44,2.11)
Number of male sex partners in the past 6 months
0-1
ref ≥2
0.72( 0.53,0.96)
1.62 (1.12,2.40)
Number of prior births
1-2
6.49 (4.43,9.50)
0.24 (0.16 ,0.35) ≥3
12.63(8.40,19.00)
0.14 (0.09,0.21)
-Adjusting for confounders, there is still a statistically signifigant lower rate of pregnancy among HIV infected women
* Models adjusted for all variables listed plus contraception and alcohol consumption
Bold indicates p-value<0.05
Bold +Italic indicates p-value<0.001

13. KM Curve for time to first pregnancy by parity, 2002-2009
Proportion Pregnancy Free

14. Table 3: Clinical Characteristics, HIV+ N = 941
Characteristic N (%)
HIV+
N=941
Viral load copies/ml: Median (IQR)
540 ( )
CD4+ cells/µL : Median (IQR)
497 ( )
Therapy used since last visit
619 (66)
321 (34%) women not on therapy at baseline: 119 (37%) initiated HAART at a subsequent visit

15. Incident Rate Ratio (95%CI)
Table 4: Multivariate risk factors for pregnancy among HIV+ women, N=941
Unadjusted Models
Final Model*
Incident Rate Ratio (95%CI)
Age
0.87 (0.85, 0.89)
0.85 (0.83 , 0.88)
Log Viral Load (cp/ml)
1.10 (0.99 , 1.23)
CD4+ ( cells/ml)
<200
0.64 (0.42, 0.99)
0.78 (0.49 , 1.22)
0.79 (0.55, 1.12)
0.90 (0.63 , 1.29)
0.99 (0.74, 1.32)
1.06 (0.78 , 1.41)
≥500
ref
Therapy used since last visit
No Therapy
Non-HAART Therapy
1.89 (0.99 , 3.66)
HAART
0.89 (0.67 , 1.19)
Number of prior births
1-2
8.19 (4.60 , 14.56)
8.13 (4.44 , 14.88) ≥3
10.87 (5.99 , 19.73)
16.83 (9.00 , 31.38)
*Final model adjusted for age, CD4+ cell count, parity, exchange sex since last visit, number of male partners in the past 6 months, alcohol consumption and contraception use
Bold indicates
p-value<0.05
Bold +Italic indicates
p-value<0.001
Because it was not significant in bivariate analyses, and due to its relationships with both HIV RNA and CD4+ count, antiretroviral therapy was not included in this model. However, to examine any potential interaction between viral load and HAART, the final model was stratified by therapy (yes/no). This analysis showed no effect modification by therapy.

16. KM Curve for time to first pregnancy by CD4+ category 2002-2009
Proportion Pregnancy Free

17. Discussion Lower incidence of pregnancy among HIV+ women
Lower rate of pregnancy for women with two or more male sex partners (versus <2)
Women with more sexual partners may be engaging in sex differently than women with fewer partners, in a way that is not discernable from the data (definition of sex includes: oral, vaginal and anal sex)
192/766 pregnancies occurred at the same visit hormonal contraception was reported
Women may be taking “time outs” from contraception, or not using it correctly
In this cohort of US women, there was a lower incidence of pregnancy among HIV + women compared to HIV-
Women with more partners are not necessarily protecting themselves against pregnancy more than women with fewer partners

18. Discussion
As parity increased, the time to first reported pregnancy was faster, regardless of HIV status
HIV-infected women consistently had slower times to pregnancy, in each category of parity
No way of knowing whether women with parity=0 experienced a lack of conception due to inability or lack of desire.
Further Research:
Collect data concerning menstrual cycles (examine ovulation cycle and eliminate immortal person-time when women are not at risk for pregnancy)
Collect data concerning frequency of sexual intercourse
Collect data and assess adherence to contraceptives, time on contraceptives between visits
This analysis did not investigate measures of biologic infertility; however these results do indicate lower incidence of conception among HIV-infected women as compared to uninfected women
Word of caution…this analysis…

19. Thank You! blinas@jhsph.edu