Enrollment and Follow-Up
Of 535 women enrolled, 501 (93.6%) were followed to delivery, 489 (97.6%) of whom had data from at least 1 visit after delivery and were included in this analysis. During the follow-up period, 12 women initiated antiretrovirals (ARVs) and 21 women died. Thirty-two women became pregnant with another child (second pregnancy), and 1 woman became pregnant and started ARVs (). The data included in this analysis represent 7746 person-months of follow-up. Three hundred twenty-eight (67%) women completed 1 year of follow-up, and 102 (32%) of 319 women completed 24 months of planned follow-up. Women who completed follow-up tended to be younger and were less likely to breast-feed than those who were lost to follow-up. The women who completed 2 years of follow-up were also more likely to have plasma viral loads higher than the median at baseline.
Trial profile. Over the course of the study period, 12 women initiated ARVs, 32 became pregnant again, 21 died, and 1 became pregnant again and initiated ARVs.
Overall, data were collected on 7147 separate encounters in the first 2 years postpartum (an average of 14.6 visits per woman). The women completed an average of 11.5 scheduled follow-up visits and 3.1 as-needed visits for clinical care. In the first year, there were 5635 encounters by 488 women, representing 11.4 visits per woman. In the second year, there were 1536 encounters by 353 women, representing 4.4 visits per woman. Among the 485 women who attended a scheduled visit in the first year, the mean time between scheduled visits in the first 390 days was 31.5 days.
Baseline Characteristics of the Women in the Cohort
Women were enrolled into the study at approximately 32 weeks of gestation. Baseline characteristics of the cohort are presented in . At the enrollment visit, 69 women (14.1%) reported a history of STD and 41 (8.4%) reported having been diagnosed with TB in the past. In addition, 67 women (13.7%) reported a history of fever, 43 (8.8%) reported having had malaria, 29 (5.9%) reported having had diarrhea, and 7 (1.4%) reported having had oral thrush during their current pregnancy. Prior use of multivitamins in pregnancy was reported by 169 women (34.6%), and 107 (21.9%) reported having used an antibiotic during their pregnancy.
Demographic and Clinical Characteristics of the Cohort
CD4 cell counts were available for 466 women at enrollment (95.3%), and HIV-1 RNA levels were available for 451 women (92.2%). The median CD4 count was 433 cells/mm3, and 10.6% of the women had a CD4 count <200 cells/mm3 at enrollment. The median HIV-1 RNA level at enrollment in this cohort was 4.71 log10 copies/mL (see ).
Cofactors associated with an increased likelihood of coming for an unscheduled (as needed) visit included having a CD4 count <200 cells/mm3, having an HIV-1 RNA level higher than the median, being formula-feeding, being older than the median, not having a flush toilet, and not being primigravida ().
Predictors of an As-Needed Visit in the First Year
Over the first year of follow-up, 11.4% (IQR: 8.1, 14.6) of subjects who had a CD4 count >200 cells/mm3 at baseline and who had follow-up CD4 measurements had at least 1 CD4 count less than 200 cells/mm3. At 24 months of follow-up, the percentage of participants with at least 1 CD4 count less than 200 cells/mm3 increased to 17.5% (IQR: 12.6, 22.1) (). Time between visits (scheduled and as needed) was similar when comparing subjects with CD4 counts greater than and less than 200 cells/mm3 (1 day more for those with a CD4 count <200 cells/mm3). Women with a CD4 count <200 cells/mm3 had 42 days fewer total scheduled follow-up time than women with higher CD4 counts (P = 0.002), however. Baseline viral load was not associated with time between visits. There was no association between baseline viral load and total follow-up time.
FIGURE 2 CD4 cell count decline over 2 years of follow-up. Survival curve for time to CD4 count <200 cells/mm3. The vertical axis is the percentage of patients not yet having met the endpoint, and the horizontal axis is time in months. Overall, most women (more ...)
During follow-up, 42 women were hospitalized a total of 44 times. Information on the cause of illness leading to hospitalization was available for 39 of these hospitalizations (88.6%). These included 9 episodes of malaria, 7 episodes of pneumonia, 6 episodes of TB, 6 episodes of typhoid fever, 5 episodes of diarrhea, 4 episodes of chest pain, and 1 episode each of shingles and yellow fever. There was no correlation between baseline CD4 cell count, log10 HIV RNA level, or prior history of AIDS-defining illness and the risk of hospitalization in this cohort. The incidence of hospitalization did not increase over time during the follow-up period.
Twenty-one women were confirmed to have died during the course of the study period. The estimated mortality at 12 months was 1.9% (95% confidence interval [CI]: 0.6% to 3.2%), and it was 4.8% (95% CI: 2.3% to 7.3%) at 24 months. The cause of death was reported as “AIDS related” in 15 women (71.4%). Mortality was associated with a higher viral load and immunosuppression at baseline (hazard ratio for viral load higher than median = 3.02 (IQR: 0.972, 9.35); P = 0.06 and hazard ratio for CD4 count <200 cells/mm3 = 13.6 (IQR: 5.06, 36.5); P < 0.001).
Incidence and Correlates of Illness in the Cohort
During the first year of follow-up postpartum, frequent causes of morbidity included URTIs, malaria, and diarrhea (). At scheduled visits during the first year, 204 women reported fever since their last visit (41.7%), 122 reported diarrhea (24.9%), 89 reported malaria (18.2%), and 78 reported a history of pneumonia (16.0%). Fever, URTI, malaria, and diarrhea all occurred at more than 50 cases per 100 person-years during the first year of follow-up. UTI, genital ulcers, STD, thrush, and PID were all reported less frequently at rates of <25 cases per 100 person-years of follow-up during this period. Incidence rates of morbidity were calculated for all visits (scheduled and as needed) and were similar between the first and second years of follow-up in this cohort (see ). Women were rarely diagnosed with more than 1 serious morbidity at a single visit (4 visits with diarrhea and pneumonia and 2 visits with diarrhea and TB reported).
Incidence of Morbidity During the First and Second Years of Postpartum Follow-Up (Numbers per 100 Person-Years of Follow-Up)
The incidence of common morbidities such as pneumonia, TB, and malaria seemed to remain relatively stable over the follow-up period, whereas the incidence of diarrhea seemed to increase in a linear fashion (). These trends in morbidity incidence over the first year of follow-up were stratified by CD4 count (>350 cells/mm3 and <350 cells/mm3). Pneumonia incidence increased significantly over the follow-up period in the women with CD4 counts <350 cells/mm3 but remained stable in those women with higher CD4 counts, whereas the incidence of TB remained stable regardless of CD4 cell count over the first year of follow-up. The increasing incidence of diarrhea in the cohort was independent of CD4 cell count (see ).
FIGURE 3 Individual morbidity increase over the first year of follow-up. The vertical axis shows the number of cases reported per 100 person-years of follow-up. Participants are stratified by CD4 cell count at enrollment. Participants with CD4 counts < (more ...)
Upper Respiratory Tract Infections and Pneumonia
URTIs were the most commonly reported illnesses in the cohort, with an incidence of 161 episodes per 100 person-years and 145 episodes per 100 person-years of follow-up in the first and second years, respectively. Primigravid status was associated with a significantly reduced risk of URTI during the first year of follow-up (relative risk [RR] = 0.68, 95% CI: 0.55 to 0.85). This effect remained after adjusting for maternal age.
Pneumonia was diagnosed with an incidence of 33 cases per 100 person-years in the first year of follow-up and 29 cases per 100 person-years in the second year. Cofactors significantly associated with developing pneumonia in the first year of follow-up included age older than the median (RR = 1.75, 95% CI: 1.15 to 2.68), CD4 count <200 cells/mm3 (RR = 2.87, 95% CI: 1.71 to 4.83), and viral load higher than the median (RR = 1.77, 95% CI: 1.15 to 2.73).
The incidence of pulmonary TB was 11 cases per 100 person-years in the 2 years of follow-up. A CD4 count <200 cells/mm3 at baseline was associated with an increased risk of TB during the first year postpartum (RR = 7.14, 95% CI: 2.93 to 17.40). Having a viral load greater than the median was also associated with a significantly greater risk of TB in the first year postpartum (RR = 3.37, 95% CI: 1.23 to 9.23).
During the first year postpartum, diarrhea incidence was 63 cases per 100 person-years. This risk increased throughout the first year. Incidence of diarrhea was slightly less in the second year (49 episodes per 100 person-years). Having only 1 room in the home was associated with an increased risk of diarrhea (RR = 1.86, 95% CI: 1.19 to 2.92), and there was a trend toward an association between diarrhea and not having a flush toilet. In addition, breast-feeding was significantly associated with maternal diarrhea when compared with formula-feeding (RR = 1.71, 95% CI: 1.19 to 2.44). The association between diarrhea and breast-feeding seemed to be independent of level of education or socioeconomic status (as measured by having more than 1 room and having a flush toilet) when included in a multivariate analysis (RR = 1.48; P = 0.053).
In the first year of follow-up, the incidence of clinical mastitis was 25 per 100 person-years, declining to 4 per 100 person-years in the second year. Breast-feeding was associated with an increased risk of developing mastitis in this cohort (RR = 5.65, 95% CI: 2.47 to 12.96). Older age and higher socioeconomic status seemed to be associated with a lower risk of developing mastitis.
During the first year of follow-up, 59 women presented with an illness consistent with WHO stage III or IV HIV disease. After adjusting for baseline CD4 cell count, having a viral load higher than the median was associated with the development of an AIDS-defining illness (RR = 1.87, 95% CI: 1.02 to 3.43; P = 0.04).
The incidences of other morbidities, including malaria, PID, oral thrush, bronchitis, genital ulcers, STD, and UTI, are presented in . Cofactors for these morbidities are presented in .
Cofactors for Overall Morbidity Among HIV-1–Infected Women During the First Year Postpartum