Walson JL, Brown ER, Otieno PA, Mbori-Ngacha DA, Wariua G, Obimbo EM, et al. Morbidity among HIV-1-infected mothers in Kenya: prevalence and correlates of illness during 2-year postpartum follow-up. J Acquir Immune Defic Syndr. 2007;46:208-215.
To determine the incidence and correlates of illness among HIV-1-infected mothers in Kenya during a two-year postpartum follow-up period.
Prospective cohort study.
The study was conducted in Nairobi, Kenya at Kenyatta National Hospital.
Five hundred and thirty-five HIV-1-infected pregnant women were enrolled at approximately 32 weeks of gestation. Women were referred from Nairobi City Council clinics to the study clinic at Kenyatta National Hospital.
The study was conducted from July 1999 to June 2005. The study initially enrolled 216 women with a follow-up period of 12 months. An additional cohort of 319 were enrolled subsequently and followed for 24 months. All 535 women from both cohorts were included for analyses of morbidity. Baseline sociodemographic and medical information was collected using a standardized questionnaire at enrollment. Risk of HIV-1 transmission through breast milk and instructions for proper preparation of formula were explained. Those with severe immunosuppression (CD4 count <200 cells/mm3) were provided with cotrimoxazole prophylaxis and referred to HIV treatment programs providing antiretroviral therapy. Participants received standard antenatal care, including zidovudine to reduce risk of HIV-1 transmission to the baby and iron and multivitamin supplements. Participants were followed with routine scheduled visits. Between 1999 and 2002, women were followed monthly for 12 months after delivery of a baby. From 2002 to 2005, all study participants were followed monthly for the first 12 months, then every 3 months for an additional 12 months after delivery. Blood was collected for T-cell subset analyses and HIV-1 RNA levels at postpartum months 1, 3, 6, 9 and 12 for all women and at 18 and 24 months postpartum in the women followed for the extended study period. Outcome measurements included both self-reported and clinically diagnosed illnesses at scheduled and unscheduled (as needed) visits. To prevent bias caused by missed visits, a woman's at-risk time was defined as the number of intervals in which she had a visit times the length of the interval. Incidence (in 100 person-years) over a year was defined as the number of incident illnesses over the year, divided by the total number of at-risk intervals for the cohort, multiplied by the number of intervals in a year (4 for 90 days and 6 for 60 days) times 100. Associations between baseline variables and morbidity outcomes were restricted to illnesses reported at scheduled visits. Women were censored at reported second pregnancy, initiation of highly active antiretroviral therapy (HAART) or death.
Incidence of morbidity, diagnosed at routine scheduled clinic visits.
Of 535 women enrolled, 501 (93.6%) were followed to delivery, 489 (97.6%) of whom had data from at least one visit after delivery. Three hundred twenty-eight (67%) women completed one year of follow-up, and 102 (32%) of 319 women completed 24 months of planned follow-up. Twelve women initiated ARVs, 32 became pregnant (2nd pregnancy), 21 died, and one became pregnant and started ARVs. The study analysis represents 7746 person-months of follow-up. Overall, data were collected on 7147 separate encounters in the first two years postpartum. The first year averaged 11.4 visits per woman and the second year averaged 4.4 visits. 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. 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 <200cells/mm3 at enrollment. The median HIV-1 RNA level at enrollment was 4.71 log10 copies/mL. Baseline viral load was not associated with time between visits and total follow-up time. Fifteen of the 21 deaths were "AIDS-related". Mortality was associated with a higher viral load and immunosuppression at baseline.
The most common illnesses in order of incidence were: 1. Upper respiratory tract infections (URTI), 161 episodes per 100 person-years and 145 episodes per 100 person-years of follow-up in the first and second years, respectively; 2. Fever, 83 episodes per 100 person-years in both years one and two; 3. Diarrhea, 63 cases per 100 person-years, and increased throughout the first year, but slightly lower in the second year (49 cases per 100 person-years); 4. Malaria, 54 and 48 episodes per 100 person-years in years one and two; and 5. Pneumonia, 33 and 29 per 100 person-years in years one and two. UTI, genital ulcers, STD, thrush, and PID were all reported less frequently at rates of <25 cases per 100 person-years during the first year. Incidence of pulmonary TB was 11 cases per 100 person-years in the two years of follow-up. Women were rarely diagnosed with more than one serious morbidity at a single visit. Incidence of common morbidities remained stable over the follow-up period, except for diarrhea, which increased in a linear fashion.
Primagravid status was associated with reduced risk of URTI during the first year. The increased risk of diarrhea was associated with having only one room in the home (RR=1.86, 95% CI: 1.19 to 2.92), breastfeeding as opposed to formula-feeding (RR=1.71, 95% CI: 1.19 to 2.44). Cofactors 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: 1.23 to 9.23). Increased risk of TB during the first year postpartum was associated with a CD4 count <200 cells/mm3 at baseline (RR=7.14, 95% CI: 2.93 to 17.40) and a viral load greater than the median (RR=3.37, 95% CI: 1.23 to 9.23).
The results of this analysis suggest that in the two-year period after delivery of a baby, HIV-infected Kenyan women experience a high incidence of URTIs, diarrhea, malaria, pneumonia, and TB. The authors conclude that the high rates of disease and low mortality observed in this study suggest that much of the illness leading to death in HIV-1-infected postpartum women may be preventable with access to appropriate healthcare. The authors also suggest further studies to identify the most effective screening programs and interventions for HIV-1-infected women in resource-limited settings.
Based on the Newcastle-Ottawa quality rating for observational cohort studies, this study would receive 5 stars. Its chief weaknesses are the lack of a comparison control group of HIV-uninfected mothers, self-report of illnesses without microbiological or radiographic confirmation, and a high rate of loss to follow-up, with 67% of women completing one-year of follow-up and only 32% completing two years. Although the lack of an HIV-uninfected control group makes the rates more difficult to interpret, rates of illness observed in this study were consistent with those from other published studies.(3,4,5) Frequent scheduled follow-up visits allowed documentation of thorough history and medical findings.
Few studies have evaluated morbidities among women beyond the immediate postpartum period. This study provides new data by extending follow-up to two years postpartum. High incidence rates of URTIs, pneumonia and pulmonary TB are consistent with other studies done in Africa.(3,5,6) Association between incidence of these illnesses and seropositivity and higher CD4 counts were also consistent with other studies.(7) One study in Zimbabwe reported lower incidence rates compared to this study.(3)
This analysis underscores the importance of identifying HIV-1-infection in pregnant women, and integrating routine HIV care with peripartum and postnatal care programs in resource-limited settings, especially in scaling up PMTCT programs and other maternal-child healthcare programs in Africa. The high incidence of postpartum morbidities warrants further studies to determine if women in the postpartum period may benefit from extended cotrimoxazole prophylaxis, regardless of CD4 cell count.
- Zvandasara P, Hargrove JW, Ntozini R, et al. Mortality and morbidity among postpartum HIV-positive and HIV-negative women in Zimbabwe: risk factors, causes, and impact of single-dose postpartum vitamin A supplementation. J Acquir Immune Defic Syndr. 2006;43:107-116.
- Khan M, Pillay T, Moodley JM, et al. Maternal mortality associated with tuberculosis-HIV-1 co-infection in Durban, South Africa. AIDS 2001;15:1857-1863.
- van Oosterhout JJ, Laufer MK, Graham SM, et al. A community-based study of the incidence of trimethoprim-sulfamethoxazole-preventable infections in Malawian adults living with HIV. J Acquir Immune Defic Syndr 2005;39:626-631.
- Watera C, Todd J, Muwonge R, et al. Feasibility and effectiveness of cotrimoxazole prophylaxis for HIV-1-infected adults attending an HIV/ AIDS clinic in Uganda. J Acquir Immune Defic Syndr. 2006;42:373-378.
- Mwachari CW, Shepherd BE, Cleopa A, et al. Mortality and burden of disease in a cohort of HIV-seropositive adults in Nairobi, Kenya. Int J STD AIDS 2004;15:120-126.
- Zvandasara P. Primary school children's knowledge of health and illness in The Gambia: its implication for teaching children about disease. J Trop Pediatr 1987;33:110-112.
- Collin SM, Chisenga MM, Kasonka L, et al. Factors associated with postpartum physical and mental morbidity among women with known HIV status in Lusaka, Zambia. AIDS Care. 2006;18:812-820.