In sub-Saharan Africa, HIV-positive pregnant women are being enrolled in large numbers into the antiretroviral treatment (ART) services. Although treatment outcomes such as loss to follow-up (LTFU) and mortality rates have been well described for large ART cohorts in this region , little is known of treatment outcomes for this group of patients.
To ascertain losses due to mortality and LTFU for pregnant women, a retrospective cohort analysis was carried out on all ART-naïve, adult women referred for treatment to the Hannan Crusaid Treatment Centre in Gugulethu. This is a large community-based ART service in Cape Town, South Africa that was established in 2002 and has previously been well described [2–4].
In this study, we looked at mortality and LTFU rates for 2131 HIV-infected, ART naïve women from the age of 15 years who were referred for ART between 1 September 2002 and 30 September 2007. Of the total number of women enrolled, 318 (15%) were pregnant on the date of screening. Overall, this group was younger with less advanced HIV as indicated by a lower median CD4 cell count and less WHO stage 3 and 4 disease than the nonpregnant women.
Both pretreatment and on-treatment outcomes were included in this analysis, which compared the mortality and LTFU rates between pregnant and nonpregnant women prior to starting and after commencement of ART. For the purpose of this analysis, the pretreatment LTFU was calculated as the percentage of patients referred for ART who refused treatment or did not return to the clinic. Other pretreatment losses were due to mortality, patients who accessed ART elsewhere and patients whose treatment was deferred as they did not meet the South African national treatment criteria for triple therapy.
In the pretreatment analysis, there was a crude overall programmatic loss of 19.8% among pregnant women as compared with 17.1% among nonpregnant women (P < 0.243). Pretreatment mortality was significantly lower among pregnant women (0.3% vs. 4.7%; P < 0.001) though the pretreatment LTFU rate was higher (13.2% vs. 6.0%; P < 0.001).
An on-treatment analysis was carried out on the 1677 women who started ART. On-treatment LTFU was defined as patients receiving ART who had not attended the clinic for 12 or more weeks. This would equate to having defaulted ART for at least 4 weeks. Similar to the findings in the pretreatment period, Kaplan–Meier plots showed that, over a 3-year period, cumulative mortality was lower (P = 0.045) but risk of LTFU was substantially higher (P < 0.001) for pregnant women when compared with nonpregnant women (Fig. 1). The differential risk of LTFU between the two groups continued over 3 years.
In a multivariate analysis, mortality was not associated with pregnancy, age or baseline viral load but was associated with WHO stage and baseline CD4 cell counts. Conversely, pregnancy and age were independently associated with LTFU but WHO clinical stage, baseline CD4 cell count and viral load were not. When controlled for the other variables, the relative risk of pregnancy for LTFU was 2.1 (95% CI = 1.4–3.1, P < 0.001). Younger patients were also at greater risk of LTFU with an adjusted risk of 2.2 (95% CI = 1.3–3.6, P = 0.002) for women aged less than 25 years when compared with women aged more than 35 years.
The cumulative programmatic LTFU rate for pregnant women was substantial when considering the crude pretreatment LTFU rate for pregnant women of 13.2% compared with 6.0% for nonpregnant women (P < 0.001) and the LTFU rate at 3 years on treatment of 32% for pregnant women as opposed to 13% for nonpregnant women (P < 0.001).
The high LTFU rates in this analysis are consistent with the findings presented by Wang et al. who reported patient characteristics associated with LTFU for 1507 patients starting ART at four community care sites in South Africa. Over a median follow-up period of 11.4 months, they described a higher on-treatment LTFU rate for pregnant women when compared with nonpregnant women and men .
In ART programs, LTFU rates have been shown to be influenced by programmatic characteristics, with the provision of a free service and a comprehensive treatment support system identified as contributing to higher patient retention rates [1,6,7].
The Hannan Crusaid Treatment Centre offers a free service and has an intensive treatment support program conducted by trained peer counselors who provide in-clinic counseling as well as an outreach service in the form of home visits [7–8]. This includes an active patient tracing system for defaulting patients and ensures high retention rates when compared with other developing world programs . Overall, LTFU rates at other community clinics with less intensive support systems may be higher. Pregnancy, however, is still likely to be a risk factor for LTFU in these programs.
The reasons pregnant women defaulted treatment were not ascertained from this study. Pregnant women do, however, have a number of common characteristics that could result in a higher LTFU rate. Many of them have had a recent HIV diagnosis during their antenatal assessments, leaving them little time to process their diagnosis or deal with the issues around the disclosure of their HIV status to their spouse and family members. They may therefore not be adequately prepared to start ART. They are also undergoing a major life-altering event. Of note, however, is that while the increased LTFU rate for pregnant women occurs from the start of treatment, it continues as a relatively constant hazard for the 3 years of follow-up, indicating that the mother's circumstances after delivery continue to influence adherence to the program.
The above-mentioned high LTFU rate is of particular concern as it will not only impact on the morbidity and mortality of the mother, but also is likely to result in an increased risk of HIV transmission to the child and may be detrimental to the future care of the child. This analysis points to the need for a more focused intervention to ascertain why these patients are at higher risk of defaulting treatment. It also identifies pregnant women as a special sub-group of patients who may require additional longitudinal interventions for programmatic retention.
C.O., L.G.B. and R.W. are all partially funded by the National Institutes of Health through a CIPRA grant 1U19AI53217-01. R.W. is also partially funded by a RO1 grant A1058736-01A1. R.K. wrote the article and contributed to the study design, data collection and data analysis. C.O. was responsible for establishing the study cohort, data collection, data interpretation and revising the manuscript. E.Z. performed the statistical analysis and assisted with revising the manuscript. L.G.B. was responsible for establishing the study cohort, data interpretation and data analysis. R.W. was responsible for study design, analysis, data interpretation and revising the article. All authors have seen and approved the final version of the manuscript.
There are no conflicts of interest.
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