In this cohort of HIV-infected pregnant women and their infants, we have explored the effectiveness of the Ukraine PMTCT programme in operational settings. We have documented earlier diagnosis of HIV-infected pregnant women, increasing coverage with ARV prophylaxis and decreasing MTCT rates, against a background of increasing annual enrolments. The absolute numbers of IDU women enrolling in the study actually increased in 2007 compared to 2006 (data not shown), but we report a declining proportion of women with IDU history over time, reflecting trends towards increasing heterosexual transmission in the Ukraine [3
]. MTCT rates more than halved between 2001 and 2006, with around one in fourteen women transmitting infection to their infants in 2006.
Prompt identification of HIV-infected pregnant women is essential for a successful PMTCT programme [12
]. Around one in four women here were aware of their HIV diagnosis before conception, and nearly three-quarters had been diagnosed by the start of their third trimester. Women with IDU histories or IDU sexual partners and those with HIV symptoms were more likely to have a pre-pregnancy HIV diagnosis than other women which probably indicates their increased likelihood of accessing voluntary counseling and testing (VCT) outside pregnancy compared with other women. The increased likelihood of pre-pregnancy diagnosis in 2006/07 versus 2000/01 suggests improvements in VCT coverage over time; a national protocol for VCT was not approved by the Ministry of Health until December 2005, which is consistent with this time trend. Access to harm reduction programmes for IDUs increased nationwide within the framework of a Global Fund supported programme, particularly during 2005–2007, which is also likely to have contributed to increasing coverage of VCT for IDUs, including female IDUS.
Among women becoming pregnant with unknown HIV status, IDUs were more than 3.5 times more likely to be diagnosed through intrapartum rapid testing than women with a non-IDU-related mode of acquisition, indicating reduced access to antenatal care and thus the application of less effective PMTCT interventions. It is well recognised that this marginalised group of women frequently experience problems accessing health and social services [22
]. In a study in St Petersburg, Russian Federation among women presenting in labour with unknown HIV status, largely without antenatal care, two-thirds were IDUs [24
]; HIV seroprevalence was 6.5% among women without antenatal testing, substantially higher than the 1–2% among women accessing antenatal care [25
Our results indicate the greater effectiveness of antenatal ZDV compared with sdNVP in PMTCT, consistent with previous findings [12
]. As the few women receiving antenatal HAART had clinical and/or immunological indications for HIV treatment, which are associated with increased MTCT risk [9
], one might potentially expect a greater reduction in transmission risk than the 84% seen here associated with HAART use if HAART were implemented as prophylaxis for all women [13
], which is planned for Ukraine's next PMTCT programme, from 2009. Around 18% of women delivering in 2007 received sdNVP alone or with ZDV. Although current WHO guidelines [12
] recommend that where possible a 3TC and ZDV "tail" should be provided postnatally for mothers receiving sdNVP, to reduce the likelihood of NVP resistance developing [16
], this was not included within the Ukraine PMTCT programme. It remains unclear to what extent NVP resistance could compromise success of subsequent treatment of mother and child with NNRTI-containing regimens [27
Elective CS was an effective PMTCT intervention in this setting, associated with a near-halving of risk, consistent with earlier results in Western Europe [14
]. However, we documented considerable variation in the application of this PMTCT intervention across our study sites. Ukraine is a setting where formula feeding is acceptable, feasible, affordable, sustainable and safe and this is recommended for all HIV-positive women within the national policy. Although free breast milk substitutes are theoretically available, there are historic reports of limited access for some women [18
]. Only around 1% of infants were breastfed, mostly for short durations. Breastfeeding was associated with a three-fold increased MTCT risk, although we were unable to determine the timing of transmission among HIV-positive breastfed infants. These findings are a pertinent reminder that appropriate feeding counselling and support for HIV-infected women [35
] are needed even in settings where avoidance of breastfeeding is not generally perceived as problematic.
The halving of the MTCT rate since 2001 documented here marks the success of the national PMTCT programme, although key challenges remain which must be addressed if the country is to achieve the Dublin Declaration target of "virtual elimination" of HIV transmission to infants by 2010 [36
]. Women least likely to receive ARV prophylaxis included IDUs and those diagnosed intrapartum, which mirrors findings from elsewhere in Europe [37
]. Efforts are needed to address barriers that these women may face in accessing services, particularly as many may have concurrent infections, including hepatitis C [40
] and sexually transmitted infections [41
]. Linkages between harm reduction, oral substitution therapy and PMTCT services need to be established, with development of services targeted at hard-to-reach IDU pregnant women. It will also be important to improve quality of PMTCT interventions, including better access to CD4 count monitoring and HAART and improved coverage of early infant diagnosis. Primary prevention of HIV acquisition in women is the most effective approach for preventing infections in infants [11
], but services in Ukraine remain under-developed, both those directed to at risk populations, such as IDUs, and for the general population. Nearly half of the women here reported no specific risk factors for HIV and most likely acquired infection heterosexually. As Ukraine has an HIV prevalence exceeding 1.5%, increasing heterosexual transmission and a young HIV-positive population (three-quarters aged 30 or less) [8
], it is essential that concerted effort is directed towards primary prevention, as recommended by the recent UNAIDS-coordinated External Evaluation of the National AIDS Response [38
Our study was limited by the observational nature of the data and although we adjusted for confounding factors in our multivariable analyses, there is potential for unmeasured confounding. Other limitations included the paucity of maternal CD4 counts and lack of HIV RNA measurements, which were not widely available within routine clinical practice. In a setting with limited access to early diagnosis for HIV-exposed infants, scope for loss to follow-up before infection status can be determined is considerable. Here, 15% of infants had indeterminate infection status despite being aged >18 months; applying the relevant transmission risks for the five strata of ARV prophylaxis applicable to these 535 children, we estimate that an estimated 65 (12.1%) would be infected. Adding this figure to the 1690 children with known infection status gives an overall MTCT estimate of 11.6% (c.f. 11.4% reported). Regarding the generalizability of our results, of the estimated 2731 HIV-infected women who delivered nationally in 2007 [38
], nearly a third were enrolled in the ECS, suggesting that our cohort is representative of the HIV-infected pregnant population in Ukraine. Of note, as the ECS only includes women who deliver, characteristics may differ from women terminating their pregnancies.