Five-year trends in epidemiology and prevention of mother-to-child HIV transmission, St. Petersburg, Russia: results from perinatal HIV surveillance

The HIV epidemic in Russia, historically concentrated among male injection drug users, continues to grow [1]. Russia has one of the world's highest prevalences of injection drug use and one of the world's largest numbers of injection drug users. The Reference Group to the United Nations on HIV and Injecting Drug Use estimates HIV seroprevalence to be 37.2% among this group [2]. Although injection drug use remains the driving force of the epidemic in Russia, there is growing evidence of its spread outside traditional risk groups to the general population [3, 4]. The bridging of HIV to individuals who never injected drugs primarily occurs through unprotected sexual contacts with HIV-infected injection drug users, most of whom are young and sexually active [4, 5]. The increase in sexual transmission of HIV disproportionately affects women, whose proportion among newly registered HIV cases in Russia increased from 13.0% in 1995 to 42.0% in 2008 [6].

In the absence of the full range of reproductive health services for HIV-infected women, the growing presence of women in the HIV epidemic may increase the number of infants exposed to HIV. Although prevention of mother-to-child HIV transmission is among the highest priorities in Russia, current transmission rates are still higher than observed in high-income countries, where elimination of perinatal HIV infection is a feasible goal [7, 8]. The widespread prophylactic use of highly active antiretroviral therapy throughout pregnancy, one of the mainstays of preventing perinatal HIV transmission in North America and Western Europe, is underutilized in Russia [9]. Many barriers to effective perinatal prevention relate to either behavioral characteristics of HIV-infected women themselves (e.g., lack of family planning or prenatal care) or to the quantity and quality of clinical services provided to these women and their infants during pregnancy, labor and delivery, and the postpartum period (e.g., late or inadequate antiretroviral prophylaxis, lack of HIV disease progression monitoring) [10]. It is unclear whether trends in these behavioral and clinical barriers differ among those HIV-infected women who used injection drugs, compared with those who did not.

St. Petersburg, the second largest Russian city, has the highest number of people living with HIV and one of the highest number of deliveries by HIV-infected women in Russia [6]. Although the standard HIV case-reporting system is useful for measuring trends over time, it likely underestimates the true number of HIV-infected individuals because of limited outreach to high-risk groups and exclusion of HIV-infected inhabitants who are not official residents of the city. To supplement the standard HIV surveillance system with data that would inform prevention programs, an enhanced perinatal HIV surveillance system was established in St. Petersburg to monitor uptake of prevention activities and rates of perinatal HIV transmission [10]. The objectives of our analyses were to explore five-year trends in factors influencing perinatal HIV transmission. By using the standard HIV case-reporting system, we assessed trends in HIV seroprevalence among all women giving birth and trends in birth rates among HIV-infected women. Furthermore, we used enhanced perinatal HIV surveillance among HIV-infected women giving birth to explore overall trends in proportion of women with history of injection drug use before and during pregnancy; to evaluate trends in social, perinatal, and clinical factors influencing mother-to-child HIV transmission among women with and without history of injection drug use; and to assess whether these changes were accompanied by concurrent reductions in perinatal HIV transmission rates.

Analyses of the standard HIV surveillance revealed that although the overall number of deliveries in St. Petersburg during 2004-2009 increased, HIV seroprevalence of women giving birth decreased as follows: 1.1% (466/42,846) in 2004; 1.0% (415/41,471) in 2005; 0.8% (346/41,815) in 2006; 0.8% (355/46,239) in 2007; 0.7% (357/49,978) in 2008; and 0.7% (391/53,798) in 2009 (P < 0.0001). Although the number of identified HIV-infected women in the city increased, the birth rate among HIV-infected women decreased: 6.9% (466/6,763) in 2004, 5.3% (415/7,849) in 2005, 3.9% (346/8,976) in 2006, 3.5% (355/10,125) in 2007, 3.1% (357/11,405) in 2008, and 3.1% (391/12,695) in 2009 (P < 0.0001, Figure 1).

According to the enhanced perinatal HIV surveillance system, the number and proportion of IDUs among HIV-infected women giving birth decreased from 62.3% in 2004 to 40.9% in 2008; similarly, the proportion of women coinfected with HCV decreased from 70.4% to 50.3% (both P < 0.0001). Although the decreasing proportion of IDUs was accompanied by a smaller proportion of women who reported injection drug use during pregnancy among all HIV-infected women (32.1%-25.5%, P < 0.005, Figure 2), the proportion of IDUs reporting injection drug use during pregnancy increased (51.6%-62.3%, P < 0.05, Table 1).

During the study period, we observed several significant changes in the characteristics of HIV-infected women giving birth. The proportion of women aged >30 years increased regardless of injection drug use history (2.9%-17.4% among non-IDUs, 2.9%-13.1% among IDUs); similarly and potentially related to this age trend, the proportion of women who had previous live births increased (20.6%-37.9% among non-IDUs, 26.7%-41.5% among IDUs) (all P < 0.001, Table 1). The majority of women giving birth were married or living in nonmarital unions and were city residents, and thus eligible for health-related and social services provided by the city (other HIV-infected women who live in the city but don't have official registration are usually eligible only for emergency services, including delivery, but not for routine HIV treatment, care and support). We observed a decreasing trend of unintended pregnancy (52.2%-30.2% among non-IDUs, 65.8%-46.0% among IDUs, both P < 0.0001). The proportion of women without prenatal care remained relatively stable, ranging from 9.8%-17.7% among non-IDUs, and from 29.5%-42.4% among IDUs. Among women who did receive prenatal care, we observed the tendency of its earlier initiation: e.g., the proportion of HIV-infected women who started prenatal care ≤28 weeks of gestation increased from 60.9% to 66.7% (P < 0.05) among IDUs. Although the proportion of preterm deliveries was lower among non-IDUs, it almost doubled in this group of women (10.7%-19.7%, P < 0.05). The percentage of women with vaginal deliveries decreased (85.0%-76.8% among non-IDUs, 86.6%-79.0% among IDUs, both P < 0.05).

Uptake of immunologic and virologic monitoring in both non-IDUs and IDUs also increased (Table 1). Overall, in non-IDUs and IDUs combined, the proportion of women who received CD4-cell count testing and viral load testing increased significantly (51.4%-73.6% and 8.5%-68.2%, respectively, both P < 0.0001, Figure 3). Median CD4-cell count remained relatively stable at 565 cells/mL (IQR: 422-732 cells/mL), and median viral load (community viral load) decreased from 9,170 copies/mL (IQR: 1,420-31,100 copies/mL) to 201 copies/mL (IQR: 60-794 copies/mL) (P < 0.0001).

Significant changes in the timing and completeness of antiretroviral prophylaxis during the five years of surveillance occurred among both non-IDUs and IDUs (Table 1). For the two groups combined, both initiation of antiretroviral prophylaxis ≤28 weeks gestation and dual/triple antiretroviral prophylaxis increased (44.6%-64.9% and 11.0%-52.8%, respectively, both P < 0.0001, Figure 4). Overall, infant follow-up was over 60% for the first four years of surveillance (2004-2007) (Table 1). It is important to note that since there is continuous work to increase follow-up of HIV-exposed infants who do not have determined HIV status, the rate of infant follow-up for a given year represents outreach activities conducted during the subsequent years.

The overall rate of perinatal HIV transmission during the 4-year surveillance period was 4.0% (CI 2.7%-5.8%) and 7.0% (CI 5.5%-9.0%) among non-IDUs and IDUs, respectively. For all HIV-infected women giving birth in St. Petersburg, perinatal HIV transmission initially increased from 5.3% (CI 3.5%-7.8%) in 2004 to 8.5% (CI 6.1%-11.7%) in 2005 (P < 0.05), followed by a decline to 5.3% (CI 3.4%-8.3%) in 2006, and 3.2% (CI 1.7%-5.8%) in 2007 (P for trend <0.05, Figure 4). The rates of infant abandonment decreased significantly from >15% during the first three years of surveillance (2004-2006) to <10% during 2007-2008 (P < 0.01) among IDUs, and remained unchanged at 3.0%-5.5% among non-IDUs (Table 1).

It is noteworthy that for most of the study years considered, IDUs were more likely than non-IDUs to be unmarried, to have unintended pregnancy, later initiation of or no prenatal care, preterm delivery, to receive HIV diagnosis in labor and delivery, to have hepatitis C, no immunologic and virologic monitoring, lower CD4 count, later or incomplete antiretroviral prophylaxis, higher rates of perinatal transmission and infant abandonment (Table 1).

These analyses of five years of data from standard and enhanced perinatal HIV surveillance provide important information about trends in the epidemiology and prevention of mother-to-child HIV transmission in St. Petersburg-one of the cities in Russia most affected by HIV. We observed a significant decrease in births among all HIV-infected women, and a decrease in IDUs among HIV-infected women giving birth. Regardless of injection drug use history, we noted impressive improvements in the uptake of clinical services by HIV-infected women giving birth, such as earlier initiation of prenatal care, fewer unintended pregnancies, higher uptake of immunologic and virologic monitoring, earlier initiation and more complete antiretroviral prophylaxis. Most significantly, these improvements in clinical services were followed by a decrease in the rates of mother-to-child HIV transmission from 2005 to 2007.

Our data show that in contrast to the increasing birth rate in the general population of women in St. Petersburg, HIV-infected women are having fewer births. The declining birth rate among HIV-infected women may be a result of increasing age of these women or indicate a decrease in their fertility desires, and/or improved family planning because no increase of abortions was observed in this population during the same time period (personal communication with Dr. Nikolay Belyakov, Director, St. Petersburg City AIDS Center, where 90% of abortions among HIV-infected women are performed). During the last two years of assessment, many HIV-infected women of reproductive age in St. Petersburg received free family planning services, including the contraceptives of their choice [16]. These programmatic improvements likely contributed to the decreases in the birth and unintended pregnancy rates among HIV-infected women. In addition, we observed a decreasing proportion of IDUs among HIV-infected women giving birth, which might be explained by ongoing heterosexual transmission of HIV from HIV-infected male IDUs and some heterosexual transmission outside of the traditional high-risk groups. The improvements of clinical HIV services, albeit more pronounced among women without a history of injection drug use, were evident for both non-IDUs and IDUs.

Perinatal HIV transmission during the first year of surveillance increased, coinciding with no improvements in timing or completeness of antiretroviral prophylaxis. The subsequent decrease of perinatal transmission was most likely due to multiple factors, although earlier initiation and higher effectiveness of antiretroviral prophylaxis were probably the main contributors [9]. Other factors that may have contributed to the decrease in perinatal HIV transmission include a lower rate of unintended pregnancies, earlier initiation of prenatal care, and improved immunologic and virologic HIV monitoring. However, not all women had the benefits of improved clinical services. The steady proportion of women who did not receive prenatal care and ARV prophylaxis, and the increasing trend of injection drug use during pregnancy among IDUs, both indicate that outreach programs are not reaching all women.

Standard HIV surveillance in pregnant women provides important data on trends of the epidemic and overall effectiveness of preventive measures [17], yet contributes minimally to identifying specific areas for programmatic improvement. Enhanced perinatal surveillance, on the other hand, provides supplementary detailed information on the mother-infant pair, including risk factors, clinical services, and laboratory data, which assists timely evaluation of perinatal prevention efforts [18, 19]. It can be linked with other systems or registries, such as, for example, maternal and infant records at the City AIDS Center. The annual cost of enhanced perinatal surveillance in St. Petersburg was approximately $20,000. If scaled up to a total of five metropolitan areas with highest HIV seroprevalence (i.e., Samara, Irkutsk, Yekaterinburg, Orenburg) [6], enhanced perinatal surveillance may provide valuable national data on the risk factors for perinatal HIV transmission for considerably less than one percent of the amount spent on HIV prevention in Russia [20]. In St. Petersburg, enhanced perinatal surveillance was critical in identifying areas needing improvement, such as limited use of effective family planning [21], low infant follow-up [10], and delayed and less effective antiretroviral prophylaxis [9]. Immediate, focused attention by the local public health leadership made it possible to address each of these issues in a timely fashion through program and policy improvements. As a result, we observed fewer unintended pregnancies, improved infant follow-up, earlier and more effective antiretroviral prophylaxis, and, subsequently, fewer HIV-infected infants.

Our assessment supports the evidence from other countries-improvement of clinical services for HIV-infected women results in significant reductions in perinatal HIV transmission. The success of high-income countries in reducing perinatal HIV transmission was attributed to increased coverage of HIV-infected pregnant women by combination antiretroviral prophylaxis, elective cesarean delivery, and avoidance of breastfeeding [22–24]. Despite a number of challenges in low- and middle-income countries [25, 26], a few reports provide evidence that it is possible to reduce perinatal HIV transmission with implementation of comparable preventive measures [27, 28]. In Ukraine, which had a healthcare system similar to the one in Russia, but had lower coverage by combination antiretroviral prophylaxis at the time of assessment, perinatal HIV transmission was reduced in half in five years (from 15.2% in 2001 to 7.0% in 2006) by strengthening clinical services provided to HIV-infected women [27]. In Russia, where the rate of perinatal HIV transmission has been relatively stable at 6%-8%, the St. Petersburg experience suggests that it is feasible to attain low rates of mother-to-child transmission similar to U.S. and Western European rates. Since our observation of the impact of early and effective antiretroviral prophylaxis on perinatal HIV transmission is consistent with findings from randomized controlled trials from various parts of the world [29], the data described in this report may be generalizable to other middle-income countries with a large proportion of hospital deliveries and replacement feeding among HIV-infected women giving birth.

The results of this assessment should be interpreted in light of its strengths and limitations. Strengths of the study include almost universal coverage of HIV-infected women giving birth by enhanced perinatal surveillance and standardized data collection methods that allow trend analyses. Although ours is one of the few reports to describe trends in critical indicators of perinatal HIV transmission separately for non-IDUs and IDUs, it is possible that due to social desirability, some women with a history of injection drug use were misclassified as non-IDUs. In additional subgroup analysis (not shown), critical indicators of perinatal transmission among women who reported no history of injection drug use but had hepatitis C coinfection more closely resembled non-IDUs, indicating that the effect of any misclassification of self-reported injection drug use was likely to have been minimal. Another limitation of the study is a large proportion of HIV-exposed infants with undetermined HIV status (e.g., 33.7% during 2007). Previous analysis showed that characteristics of women whose infants had known HIV status were similar to that of the entire population of HIV-infected women. There were, however, some differences: infant HIV status was more likely to be unknown for subgroups with both increased (nonresidents and those with late initiation of antiretroviral prophylaxis) and decreased (those using injection drugs during pregnancy) risk factors for transmission [9]. Therefore, HIV transmission rates can be either underestimated or overestimated.