The impact of comprehensive prevention of mother-to-child HIV transmission in Dehong prefecture,Yunnan province,2005–2010: a hard-hit area by HIV in Southern China

Abstract

The burden of HIV/AIDS in China has been disproportionately concentrated in Yunnan Province, where in Dehong prefecture, the HIV prevalence rate among pregnant women reached 1.3% in 2003, a rate that is indicative of a generalized epidemic. Since then, there have been extensive efforts to expand prevention to reduce mother-to-child transmission (MTCT) in this high-prevalence region. These intensified MTCT reduction efforts and their impact on MTCT are yet to be examined. We described the changes in access to HIV screening and antiretroviral therapy (ART) among pregnant women from 2005 to 2010 in this region and the corresponding reduction in MTCT over this period. Between 2005 and 2010, the annual number of pregnant women screened for HIV in Dehong Prefecture more than doubled. The proportion of pregnant women screened for HIV rose from an estimated 15–20% to 99.8%, and the proportion of HIV-infected pregnant women receiving ART increased from 63% to 99%. We estimate that the proportion of children born with HIV to HIV-infected mothers decreased from 15.4% to 7.2% over this period. Sustained low-level MTCT following comprehensive interventions in this region is encouraging. Over the last decade, comprehensive PMTCT efforts, coupled with national and local government policy support in this area appear to be effective.

Keywords

HIV AIDS women prevalence mother-to-child transmission prevention PMTCT antiretroviral therapy China

Background

According to China's HIV/AIDS Prevention and Control Joint Evaluation Report, there were an estimated 780,000 surviving people living with HIV/AIDS (PLWHA) in China as of the end of 2011 and 28,000 HIV/AIDS-related deaths in 2011. It is estimated that approximately 1.1% of PLWHA and 0.8% of HIV/AIDS-related deaths were due to infections from mother-to-child transmission (MTCT).¹

In 1989, the first indigenous AIDS cases were reported as an outbreak in 146 infected heroin users in Dehong prefecture, Yunnan province. Subsequently, HIV spread steadily from this province into neighbouring areas and along the major drug trafficking routes, then from injecting drug users (IDUs) to their sexual partners and children. The first case of MTCT was reported to the Chinese Center for Disease Control and Prevention (CDC) in Yunnan province in 1995.^2,3 Data from China CDC reports have shown that the proportion of reported cases of HIV and AIDS attributed to MTCT has increased from 0.1% in 1997 to 0.4% in 2002.⁴ Meanwhile, studies have shown a high prevalence of HIV infection among children born to HIV-infected mothers in certain areas of China, especially in Yunnan province (HIV prevalence reached 34%).⁵ The burden of HIV/AIDS in China has been disproportionately concentrated in Yunnan Province, where in certain areas, such as Dehong prefecture, HIV prevalence rates among pregnant women has reached 1.3% in 2003, a rate that is indicative of a generalized epidemic.⁶

Since then, this prefecture has become the epicentre with the most severe HIV epidemic in China and attracted a considerable level of attention, both domestically and internationally.^7,8 Over the last decade, there have been extensive efforts to expand interventions to reduce MTCT in this high-prevalence region.⁹ In 2004, expansion of prevention of mother-to-child transmission (PMTCT) services was initiated in Yunnan province and Dehong prefecture through ‘The First Round of Implementation Plan for Combating HIV/AIDS (2005–2007),’ which sought to increase access to antiretroviral therapy (ART) among HIV-infected pregnant women to 90%, alongside increasing access to HIV testing services in this population. After 2004, HIV screening of pregnant women in Dehong Prefecture was expanded across Women and Children’s hospitals at both the county and prefectural level. Then, these efforts were further strengthened by the Yunnan AIDS Prevention and Control Act passed in 2007, which made provisions for access to free HIV screening for all pregnant women, and subsequent waves of funding and infrastructure development for expansion of PMTCT services. In 2007, ‘The Second Round of Implementation Plan for Combating HIV/AIDS (2008–2010)’ was issued. In this programme, PMTCT work was required to be added to local routine Mother and Children’s Health (MCH) work and it set an even more ambitious goal – to expand treatment coverage among HIV-infected women to at least 98%.^10,11 Followed by this programme, a series of policy and technical guidelines have been continuously issued. These include ‘The PMTCT Work Guidance Manual in Yunnan Province’, ‘The Assessment Framework and Indicators System For PMTCT Work in Yunnan Province’, ‘Mother and Child Health Services Manual in Yunnan Province’, ‘PMTCT Data Quality Control Programme in Yunnan Province’, and ‘Ten Action Plans For AIDS Prevention and Control Work in Yunnan Province’ (see Figure 1). The specifications emphasize the key aspects of PMTCT work in Yunnan province, such as health education, HIV testing during the early period of pregnancy, prevention and referral, preventive antiviral therapy of MTCT, care and support, HIV maternal and infants’ follow-up, staff training, family planning, supervision and evaluation, and data quality control.

Figure 1.

Temporal relationship between key HIV policy documents issued and HIV MTCT rate in Dehong prefecture, 2004–2010.

These intensified MTCT reduction efforts and their impact on mother-to-child-transmission rates in this region are yet to be examined. We describe changes in access to HIV screening and ART among pregnant women from 2005 to 2010 in Dehong Prefecture in Yunnan Province, China and the corresponding reduction in mother-to-child HIV transmission over this period.

Materials and method

Data sources

Data were first obtained from the National HIV/AIDS Comprehensive Response Information Management System (CRIMS).¹² This unified, web-based platform includes subsystems, such as HIV/AIDS Case Reporting, HIV Testing and Counseling, HIV Sentinel Surveillance and ART for Adults, etc. Then, data were linked to the local obstetric surveillance network maintained by local CDCs. Local pregnancies in women with diagnosed HIV and children with HIV infection and infants born to infected women were notified through this active obstetric surveillance network. As Dehong prefecture has attracted a considerable level of attention, its obstetric surveillance network was built early from 2003, and seven related health centres were reported to this network, including four maternal and child health centres, two comprehensive hospitals and one antenatal clinic in Dehong prefecture, which could cover over 90% HIV-infected women giving births in this region from 2005 to 2010. HIV-infected women giving birth at home or other places were not included in the surveillance network.

HIV counseling and testing

Follow-up services, including counseling and testing were provided for HIV-positive women before, during, and after delivery. A woman was considered to be HIV-infected if she was screened HIV-positive, and then confirmed by Western Blot or two positive ELISA tests (enzyme-linked immunosorbent assay, Vironostika HIV Uni-Form plus O, BioMerieux, Holland). All respondents had been notified of their HIV-positive status, and were entered into the obstetric surveillance system between 2004 and 2010. HIV antibody test was given to infants at 18 months, and a child was considered to be HIV-infected if he or she: (a) had two or more blood specimens that tested positive for HIV by ELISA tests; or (b) had one or more specimens that tested positive by two different assays (e.g. enzyme immunoassay or rapid test), drawn at age 18 months or greater; or (c) died and a diagnosis of HIV had not been excluded by laboratory tests. Infants were tested by an HIV viral load (VL) assay at 1–3 months after birth (35–180 days, with 93 days in average).

Drug regimens

Before 2005, HIV-infected pregnant women were asked to take nevirapine (NVP) at onset of the labour (200 mg) and the infants took single-dose NVP in 24–48 h after birth (2 mg/kg, ≤6 mg). If the pregnant women gave birth in 2 h after taking NVP, the newborn received its first oral NVP in 60 min after birth, and the second oral NVP at least 48–72 h after birth. In the case of cesarean section, the pregnant women took NVP (200 mg) in 24 h prior to the operation. After 2005, HIV-infected pregnant women were asked to take zidovudine (AZT) + lamivudine (3TC) + NVP (CD4 < 250 cells/mm³), or AZT + 3TC + EFV (CD4 > 250 cells/mm³) after 3 months' pregnancy; and children were required to take AZT + 3TC + NVP. Among them, the infants with a body surface area at 160 mg/m² were asked to take AZT every 8 h (newborns over 90 days); infants with a body weight at 4 mg/kg were prescribed 3TC twice a day (newborns over 30 days); infants with a body surface area at 120 mg/m² were prescribed NVP once a day and treated for 14 days (newborns over 60 days), and children less than eight years took NVP at 7 mg/kg, every 12 h while children older than eight years took NVP at 4 mg/kg, every 12 h.

Maternal ART in pregnancy was categorized as none, monotherapy, dual therapy and HAART (three or more drugs); only antepartum treatment was considered in this analysis. The vertical transmission rate is the number of infants infected amongst the infants born to HIV-infected mothers, regardless of type of therapy or mode of delivery.

Infant feeding

While all women were counseled antenatally about infant-feeding options, uninterrupted access to six months’ commercial infant formula was offered free through the national and international PMTCT programmes in this region from 2005, which was expected to result in the lowest risk of disease and death. HIV-infected mothers could choose to access this supply any time in the first 12 months of the infant’s life. For those initiating formula milk from birth, an initial supply was provided antenatally.

Data analysis

As data were collected in paper forms in 2004, they were entered into the web-based system by local level public health workers. Data collected from 2005 to 2010 were directly reported to the system. Maternal sociodemographic and health information was recorded, and key variables in the collected data include: number of pregnant women registered, number of pregnant women screened for HIV, number of HIV-infected pregnant women, number of HIV-infected pregnant women on ART, ART regimens, time of receiving ART, number of live births, number of infected infants born to HIV infected mothers. Statistical analysis was carried out using SPSS 13.0 (SPSS Inc., IL). Data from 2004 to 2010 were analyzed and shown in absolute numbers and proportions.

Results

Access to HIV testing among pregnant women between 2005 and 2010

Uptake of antenatal HIV testing rose rapidly following the introduction of routine screening policies in 2008. From 2005 to 2010, the number of pregnant women undergoing HIV screening increased over two-fold. While only 70.1% of pregnant women were screened for HIV in 2005, by 2010, the proportion of pregnant women undergoing HIV screening had reached 99.8% (Table 1). Of the 19,016 pregnant women who were screened in 2010, 129 were found to be HIV-infected. Over this five-year period, the proportion of HIV-infected pregnant women decreased from 0.8% to 0.6%.

Table 1.

Proportion of pregnant women screened for HIV in Dehong Prefecture, 2005–2010.^a

Year	Total number of pregnant women	Total number of pregnant women screened for HIV	Proportion of pregnant women screened for HIV (%)
2004	11,925	–	–
2005	13,011	9,121	70.1
2006	14,725	9,811	66.6
2007	14,316	13,228	92.4
2008	17,798	17,091	96.0
2009	18,347	18,177	99.1
2010	19,049	19,016	99.8

Total number of pregnant women and pregnant women screened for HIV included women with multiple pregnancies during years 2005–2010; for example, women with three pregnancies were recorded as three pregnant women. ‘–’ indicates that the necessary data were not collected.

Access to ART among pregnant women between 2005 and 2010

Overall, between 2005 and 2010, the proportion of HIV-infected pregnant women receiving ART rose from 63.2% to 99.2%. The proportion of HIV-infected new mothers using HAART (three or more drugs) regimen increased significantly, from 1.2% in 2005 to 96.1% in 2010, while the proportion of those using monotherapy and dual therapy declined (Table 2, Figure 1). The proportion of women receiving ART before 28 weeks of gestation increased from 8.1% in 2005 to 69.8% in 2010 and the proportion of women receiving ART before 14 weeks of pregnancy rose from 1.2% in 2005 to 20.9% in 2010 (Table 2).

Table 2.

Proportion of pregnant women who knew their HIV infection status and women who received antiretroviral therapy (ART) in Dehong prefecture, 2005–2010.

Year	Number of HIV-infected pregnant women	When mother first knew HIV status					Proportion of HIV-infected pregnant women on ART (%)	Proportion on ART with different regimens (%)			ART prior to 28 weeks of pregnancy (%)
Year	Number of HIV-infected pregnant women	Before pregnancy	During pregnancy	During labor	After delivery	Missing	Proportion of HIV-infected pregnant women on ART (%)	Proportion on a monotherapy regimen	Proportion on a dual therapy regimen	Proportion on HAART (three or more drugs) regimen	ART prior to 28 weeks of pregnancy (%)
2005	87	12	59	6	8	2	63.2	42.5	19.5	1.2	8.1
2006	111	15	76	7	11	2	91.9	61.9	21.6	8.4	11.7
2007	114	13	70	10	18	3	88.6	45.9	27.8	14.9	23.7
2008	128	15	85	12	14	2	94.5	13.2	4.7	76.6	45.3
2009	147	17	89	9	28	4	95.9	5.4	0.7	89.8	55.8
2010	129	18	96	8	4	3	99.2	3.1	0	96.1	69.8
Total	716	90	475	52	83	16	90.5	2.2	0.7	87.6	56.9

The outcomes and access to ART among children born with HIV to HIV-infected women in Dehong prefecture, 2005–2010

Between 2005 and 2010, a cumulative 716 HIV-infected pregnant women were reported in Dehong prefecture. By the end of 2010, a total of 698 children were aged 18 months, and among them, 516 (73.9%) received HIV testing; 20 (2.9%) parents refused testing 110 (15.8%) were lost to follow-up, and 44 (6.3%) died. From 2005 to 2010, the number of children born with HIV to HIV-infected women were 18, 28, 10, 15 and 11, and among them, 15, 24, 9, 14 and 10 children received ART services every year, respectively (Table 3). By the end of 2010, 72 HIV-positive children were on ART; 70 of them were on the AZT + 3TC + NVP regimen. A total of 14, 16, 17 and 20 children underwent VL testing at 3, 6, 12 and 18 months, respectively, after ART, and 8, 14, 15 and 15 cases' VL results were less than 1000 copies/ml. Before treatment, CD4 + T lymphocyte count was at an average (320.1 ± 288.8) cells/mm³ and it increased to (1038.72 ± 1081.1) cells/mm³ after 18 months (see Figure 2).

Table 3.

The outcomes of children born to HIV-infected women in Dehong Prefecture, 2005–2010.

Year	Number of 18-month-old infants	Underwent HIV testing		Refused to receive HIV testing		Lost to follow-up		Died
Year	Number of 18-month-old infants	Number	Proportion (%)	Number	Proportion (%)	Number	Proportion (%)	Number	Proportion (%)
2005	0	0	–	0	–	0	–	0	–
2006	54	35	64.8	2	3.7	15	27.8	1	1.9
2007	148	102	68.9	4	2.7	27	18.2	13	8.8
2008	175	123	70.3	5	2.9	35	20.0	10	5.7
2009	139	108	77.7	4	2.9	18	12.9	9	6.5
2010	182	148	81.3	5	2.7	15	8.2	11	6.0
Total	698	516	73.9	20	2.9	110	15.8	44	6.3

Figure 2.

Rate of children receiving ART prophylaxis in Dehong prefecture, 2006–2010.

The estimated mother-to-child HIV transmission between 2005 and 2010

According to World Health Organization 2010 guidelines,¹³ there are a number of children who were not tested and reported and should be considered. This number of children should be added to the numerator when estimating mother-to-child HIV transmission. We estimated the proportion of children born with HIV to HIV-infected mothers annually between 2005 and 2010 based on this guideline and our estimation attempts to take in to consideration those children who were not reported in the web-based subsystems in CRIMS and may have become infected through MTCT. Therefore, the numerator is calculated as ‘the reported number of infected infants’ plus ‘the estimated non-reported number of infected infants’. The ‘non-reported number of infected infants’ part is estimated as ‘the number of children born to HIV-positive mothers who were not tested or reported’ multiplied by ‘the estimated rate of HIV infection of non-reported number of infected infants’. It is estimated that the proportion of children born with HIV to HIV-infected mothers was 14.4% in 2006 and declined to 6.7% in 2010 (Table 4).

Table 4.

Estimated proportion of children born with HIV to HIV-infected women in Dehong Prefecture, 2006–2010^a

Year	A	B	C	D	E	F	G = A × B	H = (C − D + E) × 34.8%^b	I = D × F	J = (H + I)/G
Year	Number of live births	HIV prevalence among pregnant women	Estimated number of HIV-Infected pregnant women	Reported number of HIV-infected pregnant women detected through testing	Reported number of HIV-infected pregnant women who were not on ART	Proportion of children born with HIV to HIV-infected pregnant women on ART (%)	Calculated number of infants born to HIV-infected mothers	Estimated non-reported number of infected infants	Reported number of infected infants	Calculated proportion of children born with HIV to HIV-Infected women (%)
2006	12,649	0.009	116	114	12	11.1	113.841	4.872	12.654	15.4
2007	13,786	0.01	140	134	33	10.4	137.86	13.572	13.936	20.0
2008	17,255	0.007	128	127	4	6.7	120.785	1.74	8.509	8.5
2009	18,164	0.009	147	143	25	3.6	163.476	10.092	5.148	9.3
2010	19,025	0.008	129	128	30	0.1	152.2	10.788	0.128	7.2

The numerator: (Estimated Number of HIV-Infected pregnant women − Reported Number of HIV-Infected pregnant women detected through testing + Reported number of HIV-infected pregnant women who were not on ART) × 34.8%+Reported Number of HIV-Infected pregnant women detected through testing × Proportion of children born with HIV to HIV-infected pregnant women on ART; The denominator: Number of live births × HIV prevalence among pregnant women.¹³

The estimated rate of HIV infection of the children born to HIV-positive mothers who have not taken any preventive measures.

Discussion

Our study reveals that between 2005 and 2010, there were concerted efforts to increase access to HIV screening and ART to reduce mother-to-child HIV transmission; nearly universal HIV screening and treatment coverage was attained among pregnant women. We estimated a two-fold decrease in mother-to-child HIV transmission over the same period. Though mother-to-child-HIV transmission remains high at 7.2%, our findings support that owing to expanded HIV testing coverage, timely effective ART and appropriate management of delivery, and related policies in local areas, the transmission could be reduced enormously,^14–16 which we believe will continue to be feasible given the vast infrastructure for HIV screening and linkage to treatment and care for this population in this area that has been developed over the last decade.

Sustained low-level mother-to-child-HIV transmission following comprehensive interventions in this hardest-hit region by HIV is encouraging. The issued policies and guidelines, current testing strategy, options for treatment in this area appear to be effective. It is indicated that the two rounds of large-scale action plan for combating HIV/AIDS (2007–2010, 2008–2010), coupled with aggressive national and local policies, may have contributed to the significant reduction in MTCT in this region. Meanwhile, there may be also other factors that can explain the reductions in HIV MTCT, such as the increased financial and technical support from the central, provincial and prefectural government, the strong presence of local and international HIV/AIDS organizations in Yunnan, the well-trained local experts and public health workers. The HIV MTCT reduction could not be attained unless these factors combined.

One of the limitations of our study was selection bias. The study respondents included in the database were registered participants who were already willing to participate in routine health check-ups and HIV testing services. Our study did not include those HIV-infected women giving birth at home or other places; as this proportion is small, we included those non-reported number of infected infants in the estimation and calculation of HIV MTCT. In addition, as the study time was from 2004 to 2010, there were situations when cases got lost of follow-ups, and when drug regimens changed slightly over the years; this might influence the overall estimation. However, it was predicted that with further increased access to screening and linkage to HIV treatment and care among pregnant women and newborns and sustained levels of coverage, over time mother-to-child HIV transmission could be further reduced in this region and perhaps eventually eliminated, as has been achieved in other settings globally.^17–19

More evaluation programmes of the prevention efforts in this area should be implemented and focus on specific programmatic elements along the testing and treatment service cascade that can be strengthened and will be critical to sustaining ongoing declines in mother-to-child HIV transmission.

Footnotes

Conflict of interest

The authors declare no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

SCAWCO, UN Theme Group on HIV/AIDS in China. China HIV/AIDS Prevention and Control Joint Evaluation Report, Beijing, 2011.

Sullivan

Wang

. Evolution of China’s response to HIV/AIDS. Lancet 2007; 369: 679–90.

Duan

Shen

Bulterys

. Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route. BMC Public Health 2010; 10: 180–180.

Katherine

Qian

. Mother to child transmission of HIV in China. BMJ 2005; 330: 1282–1283.

Zhang

. Epidemiology of HIV in China. BMJ 2002; 324: 803–804.

Cohen

. Asia and Africa: on different trajectories? Science 2004; 304: 1932–1938.

Wang

Shan

Chan

. Disclosure of HIV-positive serostatus to sexual partners and associated factors in southern China. Int J STD AIDS 2010; 21: 685–690.

Sun

Liu

. Contributions of international cooperation projects to the HIV/AIDS response in China. Int J Epidemiol 2010; 39: ii14–ii20.

Jia

Sun

Fan

. Estimates of HIV prevalence in a highly endemic area of China: Dehong Prefecture, Yunnan Province. Int J Epidemiol 2008; 37: 1287–1296.

10.

Wang

Qiao

. PMTCT on HIV-infected pregnant women and new mothers and countermeasure analysis. Chin J Women Children’s Health 2006; 21: 1765–1766.

11.

Zhou

Meyers

. Prevention of mother-to-child transmission of HIV-1 using highly active antiretroviral therapy in rural Yunnan, China. Int J STD AIDS 2012; 53: S15–22.

12.

Mao

Poundstone

. Development of a unified web-based national HIV/AIDS information system in China. Int J Epidemiol 2010; 39: ii79–ii89.

13.

WHO revised guidelines for PMTCT. [EB/OL], http://www.who.int/hiv/pub/mtct/PMTCTfactsheet/en/index.html (2010, accessed 3 November 2012).

14.

Bulterys

Catherine

. HAART during pregnancy and during breastfeeding among HIV-infected women in the developing world: has the time come? AIDS 2009; 23: 2473–2477.

15.

Plipat

Naiwatanakul

Rattanasuporn

. Reduction in mother-to-child transmission of HIV in Thailand, 2001–2003: results from population-based surveillance in six provinces. AIDS 2007; 21: 145–151.

16.

Kourtis

Lee

Abrams

. Mother-to-child transmission of HIV-1: timing and implications for prevention. Lancet Infect Dis 2006; 6: 726–732.

17.

European Collaborative Study. Mother-to-child transmission of HIV infection in the era of highly active antiretroviral therapy. Clin Infect Dis 2005; 40: 458–465.

18.

Becquet

Ekouevi

Arrive

. Universal antiretroviral therapy for pregnant and breast-feeding HIV-1-infected women: towards the elimination of mother-to-child transmission of HIV-1 in resource-limited settings. Clin Infect Dis 2009; 49: 1936–1945.

19.

Fowler

Gable

Lampe

. Perinatal HIV and its prevention: progress toward an HIV-free generation. Clin Perinatol 2010; 37: 699–719.