| Objective:HIV is emerging rapidly in the world, spreading from high risk population to common population. The number of infected women and pregnant women is increasing, and more infants are infected through vertical transmission. So antiretroviral therapy is very important to infected pregnant women, improving the immunity status and decreasing vertical transmission. Resistance genotyping is important baseline information for the regimen selection of women therapy and prevention of mother-to-child transmission(PMTCT).There have not been reports about the drug resistance(DR) of HIV infected pregnant women in China. In the study, we performed resistance genotyping of HIV infected pregnant women at baseline in part of Henan, Yunnan, Xinjiang and Guangxi Provinces to know the DR prevelance and provided useful information to regimen selection of PMTCT and women therapy.Many regimens were used for PMTCT, resulting the decrease of vertical transmission and DR in mothers and infants. There have not been reports about the impact of PMTCT regimen on the DR of HIV infected mothers in China. We also studied the DR of infected mothers after they administered PMTCT regimen(sdNVP and ZDV-sdNVP). We also performed early diagnosis of infants born to these women, and did resistance genotyping of infected infants, and compared vertical transmission rate and infant DR in the two regimen.Sample:1. Samples of 181 drug-na(?)ve HIV infected women, i.e. 33 in Henan, 55 in Guangxi, 37 in Yunnan and 56 in Xinjiang.2. Samples of 80 infected women with PMTCT regimen information (included in the 181 samples), i.e. 62 in sdNVP group, 18 in ZDV-sdNVP group.3. Samples of 59 infected women with PMTCT regimen information followed up at 3m postpartum, i.e. 43 in sdNVP group, 16 in ZDV-sdNVP group.4. DBS samples of 80 matched infants of infected women (2d, 1m, 3m, 6m)Methods: 1. Viral-load and CD4 cell counts of 181 HIV infected women were tested by Cobas(Roche) and FACSCount (BD) method. DR and genotype of them were tested by in-house nest RT-PCR.2. Proportion of recent infection of 181 infected women was perfomed by BED-CEIA(Calypte).3. Viral-load and CD4 cell counts of HIV infected women with PMTCT regimen information followed up at postpartum were tested. DR and genotype of them were also tested.4. Early diagnosis of infants born to these women were performed by in-house nest RT-PCR and resistance genotyping of infected infants were performed.Results:1. 153 samples were successfully amplified. 16 women had drug resistance mutation(DRM). 2 had multiple DRMs. 12 had NNRTI DRMs. 5 had NRTI DRMs. Nobody had PI major mutations.2. The pol gene amplification rate was in good correlation with plasma viral-load. The amplification rate is 100% when the viral-load is above 10~3 , The amplification rate is 50% when the viral-load is below 10~3, 37.5% when the viral-load is below 400 and 81.3% when the viral-load is between 400-1000.3. The subtype of HFV infected women in Henan Province is B', with resistant mutation rate of 25%. The subtype of HIV infected women in Yunnan Province is B', CRF 01AE, CRF 07BC, CRF 08BC, BC, C, with resistant mutation rate of 16.7%. The subtype of HIV infected women in Xinjiang Province is CRF 07BC, with resistant mutation rate of 8.5%. The subtype of HIV infected women in Guangxi Province is CRF 01 AE, CRF 07BC, CRF 08BC, with no resistant mutation.4. The mutation rate among different subtypes is B'(21.4%, 6/28), BC (14.3%, 9/63), C (14.3%, 1I7), CRF 01AE ( 0%, 0/46) . The resistant mutation rate of B' is the highest. There are no mutation in subtype CRF 01AE.5. Proportion of recent infection of pregnant infected women in Henan, Yunnan, Xinjiang and Guangxi Province was 0% (0/33), 8.1% (3/37), 12.5% (7/56) and 12.7% (7/55)6. 62 women enrolled in sdNVP group, 43 were followed up at 3m postpartum. 18 women enrolled in ZDV-sdNVP group, 16 were followed up at 3m postpartum. The mutation rate selected by sdNVP and ZDV-sdNVP was 16.3%(7/43) and 0% (0/16) respectively. The CD4 cell counts increases more significantly in ZDV-sdNVP group than sdNVP group(166 vs -74, P<0.05). The CD4 cell counts at delivery of HIV infected women in sdNVP group was significantly less than those in ZDV-sdNVP group (335 vs. 484 cells/mm3, P<0.01). In sdNVP group, the CD4 cell counts of women at delivery with selected mutations at postpartum was less than those without mutation at postpartum(178 vs.364 cells/mm3, P<0.05), moreover, the age of the former was older than the latter (32.7 vs 27.5, P<0.01) .7. 14 of the infants born to 80 infected women got infected with HIV. The vertical transmission rate of women with mutation at delivery was similar to those without mutation (1/7 vs. 13/73, P>0.05). Among the infected infants, 6 were infected in utero, and 8 were infected at intrapartum. 3 infants had DRMs, 2 were selected by PMTCT regimen, and 1 were obtained by vertical transmission.8. The CD4 cell counts and viral-load of women with baseline resistance were similar to those without baseline resistance.Conclusion:1. Drug resistant strains in pregnant infected women in Henan, Yunnan and Xinjiang Province has prevailed. DR monitoring should be performed on these women, to provide useful information to regimen selection of PMTCT and women therapy.2. DR was correlated with ART time of the province. Long ART time leads to high DR prevelance.3. DR mutation was in negative correlation with proportion of recent infection of pregnant infected women, indicating recent infection of DR strain is not common.4. ZDV-sdNVP regimen is not significantly different from sdNVP regimen in PMTCT effect.But ZDV-sdNVP is better in controlling in-utero infection and DR in mothers and infants, and increasing immunity status in mothers. We recommend ZDV-sdNVP for PMTCT.5. Intrapartum transmission rate is relatively high, indicating that intrapartum nursing should be enhanced to avoid disruption of placental or cervical-vaginal tissue.6. DR after sdNVP was correlated with immunity level (CD4 cell counts). Increasing immunity can help control DR.7. Resistance baseline was not correlated with baseline viral-load and CD4 cell counts. |
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