246 pregnant HIV-infected women were divided into 3 groups: 1) receiving or continuing treatment with combined ARV, 2) ARV initiated for PMTCT, as scheduled or during ANC, 3) ARV only in labor due to lack of, or inadequate ANC. The maternal characteristics of the 246 pregnant HIV-infected women are shown in Table . Their age range was 16-41 years (median 27 years). The majority (61.8%) were in the age group 20-29 years, followed by 30-39 years (29.3%). The rate of teenage pregnancy was 8.1%. The majority of the pregnant women were currently in spousal relationships (60.16%), while 7.3% were separated and 1.2% widowed. 0.4% reported having multiple sex partners. Among the women in spousal relationships, 54% of their current spouses were also HIV seropositive whereas 46% were not. 29.3% had no income and most of the pregnant women had an average monthly income <10,000 Baht. Regarding HIV seroconversion, 73.2% were firstly detected when attending ANC, 15% prior to the current pregnancy, and 11.8% during labour.
Maternal Characteristics of Pregnant HIV-Infected Women, Antenatal Care and HIV History (n=246)
Among the 37 pregnant women who had known their HIV serostatus before the current pregnancy, 19 (51.4%) had experience with ARV; 16 continued combined ART, 2 had already withdrawn from ART, and one had used AZT plus a single dose of NVP once for PMTCT in the previous pregnancy. The other 18 (48.6%) pregnant women had no experience of ARV. Regarding the ART regimens used by 16 pregnant HIV-infected women, 2NRTIs + NVP (21.6%), 2NRTIs + efavirenz (EFV) (13.5%) and 2NRTIs + boosted indinavir (IDV/r) (8.1%) were noted. EFV was stopped and substituted with NVP among 4 pregnant women at 8, 11, 23, and 25 weeks' gestation; however, one did not stop taking EFV because of late presentation at ANC (35 weeks' gestation). Among the 180 pregnant women whose HIV-seroconversion was firstly detected during ANC, the median gestational age was 19.5 weeks; 83.9% were detected before or at 28 weeks' gestation. 98.2% were in WHO clinical stage [7
] 1 (asymptomatic), or CDC classification [8
] A. Median CD4 count was 325.5 cells/µL; 13.3% of these were <200 cells/µL. One pregnant woman with a CD4 count of 2 (0%) cells/µl, was classified as WHO clinical stage 3 (or CDC stage B), with perianal abscess and herpes labialis. Five (2.0%) pregnant women had late latent syphilis, and 15 (6.1%) of pregnant women had HBV coinfections.
Of the 246 pregnant women in ANC, 40 (16.3%) received combined ART, 164 (66.7%) PMTCT regimens, and 42 only PMTCT in labor, because of irregular or no ANC. Of those receiving PMTCT during ANC, only 76 (46.3%) started PMTCT before or at 28 weeks; 88 (53.7%) started after 32 weeks' gestation. The common combined ART regimen used in this study was AZT+ lamivudine (3TC)+ NVP (50%) followed by AZT+3TC+IDV/r (20%). Other regimens included stavudine (d4T)+3TC +NVP, d4T+3TC+IDV/r and didanosine (ddI)+3TC+ NVP. Among 164 pregnant HIV-infected women receiving PMTCT during ANC, 118 (72%) received AZT + single dose NVP; 36 (22%) received AZT + single dose NVP with tailed end of AZT+3TC or AZT+ ddI extending for 2-4 weeks' postpartum, to prevent NNRTI resistance mutation; the remaining 6% received AZT alone. Of 42 pregnant women who initiated PMTCT in labor, 38 (90.5%) received AZT + single dose NVP. Two cases received AZT alone, and another 2 received single-dose NVP in labor.
Adverse ARV Events During Pregnancy
Overall, 24 adverse ARV related events were documented from 21 (8.5%, 95%CI: 5.4%-12.8%) pregnant HIV-infected women. The prevalence of each adverse event is shown in Fig. (); 13 (5.3%) pregnant women developed anemia, 4 (1.6%) nausea and vomiting, 3 (1.2%) dyslipidemia (1 also reported gestational DM), and 1 (0.4%) hepatotoxicity and rash. No pregnant HIV-infected women initiating PMTCT in labor reported an adverse event. The prevalence of adverse events among pregnant women receiving combined ART (32.5%), and those starting PMTCT during ANC (4.9%), was significantly different (P value < 0.001). Table compares adverse events among 40 pregnant HIV-infected women receiving combined ART vs 164 pregnant HIV-infected women starting PMTCT during ANC. Table compares adverse events among 161 pregnant HIV-infected women receiving ARV grouped by CD4-cells counts during ANC of < 200 vs ≥ 200 cells/μL. Anemia was significantly more common among pregnant women with CD4 cells counts < 200 cells/μL (17.2%) than those with counts ≥ 200 cells/μL (P value =0.04).
All adverse events among 246 pregnant HIV-infected women receiving antiretroviral drugs for either combined antiretroviral therapy and prevention of mother to child HIV transmission.
Adverse ARV Events in Pregnant Women Receiving Antiretroviral Drugs During Antenatal Care (n=204)
CD4 Count Level Associated with Adverse ARV Events Among Pregnant Women (n=161)
Twenty-two of 204 (10.8%) developed anemia (cut-off haemoglobin level ≤ 9.4 g/dl; ACTG grading; 13 (60%) of these developed anemia after 4 weeks' ARV exposure. The cause of anemia among the other 9 was not identified, and occurred before ART. The median red cell mean corpuscle volume (MCV) among 13 pregnant women with ARV-related anemia was slightly increased, from 81.5 to 86.7%, whereas among the pregnant women with anemia of unidentified cause, it was lower, and decreased slightly from 71.9 to 68.8%. Of the women with ARV-related anemia, 10 were classified as ACTG severity grade 1, 2 were grade 2, and 1 was grade 4. The median duration from AZT initiation to anemia detection was 5 (range: 4-9) weeks. Regarding management of anemia, 3 were given blood transfusions; 2 were given reduced AZT dosage, and 2 were changed to d4T instead of AZT.
Other Adverse Events
Nausea and vomiting were documented in only 4 (1.6%) of 246 pregnant women after taking ARV, of which AZT, ddI, and EFV, were suspected culprits in 2, 1, and 1 cases, respectively. Three pregnant women treated with a protease inhibitor (PI) based regimen developed dyslipidemia during pregnancy. EFV was switched to IDV/r in 2 cases at 8 and 12 weeks' gestation, and dyslipidemia was detected after taking IDV/r for 25 and 13 weeks, respectively. For the other, the ART was changed regimen from AZT+3TC+NVP to boosted saquinavir and indinavir (SQV+ IDV/r) at 25 weeks' gestation due to treatment failure; her dyslipidemia was detected after 13 weeks of the new regimen.
The modes of delivery among the 246 pregnant women were normal labor (72.0%), caesarean section (19.0%), vacuum extraction (2.8%), and forceps extraction (0.8%). Among the 49 women who delivered by caesarean section, indications included previous caesarean section (30.6%), cephalo-pelvic disproportion (18.4%), and breech presentation (10.2%). Four had elective caesareans section due to low CD4 count; 208 (84.6%) had full-term deliveries, 25 (10.2%) pre-term, and one stillbirth; 209 (85.0%) had no delivery-related complication, 17 (6.9%) had pre-term labor pain, 4 (1.6%) premature membrane rupture, and 4 (1.6%) pre-eclampsia. Pre-term delivery was significantly higher among pregnant women on combined ART and among those who started PMTCT in labor because of no ANC (19.4% and 19%, respectively), than among those receiving PMTCT during ANC (6.9%, p=0.02). The incidence of pre-term labor pain among the pregnant women who initiated PMTCT during ANC was significantly lower than the other two groups (p = 0.01). However, when factors affecting maternal status--elderly pregnancy, multigravida, low CD4 count, and anemia--were examined by multivariate analysis, only pregnant women who started PMTCT in labor had a significant association with pre-term delivery (p value = 0.01).
Four infants (1.6%) had congenital defects (stillbirth with hydrocephalus, sensorineural hearing loss, gastroscrisis, and polydactyly). Only 2 (0.8%) had congenital pneumonia. 51 infants showed the results of perinatal HIV infection; the perinatal HIV infection rate was 3.9%. None of the infants born to pregnant women who received combined ART had perinatal HIV infections. Overall, the incidence of low birthweight was high, at 49 (20.0%), comprising 39 low and 10 very low. Infants born to pregnant women who started PMTCT in labor had a higher incidence of both low birthweight (8; 19.0%), and very low birthweight (5; 11.9%) than those receiving PMTCT during ANC (p=0.065). The incidence of low Apgar score was 3.6%; of whom 55.6% were low and the rest very low, including one stillbirth (Agar score = 0). Low Apgar scores were significantly higher among infants born to pregnant women who started PMTCT in labor (11.9%; p=0.004).