Objective To evaluate the pharmacokinetics and HIV viral load (VL) response following initiation during the third trimester of pregnancy of zidovudine (ZDV) plus standard dose lopinavir boosted with ritonavir (LPV/r), twice daily, until delivery for the prevention of mother-to-child transmission of HIV (PMTCT). Design Prospective study nested within a multicenter, three arm, randomised, phase III PMTCT trial in Thailand (PHPT-5, ClinicalTrials.gov Identifier: NCT00409591). Methods Women randomized to receive 300 mg ZDV and 400/100 mg LPV/r twice daily from 28 weeks’ gestation, or as soon as possible thereafter, until delivery had intensive steady-state 12-hour blood sampling performed. LPV/r pharmacokinetic parameters were calculated using non-compartmental analysis. Rules were defined a priori for a LPV/r dose escalation based on the proportion of women with an LPV AUC < 52 mcg.hr/mL (10th percentile for LPV AUC in non-pregnant adults). HIV-1 RNA response was assessed during the third trimester. Results Thirty-eight women were evaluable; at entry median (range) gestational age was 29 weeks (28–36), weight 59.5 kg (45.0–91.6), CD4 cell count 442 cells/mm3 (260–1327) and HIV-1 RNA viral load 7,818 copies/mL (<40–402,015). Geometric mean (90% confidence interval) LPV AUC, Cmax and Cmin were 64.6 mcg.hr/mL (59.7–69.8), 8.1 mcg/mL, (7.5–8.7) and 2.7 mcg/ml (2.4–3.0), respectively. 31 of 38 (81%) women had an LPV AUC above the AUC target. All women had a HIV-1 viral load less than 400 copies/mL at the time of delivery. Conclusion A short course of ZDV plus standard dose LPV/r initiated during the 3rd trimester of pregnancy achieved adequate LPV exposure and virologic response.
BackgroundCouples HIV testing and counseling (CHTC) at antenatal care (ANC) settings allows pregnant women to learn the HIV status of themselves and their partners. Couples can make decisions together to prevent HIV transmission. In Thailand, men were tested at ANC settings only if their pregnant partners were HIV positive. A CHTC program based in ANC settings was developed and implemented at 16 pilot hospitals in 7 provinces during 2009–2010.MethodsCross-sectional data were collected using standard data collection forms from all pregnant women and accompanying partners who presented at first ANC visit at 16 hospitals. CHTC data for women and partners were analyzed to determine service uptake and HIV test results among couples. In-depth interviews were conducted among hospital staff of participating hospitals during field supervision visits to assess feasibility and acceptability of CHTC services.ResultsDuring October 2009-April 2010, 4,524 women initiating ANC were enrolled. Of these, 2,435 (54%) women came for ANC alone; 2,089 (46%) came with partners. Among men presenting with partners, 2,003 (96%) received couples counseling. Of these, 1,723 (86%) men and all pregnant women accepted HIV testing. Among 1,723 couples testing for HIV, 1,604 (93%) returned for test results. Of these, 1,567 (98%) were concordant negative, 6 (0.4%) were concordant positive and 17 (1%) were HIV discordant (7 male+/female- and 10 male-/female+). Nine of ten (90%) executive hospital staff reported high acceptability of CHTC services.ConclusionsCHTC implemented in ANC settings helps identify more HIV-positive men whose partners were negative than previous practice, with high acceptability among hospital staff.
IntroductionEarly infant diagnosis (EID) has been a component of Thailand's prevention of mother-to-child HIV transmission (PMTCT) programme since 2007. This study assessed the uptake, EID coverage, proportion of HIV-exposed infants receiving a definitive HIV diagnosis, mother-to-child transmission (MTCT) rates and linkage to HIV care and treatment.MethodsInfant polymerase chain reaction (PCR) testing data from the National AIDS Program database were analyzed. EID coverage was calculated as the percentage of number of HIV-exposed infants receiving ≥1 HIV PCR test divided by the number of HIV-exposed infants estimated from HIV prevalence and live-birth registry data. Definitive HIV diagnosis was defined as having two concordant PCR results. MTCT rates were calculated based on infants tested with PCR and applied as a best-case scenario, and a sensitivity analysis was used to adjust these rates in average and worst scenarios. We defined linkage to HIV care as infants with at least one PCR-positive test who were registered with Thailand's National AIDS Program. Chi-squared tests for linear trend were used to analyze changes in programme coverage.ResultsFor 2008 to 2011, the average EID coverage rate increased from 54 to 76% (p<0.001), with 65% coverage (13,761/21,099) overall. The number of hospitals submitting EID samples increased from 458 to 645, and the percentage of community hospitals submitting samples increased from 75 to 78% (p=0.044). A definitive HIV diagnosis was made for 10,854 (79%) infants during this period. The adjusted MTCT rates had significantly decreasing trends in all scenarios. Overall, an estimated 53% (429/804) of HIV-infected infants were identified through the EID programme, and 80% (341/429) of infants testing positive were linked to care. The overall rate of antiretroviral treatment (ART) initiation within one year of age was 37% (157/429), with an increasing trend from 28 to 52% (p<0.001).ConclusionsEID coverage increased and MTCT rates decreased during 2008 to 2011; however, about half of HIV-infected infants still did not receive EID. Most HIV-infected infants were linked to care but less than half initiated ART within one year of age. Active follow-up of HIV-exposed infants to increase early detection of HIV infection and early initiation of ART should be more widely implemented.
Thailand has been one of the leading developing countries to implement a national program to prevent mother-to-child transmission (MTCT) of HIV. Although the recent transmission rate has been low, the goal is to eliminate MTCT altogether. The Thai National HIV Guidelines Working Group issued treatment guidelines to prevent MTCT in Thailand in March 2010. These guidelines will be implemented nationwide within a year. The most important aspects of these new guidelines are as follows: Treatment in HIV-infected pregnant women who have not been on antiretroviral treatment prior to pregnancy. Antepartum treatment is recommended for all pregnant women regardless of CD4 count with highly active antiretroviral therapy (HAART) containing zidovudine (AZT) + lamivudine (3TC) + lopinavir/ritonavir (LPV/r). Treatment should be started immediately irrespective of gestational age in women with CD4 count <350 cells/ mm3, and as early as 14 weeks of gestation in those with CD4 count >350 cells/mm3. After delivery, women with baseline CD4 count <350 cells/mm3 are referred for long-term care and HAART according to the National Adult HIV Treatment and Care Guidelines 2010. Women with CD4 count >350 cells/mm3 do not need HAART and can stop all drugs after delivery. The treatment in infants includes AZT syrup for four weeks and exclusive formula feeding. Treatment in HIV-infected pregnant women who conceive while on HAART. Women who are stable on HAART should continue the treatment during the whole period of pregnancy. Those who are taking efavirenz (EFV) and present during the first trimester should have EFV switched to another drug. Whenever possible, AZT should be used during pregnancy. Treatment in infants is similar to the above scenario. Treatment in women who present in labor without antenatal care. Single-dose nevirapine (SD-NVP) 200 mg must be given immediately along with oral AZT 300 mg every three hours until delivery, or oral AZT 600 mg given as a single dose. The tail therapy of AZT + 3TC + LPV/r for four weeks should be given unless these women have a CD4 count of <350 cells/mm3 and therefore require life-long HAART. SD-NVP should not be given if the women are to deliver within two hours. The infants in this situation should receive AZT + 3TC + NVP for four weeks. Treatment during delivery and mode of delivery. During labor, oral AZT 300 mg every three hours or oral AZT 600 mg given as a single dose is recommended regardless of antepartum antiretroviral (ARV) regimen or the woman’s history of AZT resistance. Elective caesarean section is suggested in women who did not receive HAART (including those without antenatal care), received HAART for less than four weeks prior to delivery, had poor adherence, or had incomplete viral suppression at 36 weeks of gestation.
The current program for prevention of mother-to-child HIV transmission in Thailand recommends a 2-drugs regimen for HIV-infected pregnant women with a CD4 count >200 cells/mm(3). This study assesses the value for money of 3 antiretroviral drugs compared with zidovudine (AZT)+single-dose nevirapine (sd-NVP). A decision tree was constructed to predict costs and outcomes using the governmental perspective for assessing cost-effectiveness of 3-drug regimens: (1) AZT, lamivudine, and efavirenz and (2) AZT, 3TC, and lopinavir/ritonavir, in comparison with the current protocol, AZT+sd-NVP. The 3-drug antiretroviral regimens yield lower costs and better health outcomes compared with AZT+sd-NVP. Although these 3-drug regimens offer higher program costs and health care costs for premature birth, they save money significantly in regard to pediatric HIV treatment and treatment costs for drug resistance in mothers. The 3-drug regimens are cost-saving interventions. The findings from this study were used to support a policy change in the national recommendation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.