Single-dose Nevirapine Research Articles

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

BackgroundRandomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.MethodsWe randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum “tail” of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir–ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir–ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety.ResultsThe median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, −1.3 percentage points; repeated confidence interval, −2.1 to −0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART.ConclusionsAntenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538.)

HIV-1 Drug Resistance by Ultra-Deep Sequencing Following Short Course Zidovudine, Single-Dose Nevirapine, and Single-Dose Tenofovir with Emtricitabine for Prevention of Mother-to-Child Transmission.

Antiretroviral drug resistance following pMTCT strategies remains a significant problem. With rapid advancements in next generation sequencing technologies, there is more focus on HIV drug-resistant variants of low frequency, or the so-called minority variants. In South Africa, AZT monotherapy for pMTCT, similar to World Health Organization option A, has been used since 2008. In 2010, a single dose of co-formulated TDF/FTC was included in the strategy for prevention of resistance conferred by single-dose nevirapine (sd NVP). The study was conducted in KwaZulu-Natal, South Africa, among pMTCT participants who received AZT monotherapy from 14 weeks of gestation, intrapartum AZT and sd NVP, and postpartum sd TDF/FTC. Twenty-six specimens collected at 6 weeks post-delivery were successfully sequenced using 454 ultra-deep sequencing. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was detected in 17 of 26 (65%) patients, 2 (7%) had Thymidine analogue mutations, and 3 (11%) had K65R. Of the 17 patients with NNRTI resistance, 11 (65%) had high-level NNRTI resistance, whereas 6 (35%) had intermediate NNRTI resistance. The levels of NNRTI resistance are much higher than would be expected, given the inclusion of antepartum AZT and postpartum TDF/FTC. This high level of NNRTI resistance could impact future NNRTI-containing treatment for a large proportion of pMTCT-exposed women. The detection of Thymidine analogue mutations highlights the need to understand the clinical impact of these on AZT-containing antiretroviral treatment in women exposed to AZT monotherapy.

Timely antiretroviral prophylaxis during pregnancy effectively reduces HIV mother-to-child transmission in eight counties in China: a prospective study during 2004-2011.

This study investigates the improvement of the prevention of mother-to-child transmission (PMTCT) of Human Immunodeficiency Virus (HIV) in China during 2004–2011. A clinic-based prospective study was conducted among HIV-positive pregnant women and their children in eight counties across China. Associated factors of mother-to-child transmission were analyzed using regression analysis. A total of 1,387 HIV+ pregnant women and 1,377 HIV-exposed infants were enrolled. The proportion of pregnant women who received HIV testing increased significantly from 45.1% to 98.9% during 2004–2011. Among whom, the proportion that received antiretroviral (ARV) prophylaxis increased from 61% to 96%, and the corresponding coverage in children increased from 85% to 97% during the same period. In contrast, single-dose nevirapine treatment during delivery declined substantially from 97.9% to 12.7%. Vertical transmission of HIV declined from 11.1% (95% confidence interval [CI]: 5.7–23.3%) in 2004 to 1.2% (95% CI: 0.1–5.8%) in 2011. Women who had a vaginal delivery (compared to emergency caesarian section (odds ratio [OR] = 0.46; 0.23–0.96)) and mothers on multi-ARVs (OR = 0.11; 0.04–0.29) were less likely to transmit HIV to their newborns. Increasing HIV screening enabled timely HIV care and prophylaxis to reduce vertical transmission of HIV. Early and consistent treatment with multi-ARVs during pregnancy is vital for PMTCT.

Efficacy of Six-Week Extended-Dose Nevirapine Varies by Infant Birth Weight with Greatest Relative Efficacy in Low Birth Weight Infants.

Latest World Health Organization guidelines recommend weight-based nevirapine prophylaxis for all HIV-exposed infants in resource-limited settings, yet low birth weight (LBW) infants (< 2500 g) have been understudied. Using data from the NIH-funded India six-week extended-dose nevirapine (SWEN) study, a randomized clinical trial of SWEN versus single-dose nevirapine (SD) for prevention of breast-milk HIV-1 transmission, we examined the relative impact of SWEN among 737 mother-infant pairs stratified by infant birth weight. Birth weight groups were defined as very LBW (VLBW) ≤ 2000 g, moderate LBW (MLBW) >2000 g and ≤ 2500 g, and normal birth weight (NBW) > 2500 g. Outcomes were HIV-1 infection, HIV-1 infection or death by 12 months, and severe adverse events (SAEs). The Kaplan-Meier method was used to estimate probability of efficacy outcomes in birth weight groups, and differential effects of SWEN by birth weight group were examined using Cox proportional hazards models adjusting for independent risk factors for HIV maternal-to-child transmission and significant covariates. Among 50 VLBW, 249 MLBW, and 433 NBW infants, 50% were randomized to SWEN; median gestational age was 36, 38 and 38 weeks, respectively; and there was no difference in breastfeeding duration (p = 0.99). Compared to SD: SWEN-treated VLBW had lower estimates of HIV-1 infection (13% vs. 38%, p = 0.004) and HIV-1 infection or death (13% vs. 41%, p = 0.002); SWEN-treated MLBW had lower estimated HIV-1 infection (13% vs. 17%, p = 0.042); and efficacy endpoints were similar by treatment arm in NBW. In multivariate analysis, SWEN was associated with reduced risk of HIV-1 infection or death by 83% (p = 0.03) in VLBW versus 45% (p = 0.05) in MLBW. SAE frequency was similar by treatment arm in VLBW (68% vs. 76%, p = 0.53) and MLBW (37% vs. 36%, p = 0.93). SWEN may safely increase HIV-free survival among HIV-exposed LBW infants with greatest protective advantage among infants ≤ 2000 g.

Early infant diagnosis of HIV infection using DNA-PCR at a referral center: an 8years retrospective analysis.

BackgroundOver the last decade, Ethiopia adopted different strategies of prevention of mother to child transmission of HIV (PMTCT). Prior to implementation of Option A in 2011, there was no provision of prophylaxis for PMTCT. With ‘Option A’, PMTCT interventions relied on maternal CD4 count. In early 2013, ‘‘Option B+’’ has been started; with this option, antiretroviral therapy is started and continued for life to any HIV positive pregnant mother irrespective of CD4 count with an enhanced treatment for the baby. Though there are a number of studies which evaluated the effectiveness of PMTCT interventions, the current study assessed the real-world effectiveness of PMTCT options in a setting where there is limitation of resources.ObjectiveThis study tried to address three questions: what proportion of babies tested by DNA-PCR are HIV infected in the first 2 months of life? How does the type of PMTCT intervention affect presence of HIV infection at this age? What are the factors affecting HIV transmission, after controlling for type of PMCT-HIV intervention?MethodsWe assessed records of 624 registered HIV exposed infants and 412 mothers who were delivered at Bishoftu Hospital from May 2006 to August 2014. Presence of HIV infection at 6–8 weeks of age was assessed from the records. Maternal and infant risk factors for infection at this age were analyzed. Data were collected using standard data abstraction format and were analyzed using SPSS version 20.ResultsAmong all the infants who were delivered at the hospital during the study period, 624/936 (66.7 %) had undergone early infant diagnosis at 6–8 weeks. Twenty-seven (4.3 %) were positive for HIV DNA PCR at the age of 6–8 weeks. None of the infants who received ‘‘Option B+’’ had a positive HIV DNA PCR result. HIV infection rate was highest among those who took either no prophylaxis or single dose Nevirapine (11.5 and 11.1 % respectively). Those who took single dose Nevirapine and Zidovudine had HIV positivity rate of 3.9 %. Many of the covariates which were shown to be predictors on bivariate analysis were found not to be independent predictors on multivariate analysis.ConclusionPMTCT ‘’Option B+’’ resulted in zero HIV infection rates among the included infants. There was a high loss to follow up rate at 6–8 weeks of age. The authors recommend that a better strategy of linkage to care and treatment should be devised for HIV exposed infants.

A Retrospective Cohort Study on Protective Efficacy of Intrapartum Nevirapine Prophylaxis to Prevent Parent to Child Transmission of Human Immunodeficiency Virus in West Bengal

Background: : In Prevention of Parent to Child Transmission (PPTCT) program in India, single dose Nevirapine was used for prevention of intrapartum transmission of HIV, but the protective efficacy of this regimen in Indian population is not beyond question. Objective: To analyze the protective efficacy of single dose Nevirapine prophylaxis in preventing mother to child transmission of HIV and comparing the effect of Nevirapine prophylaxis in different types of infant feeding practices and modes of delivery. Methods: A retrospective cohort study was carried out through analysis of secondary data during October 2010 to September 2011 from 16 Integrated Counseling and Testing Centers (ICTCs) having DNAPCR (Polymerase Chain Reaction) collection facility in West Bengal among 224 babies born of HIV infected mothers, 168 unexposed (covered with intrapartum Nevirapine) and 56 exposed (not covered with intrapartum Nevirapine) to risk of transmission. HIV reactivity in babies was confirmed by DNA PCR of Dry Blood spot from 6 weeks age onwards. Data was entered and analyzed using Epi Info version 3.5.1 and Statistical Package for Social Sciences software version (SPSS 16.0). Results: About 10.12% of those received Nevirapine were found HIV reactive compared to 26.79% of those who did not. Overall Relative Risk of non coverage of Nevirapine for vertical transmission of HIV was 2.65 (95% CI : 1.42 ‐ 4.95). Overall Attributable Risk was 62.22%. Conclusion: Since in 62.2% cases vertical transmission of HIV was prevented, additional regimen may be thought of for rest 37.8% cases.

Malnutrition among HIV- infected Children by Anthropometric Measures in Poor Outreach Area of a Developing Country and its Relationship with CD4 Counts

Background: Diagnosis and management of malnutrition in HIV- infected children is important as it is both a manifestation as well as an independent risk factor for death. Extent in hilly poor outreach areas of North India has been poorly studied. Aim: to study the prevalence of malnutrition among children with HIV/AIDS using WHO z- score and Indian Academy of Pediatrics (IAP) method and effect of malnutrition on immune status. Material and Methods: Setting-Antiretroviral (ART) Centre of a teaching medical college in Uttarakhand-India. Anthropometric measurements (weight, height) and CD4 counts were taken on registration and follow up and duly recorded. Data analysis was done using SPSS -18 and WHO z- score value was calculated using WHO AntroPlus software. Result: A total of 107 children ( 67 male and 40 female) were studied with mean age of 7.15years.Valid z- score could be calculated only for 46 children and it showed stunting in 69.8%(30/43), wasting in 22.4%(10/46), underweight in 58.9%(27/46). Using IAP method 75% (81/107) had PEM, 85.5% (93/107) stunting. There was no difference between male and female (P>0.05) and no relation between CD4 count and nutritional status (P>0.05). Single dose nevirapine used earlier for Prevention of Parent to Child Transmission (PPTCT) used in 10 newborns resulted in 3/10 HIV negative, 3/10 positive, 4/10 deaths at 18 months. Conclusion: Malnutrition is rampant in children with HIV/AIDS in hilly poor Outreach areas of India. Chronic malnutrition or stunting was the most common abnormality seen in three fourth of all the children. Hence sensitizing health care workers for timely recognition and prompt remedial measures (ART, nutritional interventions) are need of the hour to reduce mortality and prevent growth failure. It also provides baseline data of efficacy of single dose nevirapine to compare efficacy of newer regimes in prevention of PPTCT.

A cross sectional study to find out the efficacy of prevention of parent to child transmission services providing centers of Indore division

Background: The HIV and AIDS epidemic is not just a public health concern, but a major socio-economic problem in India as it is in other parts of the world. In India PPTCT interventions under NACP was started in2002, using single dose NVP prophylaxis For HIV positive pregnant women during labour & also for her new born child immediately after birth. The objective of the study was t o find out the proportion of HIV among ANC registered & the efficacy of PPTCT by determining seroconversion rate in children born to HIV positive mothers during study period. Methods: All PPTCT Services providing centres located in four districts of Indore division were taken in study. The required information (data of 1 st January to 31 st December 2014) was collected through pre-designed semi structured questionnaire undertaken nodal in charge, counselling staff/ laboratory technicians of each centre during the study period of January to October 2015. The data collected was entered into Microsoft excel spread sheet and analysis was done by SPSS. Results: The number of HIV positive registered ANC cases & positivity rate among them, both were highest at medical college level as they are catering highest numbers of ANC OPDs & referral too while it is lowest at CHCs level. Among total 67 positive pregnant women, two babies died before 6 weeks. Out of 65 babies tested & 2(3%) babies were found positive. Conclusions: There has been an improvement in number of pregnant women undergoing HIV testing with appropriate pre-test & post-test counselling over years but ANC load in hospitals of urban areas, were higher in comparison to rural, so up gradations of hospitals at primary level should be done.

Outcome of Prevention of Parent-to-Child Transmission of HIV in an Urban Population in Southern India.

To analyze the outcomes of Prevention of Parent to Child Transmission (PPTCT) of HIV program in an urban Southern Indian setting. Observational study. Anti-retroviral Therapy (ART) Centers/ Integrated Counseling and Testing Centers (ICTC) at four government Obstetrics Institutes in an urban area. 100 HIV-positive pregnant women and their infants delivered in the study centers. Triple drug ART to HIV-positive pregnant women was started for maternal indications only. Rest of the pregnant women were given single dose Nevirapine (200 mg) at the onset of labor. All infants were given single dose Nevirapine (2 mg/kg) prophylaxis, according to National AIDS Control Organization guidelines. Mothers were counseled regarding breastfeeding and artificial feeding, and the choice was left to them. Whole blood HIV 1 DNA PCR was done for all infants at 6 weeks of life. A second PCR was done at 6 months or 6 weeks after stopping breastfeeds. PCR-positive infants were started on ART, and were followed-up till18 months of life. Four infants were PCR-positive for HIV. All of them were breastfed. They were born to mothers of HIV stage 1 or 2 who were not on ART as CD4 counts were >350 cells/mm3. Among the mothers in Stage 3 or 4 or CD4 count <200 cells/mm3 and on ART, none of the infants was HIV-positive. The cumulative HIV-free survival at 18 months was 94%. Parent-to-child transmission rate in HIV was low with the currently used strategies. Triple drug ART to mother reduces mother-to-child transmission despite advanced maternal stage or low CD4 counts.

P17.44 An assessment of hiv knowledge among traditional birth attendants in rural setting in chipata, zambia

Background Involving women in HIV programmes such as Prevention from Mother To Child Transmission of HIV is important because they are one of the most affected population groups. However, in rural settings PMTCT is a challenge lack easy access to health centres where they can be tested for HIV and for safer child births. This health service gap is filled-in by traditional birth attendants, who mostly lack adequate knowledge of HIV and how to prevent mother-child transmission. Methods The Zambia Traditional Births Attendants Association conducted a workshop for Traditional Birth Attendants in the Eastern Province. 24 Traditional Birth Attendants, 5 chiefs and their wives, from 5 villages attended the workshop. Clinical staff from a health, approximately 150 Km away facilitated. Pre-and post-workshop questionnaires were administered. Results 80% of the participants were aware of HIV but were not sure how to prevent it. 20% believed HIV was due to witchcraft. 72% did not see the wearing protective gear when helping women in labour as important. 97% were ignorant of HIV basic science. 93% had no idea of PMTCT. Myths and misconceptions included that children cannot get the HIV because they do not indulged in sex; that traditional medicine can treat and cure HIV/AIDS. The workshop noted the need to train Traditional Birth Attendants in PMTCT services counselling and oral rapid testing for HIV in pregnant women. The other need was training them how to administer single-dose Nevirapine to HIV positive pregnant women during labour and to their newborn babies. Conclusion It is important to involve traditional birth attendant in HIV and PMTCT programmes stop the spread of HIV. Village health committees should be established were they do not exist and integrated with HIV and PMTCT services. Sustained provision of PMTCT and HIV testing kits, and follow-ups by health staff is needed.

Single-dose nevirapine exposure does not affect response to antiretroviral therapy in HIV-infected African children aged below 3 years.

To assess the impact of exposure to single-dose nevirapine (sdNVP) on virological response in young Ugandan/Zimbabwean children (<3 years) initiating antiretroviral therapy (ART), and to investigate other predictors of response. Observational analysis within the ARROW randomized trial. sdNVP exposure was ascertained by the caregiver's self-report when the child initiated non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Viral load was assayed retrospectively over a median 4.1 years of follow-up. Multivariable logistic regression models were used to identify independent predictors of viral load below 80 copies/ml, 48 and 144 weeks after ART initiation (backwards elimination, exit P = 0.1). Median (IQR) age at ART initiation was 17 (10-23) months in 78 sdNVP-exposed children vs. 21 (14-27) months in 289 non-exposed children (36 vs. 20% <12 months). At week 48, 49 of 73 (67%) sdNVP-exposed and 154 of 272 (57%) non-exposed children had viral load below 80 copies/ml [adjusted odds ratio (aOR) 2.34 (1.26-4.34), P = 0.007]; 79 and 77% had viral load below 400 copies/ml. Suppression was significantly lower in males (P = 0.009), those with higher pre-ART viral load (P = 0.001), taking syrups (P = 0.05) and with lower self-reported adherence (P = 0.04). At week 144, 55 of 73 (75%) exposed and 188 of 272 (69%) non-exposed children had less than 80 copies/ml [aOR 1.75 (0.93-3.29), P = 0.08]. There was no difference between children with and without previous sdNVP exposure in intermediate/high-level resistance to NRTIs (P > 0.3) or NNRTIs (P > 0.1) (n = 88) at week 144. Given the limited global availability of lopinavir/ritonavir, its significant formulation challenges in young children, and the significant paediatric treatment gap, tablet fixed-dose-combination NVP-based ART remains a good alternative to syrup lopinavir-based ART for children, particularly those over 1 year and even if exposed to sdNVP.

Prevention of mother-to-child HIV transmission: MTCT-PLUS initiative program

Purpose: To evaluate the safety and efficacy of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infected pregnant women to prevent mother-to-child transmission of HIV. Design of the study is observational retrospective evaluation of a prospective cohort. Setting of the study is King Chulalongkorn Memorial Hospital. Participants are HIV-infected Thai women and their offspring. HIV-positive pregnant women who received antenatal care were given antepartum and intrapartum zidovudine (ZDV) plus single dose nevirapine (NVP) or HAART [ZDV + lamivudine (3TC) + NVP] to prevent HIV transmission to the neonate. All newborns received single dose NVP plus 6-weeks of ZDV.HAART was given to their parents if indicated. We followed the infants from February 2003 to June 2006 to determine HIV-status. Calculated HIV maternal-child transmission rate is the main outcome. Among 157 mother-infant pairs, 44 mothers received ZDV plus single dose NVP and 113 mothers received HAART. There was one HIV-infected child in the first group and 3 in the second group, resulting in 2.3% (95% confidence interval, −2.1 to 6.7) transmission rate in the first group versus 2.7% (95% confidence interval, −0.3 to 5.6) in the second group (P = 1.000). All non-infected infants had a normal physical examination at 18 months. Initiation of HAART in HIV-infected pregnant women had comparable efficacy with ZDV plus single dose NVP to prevent mother-to-child transmission of HIV. In addition, the program may have strengthened the role of the family unit and stimulated public awareness reproductive health planning can help in prevention of HIV/AIDS.

Drug resistance mutations 18 months after discontinuation of nevirapine-based ART for prevention of mother-to-child transmission of HIV in Malawi.

The objective of this study was to determine the prevalence of drug resistance mutations among HIV-positive women in Malawi 18 months after discontinuing nevirapine-based ART for the prevention of mother-to-child transmission. HIV-infected antiretroviral-naive (except for single-dose nevirapine) pregnant Malawian women receiving a nevirapine-based triple antiretroviral regimen from Week 25 of gestation until 6 months of breastfeeding were included in this analysis. Drug resistance was assessed in HIV-DNA 24 months post-partum and at baseline (before the initiation of treatment). In patients with resistance, the presence of mutations was also evaluated in the corresponding plasma samples. Seven out of 42 (16.7%) women studied had archived drug resistance at Month 24 [six cases had NNRTI-associated mutations and two cases the M184I mutation]. In four cases, resistance mutations were already present at baseline (all NNRTI mutations). In three cases, there was an emergence of 'new' resistance (also present in the plasma in one case). Of the 35 women without resistance mutations at Month 24, only one subject had resistance mutations at baseline. Baseline resistance was significantly more common among women with mutations at 24 months compared with those harbouring a WT virus (4/7 versus 1/35, P < 0.001). Among women who had discontinued drugs 6 months post-partum, only 3/42 (7.1%) had accumulated new resistance mutations in HIV-DNA 2 years after delivery. These findings are reassuring in terms of the safety of the Option B strategy for the prevention of HIV mother-to-child transmission.

Comparison of anti-retroviral therapy treatment strategies in prevention of mother-to-child transmission in a teaching hospital in Ethiopia.

More than 90% of Human immunodeficiency virus (HIV) infection in children is acquired due to mother-to-child transmission, which is spreading during pregnancy, delivery or breastfeeding. To determine the effectiveness of highly active antiretroviral and short course antiretroviral regimens in prevention of mother-to-child transmission of HIV and associated factors Jimma University Specialized Hospital (JUSH). A hospital based retrospective cohort study was conducted on HIV infected pregnant mothers who gave birth and had follow up at anti-retroviral therapy (ART) clinic for at least 6 months during a time period paired with their infants. The primary and secondary outcomes were rate of infant infection by HIV at 6 weeks and 6 months respectively. The Chi-square was used for the comparison of categorical data multivariate logistic regression model was used to identify the determinants of early mother-to-child transmission of HIV at 6 weeks. Cox proportional hazard model was used to analyze factors that affect the 6 month HIV free survival of infants born to HIV infected mothers. A total of 180 mother infant pairs were considered for the final analysis, 90(50%) mothers received single dose nevirapine (sdNVP) designated as regimen-3, 67 (37.2%) mothers were on different types of ARV regimens commonly AZT + 3TC + NVP (regimen-1), while the rest 23 (12.8%) mothers were on short course dual regimen AZT + 3TC + sdNVP (regimen-2). Early mother-to-child transmission rate at 6 weeks for regimens 1, 2 and 3 were 5.9% (4/67), 8.6% (2/23), and 15.5% (14/90) respectively. The late cumulative mother-to-child transmission rate of HIV at 6 months regardless of regimen type was 15.5% (28/180). Postnatal transmission at 6 months was 28.5% (8/28) of infected children. Factors that were found to be associated with high risk of early mother-to-child transmission of HIV include duration of ARV regimen shorter than 2 months during pregnancy (OR=4.3, 95%CI =1.38-13.46), base line CD4 less than 350 cells/cubic mm (OR=6.98, 95%CI=0.91-53.76), early infant infection (OR=5.4, 95%CI=2.04-14.4), infants delivered home (OR=13.1, 95%CI=2.69-63.7), infant with birth weight less than 2500 g (OR=6.41, 95%CI=2.21-18.61), and mixed infant feeding (OR=6.7, 95%CI=2.2-20.4). Antiretroviral regimen duration less than 2 months, maternal base line CD4 less than 350 cells/cubic mm and mixed infant feeding were also important risk factors for late infant infection or death. The effectiveness of multiple antiretroviral drugs in prevention of early mother-to-child transmission of HIV was found to be more effective than that of single dose nevirapine, although, the difference was not statistically significant. But in late transmission, a significant difference was observed in which infants born to mother who received multiple antiretroviral drugs were less likely to progress to infection or death than infants born to mothers who received single dose nevirapine.

Single Genome Analysis for the Detection of Linked Multiclass Drug Resistance Mutations in HIV-1-Infected Children After Failure of Protease Inhibitor-Based First-Line Therapy.

The WHO recommends protease inhibitor (PI)-based antiretroviral therapy (ART) for vertically infected children after failed nevirapine (NVP) prophylaxis. Emergence of PI resistance on the backdrop of preexisting non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance could compromise long-term treatment options in such children. We characterized multiclass drug resistance using single genome sequencing (SGS) in children with viremia while receiving PI-based ART. We applied SGS of HIV-1 protease (PR) and reverse transcriptase to longitudinal samples from a cohort of the Children with HIV Early Antiretroviral Therapy trial with viral loads >1000 copies per milliliter after 40 weeks of early ART. Bulk sequencing revealed NVP-selected resistance in 50% of these children, whereas SGS revealed NVP-selected resistance in 70%. Two children had baseline NRTI and PI mutations, suggesting previous maternal ART. Linked multiclass drug resistance after PI-based ART was detected by SGS in 2 of 10 children. In one child, the majority species contained M184V in reverse transcriptase linked to L10F, M46I/L, I54V, and V82A in PR and a triple-class drug-resistant variant with these mutations linked to the NNRTI mutation V108I. In the second child, the majority species contained M184V and V82A linked within viral genomes. We conclude that when PI-based ART is initiated soon after birth after single dose-NVP prophylaxis, PI and NRTI resistance can occur in the majority species as expected and also be selected on the same genomes as preexisting NNRTI-resistant mutations. These observations highlight a future therapeutic challenge for vertically infected children where antiretroviral drug classes are limited.

THE ASIA PACIFIC BIOETHICS PROGRAM OF THE UNESCO CHAIR IN BIOETHICSCAN RESEARCH IN DEVELOPING COUNTRIES BE BOTH ETHICAL AND BENEFICIAL TO LOGAL COMMUNITY ?

Abstract ln 2005 at the 33rd Session of General Conference at UNESCO, it adapted the Universal declaration on Bioethics and Human Rights. Declaration article 1.1 outlines the principals that respond to ethical issue related to medicine, life sciences and associated technologies as applied to human beings. Thus the international standards for Bioethics are grounded in a language of rights -to safe guard human dignity and human rights. UNESCO made ethics of Science and technology one of its 5 priority areas. lt is charged with promoting the education of ethical issues of Science and Technology. The UNESCO Program in this area aims to strengthen lhe ethical link between scientific advancement that is taking place and the Cultural, Legal, Philosophical and religious context in which it occurs.The disparity of health amongst the world's communities is largely determined by the wealth of the countries. Developed countries have access to clean waters, vaccines and new medical technologies whereas developing countries do not. Researches in these countries are also funded by the wealthy countries and we will need to protect these countries from exploitation by those with the means in the name of clinical research.Hence, we have to discuss the necessary conditions for models allowing lnstitutional Review Boards to grani exceptions in low income countries to circumvent the need for Best Practices in their research requirements. There are commentators arguing that World's Best Practiees sheuld always be used in ali countries, but financial burden in the developing couniries prevents this. A total ban cn any research other than the world's best practice would prevent exploitation, but this may block important research that can improve health care in these countries. So is it possibie to address the potentiai for exploitation while allowing research that has the potential to benefit the host communities.We argue that lnstitutional Review Boards should be allowed to grant exceptions for research on grounds that the research satisfies the Scientific Necessity, Relevance for the host communities, sufficient host community benefits and Subject and Host Community nonrnaleficence.The argument has focused on the controversial HIV vertical transmission, and the trials used. World Best Practice is currently the long course treatment using AZT (zidovudine), but this is expensive involving early prenatal visits, frequent visits and lV infusions during labour, which is not feasible nor affordable in these countries. However studies in South Africa has identified that apprcximalely 75% of HIV vertical transmissions occurs ciuring or after delivery. Hence, trials comparing short ccurse AZT treatment against placebo were done on ihe grounds that it is better than no treatment at all. The trials suggested that short course ti'eatment is possibly better than placebo. Yet the variability in the transmission rate may suggest that the short-course treatment was not woi-th pursuing.The knowledge thal.75% of HIV vertical transmission occurs during delivery has led investigators to the iandmark trials using nevirapine as a single dose given during labour offerring a feasible and affordable treatment for reducing the rate of vertical transmission.To justify the relevance of these issues, the Elizabeth Glaser Paediatrics AIDS Foundation has devoted $100 miilion to prevent HIV vertical transmission. Assuming a cost of $250 per mother-child treatment using the long course AZT would translate to 65,000 fewer HIV infected child. Yet devoting the same money to a single-dose nevirapine, at $4 per mother-child can translate to 270,000 fever HIV infected child, lffrttE Supplemen Majalah Kedokteran Andalas. Vol. 37. No.Supl.1, [/aret 2014 potentially saving an additional 200,000 lives. The UNESCO Chair in Bioethics was established to coordinate and stimulate an international network of lnstitutes for Medical Ethics Training. ln this role there is a need to develop an up to date syllabus for Medical ethics education which will satisfy requirements of the Medical fraternity. These followed Two lnternational Studies in 2001 that UNESCO undertook in researching the importance and quality of education in ethics in Medical Colleges and faculties all over the world. The results confirmed that there is an emerging need for introduction of teaching of Medical ethics as a consequence of several social and scientific processes that have taken place. These included the relationship between health care providers and their patients, the choice of medical interventions for the individual patient, the choice of Public health interventions, the evaluation of effects of health care interventions, the collaboration between teams engaged in health care activities and the choice of goals and methods of medical reseai'ch.Hence, research using less than the world's best practice can be ethical and has the potential to provide sufficient benefit for the host communities and IRB should be given the authority to approve such activities on a case by case basis. Affiliasi Penulis : Director Centre for Asia Pacific Bioethics Studies, Korespondensi : Theong H. Low, email : thlow@bigpond. net.au,

Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV.

BackgroundAntiretroviral treatments decrease HIV mother-to-child transmission through pre/post exposure prophylaxis and reduction of maternal viral load. We modeled in-utero and intra-partum HIV transmissions to investigate the preventive role of various antiretroviral treatments interventions.MethodsWe analysed data from 3,759 women-infant pairs enrolled in 3 randomized clinical trials evaluating (1) zidovudine monotherapy, (2) zidovudine plus perinatal single-dose nevirapine or (3) zidovudine plus lopinavir/ritonavir for the prevention of mother-to-child transmission of HIV in Thailand. All infants were formula-fed. Non-linear mixed effect modeling was used to express the viral load evolution under antiretroviral treatments and the probability of transmission.ResultsMedian viral load was 4 log10 copies/mL (Interquartile range: 3.36–4.56) before antiretroviral treatments initiation. An Emax model described the viral load time-course during pregnancy. Half of the maximum effect of zidovudine (28% decrease) and lopinavir/ritonavir (72% decrease) were achieved after 98 and 12 days, respectively. Adjusted on viral load at baseline (Odds ratio = 1.50 [95% confidence interval: 1.34, 1.68] per log10 copies/mL increment), antiretroviral treatments duration (OR = 0.80 [0.75, 0.84] per week increment) but not the nature of antiretroviral treatments were associated with in-utero transmission. Adjusted on gestational age at delivery (<37 weeks, OR = 2.37 [1.37, 4.10]), baseline CD4 (Odds ratio = 0.79 [0.72, 0.88] per 100 cells/mm3 increment) and predicted viral load at delivery (OR = 1.47 [1.25, 1.64] per log10 copies/mL increment), single-dose nevirapine considerably reduced intra-partum transmission (OR = 0.32 [0.2, 0.51]).ConclusionThese models determined the respective contributions of various antiretroviral strategies on prevention of mother-to-child transmission. This can help predict the efficacy of new antiretroviral treatments and/or prevention of mother-to-child transmission strategies particularly for women with no or late antenatal care who are at high risk of transmitting HIV to their offspring.Trial RegistrationThis analysis is based on secondary data obtained from three clinical trials. ClinicalTrials.gov. NCT00386230, NCT00398684, NCT00409591.

A post-partum single-dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre-partum ZDV and intrapartum single-dose nevirapine to prevent mother-to- child HIV-1 transmission.

Although the rates of vertical transmission of HIV in the developing world have improved to around 3% in countries like South Africa, resistance to antiretrovirals (ARV) used in Prevention of Mother‐to‐Child transmission (pMTCT) strategies may thwart such outcomes and affect the efficacy of future ARV regimens in mothers and children. This study conducted in Durban, South Africa, between 2010 and 2013 found a high rate of nevirapine (NVP) resistance among women receiving Zidovudine (AZT) from 14 weeks gestation, single dose nevirapine (sd NVP) at the onset of labor and a single dose of coformulated Tenofovir/Emtricitabine (TDF/FTC) postpartum. Using Sanger sequencing, high and intermediate levels of nevirapine (NVP) resistance were detected in 15/44 (34%) and in 1/44 (2%) of women tested, respectively. Most subjects selected the K103N mutation (22% (10/45) of all patients and 66% (10/15) of those with high‐level NVP resistance). Such rate of NVP resistance is comparable to studies where only sd NVP was used. In conclusion, a post‐partum single‐dose TDF/FTC tail does not prevent the selection of NNRTI resistance in women receiving pre‐partum ZDV and intrapartum sd NVP to prevent mother‐to‐child HIV‐1 transmission. J. Med. Virol. 87:1662–1667, 2015. © 2015 The Authors. Journal of Medical Virology published by Wiley Periodicals, Inc.

Emergence of HIV-1 drug-resistant variants in women following antiretroviral prophylaxis for the prevention of mother to child transmission.

Emergence of drug resistance following HIV prophylaxis has an important impact on ART program. To investigate the emergence of drug resistance in HIV-1 infected pregnant women. Fifty-three HIV-1 infected pregnant women who had received 4-12 weeks of antenatal AZT followed by Nevirapine during delivery and Combivir [AZT + 3TC] for 1 week postpartum (group-1, n = 48) or who come at the time of delivery and received Nevirapine followed by Combivir for 1 week (group-2, n = 5) were recruited. Samples were collected prior to the start of the prophylaxis and 5-8 weeks postpartum. In addition, a third sample was collected between 26-65 weeks postpartum from 7 women. Amplification of HIV-1 pol gene and drug resistance analysis was done. Two (3.8%) women in group-1 showed transmitted drug resistance and they continued to show this even at 6 weeks postpartum. One (2%) woman from group-1 showed a mutation after 6-8 weeks of prophylaxis. Among the samples collected between 26-65 weeks postpartum, 3/7 (43%) showed mutations and all these women belong to group-1. Women belonging to group-2 didn't show mutation prior to or following prophylaxis. In contrast to the available data among pregnant women with ART prophylaxis, our data showed reduced frequency of mutations following 5-8 weeks of postpartum but an emergence of mutation later (26-65 weeks). The addition of Combivir with the single dose Nevirapine during delivery and the early stage of the disease with higher CD4 counts could be the reasons for this.

Nevirapine, sodium concentration and HIV-1 RNA in breast milk and plasma among HIV-infected women receiving short-course antiretroviral prophylaxis.

IntroductionRisk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis.ObjectiveTo determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine).MethodsMaternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant.ResultsHIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median (interquartile range, IQR) of 1.5 μg/mL (0.75–2.20 μg/mL) and 1.04 μg/mL (0.39–1.71 μg/mL), respectively (P < 0.001). At 1 week postpartum, 93% and 98% of the women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13–0.39 μg/mL) and 0.22 μg/mL (0.13–0.34 μg/mL), respectively. Maternal plasma and breast milk HIV-1 RNA correlated at all visits (R = 0.48, R = 0.7, R = 0.59; all P = 0.01). Subclinical mastitis was detected in 67% of the women at some time during 6 weeks, and in 38% of the breast milk samples. Breast milk samples with subclinical mastitis had significantly higher HIV-1 RNA at 1, 4 and 6 weeks (all P < 0.05).ConclusionAfter short-course antiretroviral prophylaxis, nevirapine was detectable in most infant cord blood samples and the concentration in maternal plasma and breast milk was high through week 1 accompanied by suppressed HIV-1 RNA in plasma and breast milk.