Single-dose Nevirapine Research Articles

In utero/peripartum antiretroviral therapy exposure and mental health outcomes at 8-18 years old: A longitudinal comparative study of children with perinatally acquired HIV, children perinatally HIV exposed but uninfected, and children unexposed uninfected from Uganda.

In utero/peripartum antiretroviral therapy (IPA) exposure type was examined in relationship to mental health symptoms among 577 children with perinatally acquired HIV (CPHIV), children perinatally HIV exposed but uninfected (CHEU), and children HIV unexposed uninfected (CHUU). IPA exposure was categorized for CPHIV and CHEU as none, single-dose nevirapine with or without zidovudine (sdNVP±AZT), sdNVP+AZT+lamivudine (3TC), or combination antiretroviral therapy (cART). Anxiety and depressive symptoms were reported at baseline, 6-, and 12-month follow-up per behavioral assessment system for children. Multivariable linear mixed models were used to estimate differences (b) with 95% confidence intervals (95% CI) for IPA exposure types versus CHEU without IPA exposure. Depressive and anxiety symptoms were lower in CHUU relative to CHEU and CPHIV but did not differ between CPHIV and CHEU. CHEU with sdNVP±AZT exposure had greater anxiety (b = 0.51, 95% CI: [0.06, 0.96]) and depressive symptoms (b = 0.48, 95% CI: [0.07, 0.89]) than CHEU without IPA exposure. CHEU with sdNVP+AZT+3TC exposure had higher anxiety (b = 0.0.45, 95% CI: [0.03, 0.86]) and depressive symptoms (b = 0.72, 95% CI: [0.27, 1.17]) versus CHEU without IPA exposure. Depressive and anxiety symptoms were not different for CHEU and CPHIV exposed to cART (b = 0.12-0.60, 95% CI: [-0.41, 1.30]) and CHEU and CHUU (b = -0.04 to 0.08, 95% CI: [-0.24, 0.29]) without IPA exposure. Among CHEU, peripartum sdNVP±AZT and sdNVP+AZT+3TC but not cART compared to no IPA exposure was associated with clinically important elevations in anxiety and depressive symptoms. Monitoring of mental health trajectory of HIV-affected children considering IPA is needed to inform mental health interventions. Patient Contribution: Caregivers and their dependents provided consent for participation and collaborated with study team to identify mutually convenient times for protocol implementation.

Growth differences by school-age and adolescence according to in utero and peripartum antiretroviral therapy exposure among Ugandan children.

In utero/peripartum antiretroviral (IPA) drug exposure in human immunodeficiency virus (HIV)-exposed children has established benefit for prevention of HIV mother-to-child-transmission but its association with height-for-age by adolescence is unknown. Hence we quantify IPA-associated growth differences at 6 to 18 years old among children with perinatally acquired HIV (CPHIV) infection and children HIV exposed but uninfected (CHEU) relative to children HIV unexposed and uninfected (CHUU). Cohort study. Kampala, Uganda. Two hundred thirty eight community controls and 490 children of women living with HIV born between 2000 and 2011 in a community were enrolled at 6 to 18 years of age and followed every 6 months for 1 year. Height-for-age determined at enrollment, 6 and 12 months after enrollment using the World Health Organization reference. IPA exposure was retrospectively determined from medical records and categorized as: no IPA, single-dose nevirapine with/without zidovudine (sdNVP ± AZT), sdNVP + AZT + lamivudine, or combination antiretroviral therapy (cART). Mean differences (β) with 95% confidence intervals (CIs) in height-for-age over 12 months were evaluated according to IPA exposure for CPHIV and CHEU and relative to CHUU using longitudinal linear mixed effects models adjusted for caregiver factors (sex, age, education, functioning in caregiving role, and lifetime adversity) in Statistical Analysis Software (v.9.4). Regardless of IPA type, CPHIV grew worse than CHUU by school-age/adolescence (β = -0.30, 95% CI: -0.48, -0.11). Relative to CHUU height-for-age was similar for CHEU exposed to sdNVP ± AZT (β = -0.16, 95% CI: -0.46, 0.14) and for CHEU exposed to sdNVP + AZT + lamivudine (β = 0.08, 95% CI: -0.20, 0.35). However, CHEU without any IPA exposure had lower height-for-age (β = -0.27, 95% CI: -0.52, -0.00) whereas CHEU with cART exposure had greater height-for-age (β = 0.41, 95% CI: 0.10, 0.71) in comparison with CHUU by 6 to 18 years old. Our findings suggest that CHEU may achieve height-for-age parity with CHUU by school-age and adolescent years- especially if provided benefit of effective cART in the peripartum period. However, CPHIV regardless of IPA exposure type and CHEU without IPA exposure remain at a disadvantage and will benefit from intervention to support their growth.

Twenty years of Prevention of Mother to Child HIV Transmission: research to implementation at a national referral hospital in Uganda.

Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Perinatal HIV prevention studies conducted at MU-JHU between 1997-2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.

Developmental Disorder Probability Scores at 6-18 Years Old in Relation to In-Utero/Peripartum Antiretroviral Drug Exposure among Ugandan Children.

(1) We examined the hypothesis that in utero/peripartum antiretroviral (IPA) exposure may affect the likelihood of developmental disorders—i.e., attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and functional impairment (FI). (2) Children and their primary caregivers were enrolled and followed for 12 months. The sample included 250 children perinatally HIV-infected (CPHIV), 250 children HIV-exposed and uninfected (CHEU) of women living with HIV, and 250 children HIV unexposed and uninfected (CHUU) at 6–18 years of age. CHEU’s IPA exposure -type was established via medical records and categorized as no IPA, single-dose nevirapine with/without zidovudine (SdNVP ± AZT), SdNVP + AZT + Lamivudine (3TC), or combination ART (cART). Developmental disorders were assessed at months 0, 6, and 12 per caregiver response to standardized questions from the third edition of Behavioral Assessment System for Children. Multivariable repeated measures linear regression models estimated standardized mean differences (SMDs) with 95% confidence intervals (95% CI) according to the IPA exposure type relative to CHUU with adjustment for the dyad’s sociodemographic and psychosocial factors. (3) Relative to the CHUU, outcomes were similar for CPHIV/CHEU with cART, SdNVP ± AZT, and no anti-retroviral drug exposure in the peripartum period. For CHEU relative to CHUU, SdNVP + AZT + 3TC exposure was associated with lower resiliency (SMD = −0.26, 95% CI: −0.49, −0.51), and elevated scores on ADHD (SMD = 0.41, 95% CI: 0.12, 0.70), ASD (SMD = 0.40, 95% CI: 0.19, 0.61), and EBD (SMD = 0.32, 95% CI: 0.08, 0.56) probability and functional impairment (SMD = 0.39, 95% CI: 0.18, 0.61) index scores. With the exception of ADHD, the adverse association between SdNVP + AZT + 3TC and outcomes were replicated for CPHIV vs. CHUU. (4) The results provided reassuring evidence that cART exposure in the peripartum period is unlikely to be adversely associated with developmental disorder probability scores in late childhood and adolescent years. However, the peripartum SdNVP + AZT + 3TC exposure associated elevation in developmental disorder probability and functional limitation at 6–18 years of life is a concern.

Nevirapine hair and plasma concentrations and HIV-1 viral suppression among HIV infected ante-partum and post-partum women attended in a mother and child prevention program in Maputo city, Mozambique.

IntroductionPrevention of mother to child transmission of HIV (PMTCT) is frequently challenged by irregular access to more effective anti-retroviral therapy. Nevirapine single dose (sdNVP), sdNVP+AZT+3TC for MTCT prophylaxis and NVP+ AZT+3TC for treatment and PMTCT were withdrawn due to low genetic resistance barrier and low efficacy. However current PMTCT lines in Mozambique include DTG+3TC+TDF, TDF+3TC+EFV, DTG +ABC+3TC, and AZT + NVP syrup prophylaxis for exposed babies. We assessed NVP hair and plasma concentrations and association with HIV-1RNA suppression among HIV+ ante-partum and post-partum women under PMTCT in Maputo, Mozambique.MethodsFrom December 2013 to November 2014, prospectively were enrolled 200 HIV+ ante-partum women on 200mg nevirapine and zidovudine 300 plus lamivudine 150mg twice daily at least with 3 months treatment and seen again at 24 weeks post-partum. Self-reported pill-taking adherence, NVP concentrations in hair, plasma, hemoglobin, CD4 cell count, HIV-1 RNA load was evaluated. NVP concentration in hair and plasma was analyzed as categorical quartile variable based on better data fit. NVP concentration was set between ≤3.77 ng/ml in plasma and ≤17,20 ng/mg in hair in quartile one to ≥5.36 ng/ml in plasma and ≥53.21 ng/mg in hair in quartile four. Logistic regression models for repeated measures were calculated. Following the World Health Organization (WHO) guidelines we set viral suppression at HIV-1RNA < 1000 c/mL. Outcome was HIV-1 RNA<1000 copies/ml. Predictor was NVP concentration in hair categorized in quartiles.ResultsIn total 369 person-visits (median of 1.85) were recorded. Self-reported adherence was 98% (IQR 97–100%) at ante-partum. In 25% person visits, NVP concentrations were within therapeutic levels (3.77 ng/ml to 5.35 ng/ml) in plasma and (17.20 ng/mg to 53.20 ng/mg) in hair. In 50% person visits NVP concentrations were above 5.36 ng/ml in plasm and 53.21 ng/mg in hair. HIV-1 RNA suppression was found in 34.7% of women with two viral loads, one at enrollment and another in post-partum. Odds of HIV-1 RNA suppression in quartile 4, was about 6 times higher than in quartile 1 (p-value = 0.006) for NVP hair concentration and 7 times for NVP plasma concentration (p-value = 0.012).ConclusionsThe study results alert for potential low efficacy of current PMTCT drug regimens in use in Mozambique. Affordable means for individual monitoring adherence, ART plasma and hair levels, drug resistant and HIV-1 RNA levels monitoring are recommended for prompt identification of inadequate drug regimens exposure patterns and adjust accordingly.

Inutero and peripartum antiretroviral exposure as predictor of cognition in 6- to 10-year-old HIV-exposed Ugandan children - a prospective cohort study.

To quantify association between in utero/peripartum antiretroviral (IPA) exposure and cognition, i.e. executive function (EF) and socioemotional adjustment (SEA), in school-aged Ugandan children who were perinatally HIV-infected (CPHIV, n=100) and children who were HIV-exposed but uninfected (CHEU, n=101). Children were enrolled at age 6-10years and followed for 12months from March 2017 to December 2018. Caregiver-reported child EF and SEA competencies were assessed using validated questionnaires at baseline, 6 and 12months. IPA type - combination antiretroviral therapy (cART), intrapartum single-dose nevirapine±zidovudine (sdNVP±ZDV), nevirapine+zidovudine+lamivudine (sdNVP+ZDV+3TC) - or no IPA (reference) was verified via medical records. IPA-related standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) in cognitive competencies were estimated from regression models with adjustment for caregiver sociodemographic and contextual factors. Models were fitted separately for CPHIV and CHEU. Among CPHIV children, cART (SMD=-0.82, 95% CI: -1.37 to -0.28) and sdNVP±ZDV (SMD=-0.41, 95% CI: -0.81 to -0.00) vs. no IPA predicted lower executive dysfunction over 12months. Intrapartum sdNVP+ZDV+3TC vs. no IPA predicted executive dysfunction (SMD=0.80, 95% CI: 0.30-1.31), SEA problems (SMD=0.63-0.76, 95% CI: 0.00-1.24) and lower adaptive skills (SMD=-0.36, 95% CI: -0.75-0.02) over 12months among CHEU. Further adjustment for contextual factors attenuated associations, although most remained of moderate clinical importance (|SMD|>0.33). Among CPHIV children, cART and sdNVP±ZDV IPA exposure predicted, on average, lower executive dysfunction 6-10years later. However, peripartum sdNVP+ZDV+3TC predicted executive and SEA dysfunction among CHEU 6-10years later. These data underscore the need for more research into long-term effects of in utero ART to inform development of appropriate interventions so as to mitigate cognitive sequelae.

Perinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before Delivery.

Infants born to women living with HIV initiating combination antiretroviral therapy (cART) late in pregnancy are at high risk of intrapartum infection. Mother/infant perinatal antiretroviral intensification may substantially reduce this risk. In this single-arm Bayesian trial, pregnant women with HIV receiving standard of care antiretroviral prophylaxis in Thailand (maternal antenatal lopinavir-based cART; nonbreastfed infants 4 weeks' postnatal zidovudine) were offered "antiretroviral intensification" (labor single-dose nevirapine plus infant zidovudine-lamivudine-nevirapine for 2 weeks followed by zidovudine-lamivudine for 2 weeks) if their antenatal cART was initiated ≤8 weeks before delivery. A negative birth HIV-DNA polymerase chain reaction (PCR) followed by a confirmed positive PCR defined intrapartum transmission. Before study initiation, we modeled intrapartum transmission probabilities using data from 3738 mother/infant pairs enrolled in our previous trials in Thailand using a logistic model, with perinatal maternal/infant antiretroviral regimen and predicted viral load at delivery as main covariates. Using the characteristics of the women enrolled who received intensification, prior intrapartum transmission probabilities (credibility intervals) with/without intensification were estimated. After including the transmission data observed in the current study, the corresponding Bayesian posterior transmission probability was derived. No intrapartum transmission of HIV was observed among the 88 mother/infant pairs receiving intensification. The estimated intrapartum transmission probability was 2·2% (95% credibility interval 0·5-6·1) without intensification versus 0·3% (0·0-1·6) with intensification. The probability of superiority of intensification over standard of care was 94·4%. Antiretroviral intensification appeared safe. Mother/infant antiretroviral intensification was effective in preventing intrapartum transmission of HIV in pregnant women receiving ≤8 weeks antepartum cART.

Diabetes and HIV

AbstractIn India, the prevalence of HIV infection among adults (15–49 years) is estimated at 0.26%. The total number of people living with HIV (PLHIV) in India was estimated at 21.17 lakhs in 2015. There has been a declining trend in the mortality rate of HIV-infected patients on antiretroviral therapy (ART). With HIV becoming a chronic manageable disease, metabolic complications like diabetes mellitus (DM) and dyslipidemia are coming to the forefront. Generally, protease inhibitors (PI) are implicated in metabolic derangement; however, nucleoside reverse transcriptase inhibitors (NRTI) like stavudine can also cause diabetes. Among HIV-infected patients, the prevalence of diabetes is reported to range from 2 to 19%, so there is strong case for screening of diabetes among HIV-infected cases. The South Asian Consensus Guidelines recommend that both fasting and postprandial glucose values should be checked at screening and during monitoring of therapy. National AIDS Control Organization (NACO) recommends fasting plasma glucose with value ≥ 126 mg% diagnostic of diabetes mellitus. HbA1c may underestimate the degree of hyperglycemia in HIV-infected individuals and may not be a good diagnostic tool. Lifestyle modification is recommended as part of treatment. Metformin should be used with caution in HIV patients. Concomitant use of metformin with non-nucleoside reverse transcriptase inhibitors (NNRTI) can cause lactic acidosis. Thiazolidinediones should be the drug of choice in HIV, particularly in patients with lipodystrophy. Insulin secretagogues (meglitinides and sulfonylureas) are safe but may not be effective in the presence of severe insulin resistance. There are concerns regarding the use of gliptins in HIV-infected patients as they have molecular targets on immune cells. Insulin should be the drug of choice for HIV-infected patients with marked hyperglycemia (HbA1c &gt; 9%), ketonuria, severe liver disease, or severe kidney disease. SGLT2 inhibitor may increase the risk of urinary tract infection and genital mycotic infections in HIV-infected diabetics. Regarding the use of ART among HIV patients with diabetes, NACO guidelines recommend that Tenofovir, lamivudine, and efavirenz should be used as first-line ART for all new patients, except known cases of severe diabetes, severe hypertension, or renal disease. Tenofovir, lamivudine, and lopinavir/ritonavir should be used as first line in women ever exposed to single dose Nevirapine in the past and also for all confirmed HIV-2 or HIV-1 &amp; 2 coinfected patients. HIV infected with diabetes mellitus and microalbuminuria or proteinuria need Abacavir-based regimen (Abacavir + Lamivudine + Efavirenz). There is some suggestion that PI-based regimes should be avoided in patients at high risk of developing diabetes, for example, those with a history of gestational diabetes, positive family history of diabetes, or impaired glucose tolerance on screening.

Erratum to: Sensitive Drug-Resistance Assays Reveal Long-Term Persistence of HIV-1 Variants with the K103N Nevirapine (NVP) Resistance Mutation in Some Women and Infants after the Administration of Single-Dose NVP: HIVNET 012.

Background. The HIV Network for Prevention Trials (HIVNET) 012 trial showed that NVP resistance (NVPR) emerged in some women and children after the administration of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP. Methods. We analyzed samples from 9 women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive resistance assays, LigAmp and TyHRT. Results. ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq 12-24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use of the TyHRT assay. Conclusions. K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. Sensitive resistance assays may provide new insight into the impact of antiretroviral drug exposure on HIV-1 evolution.

On a Shape-Invariant Hazard Regression Model with application to an HIV Prevention Study of Mother-to-Child Transmission.

In survival analysis, Cox model is widely used for most clinical trial data. Alternatives include the additive hazard model, the accelerated failure time (AFT) model and a more general transformation model. All these models assume that the effects for all covariates are on the same scale. However, it is possible that for different covariates, the effects are on different scales. In this paper, we propose a shape-invariant hazard regression model that allows us to estimate the multiplicative treatment effect with adjustment of covariates that have non-multiplicative effects. We propose moment-based inference procedures for the regression parameters. We also discuss the risk prediction and the goodness of fit test for our proposed model. Numerical studies show good finite sample performance of our proposed estimator. We applied our method to the HIVNET 012 study, a milestone trial of single-dose nevirapine in prevention of mother-to-child transmission of HIV. From the HIVNET 012 data analysis, single-dose nevirapine treatment is shown to improve 18-month infant survival significantly with appropriate adjustment of the maternal CD4 counts and the virus load.

Minority and majority pretreatment HIV-1 drug resistance associated with failure of first-line nonnucleoside reverse-transcriptase inhibitor antiretroviral therapy in Kenyan women.

Among women initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based-ART with and without a history of single-dose nevirapine (sdNVP) with or without zidovudine with or without lamivudine (ZDV with and without 3TC) for prevention of mother-to-child HIV transmission (PMTCT), we hypothesized that pre-ART HIV-drug resistance would be associated with virologic failure DESIGN/METHODS:: In a prospectively enrolled study, three genotypic drug-resistance assays [oligonucleotide-ligation-assay (OLA), consensus sequencing, and next-generation sequencing by Illumina] were retrospectively performed to detect pre-ART drug resistance. Minority or majority drug-resistant variants identified in pre-ART RNA and/or DNA, a history of antiretrovirals for PMTCT, and other risk factors were assessed for association with virologic failure. Failure occurred in 38/169 (22.5%) women, and was associated with pre-ART drug resistance detected by any assay (OLA of plasma or PBMC, consensus sequencing of PBMC and/or plasma, and next-generation sequencing of PBMC at frequencies of at least 10% and as minority variants; all P < 0.0001). Failure was also associated with PMTCT using sdNVP and ZDV with or without 3TC, but not sdNVP only; however, the longer time-interval between PMTCT and ART initiation observed for sdNVP-only women showed no interaction with failure. Viral loads and OLA of PBMC in longitudinal specimens demonstrated rapid failure and emergence of drug resistance, particularly among sdNVP and ZDV with or without 3TC-experienced women with pre-ART drug-resistant minority variants by next-generation sequencing but without drug resistance by OLA or consensus sequencing. Pre-ART drug resistance was detected similarly by OLA of PBMC or plasma and by consensus sequencing, and was associated with virologic failure soon after initiation of first-line NVP-based ART. A history of sdNVP and ZDV with or without 3TC for PMTCT or minority variants detected by next-generation sequencing identified additional women with failure. These findings emphasize the value of assessing individual antiretroviral history, particularly nonsuppressive antiretrovirals with at least two drug classes, and testing for pre-ART drug resistance, including minority variants.

Factors Influencing Maternal Adherence to Infant’s Nevirapine Prophylaxis in a Cross-Sectional Study Conducted at Mulago Hospital, Kampala, Uganda

To eliminate mother to child transmission of HIV, existing interventions might need to be scaled-up and rigorously implemented. One of the strategies to reduce vertical transmission of HIVis the 4-6weeks daily single oral dose ofNevirapine (NVP) or Zidovidinerecommended for newbornsto HIV positive mothers. Maternal optimal adherence to these anti-retroviral prophylaxis regimens is imperative to prevention of vertical transmission of HIV. Limited studies investigated maternal adherence to infant’s NVP prophylaxis regimen and associated factors. This study examined the level and factors influencing maternal adherence to infant’s NVPprophylaxis regimenat six weeks of age. Maternal adherence to infant’s NVP regimen was defined as dispensation of 95% of the total daily single dose of NVPsuspension to infants at 6 weeks of age. Maternal adherence, socio-demographic and psychosocial factors were measured using a pre-tested questionnaire. Bivariate analysis and binary logistic regression model were used to determine the level and factors influencing maternal adherence to infant’s NVP regimen respectively. Results showed that 77% of the mothers had optimal adherence. Maternal age ≥ 20 years and believe in the effectiveness of NVP in prevention of vertical transmission of HIV were associated with increased likelihood of adherence to infants NVP regimen (OR 6.18; 95% CI: 1.64-23.24) and (OR 12.69; 95% CI 3.07-52.44) respectively.In conclusion maternal maturity and perceived benefits of NVP seems to be important positive drivers of optimal adherence. This suggests the importance of considering psychosocial and demographic characteristics of mothers in policy and intervention designing.

Delayed Seroreversion in HIV-exposed Uninfected Infants.

Recent studies report delayed anti-HIV antibody clearance (seroreversion) among HIV-exposed uninfected infants that may affect diagnostic practices. We evaluated the age-specific seroreversion rates in Thailand. The medical records of HIV-exposed uninfected infants born in January 2000-December 2014 were reviewed. Anti-HIV seroreversion rates at 12, 18 and 24 months were analyzed in 3 periods according to the Thai National Guidelines of prevention of mother-to-child transmission of HIV: zidovudine with or without single dose nevirapine to all women (2000-2006), adding lamivudine plus nevirapine to zidovudine in women with CD4 count <200 cells/mm (2007-2009) and zidovudine plus lamivudine plus boosted lopinavir to all women (2010-2014). In 2013, the serologic test kit was changed from third- to fourth-generation (4G) assay. All the infants were formula fed. Among 736 infants, the overall seroreversion rates at 12, 18 and 24 months of age were 59.38%, 94.57% and 100%, respectively. The seroreversion rates at 12 months of age declined from 68% in 2000-2006 and 65.9% in 2007-2009, to 42.9% in 2010-2014 (P = 0.001). Seroreversion rates at 18 months of age were more than 96.5% before 2013 and decreased to 79.1% in 2013-2014 (P = 0.001) with use of 4G. Multivariate analysis identified antepartum protease inhibitors treatment and the use of 4G testing as independent factors associated with delayed seroreversion. Anti-HIV seroreversion delay in HIV-exposed uninfected infants was associated with use of protease inhibitors and 4G HIV testing, complicating the interpretation to exclude perinatal HIV infection.

Spatial-temporal trend for mother-to-child transmission of HIV up to infancy and during pre-Option B+ in western Kenya, 2007-13.

IntroductionUsing spatial–temporal analyses to understand coverage and trends in elimination of mother-to-child transmission of HIV (e-MTCT) efforts may be helpful in ensuring timely services are delivered to the right place. We present spatial–temporal analysis of seven years of HIV early infant diagnosis (EID) data collected from 12 districts in western Kenya from January 2007 to November 2013, during pre-Option B+ use.MethodsWe included in the analysis infants up to one year old. We performed trend analysis using extended Cochran–Mantel–Haenszel stratified test and logistic regression models to examine trends and associations of infant HIV status at first diagnosis with: early diagnosis (<8 weeks after birth), age at specimen collection, infant ever having breastfed, use of single dose nevirapine, and maternal antiretroviral therapy status. We examined these covariates and fitted spatial and spatial–temporal semiparametric Poisson regression models to explain HIV-infection rates using R-integrated nested Laplace approximation package. We calculated new infections per 100,000 live births and used Quantum GIS to map fitted MTCT estimates for each district in Nyanza region.ResultsMedian age was two months, interquartile range 1.5–5.8 months. Unadjusted pooled positive rate was 11.8% in the seven-years period and declined from 19.7% in 2007 to 7.0% in 2013, p < 0.01. Uptake of testing ≤8 weeks after birth was under 50% in 2007 and increased to 64.1% by 2013, p < 0.01. By 2013, the overall standardized MTCT rate was 447 infections per 100,000 live births. Based on Bayesian deviance information criterion comparisons, the spatial–temporal model with maternal and infant covariates was best in explaining geographical variation in MTCT.DiscussionImproved EID uptake and reduced MTCT rates are indicators of progress towards e-MTCT. Cojoined analysis of time and covariates in a spatial context provides a robust approach for explaining differences in programmatic impact over time.ConclusionDuring this pre-Option B+ period, the prevention of mother to child transmission program in this region has not achieved e-MTCT target of ≤50 infections per 100,000 live births. Geographical disparities in program achievements may signify gaps in spatial distribution of e-MTCT efforts and could indicate areas needing further resources and interventions.

Time to first positive HIV-1 DNA PCR may differ with antiretroviral regimen in infants infected with non-B subtype HIV-1

To evaluate the association of type and timing of prophylactic maternal and infant antiretroviral regimen with time to first positive HIV-1 DNA PCR test, in nonbreastfed HIV-infected infants, from populations infected predominantly with HIV-1 non-B subtype virus. Analysis of combined data on nonbreastfed HIV-infected infants from prospective cohorts in Botswana, Thailand, and the United Kingdom (N = 405). Parametric models appropriate for interval-censored outcomes estimated the time to first positive PCR according to maternal or infant antiretroviral regimen category and timing of maternal antiretroviral initiation, with adjustment for covariates. Maternal antiretroviral regimens included: no antiretrovirals (n = 138), single-nucleoside analog reverse transcriptase inhibitor (n = 165), single-dose nevirapine with zidovudine (n = 66), and combination prophylaxis with 3 or more antiretrovirals [combination antiretroviral therapy (cART), n = 36]. Type of maternal/infant antiretroviral regimen and timing of maternal antiretroviral initiation were each significantly associated with time to first positive PCR (multivariate P < 0.0001). The probability of a positive test with no antiretrovirals compared with the other regimen/timing groups was significantly lower at 1 day after birth, but did not differ significantly after age 14 days. In a subgroup of 143 infants testing negative at birth, infant cART was significantly associated with longer time to first positive test (multivariate P = 0.04). Time to first positive HIV-1 DNA PCR in HIV-1-infected nonbreastfed infants (non-B HIV subtype) may differ according to maternal/infant antiretroviral regimen and may be longer with infant cART, which may have implications for scheduling infant HIV PCR-diagnostic testing and confirming final infant HIV status.

Brief Report: High Sensitivity and Specificity of the Cepheid Xpert HIV-1 Qualitative Point-of-Care Test Among Newborns in Botswana.

HIV point-of-care (POC) testing allows for early infant HIV diagnosis and treatment, but POC accuracy at birth and in the setting of antiretroviral prophylaxis for the prevention of mother-to-child HIV transmission is unknown. We evaluated the Cepheid Xpert HIV-1 Qual POC test against the Roche Taqman HIV-1 DNA polymerase chain reaction (PCR) platform using dried blood spots from 15 HIV-infected and 75 HIV-exposed uninfected newborns. These infants were screened for HIV at <96 hours of life at 5 hospital maternity wards in Botswana; all infants received postexposure antiretroviral prophylaxis with single-dose nevirapine and zidovudine, and most mothers received 3-drug antiretroviral therapy in pregnancy and at delivery. Fourteen of the 15 PCR positive samples tested positive by Cepheid POC, yielding a sensitivity of 93.3% (95% confidence interval: 68.1 to 99.8). Baseline viral load among positive infants ranged from <40 to >10,000,000 copies/mL, with a median of 2403 copies/mL. The HIV RNA for the infant with false-negative POC testing was 1661 copies/mL. Of note, 2 infants with low HIV RNA (<40 and 272 copies/mL) were correctly identified as HIV positive by Cepheid POC. All the 75 PCR-negative samples tested negative by Cepheid POC, yielding a specificity of 100% (95% confidence interval: 96.1 to 100). Our study demonstrates high sensitivity and specificity for the Cepheid POC assay in the first week of life despite early infection and antiretroviral prophylaxis. This platform may be a useful approach for adding early infant HIV diagnosis to current testing programs.

An increase in rates of obstetric haemorrhage in a setting of high HIV seroprevalence.

Obstetric haemorrhage (OH) is the leading cause of maternal mortality worldwide, although, indirectly, HIV is also a leading cause of maternal mortality in some settings with a high HIV seroprevalence. To determine the possible association between increasing rates of OH and HIV or its treatment. We conducted a retrospective chart review of women with OH at King Edward VIII Hospital, Durban, South Africa, over a 3-year period (2009 - 2011), during which the drug regimen for the prevention of mother-to-child transmission was evolving from single-dose nevirapine to antenatal zidovudine combined with intrapartum nevirapine (also referred to as dual therapy), and finally to a combination or highly active antiretroviral therapy (cART or HAART). Cases of OH (including abruptio placentae, placenta praevia, unspecified antepartum haemorrhage (APH), and postpartum haemorrhage (PPH)) were identified from maternity delivery records, and the relevant data extracted. We analysed the records of 448 women diagnosed with OH. Even though the incidence of OH was low, the study found an increasing number of cases during the 3-year period. PPH - not APH - was associated with HIV seropositivity (odds ratio 1.84, 95% confi-dence interval 1.14 - 2.95). cART was not associated with an increased risk of haemorrhage. HIV was associated with a high risk of PPH, and its possible association with HIV treatment needs further research.

Evaluation of response to protease inhibitor based first line anti-retroviral therapy (ART) regimens in human immunodeficiency virus infected children compared to standard first line non-protease inhibitor ART regimens: an Indian experience

Background: Children exposed to single dose nevirapine at birth, if tested human immunodeficiency virus (HIV) positive, cannot be given nevirapine based anti-retroviral therapy (ART). Therefore protease inhibitor (PI) based combinations are being used as first line therapy in such children. However, experience is limited regarding their efficacy and adverse effects in the Indian population. Objectives: To document clinical and immunological responses to PI based regimens as first line therapy in HIV infected children less than 5 years old compared to responses to standard non-protease inhibitor (NPI) first line regimens recommended by National AIDS Control Organisation and World Health Organisation. Method: An observational prospective cohort study was conducted in a tertiary care hospital in Surat, India, from December 2011 to June 2013 on children less than 5 years of age with confirmed HIV status. At diagnosis, clinical staging, growth parameters and CD4 levels were assessed and the children were allotted to NPI and PI groups depending on prior nevirapine exposure. Clinical, immunological and biochemical alterations after ART initiation were assessed and compared after 6 months of therapy. Results: During the study period, there were 43 children less than 5 years of age with confirmed HIV status. Children in both NPI and PI groups showed significant improvement in clinical stage of the disease after 6 months of therapy (P Conclusions: PI based regimens were effective as first line therapy in HIV infected children less than 5 years old. Both PI and NPI regimens were equally effective at 6 months of therapy but PI based regimens achieved significantly better growth parameters and CD4 levels. Elevated total cholesterol levels were observed after therapy with PI regimens. (Key words: HIV, children, protease inhibitors) Sri Lanka Journal of Child Health, 2017; 46 (2): 160-164

Thai national guidelines for the prevention of mother-to-child transmission of human immunodeficiency virus 2017.

Thailand has made progress in reducing perinatal HIV transmission rates to levels that meet the World Health Organization targets for so-called "elimination" (<2%) of mother-to-child transmission (MTCT). To highlight the Thailand National Guidelines on HIV/AIDS Treatment Prevention Working Group issued a new version of its National Prevention of MTCT guidelines in March 2017 aimed to reduce MTCT rate to <1% by 2020. The guidelines include recommending initiation of antepartum antiretroviral therapy (ART) containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC)/emtricitabine (FTC) plus efavirenz regardless of CD4 cell count as soon as HIV is diagnosed for ART naïve HIV-infected pregnant women. An alternative regimen is TDF or zidovudine (AZT) plus 3TC/FTC plus lopinavir/ritonavir (LPV/r) for HIV-infected pregnant women suspected resistant to non-nucleoside reverse transcriptase inhibitors. Treatment should be started immediately irrespective of gestational age and continued after delivery for life. Raltegravir is recommended in addition to the ART regimen for HIV-infected pregnant women who present late (gestational age (GA) ≥32 weeks) or those who have a viral load (VL) >1000 copies/mL at GA ≥32 weeks. HIV-infected pregnant women who conceive while receiving ART should continue their treatment regimen during pregnancy. HIV-infected pregnant women who present in labor and are not receiving ART should receive single-dose nevirapine immediately along with oral AZT, and continue ART for life. Infants born to HIV-infected mothers are categorized as high or standard risk for MTCT. High MTCT risk is defined as an infant whose mother has a viral load (VL) > 50 copies/mL at GA > 36 weeks or has received ART <12 weeks before delivery, or has poor ART adherence. These infants should be started on AZT plus 3TC plus NVP for 6 weeks after delivery. Infants with standard MTCT risk should receive AZT for 4 weeks. Formula feeding exclusively is recommended for all HIV-exposed infants.

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 w...