Postpartum adherence to Option B+ until 18 months in Western Uganda

Since 2012, the WHO recommends Option B+ for the prevention of mother-to-child transmission of HIV. This approach entails the initiation of lifelong antiretroviral therapy in all HIV-positive pregnant women, also implying protection during breastfeeding for 12 months or longer. Research on long-term adherence to Option B+ throughout breastfeeding is scarce to date. Therefore, we conducted a prospective observational cohort study in Fort Portal, Western Uganda, to assess adherence to Option B+ until 18 months postpartum. In 2013, we recruited 67 HIV-positive, Option B+ enrolled women six weeks after giving birth and scheduled them for follow-up study visits after six, twelve and 18 months. Two adherence measures, self-reported drug intake and amount of drug refill visits, were combined to define adherence, and were assessed together with feeding information at all study visits. At six months postpartum, 51% of the enrolled women were considered to be adherent. Until twelve and 18 months postpartum, adherence for the respective follow-up interval decreased to 19% and 20.5% respectively. No woman was completely adherent until 18 months. At the same time, 76.5% of the women breastfed for ≥12 months. Drug adherence was associated with younger age (p<0.01), lower travel costs (p = 0.02), and lower number of previous deliveries (p = 0.04). Long-term adherence to Option B+ seems to be challenging. Considering that in our cohort, prolonged breastfeeding until ≥12 months was widely applied while postpartum adherence until the end of breastfeeding was poor, a potential risk of postpartum vertical transmission needs to be taken seriously into account for Option B+ implementation

Lack of effect of intermittent preventive treatment for malaria in pregnancy and intense drug resistance in western Uganda

Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine–pyrimethamine (SP) is widely implemented in sub-Saharan Africa for the prevention of malaria in pregnancy and adverse birth outcomes. However, in areas of intense SP resistance, the efficacy of IPTp may be compromised. Methods A cross-sectional study among 915 delivering women (728 analysable live singleton deliveries) was conducted in Fort Portal, western Uganda, to assess associations of reported IPTp use, Plasmodium falciparum infection, maternal anaemia, low birth weight, and preterm delivery, and to estimate the degree of SP resistance as reflected by pfdhfr/pfdhps mutations. Results Plasmodium falciparum infection was detected by PCR in 8.9 % and by microscopy of placental blood samples in 4.0 %. Infection was significantly associated with stillbirth, early neonatal death, anaemia, low birth weight, and pre-term delivery. Eighty percent of the women had taken at least one dose of IPTp, and more than half had taken two doses. As compared to women without chemoprophylaxis against malaria, IPTp had no significant influence on the presence of P. falciparum infection (13.8 vs. 9.6 %, P = 0.31). Nor was it associated with reductions in anaemia, low birth weight or preterm delivery. P. falciparum with intense SP resistance (pfdhfr/pfdhps quintuple or sextuple mutations) were observed in 93 % (pfdhps 581G, 36 %), and the additional high resistance allele pfhdr 164L in 36 %. Conclusions In Fort Portal, Uganda, reported use of IPTp with SP does not provide an observable benefit. The molecular markers of P. falciparum indicate high grade SP resistance reaching the threshold set by WHO for the discontinuation of IPTp with SP. Alternative approaches for the prevention of malaria in pregnancy are urgently needed

Prävention of vertical transmission of HIV in the Option B+ era with special consideration of adherence during pregnancy

Einleitung: Zur Vermeidung einer HIV-Übertragung von Mutter zu Kind während Schwangerschaft und Stillzeit empfahl die WHO in ihren Leitlinien seit 2012 die Einleitung einer lebenslangen antiretroviralen Therapie für alle HIV- positiven Schwangeren (Option B+). Bislang wurden sowohl die Durchführbarkeit der Strategie hinsichtlich der mütterlichen Therapieadhärenz als auch Einflüsse auf das Geburtsergebnis kaum untersucht. Methoden: Zur Untersuchung der Durchführbarkeit von Option B+ im Sinne einer konstanten Therapieadhärenz führten wir eine longitudinale, prospektive Beobachtungsstudie in Uganda durch. HIV-positive Frauen wurden in der Schwangerenvorsorge zweier Kliniken rekrutiert und bis 18 Monate nach Entbindung nachverfolgt. Die Therapieadhärenz wurde während und nach der Schwangerschaft in regelmäßigen Abständen evaluiert. Parallel wurden in einer Querschnittsstudie mögliche Einflüsse der antiretroviralen Medikation auf das Geburtsergebnis untersucht. Für diese Studie wurden entbindende Frauen rekrutiert, die Häufigkeit von Komplikationen erfasst und auf einen möglichen Zusammenhang mit der Einnahme antiretroviraler Medikamente untersucht. Ergebnisse: In die longitudinale Beobachtungsstudie wurden 124 HIV-positive schwangere Frauen eingeschlossen. Hiervon kehrten 45 (36.3%) nach ihrer ersten Vorstellung nicht mehr in die Schwangerschaftsvorsorge zurück. Der Verbleib in der PMTCT-Maßnahme korrelierte signifikant mit vorheriger Kenntnis sowie Offenlegung des HIV- Status. In der Gruppe der Frauen, die bis zur Geburt nachverfolgt wurden zeigte sich die Therapieadhärenz stabil und auf hohem Niveau (Median 95.7% eingenommene Tabletten). Nach der Geburt jedoch erreichte keine der Frauen längerfristig eine adäquate Adhärenz. Es zeigte sich eine Abnahme der medianen Adhärenz auf 49% nach 6 Monaten und auf 20% nach 18 Monaten. Inadäquate Therapieadhärenz korrelierte signifikant mit einer höheren Anzahl an vorausgegangenen Schwangerschaften, einem höheren Alter der Frau sowie hohen Transportkosten. Eine HIV-Übertragung von Mutter zu Kind trat bis 18 Monate nach Geburt nicht auf. Im Rahmen der Querschnittsstudie wurden 412 Gebärende untersucht. 110 Frauen (26.7%) waren HIV positiv, von diesen hatten 88.1% eine antiretrovirale Therapie bereits vor (34.5%), oder während der Schwangerschaft (53.6%) begonnen. In der Gesamtkohorte zeigte sich eine hohe Rate an Komplikationen: 40.6% der Frauen waren von Totgeburt, Frühgeburt oder niedrigem Geburtsgewicht des Babys betroffen. Ein Zusammenhang mit der Einnahme antiretroviraler Medikamente konnte jedoch unabhängig von Art und Einnahmedauer nicht festgestellt werden. Diskussion: Zusammenfassend zeigt sich Option B+ während der Schwangerschaft als prinzipiell realisierbare und effektive Strategie mit hoher und konstanter Therapieadhärenz, und ohne Anhaltspunkte für einen negativen Einfluss auf das Geburtsergebnis. Die hohe Rate an Drop-outs zu Beginn der Schwangerschaft, sowie die deutlich nachlassende Adhärenz nach Geburt, sind jedoch alarmierend. An diesen beiden kritischen Punkten der Therapie erscheint eine nachhaltigere Betreuung der Frauen unerlässlich.Introduction: For the prevention of mother to child transmission (PMTCT) of HIV, the WHO guidelines of 2012 stipulated the initiation of a lifelong antiretroviral treatment for all HIV-positive pregnant women (Option B+). Yet, feasibility in terms of treatment adherence as well as influences of this regimen on birth outcomes have barely been evaluated. Methods: In order to describe feasibility of Option B+, we conducted a longitudinal, observational study in Uganda. HIV-positive women were recruited on their first antenatal care (ANC) visit in two clinics and were followed-up until 18 months after delivery. Adherence was evaluated at regular intervals during and after pregancy. At the same time, we conducted a cross-sectional study to determine possible influences of antiretroviral drug intake on birth outcomes. Delivering women were recruted, and adverse birth outcomes were determined and assessed for possible correlations with antiretroviral drug intake. Results: In total, 124 HIV-positive women were enrolled into the longitudinal study. Among these, 45 clients (36.3%) were lost to follow-up immediately after their first ANC visit. Retention in care was significantly associated with prior knowledge and disclosure of HIV status. Among followed-up clients, the median pill count adherence remained on a high and stable level (median 95.7% pill intake) until delivery. However, no client achieved adequate adherence for a longer term period postpartum. Adherence levels decreased to a median of 49% after 6 months and 20% after 18 months. Inadequate adherence was associated with higher numbers of previous deliveries, older age of the mother and higher transport costs. HIV transmission from mother to child did not occur until 18 months postpartum. Within our cross-sectional study, 412 delivering women were included into the evaluation. Within this cohort, 110 women (26.7%) were HIV positive, most of these (88.1%) had started ART either before, (34.5%), or as Option B+ during pregnancy (53.6%). Overall, we found high rates of adverse birth outcomes: 40.6% of women were affected by stillbirth, preterm delivery or small for gestational age. However, we found no evidence of any correlation with antiretroviral drug intake. Discussion: In conclusion, we found encouraging evidence on effectiveness and adherence to Option B+ during pregnancy, without implications for adverse birth outcomes. However, the high rate of immediate loss to care on uptake, as well as the decrease of adherence after delivery, are alarming results. Substantial support at these critical points of the intervention seems to be of crucial importance

Prevention of mother-to-child transmission of HIV: Postpartum adherence to Option B+ until 18 months in Western Uganda.

Since 2012, the WHO recommends Option B+ for the prevention of mother-to-child transmission of HIV. This approach entails the initiation of lifelong antiretroviral therapy in all HIV-positive pregnant women, also implying protection during breastfeeding for 12 months or longer. Research on long-term adherence to Option B+ throughout breastfeeding is scarce to date. Therefore, we conducted a prospective observational cohort study in Fort Portal, Western Uganda, to assess adherence to Option B+ until 18 months postpartum. In 2013, we recruited 67 HIV-positive, Option B+ enrolled women six weeks after giving birth and scheduled them for follow-up study visits after six, twelve and 18 months. Two adherence measures, self-reported drug intake and amount of drug refill visits, were combined to define adherence, and were assessed together with feeding information at all study visits. At six months postpartum, 51% of the enrolled women were considered to be adherent. Until twelve and 18 months postpartum, adherence for the respective follow-up interval decreased to 19% and 20.5% respectively. No woman was completely adherent until 18 months. At the same time, 76.5% of the women breastfed for ≥12 months. Drug adherence was associated with younger age (p<0.01), lower travel costs (p = 0.02), and lower number of previous deliveries (p = 0.04). Long-term adherence to Option B+ seems to be challenging. Considering that in our cohort, prolonged breastfeeding until ≥12 months was widely applied while postpartum adherence until the end of breastfeeding was poor, a potential risk of postpartum vertical transmission needs to be taken seriously into account for Option B+ implementation

Option B+ for prevention of vertical HIV transmission has no influence on adverse birth outcomes in a cross-sectional cohort in Western Uganda

Background While most Sub-Saharan African countries are now implementing the WHO-recommended Option B+ protocol for prevention of vertical HIV transmission, there is a lack of knowledge regarding the influence of Option B+ exposure on adverse birth outcomes (ABOs). Against this background, we assessed ABOs among delivering women in Western Uganda. Methods A cross- sectional, observational study was performed within a cohort of 412 mother- newborn-pairs in Virika Hospital, Fort Portal in 2013. The occurrence of stillbirth, pre-term delivery, and small size for gestational age (SGA) was analysed, looking for influencing factors related to HIV-status, antiretroviral drug exposure and duration, and other sociodemographic and clinical parameters. Results Among 302 HIV-negative and 110 HIV-positive women, ABOs occurred in 40.5%, with stillbirth in 6.3%, pre-term delivery in 28.6%, and SGA in 12.2% of deliveries. For Option B+ intake (n = 59), no significant association was found with stillbirth (OR 0.48, p = 0.55), pre- term delivery (OR 0.97, p = 0.92) and SGA (OR 1.5, p = 0.3) compared to seronegative women. Women enrolled on antiretroviral therapy (ART) before conception (n = 38) had no different risk for ABOs than women on Option B+ or HIV-negative women. Identified risk factors for stillbirth included lack of formal education, poor socio-economic status, long travel distance, hypertension and anaemia. Pre-term delivery risk was increased with poor socio-economic status, primiparity, Malaria and anaemia. The occurrence of SGA was influenced by older age and Malaria. Conclusion In our study, women on Option B+ showed no difference in ABOs compared to HIV-negative women and to women on ART. We identified several non-HIV/ART-related influencing factors, suggesting an urgent need for improving early risk assessment mechanisms in antenatal care through better screening and triage systems. Our results are encouraging with regard to continued universal scale-up of Option B+ and ART programmes

Decreased emergence of HIV-1 drug resistance mutations in a cohort of Ugandan women initiating option B+ for PMTCT

Background: Since 2012, WHO guidelines for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in resource-limited settings recommend the initiation of lifelong antiretroviral combination therapy (cART) for all pregnant HIV-1 positive women independent of CD4 count and WHO clinical stage (Option B+). However, long-term outcomes regarding development of drug resistance are lacking until now. Therefore, we analysed the emergence of drug resistance mutations (DRMs) in women initiating Option B+ in Fort Portal, Uganda, at 12 and 18 months postpartum (ppm). Methods and findings: 124 HIV-1 positive pregnant women were enrolled within antenatal care services in Fort Portal, Uganda. Blood samples were collected at the first visit prior starting Option B+ and postpartum at week six, month six, 12 and 18. Viral load was determined by real-time RT-PCR. An RT-PCR covering resistance associated positions in the protease and reverse transcriptase HIV-1 genomic region was performed. PCR-positive samples at 12/18 ppm and respective baseline samples were analysed by next generation sequencing regarding HIV-1 drug resistant variants including low-frequency variants. Furthermore, vertical transmission of HIV-1 was analysed. 49/124 (39.5%) women were included into the DRM analysis. Virological failure, defined as >1000 copies HIV-1 RNA/ml, was observed in three and seven women at 12 and 18 ppm, respectively. Sequences were obtained for three and six of these. In total, DRMs were detected in 3/49 (6.1%) women. Two women displayed dual-class resistance against all recommended first-line regimen drugs. Of 49 mother-infant-pairs no infant was HIV-1 positive at 12 or 18 ppm. Conclusion: Our findings suggest that the WHO-recommended Option B+ for PMTCT is effective in a cohort of Ugandan HIV-1 positive pregnant women with regard to the low selection rate of DRMs and vertical transmission. Therefore, these results are encouraging for other countries considering the implementation of lifelong cART for all pregnant HIV-1 positive women

Option B+ enrolled women attending postpartum study visits.

<p>Option B+ enrolled women attending postpartum study visits.</p

Sociodemographic and clinical characteristics by adherence category.

<p>Sociodemographic and clinical characteristics by adherence category.</p

Maternal adherence at different study visits.

<p>Maternal adherence at different study visits.</p