Browsing by Author "Moodley, Dhayendre."

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Anaemia in pregnancy is associated with advanced HIV disease.
(Public Library of Science., 2014) Nandlal, Vikesh.; Moodley, Dhayendre.; Grobler, Anna Christina.; Bagratee, Jayanthilall Sarjoo.; Maharaj, Niren Ray.; Richardson, Paul.
Abstract available in pdf.
Antiretroviral drug regimens to prevent mother-to-child transmission of HIV : a review of scientific, program, and policy advances for sub-Saharan Africa.
(Springer Science., 2013) Chi, Benjamin H.; Stringer, Jeffrey S. A.; Moodley, Dhayendre.
Considerable advances have been made in the effort to prevent mother-to-child HIV transmission (PMTCT) in sub-Saharan Africa. Clinical trials have demonstrated the efficacy of antiretroviral regimens to interrupt HIV transmission through the antenatal, intrapartum, and postnatal periods. Scientific discoveries have been rapidly translated into health policy, bolstered by substantial investment in health infrastructure capable of delivering increasingly complex services. A new scientific agenda is also emerging, one that is focused on the challenges of effective and sustainable program implementation. Finally, global campaigns to “virtually eliminate” pediatric HIV and dramatically reduce HIV-related maternal mortality have mobilized new resources and renewed political will. Each of these developments marks a major step in regional PMTCT efforts; their convergence signals a time of rapid progress in the field, characterized by an increased interdependency between clinical research, program implementation, and policy. In this review, we take stock of recent advances across each of these areas, highlighting the challenges – and opportunities – of improving health services for HIV-infected mothers and their children across the region.
The association between the ratio of monocytes: lymphocytes and risk of tuberculosis among HIV-infected postpartum women.
(Lippincott Williams & Wilkins., 2014) Naranbhai, Vivek.; Moodley, Dhayendre.; Chipato, Tsungai.; Stranix-Chibanda, Lynda.; Nakabiito, Clemensia.; Kamateeka, Moreen.; Musoke, Philippa.; Manji, Karim.; George, Kathleen.; Emel, Lynda M.; Richardson, Paul.; Andrew, Philip.; Fowler, Mary Glenn.; Fletcher, Helen.; McShane, Helen.; Coovadia, Hoosen Mahomed.; Hill, Adrian V. S.
Abstract available in pdf.
Benefits and risks of antiretroviral therapy for perinatal HIV prevention.
(Massachusetts Medical Society., 2016) Fowler, Mary Glenn.; Qin, Min.; Fiscus, Susan A.; Currier, Judith S.; Flynn, Patricia M.; Chipato, Tsungai.; McIntyre, James.; Gnanashanmugam, Devasena.; Siberry, George K.; Coletti, Anne S.; Taha, Taha E.; Klingman, Karin L.; Martinson, Francis E.; Owor, Maxensia.; Violari, Avy.; Moodley, Dhayendre.; Theron, Gerhard.; Bhosale, Ramesh.; Bobat, Raziya Ahmed.; Chi, Benjamin H.; Strehlau, Renate.; Mlay, Pendo.; Loftis, Amy J.; Browning, Renee.; Fenton, Terence.; Purdue, Lynette.; Basar, Michael.; Shapiro, David E.; Mofenson, Lynne Meryl.
Abstract available in pdf.
Cryptosporidium and cryptosporidiosis.
(1990) Moodley, Dhayendre.; Jackson, Terry F. H. G.
Cryptosporidium parvum can cause debilitating disease in immunocompetent persons with cholera-like symptoms characterised by self-limiting, profuse diarrhoea; on the other hand asymptomatic infection with this organism frequently occurs. However, in immunocompromised patients, the disease is more severe and is lifethreatening. A pivotal aspect of the present survey was a comparative assessment of four commonly used staining techniques (viz. modified Ziehl-Neelsen, safranin-methylene blue, auramine phenol fluorescence and Sheather's sucrose flotation) for the detection and identification of Cryptosporidium oocysts. The Sheather's flotation method proved to be superior to the other three procedures which were not only less sensitive but also less specific. A modification of the Sheather's flotation technique was developed for use with diarrhoeal stools; this was found to be simple, reliable, costeffective and the least time consuming of the above methods; this was used exclusively in a subsequent survey of the association of Cryptosporidium infection with diarrhoea in hospitalised children. Although previous epidemiological surveys of cryptosporidiosis have been conducted in South Africa standardised methods have not been employed. This initial assessment of diagnostic techniques therefore provided a tool for accurately assessing the importance of Cryptosporidium as a causative organism of diarrhoea. In an extensive study performed on children younger than 10 years old, who were hospitalised with a primary diagnosis of diarrhoea at King Edward VIII Hospital, it was found that 9,0% (111/1229) were passing Cryptosporidium oocysts; this was the second most common enteric pathogen. In 72% (80/111) of patients with Cryptosporidium infections it was the only pathogen. The prevalence of cryptosporidiosis was highest during the months of February, March, April and May; direct correlation between the rainfall in the Durban area and the prevalence of cryptosporidiosis was demonstrated (r = 0,6125). Cryptosporidium infection was more prevalent in the 4-6 month age group (p = 0,001). The fact that Cryptosporidium infections may be symptomatic in some individuals and asymptomatic in others, suggests that strain differences in respect of pathogenic potential may occur. A prerequisite to the investigation of strain differences was to increase parasite numbers; both in vivo and in vitro culture techniques were employed. Culture in chicken embryos failed to increase the parasite population and only limited areas of the chorio-allantoic membranes showed a few developmental stages. Cell cultures proved to be more suitable for Cryptosporidium growth and parasite numbers increased proportionally with duration in culture. Attempts at infecting suckling Balb/c mice were unsuccessful; however experimental infection of immunosuppressed adult rats facilitated the examination of various developmental stages of the parasite. Isoenzyme electrophoresis is an excellent method for demonstrating polymorphism in many species. Of the five enzyme systems that were tested, glucose phosphate isomerase, malic enzyme and phosphoglucose dehydrogenase proved to be the most promising. The electrophoresis of lysates, prepared from oocysts, in an agarose gel system was found to give adequate and reproducible resolution of isoenzyme patterns. Isoenzyme polymorphism could be demonstrated in oocysts harvested from the stools of four children. Such polymorphism has not been described previously and indicates a more extensive study to investigate strain differences, and to correlate these with the clinical histories of infected subjects. This approach may be invaluable in elucidating the pathogenesis of Cryptosporidium infections in man.
Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial.
(Elsevier., 2011) Coovadia, Hoosen Mahomed.; Brown, Elizabeth R.; Fowler, Mary Glenn.; Chipato, Tsungai.; Moodley, Dhayendre.; Manji, Karim.; Musoke, Philippa.; Stranix-Chibanda, Lynda.; Chetty, Vani.; Fawzi, Wafaie.; Nakabiito, Clemensia.; Msweli, Lindiwe.; Kisenge, Rodrick Richard.; Guay, Laura.; Mwatha, Anthony.; Lynn, Diana J.; Eshleman, Susan H.; Richardson, Paul.; George, Kathleen.; Andrew, Philip.; Motenson, Lynne M.; Zwerski, Sheryl.; Maldonado, Yvonne.
Background. Nevirapine given once-daily for the first 6, 14, or 28 weeks of life to infants exposed to HIV-1 via breastfeeding reduces transmission through this route compared with single-dose nevirapine at birth or neonatally. We aimed to assess incremental safety and efficacy of extension of such prophylaxis to 6 months. Methods In our phase 3, randomised, double-blind, placebo-controlled HPTN 046 trial, we assessed the incremental benefit of extension of once-daily infant nevirapine from age 6 weeks to 6 months. We enrolled breastfeeding infants born to mothers with HIV-1 in four African countries within 7 days of birth. Following receipt of nevirapine from birth to 6 weeks, infants without HIV infection were randomly allocated (by use of a computer-generated permuted block algorithm with random block sizes and stratified by site and maternal antiretroviral treatment status) to receive extended nevirapine prophylaxis or placebo until 6 months or until breastfeeding cessation, whichever came first. The primary efficacy endpoint was HIV-1 infection in infants at 6 months and safety endpoints were adverse reactions in both groups. We used Kaplan-Meier analyses to compare differences in the primary outcome between groups. This study is registered with ClinicalTrials.gov, number NCT00074412. Findings. Between June 19, 2008, and March 12, 2010, we randomly allocated 1527 infants (762 nevirapine and 765 placebo); five of whom had HIV-1 infection at randomisation and were excluded from the primary analyses. In Kaplan-Meier analysis, 1·1% (95% CI 0·3–1·8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2·4% (1·3–3·6) of controls (difference 1·3%, 95% CI 0–2·6), equating to a 54% reduction in transmission (p=0·049). However, mortality (1·2% for nevirapine vs 1·1% for placebo; p=0·81) and combined HIV infection and mortality rates (2·3% vs 3·2%; p=0·27) did not differ between groups at 6 months. 125 (16%) of 758 infants given extended nevirapine and 116 (15%) of 761 controls had serious adverse events, but frequency of adverse events, serious adverse events, and deaths did not differ significantly between treatment groups. Interpretation. Nevirapine prophylaxis can safely be used to provide protection from mother-to-child transmission of HIV-1 via breastfeeding for infants up to 6 months of age.
Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.
(Lippincott Williams & Wilkins., 2013) Fowler, Mary Glenn.; Coovadia, Hoosen Mahomed.; Herron, Casey M.; Maldonado, Yvonne.; Chipato, Tsungai.; Moodley, Dhayendre.; Musoke, Philippa.; Aizire, Jim.; Manji, Karim.; Stranix-Chibanda, Lynda.; Fawzi, Wafaie.; Chetty, Vani.; Msweli, Lindiwe.; Kisenge, Rodrick Richard.; Brown, Elizabeth R.; Mwatha, Anthony.; Eshleman, Susan H.; Richardson, Paul.; Allen, Melissa.; George, Kathleen.; Andrew, Philip.; Zwerski, Sheryl.; Mofenson, Lynne Meryl.; Jackson, Jay Brooks.
Abstract available in PDF file.
Evaluation of adherence measures in infants receiving daily nevirapine suspension for prevention of mother-to-child transmission of HIV.
Desmond, Alicia Catherine.; Moodley, Dhayendre.
INTRODUCTION Adherence to antiretroviral treatment regimens in children has been substantially researched, however data pertaining to adherence to prophylactic regimens in the paediatric population, especially infants, is not readily available. As adherence to an antiretroviral treatment regimen is central to ensuring that expected benefits are achieved, adherence to a prophylactic regimen is as important in Human Immunodeficiency Virus (HIV) prevention. The HPTN 046 study was a prospective cohort study conducted from June 2008 to March 2010 in South Africa (Durban), Tanzania, Zimbabwe and Uganda. All enrolled infants received open label nevirapine suspension (10mg/ml) up to 6 weeks of age (day 42), at which point they were randomised to receive nevirapine suspension or placebo till 6 months of age. The dosing regimen for the first 6 weeks was as follows: 0.6ml (6mg) once daily from 3 to 7 days after birth to 2 weeks of age, 1.5ml (15mg) once daily from 2 to5 weeks of age and 1.8ml (18mg) once daily from 5 to 6 weeks (42 days) of age. Adherence to medication can be measured by various methods. The aim of this study was to ascertain the reliability of maternal verbal reports in measuring adherence to antiretroviral prophylaxis in infants in the first 6 weeks of life and evaluating the unused returned medication as an alternative method of measuring adherence. OBJECTIVES: 1. To measure adherence to daily use of nevirapine prophylaxis in infants at 2, 5 and 6 weeks of age by use of maternal verbal reports. 2. To measure adherence to daily use of nevirapine prophylaxis in infants at 2, 5 and 6 weeks of age by assessing the volume of unused returned nevirapine suspension. 3. To compare the sensitivity and specificity of maternal verbal reports and unused returned nevirapine suspension in relation to plasma nevirapine concentration. 4. To describe maternal and infant characteristics in association with adherence as measured by maternal verbal reports. METHODOLOGY: Main study: The HPTN 046 Study Measurement of adherence by maternal verbal reports: Enrolled participants’ mothers were administered a questionnaire regarding infant dosing and number of missed doses. This data was transferred into case report forms and captured into the main HPTN 046 database. Measurement of adherence by assessment of unused returned medication: Mothers of participants were requested by counsellors to return bottles with remaining medication from the previous visit at each subsequent appointment. At the 2 week, 5 week and 6 week visits, unused medication bottles were returned and weighed to determine adherence. The weight was converted to volume using the density formula (mass/volume). The dose taken was calculated by subtracting the returned volume from 20ml (volume of a full bottle). The number of missed doses was calculated from considering the expected volume that should have been taken and the actual volume taken. Substudy: The substudy was a retrospective cohort study of the HPTN 046 study. Measurement of adherence by plasma nevirapine level: In the substudy, plasma nevirapine concentrations were determined in a small sample of the substudy population for the purpose of comparing maternal verbal reports to weighed returned medication. Pharmacy records containing adherence data calculated from unused returned medication were captured and demographic and verbal report adherence data were extracted from the main electronic HPTN 046 database at 2, 5 and 6 weeks. All data were captured on a Microsoft Excel document and analysed using EPI-info (Version 3.4.3) and Stata (Version 12). RESULTS: The average adherence by maternal verbal reports and unused returned medication were 97.3% among 213 infants and 94.0% among 204 infants respectively. When evaluated against plasma NVP concentration >100ng/ml among 37 infants, the true adherence of maternal verbal reports and unused returned medication were 87.7% and 71.3% respectively. The sensitivity and specificity of maternal verbal reports against a plasma nevirapine concentration of ≤ 100ng/ml to detect a missed dose in the previous 3 days were 75% and 78% (p=0.03) respectively. Overall, among infants who were classified as adherent by maternal verbal reports and unused returned medication, 88.4% and 87.4% of infants attained a nevirapine concentration above 100ng/ml respectively. CONCLUSION: Maternal verbal reports are a more reliable measure of adherence to infant antiretroviral prophylaxis in the first 6 weeks of life when compared to assessment of unused medication returned.
Evaluation of adherence measures of antiretroviral prophylaxis in HIV exposed infants in the first 6 weeks of life.
(BioMed Central., 2015) Desmond, Alicia Catherine.; Moodley, Dhayendre.; Connolly, Catherine A.; Castel, Sandra A.; Coovadia, Hoosen Mahomed.
Abstract available in pdf.
High prevalence and incidence of asymptomatic sexually transmitted infections during pregnancy and postdelivery in KwaZulu Natal, South Africa.
(Wolters Kluwer., 2015) Moodley, Dhayendre.; Moodley, Prashini.; Sebitloane, Hannah Motshedisi.; Soowamber, Deepak.; McNaughton-Reyes, Heather Luz.; Groves, Allison K.; Maman, Suzanne.
Abstract available in pdf.
HIV disease progression in the first year after delivery among african women followed in the HPTN 046 clinical trial.
(Lippincott Williams & Wilkins., 2013) Watts, Heather D.; Brown, Elizabeth R.; Maldonado, Yvonne.; Herron, Casey.; Chipato, Tsungai.; Reddy, Leanne.; Moodley, Dhayendre.; Nakabiito, Clemensia.; Manji, Karim.; Fawzi, Wafaie.; George, Kathleen.; Richardson, Paul.; Zwerski, Sheryl.; Coovadia, Hoosen Mahomed.; Fowler, Mary Glenn.
Background: Starting lifelong antiretroviral therapy (ART) in HIV-infected pregnant women may decrease HIV progression and transmission, but adherence after delivery may be difficult, especially for asymptomatic women. We evaluated disease progression among HIV-infected women not on ART with CD4⁺ lymphocyte counts above 200 cells per microliter at delivery. Methods: We analyzed risk of death, progression to AIDS (stage IV or CD4 < 200 cells per microliter), or to CD4⁺ count <350 1 year after delivery among postpartum women enrolled to a prevention of breastfeeding transmission trial using the Kaplan–Meier method. In the primary analysis, women were censored if ART was initiated. Results: Among 1285 women who were not WHO stage IV or less at 6 weeks postpartum, 49 (4.3%) progressed to stage IV/CD4 <200 cells per microliter or death by 1 year. Progression to CD4 <200 cells per microliter or death occurred among 16 (4.3%) of 441 women with CD4 count of 350–549 cells per microliter and 10 (1.6%) of 713 with CD4 counts >550 cells per microliter at delivery. CD4 <350 cells per microliter by 12 months postpartum occurred among 116 (37.0%) of 350 women with CD4 count 400–549 cells per microliter and 48 (7.4%) of 713 with CD4 count >550 cells per microliter at delivery. Conclusions: Progression to AIDS or CD4 count <350 cells per microliter is uncommon through 1 year postpartum for women with CD4 counts over 550 cells per microliter at delivery, but occurred in over one third of those with CD4 counts under 550 cells per microliter. ART should be continued after delivery or breastfeeding among women with CD4 counts <550 cells per microliter if follow-up and antiretroviral adherence can be maintained.
Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants.
(Pediatric Infectious Disease Journal, 2013) Fogel, Jessica M.; Mwatha, Anthony.; Brown, Elizabeth R.; Richardson, Paul.; Chipato, Tsungai.; Alexandre, Michel.; Moodley, Dhayendre.; Elbireer, Ali.; Mirochnick, Mark.; George, Kathleen.; Mofenson, Lynne Meryl.; Zwerski, Sheryl.; Eshleman, Susan H.; Coovadia, Hoosen Mahomed.
Background: The HIV Prevention Trials Network (HPTN) 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV infection despite prophylaxis. Methods: HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher exact tests were used to evaluate associations between categorical variables. Results: NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIVuninfected at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a nonnucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all 4 of those infants by 6 months of age (4/4 = 100%). In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate antiretroviral treatment developed NVP resistance (P = 0.003). Conclusions: Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.
Improving adolescent maternal health.
(South African Medical Association., 2015) Baxter, Cheryl.; Moodley, Dhayendre.
Abstract available in pdf.
Pharmaco-immunological-virological dynamics in intrapartum HIV-1 transmission (PIVD study)
(2009) Singh, Michelle.; Moodley, Dhayendre.; Moodley, Jagidesa.
Background: Multiple factors contribute to mother-to-child transmission (MTCT) of HIV-1, including virological, obstetric and biological factors. Other possible contributory determinants for high MTCT rates include immunological factors such as host genetics and viral genetic variations. Despite several therapeutic, prophylactic and obstetric interventions to reduce the proportion of infants infected during labour and delivery, mechanisms for intrapartum HIV-1 transmission remain elusive and current interventions, could, therefore remain sub-optimal. Much controversy has surrounded the correlation of HIV-1 RNA (viral load) in the systemic and genital compartments of women. The influence of short-term antiretroviral (ARV) drugs on genital tract HIV-1 is also unclear. At the time the present study was initiated, a regimen of maternal intrapartum and neonatal postpartum single-dose Nevirapine (sdNVP) was the standard of care for the prevention of mother-to-child transmission (PMTCT). In most low and middle-income countries, including South Africa, sdNVP has been documented as effective intrapartum HIV-1 prevention based on plasma pharmacokinetic levels, decreased viral loads (HIV-1 RNA) and reduced rates of intrapartum transmission, yet operational studies continue to report high intrapartum transmission rates despite the administration of sdNVP. As a result perinatal HIV-1 transmission remains a significant public health concern in several African countries. Aim: The primary aim of this study was to describe the pharmacological dynamics of Nevirapine in association with virological and immunological risk factors for intrapartum HIV-1 transmission in a South African PMTCT programme where sdNVP was the standard of care. Methods: Following regulatory approval from the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (UKZN), one hundred and twenty pregnant HIV-infected women who received the sdNVP regimen for prevention of mother-to-child HIV-1 transmission were enrolled between April-December 2006 at King Edward VIII Hospital (KEH) in Durban. Blood and cervicovaginal lavage (CVL) samples were collected from women at pre-NVP (during pregnancy) and post-NVP dosing (during labour/delivery). In addition to infant blood sampling at birth (post-NVP), postnatal infants were assessed at four and six weeks postnatally. Pharmacological laboratory investigations involved measurement of NVP drug concentration by Tandem Mass spectrophotometry. Virological investigations comprised HIV-1 RNA (viral load) quantitation, HIV-1 drug resistance testing (HIV-1 transmitting women only) and HIV-1 DNA PCR testing (infants only). Immunological investigations were only undertaken in a selected case-control subset of HIV-1 transmitting women and their infants. In this component, laboratory investigations included the determination of CCL3 and CCL3-L1 gene copy numbers, identification of single nucleotide polymorphisms (SNP’s) and haplotype characterisation of the CCL3 gene. All women were also screened for the presence of sexually transmitted infections (STI’s) during pregnancy. Results: One hundred and twenty women were enrolled onto this study. Of these, 110 women delivered 117 live infants (103 singletons and 7 twin pairs). Twelve (10.9%) women transmitted HIV-1 to their infants, while 95 (86.0%) were classified as non-transmitters. As a result of seven twin deliveries, the infant cohort comprised of 117 infants in total. Following two separate DNA PCR tests, HIV-1 infection was identified in 14 (11.9%) of study infants while the remaining 90 (76.9%) were exposed-uninfected. HIV infection status remained unknown for 13 infants due to infant demise (1.7%), lost to follow-up (7.7%) or study withdrawal (1.7%). During active labour (sampling that was best representative of the intrapartum phase) and within 20 hours of dosing, the median NVP concentration of 1070 ng/ml in the maternal systemic compartment was almost 44 times higher than the NVP levels detected in the genital compartment [24.5 ng/ml] (p < 0.001). NVP drug levels were below the 100 ng/ml therapeutic target in seven (13.7%) of 51 plasma and in all 39 CVL samples. While no significant association was found between NVP concentration in the systemic compartment and HIV-1 transmission (p = 0.4), this association was statistically significant in the genital compartment(p = 0.02). The median plasma NVP level detected among infants at birth was 83 times above the IC50 WT (10 ng/ml) and eight times higher than the 100 ng/ml therapeutic target for NVP. More than 71.0% of the infants achieved NVP drug levels above the therapeutic target. In general, higher levels of HIV-1 RNA (viral load) were observed in maternal plasma when compared to CVL. Following intrapartum sdNVP dosing, reduction in HIV-1 RNA levels did occur, however R80.0% of the women experienced no change to their HIV-1 RNA levels in both systemic and genital compartments during active labour. These findings were further supported by the strong correlation observed when comparing pre and post-NVP HIV-1 RNA levels in both maternal systemic [r = 0.81, p < 0.0001] and genital compartments [r = 0.80, p < 0.0001] during active labour. HIV-1 transmitting women had significantly higher viral loads than their non-transmitting counterparts in systemic and genital compartments, before and after intrapartum sdNVP administration. In terms of perinatal transmission this observation was only statistically significant for plasma (p = 0.02) and not CVL (p = 0.7). Maternal viral load was inversely correlated with maternal CD4 cell counts in both systemic and genital compartments. Almost 40.0% of women in this study had at least one type of STI detected during pregnancy. Maternal STI’s were detected in four (66.6%) intrapartum transmitting women and in 38 (38.8%) of non-transmitting women. No significant association was observed between the presence of maternal STI’s and the risk for intrapartum MTCT (p = 0.2,RR: 2.90, 95% CI: 0.60-15.40). The presence of maternal STI’s was associated with higher median viral loads in both systemic and genital compartments of all women, independent of intrapartum HIV-1 transmission. Despite trial-like conditions and optimal sdNVP dosing, the overall MTCT rate in this exclusively formula-fed cohort was 11.9%, of which 50.0% were in utero and 50.0% were intrapartum HIV-1 transmissions. In utero and intrapartum MTCT rates were 5.9% and 5.9% respectively. Discussion/Conclusion: Detectable CVL HIV-1 RNA that correlated well with plasma HIV-1 RNA, in conjunction with sub-optimal NVP drug concentration in maternal CVL during active labour, suggests that intrapartum HIV-1 infected women continue to act as reservoirs for both vertical and horizontal HIV-1 transmission throughout the duration of pregnancy. These findings confirm that the role of sdNVP in PMTCT was primarily one of infant prophylaxis. This was further supported by relatively unchanged maternal HIV-1 RNA (viral load) during active labour, in both systemic and genital compartments. Early identification of women who need highly active antiretroviral therapy (HAART), and initiation of such therapy as early as possible during pregnancy, not only benefits maternal health but remains the best prophylaxis against mother-to-child HIV-1 transmission. Universal access to HAART and improving strategies to optimize coverage of the current dual ARV regimen sdNVP and Zidovudine for PMTCT remain urgent research priorities in several resource-limited settings. Ongoing STI counseling, intensive screening/testing of women and their partners together promotion of condom usage, safer sex practices and aggressive STI treatment are simple interventions with tremendous impact for PMTCT in resource-limited settings.
Prevention of HIV-1 transmission through breastfeeding: efficacy and safety of maternal antiretroviral therapy versus infant nevirapine prophylaxis for duration of breastfeeding in HIV-1-infected women with high CD4 cell count (IMPAACT PROMISE): a randomized, open label, clinical trial.
(Wolters Kluwer., 2018) Flynn, Patricia M.; Taha, Taha E.; Cababasay, Mae.; Fowler, Mary Glenn.; Mofenson, Lynne Meryl.; Owor, Maxensia.; Fiscus, Susan A.; Stranix-Chibanda, Lynda.; Coutsoudis, Anna.; Gnanashanmugam, Devasena.; Chakhtoura, Nahida.; McCarthy, Katie.; Mukuzunga, Cornelius.; Makanani, Bonus.; Moodley, Dhayendre.; Nematadzira, Teacler.; Kusakara, Bangini.; Patil, Sandesh.; Vhembo, Tichaona.; Bobat, Raziya Ahmed.; Mmbaga, Blandina T.; Masenya, Maysseb.; Nyati, Mandisa M.; Theron, Gerhard.; Mulenga, Helen.; Butler, Kevin.; Shapiro, David E.
Abstract available in pdf.