Search

Please cite this paper as: Dorton B, Mulindwa J, Li M, Chintu N, Chibwesha C, Mbewe F, Frenkel L, Stringer J, Chi B. CD4 cell count and risk for antiretroviral drug resistance among women using peripartum nevirapine for perinatal HIV prevention. BJOG 2011;118:495-499. To determine the association between the antenatal CD4 cell count and the development of viral drug resistance following the use of peripartum nevirapine (NVP) for perinatal HIV prevention. Secondary analysis of data from a previously conducted randomised controlled trial. Lusaka, Zambia. HIV-positive pregnant women. We analysed the data from a clinical trial of single-dose tenofovir/emtricitabine (TDF/FTC) to reduce viral drug resistance associated with peripartum NVP. The trial population was categorised according to antenatal CD4 cell count (200-350, 351-500 and >500 cells/μl). The relative risk for acquiring drug resistance, determined by consensus sequencing and oligonucleotide ligation assay (OLA), was estimated using multivariable logistic regression. Of the 397 study participants, 119 (30%) had a CD4 count of 200-350 cells/μl, 135 (34%) had a CD4 count of 351-500 cells/μl and 143 (36%) had a CD4 count of >500 cells/μl. Among women receiving no intervention, the risk for drug resistance appeared to increase as the CD4 cell count decreased. Participants with CD4 cell counts of 200-350 cells/μl randomised to the study arm had the lowest risk, suggesting a higher efficacy of the intervention within this stratum. These results were consistent at 2 and 6 weeks, regardless of how drug resistance was measured. Women with CD4 cell counts of 200-350 cells/μl may be at increased risk for viral drug resistance following the use of peripartum NVP. Given the high prevalence of NVP resistance and the clear benefits of treatment, antiretroviral therapy should be initiated among pregnant women with CD4 cell counts of ≤350 cells/μl. [ABSTRACT FROM AUTHOR]

Abstract Background There is great interest in providing primary eye care (PEC) through integration into primary health care (PHC). However, there is little evidence of the productivity of PHC workers in offering primary eye care after training and integration, and there is need to compare their effectiveness to alternative methods. The current study compared the effectiveness of trained Health Surveillance Assistants (HSAs) versus trained volunteer Key Informants (KIs) in identifying blind children in southern Malawi. Methods A cluster community based study was conducted in Mulanje district, population 435 753. Six clusters each with a population of approximately 70 000 to 80 000, 42% of whom were children were identified and randomly allocated to either HSA or KI training. From each cluster 20 HSAs or 20 KIs were selected for training. Training emphasized the causes of blindness in children and their management, and how to identify and list children suspected of being blind. HSAs and KIs used multiple methods (door to door, school screening, health education talks, village announcements, etc.) to identify children. Using the World Health Organization (WHO) estimates (eight blind children per 10 000 children); approximately 144 to 162 blind children were expected in the chosen clusters. Listed children were brought to a centre within the community where they were examined by an ophthalmologist and findings recorded using the WHO form for examining blindness in children. Results A total of 59 HSAs and 64 KIs were trained. HSAs identified five children of whom two were confirmed as blind (one blind child per 29.5 HSAs trained). On the other hand, the KIs identified a total of 158 children of whom 20 were confirmed blind (one blind child per 3.2 KIs trained). More blind boys than girls were identified (77.3% versus 22.7%) respectively. Conclusion Key Informants were much better at identifying blind children than HSAs, even though both groups identified far fewer blind children compared with WHO estimates. HSAs reported lack of time as a major constraint in identifying blind children. Based on these findings using HSAs for identifying blind children would not be successful in Malawi. Gender differences need to be addressed in all childhood blindness programs to counteract the imbalance.

Background: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART)., Methods: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months., Results: Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22-30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6-2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15-34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16-43%) infants in the POC group vs 7 (19%; 6-32%) in the SOC group (RR: 1.56; .7-3.50)., Conclusions: POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes., Clinical Trials Registration: This trial is registered at https://clinicaltrials.gov (NCT02682810)., Competing Interests: Potential conflicts of interest. J. S. A. S. reports support from the Bill and Melinda Gates Foundation, outside the submitted work. All other authors report no potential conflicts. The authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Introduction: Neonatal mortality associated with preterm birth can be reduced with antenatal corticosteroids (ACS), yet <10% of eligible pregnant women in low-middle income countries. The inability to accurately determine gestational age (GA) leads to under-identification of high-risk women who could receive ACS or other interventions. To facilitate better identification in low-resource settings, we developed a color-coded tape for uterine height (UH) measurement and estimated its accuracy identifying preterm pregnancies., Methods: We designed a series of colored-coded tapes with segments corresponding to UH measurements for 20-23.6 weeks, 24.0-35.6 weeks, and >36.0 weeks GA. In phase 1, UH measurements were collected prospectively in the Democratic Republic of Congo, India and Pakistan, using distinct tapes to address variation across regions and ethnicities. In phase 2, we tested accuracy in 250 pregnant women with known GA from early ultrasound enrolled at prenatal clinics in Argentina, India, Pakistan and Zambia. Providers masked to the ultrasound GA measured UH. Receiver operating characteristics (ROC) analysis was conducted., Results: 1,029 pregnant women were enrolled. In all countries the tapes were most effective identifying pregnancies between 20.0-35.6 weeks, compared to the other GAs. The ROC areas under the curves and 95% confidence intervals were: Argentina 0.69 (0.63, 0.74); Zambia 0.72 (0.66, 0.78), India 0.84 (0.80, 0.89), and Pakistan 0.83 (0.78, 0.87). The sensitivity and specificity (and 95% confidence intervals) for identifying pregnancies between 20.0-35.6 weeks, respectively, were: Argentina 87% (82%-92%) and 51% (42%-61%); Zambia 91% (86%-95%) and 50% (40%-60%); India 78% (71%-85%) and 89% (83%-94%); Pakistan 63% (55%-70%) and 94% (89%-99%)., Conclusions: We observed moderate-good accuracy identifying pregnancies ≤ 35.6 weeks gestation, with potential usefulness at the community level in low-middle income countries to facilitate the preterm identification and interventions to reduce preterm neonatal mortality. Further research is needed to validate these findings on a population basis.

Objective: To determine the association between the antenatal CD4(+) cell count and the development of viral drug resistance following the use of peripartum nevirapine (NVP) for perinatal HIV prevention., Design: Secondary analysis of data from a previously conducted randomised controlled trial., Setting: Lusaka, Zambia., Population: HIV-positive pregnant women., Methods: We analysed the data from a clinical trial of single-dose tenofovir/emtricitabine (TDF/FTC) to reduce viral drug resistance associated with peripartum NVP. The trial population was categorised according to antenatal CD4(+) cell count (200-350, 351-500 and >500 cells/μl)., Main Outcome Measures: The relative risk for acquiring drug resistance, determined by consensus sequencing and oligonucleotide ligation assay (OLA), was estimated using multivariable logistic regression., Results: Of the 397 study participants, 119 (30%) had a CD4(+) count of 200-350 cells/μl, 135 (34%) had a CD4(+) count of 351-500 cells/μl and 143 (36%) had a CD4(+) count of >500 cells/μl. Among women receiving no intervention, the risk for drug resistance appeared to increase as the CD4(+) cell count decreased. Participants with CD4(+) cell counts of 200-350 cells/μl randomised to the study arm had the lowest risk, suggesting a higher efficacy of the intervention within this stratum. These results were consistent at 2 and 6 weeks, regardless of how drug resistance was measured., Conclusions: Women with CD4(+) cell counts of 200-350 cells/μl may be at increased risk for viral drug resistance following the use of peripartum NVP. Given the high prevalence of NVP resistance and the clear benefits of treatment, antiretroviral therapy should be initiated among pregnant women with CD4(+) cell counts of ≤350 cells/μl., (© 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.)

A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of <25-50%. We conducted a randomized trial of single-dose TDF/FTC added to peripartum nevirapine to reduce drug resistance associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs). To detect mutations for NNRTIs comprising > or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.

Objective: To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission., Methods: In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens., Results: Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8)., Conclusions: Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.