Published randomized clinical trials evaluating treatment strategies in infants and young children with HIV.

<p>ZDV, zidovudine; 3TC, lamivudine; NVP, nevirapine; LPV/r, lopinavir/ritonavir; NFV, nelfinavir; d4T, stavudine; CDC, Centers for Disease Control; DSMB, Data and Safety Monitoring Board.</p

*Longitudinal samples from women in the HIV Prevention Trials Network (HIVNET) 012 trial and HIVNET 012 follow-up study were analyzed using the BED-Capture enzyme immunoassay (BED) [<b>8</b>] and an antibody avidity assay based on the BioRad 1/2 + O ELISA test (avidity) [<b>9</b>].

<p>Baseline samples were collected near the time of delivery in the HIVNET 012 trial. Data from the baseline samples is shaded, as well as data from follow-up visits where a woman was pregnant (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0013259#s2" target="_blank">Methods</a>). Results from the BED and avidity assays that indicate recent infection (BED: results OD-n<0.8; for avidity: results <40%) are shown in bold text. Results are shown for baseline samples (obtained in the HIVNET 012 trial from the time of delivery or 7 days after delivery), and for samples collected 3, 4, and 5 years later (3Y, 4Y, 5Y). ^aThese women were identified as falsely incident at follow-up using the BED assay; two of these women had subtype A infection and two had subtype D infection. ^bThese women may have had incident infection in the HIVNET 012 trial. ^cThese samples were obtained when women were on antiretroviral therapy.</p

(a) Predicted drug susceptibility at rebound and (b) change in susceptibility over a median 2 years in those randomised to 2NRTI+NNRTI maintenance (<i>n</i> = 12).

<p>Abbreviations: 3TC, lamivudine; ABC, abacavir; D4T, stavudine; DDI, didanosine; EFV, efavirenz; ETR, etravirine; FTC, emtricitabine; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NVP, nevirapine; RPV, rilpivirine; TDF, tenofovir; ZDV, zidovudine.</p

Predicted NRTI and NNRTI susceptibility in 2NRTI+NNRTI with VL >1,000 copies/ml after median 4 years on ART (<i>n</i> = 110).

<p>Note: risk differences and 95% CI between CD4 monitoring versus no CD4 monitoring with intermediate/high-level resistance were 3TC 1.0% [−13.4% to +15.4%], ABC 1.4% [−15.5% to +18.2%], ZDV 5.0% [−5.9% to +15.9%], DDI 1.1% [−16.1% to +18.3%], D4T 8.0% [−6.3% to +22.3%], FTC 1.0% [−13.4% to +15.4%], TDF 7.7% [−5.9% to +21.4%], NVP 4.7% [−14.6% to +5.2%], EFV 1.3% [−12.2% to +9.5%], ETR 0.0% [−18.1% to +18.2%], and RPV 11.6% [−28.6% to +5.5%]. Abbreviations: ART, antiretroviral therapy; CDM, clinically driven monitoring; LCM, laboratory plus clinical monitoring; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; VL, viral load.</p

Flow diagram of children included in virological analyses.

<p>* Results presented in main text. ** Results presented in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1002432#pmed.1002432.s008" target="_blank">S1 Appendix</a>. † 97% of children enrolled after 29 May 2008. Abbreviations: ART, antiretroviral therapy; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; VL, viral load.</p

VL suppression in 2NRTI+NNRTI maintenance regimen after median 4 years on ART.

<p>Note: 95% CI for risk differences were <80 copies/ml [−4.4% to +8.0%], <200 copies/ml [−4.5% to +7.5%], <400 copies/ml [−3.6% to +8.2%], <1,000 copies/ml [−3.4% to +8.0%], <5,000 copies/ml [−1.1% to +8.7%], and <10,000 copies/ml [−0.8% to +8.4%]. Abbreviations: ART, antiretroviral therapy; CDM, clinically driven monitoring; LCM, laboratory plus clinical monitoring; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; VL, viral load.</p

Characteristics at ART initiation of all children in the trial; children randomised to 2NRTI+NNRTI followed in the longitudinal cohort; and those subsequently experiencing VL blips, pLLVL, and/or rebound.

<p>Characteristics at ART initiation of all children in the trial; children randomised to 2NRTI+NNRTI followed in the longitudinal cohort; and those subsequently experiencing VL blips, pLLVL, and/or rebound.</p

VL response in 204 children randomised to 2NRTI+NNRTI initially responding to ART.

<p>(a) VL classification by week on ART. (b) Mean VL during pLLVL and rebound. Note: (a) carrying forwards current state where VL was missing; carrying backwards, “VL response”, where week 4 VL was missing (<i>n</i> = 16). Abbreviations: ART, antiretroviral therapy; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; pLLVL, persistent low-level viral load; VL, viral load.</p

Additional file 1 of Strengthening capacity of health workers to diagnose birth defects in Ugandan hospitals from 2015 to 2021

Supplementary Material

Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060

<div><p>Background</p><p>HIV and malaria geographically overlap. HIV protease inhibitors kill <i>malaria</i> parasites <i>in vitro</i> and <i>in vivo</i>, but further evaluation in clinical studies is needed.</p><p>Methods</p><p>Thirty-one children from Malawi aged 4–62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor.</p><p>Results</p><p>We found an association between increased time to recurrent positive BS, but not CCM, when anti-malarial treatment and LPV-rtv based ART were used concurrently and when accounting for a LPV-rtv and antimalarial treatment interaction (adjusted HR 0.39; 95% CI (0.17,0.89); p = 0.03).</p><p>Conclusions</p><p>LPV-rtv in combination with malaria treatment was associated with lower risk of recurrent positive BS, but not CCM, in HIV-infected children. Larger, randomized studies are needed to confirm these findings which may permit ART optimization for malaria-endemic settings.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00719602" target="_blank">NCT00719602</a></p></div