HIV and urethritis: time required for antiretroviral therapy to suppress HIV in semen.

OBJECTIVES: To examine the time required to suppress HIV in the genital tract with antiretroviral therapy (ART) in men with urethritis. DESIGN: An observational cohort study. METHODS: Men with HIV and urethritis not on ART were enrolled at an STI clinic in Malawi and offered to initiate ART. Blood and semen samples were collected pretreatment and at 1, 2, 4, 8, 12 and 24 weeks posturethritis treatment. Median viral loads (VLs) were calculated by ART initiation groups: 'within 1 week', 'between 1 and 4 weeks' and 'no ART before 4 weeks', based on the men's choice about whether or not to initiate ART. The presence of ART at each visit was confirmed by bioanalytical methods. FINDINGS: Between January 2017 and November 2018, 74 men presented with urethritis and HIV and were confirmed ART naive. The median age was 32 years. Forty-one (55% of men) initiated ART within 1 week; 12 (16%) between 1 and 4 weeks; and 21 (28%) did not initiate ART by week 4. Within the 1 week group, median VL was suppressed within 4 weeks in both semen and blood. Among the 1-4 weeks group, VL was suppressed within 4 weeks in semen and 5 weeks in blood. Among the no ART before 4 weeks group, VL in semen declined within the first 4 weeks but remained unsuppressed through week 24, and there was no significant decline in blood HIV. CONCLUSION: Treatment of urethritis and prompt initiation of ART with counseling for safer sex for at least one month is a critical measure to reduce transmission of HIV.

Infectious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Virus in Symptomatic Coronavirus Disease 2019 (COVID-19) Outpatients: Host, Disease, and Viral Correlates.

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection. METHODS: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. RESULTS: Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]: .04, .36; P = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI: .71, .88 per day; P < .0001). CONCLUSIONS: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. CLINICAL TRIALS REGISTRATION: NCT04405570.

A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus.

There is an urgent need for an effective, oral, direct-acting therapeutic to block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent progression to severe coronavirus disease 2019 (COVID-19). In a phase 2a double-blind, placebo-controlled, randomized, multicenter clinical trial, we evaluated the safety, tolerability, and antiviral efficacy of the nucleoside analog molnupiravir in 202 unvaccinated participants with confirmed SARS-CoV-2 infection and symptom duration <7 days. Participants were randomized 1:1 to receive molnupiravir (200 mg) or placebo and then 3:1 to receive molnupiravir (400 or 800 mg) or placebo, orally twice daily for 5 days. Antiviral activity was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) for SARS-CoV-2 RNA in nasopharyngeal swabs. Infectious virus was assessed by inoculation of cultured Vero cells with samples from nasopharyngeal swabs and was detected by RT-PCR. Time to viral RNA clearance (primary endpoint) was decreased in the 800-mg molnupiravir group (median 14 days) compared to the placebo group (median 15 days) (log rank P value = 0.013). Of participants receiving 800 mg of molnupiravir, 92.5% achieved viral RNA clearance compared with 80.3% of placebo recipients by study end (4 weeks). Infectious virus (secondary endpoint) was detected in swabs from 1.9% of the 800-mg molnupiravir group compared with 16.7% of the placebo group at day 3 of treatment (P = 0.016). At day 5 of treatment, infectious virus was not isolated from any participants receiving 400 or 800 mg of molnupiravir compared with 11.1% of placebo recipients (P = 0.034 and 0.027, respectively). Molnupiravir was well tolerated across all doses.

Machine Learning Algorithms Using Routinely Collected Data Do Not Adequately Predict Viremia to Inform Targeted Services in Postpartum Women Living With HIV.

BACKGROUND: Adherence to antiretroviral treatment (ART) among postpartum women with HIV is essential for optimal health and prevention of perinatal transmission. However, suboptimal adherence with subsequent viremia is common, and adherence challenges are often underreported. We aimed to predict viremia to facilitate targeted adherence support in sub-Saharan Africa during this critical period. METHODS: Data are from PROMISE 1077BF/FF, which enrolled perinatal women between 2011 and 2014. This analysis includes postpartum women receiving ART per study randomization or country-specific criteria to continue from pregnancy. We aimed to predict viremia (single and confirmed events) after 3 months on ART at >50, >400, and >1000 copies/mL within 6-month intervals through 24 months. We built models with routine clinical and demographic data using the least absolute shrinkage and selection operator and SuperLearner (which incorporates multiple algorithms). RESULTS: Among 1321 women included, the median age was 26 years and 96% were in WHO stage 1. Between 0 and 24 months postpartum, 42%, 31%, and 28% of women experienced viremia >50, >400, and >1000 copies/mL, respectively, at least once. Across models, the cross-validated area under the receiver operating curve ranged from 0.74 [95% confidence interval (CI): 0.72 to 0.76] to 0.78 (95% CI: 0.76 to 0.80). To achieve 90% sensitivity predicting confirmed viremia >50 copies/mL, 64% of women would be classified as high risk. CONCLUSIONS: Using routinely collected data to predict viremia in >1300 postpartum women with HIV, we achieved moderate model discrimination, but insufficient to inform targeted adherence support. Psychosocial characteristics or objective adherence metrics may be required for improved prediction of viremia in this population.

Molnupiravir, an Oral Antiviral Treatment for COVID-19.

BACKGROUND: Easily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 ( ClinicalTrials.gov NCT04405570 ). METHODS: Eligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. RESULTS: Among 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. CONCLUSIONS: Molnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

Infectious SARS-CoV-2 Virus in Symptomatic COVID-19 Outpatients: Host, Disease, and Viral Correlates.

BACKGROUND: While SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection. METHODS: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. RESULTS: Among 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001). CONCLUSIONS: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. CLINICALTRIALSGOV IDENTIFIER: NCT04405570.

Effects of Urethritis on Human Immunodeficiency Virus (HIV) in Semen: Implications for HIV Prevention and Cure.

BACKGROUND: Prior to the widespread availability of antiretroviral therapy (ART), men living with human immunodeficiency virus (HIV) with urethritis had increased concentrations of HIV in semen. This study aims to better evaluate HIV shedding in men with urethritis receiving ART, and its implications for the cure of HIV. METHODS: Men living with HIV with urethritis taking ART ≥12 weeks were enrolled at a sexually transmitted infections clinic in Lilongwe, Malawi. Study follow-up included visits at 1, 2, 4, 8, 12, 24, 36, and 48 weeks after urethritis diagnosis and treatment. Matched blood and semen samples were collected at all visits, and all additional episodes of urethritis were followed with extra visits 1, 2, and 4 weeks after treatment. RESULTS: There were 111 men enrolled in the study between January 2017-March 2019, and 77 (69%) were suppressed in the blood (<400 copies/mL). Among the 77 men, 87 episodes of urethritis were evaluated during follow-up. Of the 87 episodes, 15 episodes (17%) had instances of seminal viral shedding ≥400 copies/mL despite viral suppression in the blood. During nonurethritis follow-up, ≤6% of men at each visit had a viral load ≥400 copies/mL in the semen while maintaining viral suppression in the blood. CONCLUSIONS: An HIV cure requires the elimination of HIV from every body compartment, but available ART does not currently accomplish this. Our study highlights the male genital tract as a local source of HIV that can be reversibly activated. A better understanding of this phenomenon is important to advance the HIV cure field.

Individual and Composite Adverse Pregnancy Outcomes in a Randomized Trial on Isoniazid Preventative Therapy Among Women Living With Human Immunodeficiency Virus.

BACKGROUND: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1078, a randomized noninferiority study designed to compare the safety of starting isoniazid preventive therapy (IPT) in women living with human immunodeficiency virus (HIV) either during pregnancy or after delivery, showed that IPT during pregnancy increased the risk of composite adverse pregnancy outcomes, but not individual outcomes. Many known factors are associated with adverse pregnancy outcomes: these factors' associations and effect modifications with IPT and pregnancy outcomes were examined. METHODS: Pregnant women living with HIV from 8 countries with tuberculosis incidences >60/100 000 were randomly assigned to initiate 28 weeks of IPT either during pregnancy or at 12 weeks after delivery. Using univariable and multivariable logistic regression and adjusting for factors associated with pregnancy outcomes, composite and individual adverse pregnancy outcome measures were analyzed. RESULTS: This secondary analysis included 925 mother-infant pairs. All mothers were receiving antiretrovirals. The adjusted odds of fetal demise, preterm delivery (PTD), low birth weight (LBW), or a congenital anomaly (composite outcome 1) were 1.63 times higher among women on immediate compared to deferred IPT (95% confidence interval [CI], 1.15-2.31). The odds of fetal demise, PTD, LBW, or neonatal death within 28 days (composite outcome 2) were 1.62 times higher among women on immediate IPT (95% CI, 1.14-2.30). The odds of early neonatal death within 7 days, fetal demise, PTD, or LBW (composite outcome 3) were 1.74 times higher among women on immediate IPT (95% CI, 1.22-2.49). CONCLUSIONS: We confirmed higher risks of adverse pregnancy outcomes associated with the initiation of IPT during pregnancy, after adjusting for known risk factors for adverse pregnancy outcomes.

The impact of short term Antiretroviral Therapy (ART) interruptions on longer term maternal health outcomes-A randomized clinical trial.

BACKGROUND: Given well documented challenges faced by pregnant women living with HIV taking lifetime ART, it is critical to understand the impact of short-term ART exposure followed by treatment interruption on maternal health outcomes. METHODS: HIV+ breastfeeding (BF) and Formula Feeding (FF) women with CD4 counts > 350 cells/mm3, enrolled in the 1077BF/1077FF PROMISE trial were followed to assess the effect of ART during pregnancy and breastfeeding respectively. The first analysis compared ART use limited to the antepartum period (AP-only) relative to women randomized to Zidovudine. The second analysis included women with no pregnancy combination ART exposure; and compared women randomized to either ART or no ART during postpartum (PP-only). Both analyses included follow-up time beyond breastfeeding period. The primary outcome was progression to AIDS and/or death. Secondary outcomes included adverse events and HIV-related events. RESULTS: 3490 and 1137 HIV+ women were enrolled from 14 sites in Africa and India from April 2011 through September 2014 in cohort AP-only and PP-only, respectively. Most were Black African (96%); median age was 27 years; 97% were WHO Clinical Stage I; and most had a screening CD4 count ≥500 cells/mm3 (78%). The rate of progression to AIDS and/or death was similar and low across all comparison arms (AP comparison, HR = 1.14, 95%CI (0.44, 2.96), p-value = 0.79). In the PP-only cohort, the rate of WHO stage 2-3 events was lower for women randomized to ART(HR = 0.65, 95% CI 0.42, 1.01, p-value = 0.05). CONCLUSION: The incidence of AIDS and/or death was low in pregnant/postpartum HIV+ women with highCD4 cell counts for all comparison arms. This provides some reassurance that there were limited consequences for short term ART interruption in this group of asymptomatic HIV+ women during up to 4 years of follow up; and underscores that even short term ART exposure postpartum may reduce the risk of WHO grade 2-3 disease progression.

Predictors of Viremia in Postpartum Women on Antiretroviral Therapy.

BACKGROUND: HIV-infected, postpartum women on antiretroviral therapy (ART) have high rates of viremia. We examined predictors of postpartum viremia in the PROMISE study. METHODS: Women with pre-ART CD4 T-cell counts ≥400 cells/mm who started ART during pregnancy were randomized postpartum to continue ART (CTART) or discontinue ART (DCART). Viral load and self-reported adherence were collected every 12 weeks, up to 144 weeks. Women in DCART reinitiated therapy when clinically indicated. Viremia was defined as 2 consecutive viral loads >1000 copies/mL after 24 weeks on ART. Adherence was dichotomized as missing versus not missing ART doses in the past 4 weeks. Predictors of viremia were examined using Cox proportional hazards regression with adherence as a time-varying covariate. RESULTS: Among 802 women in the CTART arm, median age at entry was 27 years and median CD4 T-cell count 696 cells/mm. Of 175 women in CTART with viremia (22%), 141 had resistance data, and 12% had resistance to their current regimen. There was an estimated 0.12 probability of viremia by week 48 and 0.25 by week 144. Predictors of viremia included missed ART doses within the past 4 weeks, younger age, shorter duration of pre-entry ART, and being from the South American/Caribbean region. Of 137 women in DCART who reinitiated therapy, probability of viremia was similar to CTART (0.24 by week 96; 0.27 by week 144). CONCLUSIONS: Rates of postpartum viremia are high and viremia is more likely in younger postpartum women who start ART later in pregnancy. Interventions should target these higher-risk women.

Long-term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation.

BACKGROUND: Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola virus disease (EVD) survivors. However, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms. METHODS: The presence and patterns of 8 cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors who participated in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation. RESULTS: At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least 1 new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors, with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache, while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up. CONCLUSIONS: Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.

CYP2B6 genotype-directed dosing is required for optimal efavirenz exposure in children 3-36 months with HIV infection.

OBJECTIVES: To determine safety-specific, efficacy-specific and genotypic-specific dose requirements of efavirenz (EFV) in children aged 3 to less than 36 months with HIV infection. DESIGN: IMPAACT P1070 was a 24-week prospective cohort trial of EFV (as open capsules) and two nucleoside reverse transcriptase inhibitors in children with HIV infection 3 to less than 36 months without tuberculosis (Cohort 1). METHODS: CYP2B6 G516T genotype was determined, and intensive pharmacokinetics was performed at week 2. EFV dose was adjusted if outside the target area under the curve (AUC) 35-180 µg*h/ml. Pharmacokinetic and CYP2B6 G516T genotype data were used to model EFV exposures based on Food and Drug Administration (FDA)-approved doses. RESULTS: Forty-seven participants, median age 19 months, initiated the study regimen with 24 weeks median follow-up; 38 516GG/GT and 9 516TT genotypes. Initially, median EFV AUC was higher in 516TT vs. 516GG/GT (median 490 vs. 107 µg*h/ml; P = 0.0001) with all 516TT above AUC target. Following an amendment that reduced the 516TT EFV dose by 75%, pharmacokinetic modeling predicted that 83% of participants met the AUC target (31/38 516GG/GT, 8/9 516TT). In contrast, modeling using P1070 data predicted that FDA-approved doses would produce subtherapeutic AUCs in almost one-third of participants with 516GG/GT and excessive AUCs in more than 50% with 516TT genotypes. CONCLUSION: CYP2B6 G516T genotype strongly influences EFV exposures in this age group. Genotype-directed dosing yields therapeutic EFV concentrations and appears to outperform other dosing approaches.

Ebola Virus Ribonucleic Acid Detection in Semen More Than Two Years After Resolution of Acute Ebola Virus Infection.

Among 149 men who survived Ebola virus disease (EVD) and donated semen 260-1016 days after EVD onset, Ebola virus (EBOV) ribonucleic acid (RNA) was detected in 13 (9%). Of 137 men who donated semen 2 years after EVD onset, 11 (8%) had an EBOV RNA-positive specimen. The mechanism underlying the persistence of EBOV RNA in semen is unclear, and it is unclear whether the detection of viral RNA represents the presence of infectious virus.

Validation of the Cepheid GeneXpert for Detecting Ebola Virus in Semen.

BACKGROUND: Ebola virus (EBOV) RNA persistence in semen, reported sexual transmission, and sporadic clusters at the end of the 2013-2016 epidemic have prompted recommendations that male survivors refrain from unprotected sex unless their semen is confirmed to be EBOV free. However, there is no fully validated assay for EBOV detection in fluids other than blood. METHODS: The Cepheid Xpert Ebola assay for EBOV RNA detection was validated for whole semen and blood using samples obtained from uninfected donors and spiked with inactivated EBOV. The validation procedure incorporated standards from Clinical and Laboratory Standards Institute and Good Clinical Laboratory Practices guidelines for evaluating molecular devices for use in infectious disease testing. RESULTS: The assay produced limits of detection of 1000 copies/mL in semen and 275 copies/mL in blood. Limits of detection for both semen and blood increased with longer intervals between collection and testing, with acceptable results obtained up to 72 hours after specimen collection. CONCLUSIONS: The Cepheid Xpert Ebola assay is accurate and precise for detecting EBOV in whole semen. A validated assay for EBOV RNA detection in semen informs the care of male survivors of Ebola, as well as recommendations for public health.

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

BACKGROUND: Randomized-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. METHODS: We 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. RESULTS: The 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 was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. CONCLUSIONS: Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).

Nevirapine resistance in human immunodeficiency virus type 1-positive infants determined using dried blood spots stored for up to six years at room temperature.

Dried blood spots that had been stored ambiently for 3 to 6 years lost approximately 1 log(10) of human immunodeficiency virus type 1 (HIV-1) RNA, but the majority could still be genotyped for resistance. Nevirapine resistance was found in 7/16 (43.5%) HIV-1-positive HIVNET 024 infants at 4 to 6 weeks, but no resistance was found at other time points.