Median Human Immunodeficiency Virus RNA Level Research Articles

In Utero Tenofovir Exposure Is not Associated With Fetal Long Bone Growth.

Despite widespread use of tenofovir disoproxil fumarate (TDF) in pregnant and breastfeeding women, few data exist on fetal bone development after in utero TDF exposure. We evaluated fetal long bone growth in human immunodeficiency virus (HIV)-infected pregnant woman/fetus dyads in Cape Town, South Africa. Women were recruited from primary care antenatal services and underwent ultrasonography to determine femur (FLZ) and humerus (HLZ) length z scores. The duration of in utero TDF exposure was calculated in weeks. Linear regression models were applied to assess the associations between the duration of in utero TDF exposure and change in FLZ and HLZ. A total of 646 woman/fetus dyads contributed 1376 ultrasonographic scans to this analysis: 132 dyads with ≥25 weeks, 326 with 10-24 weeks, and 188 with <10 weeks of TDF exposure. Women receiving TDF for ≥25 weeks were older than those receiving TDF for 10-24 or <10 weeks (median age, 31 vs 28 and 28 years, respectively; P < .01), and had lower HIV RNA levels (median log10 HIV RNA level, 1.59 vs 4.08 and 3.83, respectively; P < .01). Throughout gestation, overall median FLZ and HLZ were 0.30 (interquartile range, -0.03 to 0.63) and 0.22 (-0.26 to 0.59) respectively. In multivariate analysis, there was no association between duration of in utero TDF exposure per 1-week increment and change in FLZ (ß = .00; P = .51) or change in HLZ (ß = .00; P = .40). Results were similar using mixed-effects models. Although longer follow-up is needed, these in utero data are reassuring and support the continued use of TDF in pregnancy.

Differences in HIV Burden and Immune Activation within the Gut of HIV‐Positive Patients Receiving Suppressive Antiretroviral Therapy

The gut is a major reservoir for human immunodeficiency virus (HIV) in patients receiving antiretroviral therapy (ART). We hypothesized that distinct immune environments within the gut may support varying levels of HIV. In 8 HIV-1-positive adults who were receiving ART and had CD4(+) T cell counts of >200 cells/μL and plasma viral loads of <40 copies/mL, levels of HIV and T cell activation were measured in blood samples and endoscopic biopsy specimens from the duodenum, ileum, ascending colon, and rectum. HIV DNA and RNA levels per CD4(+) T cell were higher in all 4 gut sites compared with those in the blood. HIV DNA levels increased from the duodenum to the rectum, whereas the median HIV RNA level peaked in the ileum. HIV DNA levels correlated positively with T cell activation markers in peripheral blood mononuclear cells (PBMCs) but negatively with T cell activation markers in the gut. Multiply spliced RNA was infrequently detected in gut, and ratios of unspliced RNA to DNA were lower in the colon and rectum than in PBMCs, which reflects paradoxically low HIV transcription, given the higher level of T cell activation in the gut. HIV DNA and RNA are both concentrated in the gut, but the inverse relationship between HIV DNA levels and T cell activation in the gut and the paradoxically low levels of HIV expression in the large bowel suggest that different processes drive HIV persistence in the blood and gut. ClinicalTrials.gov identifier: NCT00884793 (PLUS1).

Discordance Between Cerebral Spinal Fluid and Plasma HIV Replication in Patients with Neurological Symptoms Who Are Receiving Suppressive Antiretroviral Therapy

We report data on 11 patients with neurological symptoms and human immunodeficiency virus (HIV) cerebrospinal fluid (CSF) viremia contrasting with suppressed plasma HIV RNA during receipt of combined antiretroviral therapy. We retrospectively identified instances of central nervous system (CNS) symptoms in patients who had been receiving stable combination antiretroviral therapy. Discordance between plasma and CSF HIV RNA levels was defined by any detectable CSF HIV RNA level >200 copies/mL while plasma levels were <50 copies/mL or by a CSF HIV RNA level that was 1 log greater than the plasma HIV RNA level. Eleven patients had experienced acute or subacute neurological symptoms. All but one patient had CSF pleocytosis and/or elevated protein levels. The median CSF HIV RNA level was 880 copies/mL (range, 558-12,885 copies/mL). Patients had been receiving stable combination antiretroviral therapy for a median of 13 months (range, 10-32 months). Eight of 11 patients had a plasma HIV RNA level <50 copies/mL, and 3 had plasma HIV RNA blips with their CSF HIV RNA level >1 log higher than their plasma HIV RNA level. Resistance-associated mutations were detected in 7 of 8 CSF HIV RNA genotypic strains. The median number of resistance-associated mutations was 6 (range, 2-8) to nucleoside reverse-transcriptase inhibitors and 3 (range, 1-9) to protease inhibitors. One patient had a virus harboring nonnucleoside reverse-transcriptase inhibitor mutations. The median central nervous system penetration-effectiveness (CPE) rank was 2 (range, 1-3), and 5 patients had a CPE 1.5. After antiretroviral therapy optimization based on genotypes and CPE, all patients clinically improved, with normalization of CSF. Despite successful suppression of plasma viremia with antiretroviral therapy, HIV may replicate in CSF, with development of CSF HIV resistance resulting in acute or subacute neurological manifestations.

Factors Associated with the Selection of Mutations Conferring Resistance to Protease Inhibitors (PIs) in PI-Experienced Patients Displaying Treatment Failure on Darunavir

The objective of this study was to characterize the mutations selected by darunavir (DRV) use in protease inhibitor (PI)-experienced patients and the associated factors. We analyzed treatment failure in 54 PI-experienced human immunodeficiency virus (HIV)-infected patients on a DRV- and ritonavir-containing regimen. Viral genotyping was carried out at the baseline, at between 1 and 3 months of treatment, and at between 3 and 6 months of treatment to search for the selection of mutations conferring resistance to PIs. The median baseline HIV RNA level was 4.9 log(10) copies/ml, and the median CD4 count was 87 cells/mm(3). At the baseline, the median numbers of resistance mutations were as follows: 3 DRV resistance mutations, 4 major PI resistance mutations, and 10 minor PI resistance mutations. The most common mutations that emerged at rebound included V32I (44%), I54M/L (24%), L33F (25%), I84V (21%), and L89V (12%). Multivariate analysis showed that higher baseline HIV RNA levels and smaller numbers of nucleoside reverse transcriptase inhibitor simultaneously used with DRV were associated with a higher risk of DRV resistance mutation selection. By contrast, L76V, a known DRV resistance mutation, was found to decrease the risk of selection of another DRV resistance mutation. The occurrence of virological failure while a patient was on DRV was associated with the selection of mutations that increased the level of DRV resistance without affecting susceptibility to tipranavir (TPV). In these PI-treated patients who displayed treatment failure while they were on a DRV-containing regimen, we confirmed the set of emerging mutations associated with DRV failure and identified the factors associated with the selection of these mutations. TPV susceptibility does not seem to be affected by the selection of a DRV resistance mutation.

Influenzavirus Infection Is a Primary Cause of Febrile Respiratory Illness in HIV-Infected Adults, Despite Vaccination

There are, to our knowledge, no prospective studies of respiratory tract infections in human immunodeficiency virus (HIV)-infected adults in the highly active antiretroviral therapy (HAART) era. We performed a surveillance study of outpatients who presented with fever and respiratory symptoms to examine the role of viral pathogens in these patients. Consecutive patients with a temperature of >38.0 degrees C and respiratory symptoms were recruited from a tertiary care HIV clinic during the period 2003-2006. Nasal pharyngeal samples were tested for influenzavirus A and B, respiratory syncytial virus, and human metapneumovirus using real-time multiplex polymerase chain reaction assays. Paired acute- and convalescent-phase serum samples were tested for respiratory viruses by complement fixation. Fifty patients (90% of whom were receiving HAART) were included in the study (median CD4(+) T cell count, 325 cells/microL; median HIV RNA level, <50 copies/mL). A causative pathogen was identified in 25 patients (50%). Even though 76% of subjects had received influenza vaccine, viral infections were diagnosed in 21 patients (42%), as follows: influenza A, 10 patients; influenza B, 10; and parainfluenza virus type 3 infection, 1. Patients with and those without viral infection had similar demographic characteristics and HIV statuses. No patients with influenza and 23% of patients with other conditions had radiography-confirmed pneumonia (P=.07). Antibiotic prescriptions were common: 70% of patients received antibiotics. No patients with influenza required hospitalization, compared with 21% of other patients (P=.03). Although illness was mild, influenza accounted for a large proportion of unscheduled visits to a health care provider for respiratory illness and was associated with unnecessary antibiotic prescriptions that may contribute to antimicrobial resistance. Vaccination alone was insufficient to prevent infection. Thus, specific identification and management of influenza should be performed in HIV-infected outpatients who present with fever and respiratory symptoms.

HIV-Related Wasting in HIV-Infected Drug Users in the Era of Highly Active Antiretroviral Therapy

A decrease in the rate of human immunodeficiency virus (HIV) infection-related wasting has been reported in the era of highly active antiretroviral therapy (HAART). We investigated this concern in a hard-to-reach population of HIV-infected drug users in Miami, Florida. After informed consent was obtained, 119 HIV-infected drug users were administered questionnaires involving demographic, medical history, and food-security information. Blood samples were drawn for immunological and viral studies. HIV-related wasting over a period of > or =6 months was defined as a body mass index of <18.5 kg/m2, unintentional weight loss of > or =10% over 6 months, or a weight of <90% of the ideal body weight. The prevalence of HIV-related wasting was 17.6%. A significantly higher proportion of those who experienced wasting (81%) reported that there were periods during the previous month when they went for > or =1 day without eating (i.e., food insecurity), compared with those who did not experience wasting (57%). Although a greater percentage of patients who experienced wasting were receiving HAART, their HIV RNA levels were more than twice as high (mean+/-standard deviation [SD], 166,689+/-238,002 copies/mL; median log HIV RNA level +/- SD, 10.2+/-2.7 log10 copies/mL) as those for the group that did not experience wasting (mean+/-SD, 72,156 +/- 149,080; median log HIV RNA level+/-SD, 9.2+/-2.3 log10 copies/mL). Participants who experienced wasting were more likely to be heavy alcohol drinkers and users of cocaine. In multivariate analysis that included age, sex, food security, alcohol use, cocaine use, viral load, and receipt of antiretroviral therapy, the only significant predictors of wasting were > or =1 day without eating during the previous month (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.18-3.26; P=.01) and viral load (OR, 1.64; 95% CI, 1.00-2.69; P=.05). HIV-related wasting continues to be common among HIV-infected drug users, even among HAART recipients. Food insecurity and viral load were the only independent predictors of wasting. The social and economic conditions affecting the lifestyle of HIV-infected drug users constitute a challenge for prevention and treatment of wasting.

Long-term outcomes among antiretroviral-naive human immunodeficiency virus-infected patients with small increases in CD4+ cell counts after successful virologic suppression.

To evaluate the frequency and predictive factors of discordant immune response, we performed a prospective cohort study of 288 antiretroviral-naive human immunodeficiency virus (HIV)-infected patients who initiated highly active antiretroviral therapy (HAART) and maintained complete virus suppression for > or =24 months. The median CD4+ cell count was 186x10(6) cells/L, and the median HIV RNA level was 5 log(10) copies/mL. After 24 months of therapy, 42 (16.5%) of 255 patients had a median CD4+ cell count increase of <100x10(6) cells/L. By logistic regression analysis, previous injection drug use was associated with a CD4+ cell count increase of <100x10(6) cells/L (risk ratio [RR], 2.326; 95% confidence interval [CI], 1.077-5.023; P=.032); inclusion of a protease inhibitor (PI) in the HAART regimen reduced the risk of poor immunologic recovery (RR, 0.160; 95% CI, 0.061-0.417; P<.001). Failure of the CD4+ cell count to increase was relatively common among antiretroviral-naive patients in the year after the initiation of HAART and the achievement of complete virus suppression. PI-containing regimens provided better immunologic response.

Suppression of human immunodeficiency virus replication during acute measles.

To determine the effect of measles virus coinfection on plasma human immunodeficiency virus (HIV) RNA levels, a prospective study of hospitalized children with measles was conducted between January 1998 and October 2000 in Lusaka, Zambia. Plasma HIV RNA levels were measured during acute measles and 1 month after hospital discharge. The median plasma HIV RNA level in 33 children with measles who were followed longitudinally was 5339 copies/mL at study entry, 60,121 copies/mL at hospital discharge, and 387,148 copies/mL at 1-month follow-up. The median plasma HIV RNA level in children without acute illness was 228,454 copies/mL. Plasma levels of immune activation markers were elevated during the period of reduced plasma HIV RNA. Plasma levels of several potential HIV suppressive factors also were elevated during acute measles. HIV replication is transiently suppressed during acute measles at a time of intense immune activation.

Relationships among the detection of p24 antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and disease progression in HIV-infected individuals with hemophilia.

The aim of this study was to assess the relationships among the detection of p24 antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and disease progression in 111 males with hemophilia who were infected with HIV for < or =20 years. Sixty-four individuals (58%) developed p24 antigenemia a median of 11.6 years after seroconversion. The time to first detection of p24 antigen was shorter among those who were older (P=.04) and those with a high initial HIV RNA level (P=.006). The median HIV RNA level and CD4 cell count at the time of the detection of p24 antigen were 4.95 log(10) copies/mL and 100 cells/mm(3), respectively. In univariate analyses, p24 antigenemia was associated with more-rapid progression to AIDS (relative hazard [RH], 5.50; P=.0001). The effect was reduced (RH, 1.85; P=.06) after adjusting for CD4 cell counts and HIV RNA levels during follow-up, age, and calendar year. A significant relationship between p24 antigenemia and death was nonsignificant after adjusting for CD4 cell count.

Once‐Daily Combination Therapy with Emtricitabine, Didanosine, and Efavirenz in Human Immunodeficiency Virus–Infected Patients

The safety and efficacy of a once-daily regimen that combines emtricitabine, didanosine, and efavirenz was studied among 40 previously untreated human immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10) copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373 cells/microL at baseline and increased by a median of 159 cells/microL at week 24. The most common treatment-related adverse events were mild to moderate central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%), and biochemical abnormalities. Adverse reactions led to permanent drug discontinuation in only 1 patient. The once-daily combination therapy of emtricitabine, didanosine, and efavirenz was safe and demonstrated strong antiviral and immunologic effects that lasted for the 24-week period of the study.

Maternal virus load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand. Bangkok Collaborative Perinatal HIV Transmission Study Group.

To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission.