Detectable HIV Viral Load Research Articles

Effects of human immunodeficiency virus and methamphetamine on cerebral metabolites measured with magnetic resonance spectroscopy

Human immunodeficiency virus (HIV) and methamphetamine (METH) use disorders are associated with cerebral dysfunction. To determine whether these effects were evident on in vivo neuroimaging, quantitative, single voxel magnetic resonance (MR) spectroscopy was used to assess frontal white matter, frontal gray matter, and basal ganglia in 40 HIV+/METH+, 66 HIV+/METH-, 48 HIV-/METH+, and 51 HIV-/METH- participants. HIV was associated with lower N-acetylaspartate (NAA) in frontal white and frontal gray matter but METH was not associated with cerebral metabolite differences in any region. Among HIV+ individuals, lower CD4 counts and higher plasma HIV viral loads were associated with lower NAA in frontal gray matter and basal ganglia. The relationship between detectable plasma HIV viral load and NAA in frontal white matter was significantly stronger in the HIV+/METH+ group, compared to HIV+/METH-. Higher detectable plasma HIV viral load was significantly associated with higher myo-inositol (MI) in frontal white and gray matter for HIV+/METH+, but not HIV+/METH-. For the HIV-/METH+ group, lifetime duration of METH use was associated with higher choline levels in frontal gray matter and higher MI levels in basal ganglia. Our findings are consistent with significant disruption of neuronal integrity in the frontal lobes of HIV-infected individuals. Although METH was not associated with cerebral metabolite levels, other findings suggested that METH use did affect the brain. For example, the relationship between detectable plasma HIV viral load and NAA levels was limited to HIV+/METH+ individuals. This evidence indicates when HIV is poorly suppressed, METH may modify the effects of the virus on neuronal integrity.

Striving toward Comprehensive HIV/AIDS Surveillance: The View from New York City

Striving toward Comprehensive HIV/AIDS Surveillance: The View from New York City

Predictors of Adherence to Antiretroviral Medications in Children and Adolescents With HIV Infection

Most evaluations of adherence to antiretroviral therapy in children with HIV infection have focused on validation of adherence measures via their association with virological outcomes. However, few studies have fully explored associations with other factors to guide development of adherence interventions. In this study, we examined the relationship of self-reported medication adherence to health, demographic, and psychosocial characteristics of children and their caregivers, using data from an ongoing multicenter prospective observational study of long-term outcomes of HIV infection conducted by the Pediatric AIDS Clinical Trials Group. Child and caregiver characteristics were evaluated for association with adherence via univariate and multiple logistic regression models. Of the 2088 children and adolescents, 84% reported complete adherence to antiretroviral therapy medications over the past 3 days. The median viral load was approximately 10 times higher among nonadherent than adherent children, and the strength of this association increased with age. Factors associated with at least marginally significant increases in nonadherence in a multiple logistic regression model included increasing age in years, female gender, detectable HIV viral load, occurrence of recent stressful life events, repeating a grade in school, self-assessment of adherence by the subject, and diagnosis of depression or anxiety. Having an adult other than the biological parent as the primary caregiver, using a buddy system to remember to take antiretroviral therapy medications, higher caregiver education level, previous adherence assessments, and taking antipsychotic medications were each associated with improved adherence. After controlling for these characteristics, there was no significant association of adherence with race, knowledge of HIV status, medication burden, CD4 percentage, or current antiretroviral therapy. Rates of self-reported adherence were relatively high and were influenced by multiple child and family characteristics. These findings identify targets for adherence interventions and highlight the importance of evaluating and supporting the family environment to optimize adherence.

Factors affecting attrition in a longitudinal study of patients with AIDS

Anecdotal data have suggested that retention of HIV-infected patients with immune recovery in longitudinal studies may be difficult as they resume normal activities. This study evaluated risk factors for attrition among patients with AIDS in a cohort study in the era of highly active antiretroviral therapy. Patients with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS were evaluated every three months with demographic, clinical and laboratory data collected. Lost to follow-up was defined as any patient who missed all study visits and could not be contacted for 12 consecutive months, who had not died and who did not re-enter the study at a later date. Of the 1,052 patients studied, 77 (7.3%) were lost to follow-up (rate = 0.03/person year). In the multivariate analysis, factors associated with attrition were CD4+ T-cell count category (hazard ratio (HR) = 2.03; 95%CI: 1.01, 4.24; P=0.05 for CD4+ count ≤ 50 cells/µL and HR = 1.96; 95%CI: 1.12, 3.40; P=0.02 for CD4+ count 51–200 cells/µL) and detectable HIV viral load (HR = 1.29; 95%CI: 1.07, 1.53; P<0.001 for HIV viral load >400 copies/mL). These data suggest that patients with compromised immunologic status are at an increased risk for being lost to follow-up.

Predictors of Hepatitis C Virus RNA Levels in a Prospective Cohort Study of Drug Users

High levels of hepatitis C virus (HCV) RNA are associated with a poor response to treatment of chronic hepatitis C, and a substantial reduction in HCV RNA levels predicts a favorable treatment response. We prospectively studied time-dependent and time-independent predictors of HCV RNA levels in 264 drug users with chronic HCV infection. Interviews on medical history and high-risk behaviors, phlebotomy for HIV viral load, serum HCV RNA levels as measured by the COBAS Amplicor HCV Monitor (Roche Diagnostics, Branchburg, NJ), and a lymphocyte subset assay were performed. Factors associated with HCV RNA levels over time were analyzed using a linear mixed model. Nearly 70% of the participants were men, two thirds were Hispanic, and the mean age was 46 years. HCV RNA levels increased over time. Older age (P < 0.001), HIV seropositivity (P = 0.03), and HCV nongenotype 1 (P = 0.05) were predictors of higher HCV RNA levels on multivariate analysis. Among 142 HIV-seropositive participants, a detectable HIV-1 viral load (P < 0.001) and recent alcohol use (P = 0.02) were predictors of higher HCV RNA levels. The predictors of higher HCV RNA levels found in this longitudinal study are consistent with those of prior cross-sectional studies. Further studies are warranted to determine if treatment of alcohol use affects HCV RNA levels.

Accouchement des patientes enceintes infectées par le VIH : étude rétrospective de 358 grossesses suivies entre 2000 et 2004

Evaluate the mode of delivery of HIV-infected women and the risk of mother-to-child transmission. A retrospective study conducted on HIV-infected women who delivered at the maternity ward of Bichat Hospital in Paris between 1st January 2000 and 31(st) December 2004. Pregnancy care, antiretroviral therapy, decision of the mode of delivery and neonate treatment were conformable to the French recommendations. The analysis was performed on 332 cases out of 358 pregnancies followed during this period. 75% received a Highly Active Anti Retroviral Therapy (HAART), 24% an AZT monotherapy and 1% did not receive any antiretroviral treatment. Plasmatic HIV viral load was under the level of detectability (50 copies/ml) for 64,6% of women under HAART and 28,7% of women under AZT monotherapy. Only 31,7% of women under HAART delivered vaginally. 44,7% of women under HAART with undetectable viral load at the moment of delivery delivered vaginally. 59,5% of women who were allowed to deliver vaginally had finally a vaginal delivery. 332 women gave birth to 341 babies with 9 twin pregnancies and one still-birth at 22 WA. Out of these 340 babies, 3 babies whose mother received HAART were HIV infected (2 in utero and 1 per-partum). The reasons why only one third of HIV-infected women could deliver vaginally in this study are primarily the persistence of a detectable HIV viral load under HAART. Women's choice of the mode of delivery comes next, which depends on the quality of the counselling about the benefits and risks of the cesarean section in the context of HIV infection. The third reason is obstetrical contra indications to vaginal delivery in the context of HIV infection. In the future, it is possible to reduce the incidence of cesarean section in HIV-infected women by elevating the level of HIV plasmatic viral load which allowed vaginal delivery (1000 copies/ml), by improving the observance to antiretroviral treatment, by adaptating antiretroviral medications posology using determination of serum protease inhibitors concentration and by modifying obstetrical management with less restrictive contra indications to vaginal delivery. However the impact of prophylactic cesarean section when plasmatic HIV viral load is undetectable must still be evaluated.

VEBEP Regimen and Highly Active Antiretroviral Therapy (HAART) in Patients (pts) with HD and HIV Infection (HD-HIV).

Background: The outcome of pts with HD-HIV is still poor, because the duration of complete remission (CR) is short. To improve the prognosis of HD-HIV, a feasibility study with the VEBEP regimen and radiotherapy and concomitant HAART was started in previously untreated HD-HIV pts.Methods: CT included epirubicin 30 mg/m2/day (days 1–3), cyclophosphamide 1000 mg/m2 (day 1), vinorelbine 25 mg/m2 (day 1), bleomycin 10 mg/m2 (day 3) and prednisone 100 mg/m2/day (days 1–3).Results: Since September 2001, 28 pts have been enrolled. The median age was 39 yrs. The median CD4+ cell count at entry was 256/mm3 (range 44–589) and 15 pts had a detectable HIV viral load (median 9402 copies/mm3, range 89->500000). Stage III and IV disease was present in 19/28 (68%) pts. Histologic subtypes were: MC 75%, NS 14%, not determined 7%, LP 4%. One toxic death, due to hepatic failure in a HCV positive pt was observed. An absolute neutrophil count <500 was noted in 12/28 pts (43%). Grade 3–4 anemia was observed in 8/28 pts (29%) and severe thrombocytopenia in 5/28 pts (18%). Nine pts (32%) had febrile neutropenia with 6 documented infections in 5 pts (one PCP, one cerebral toxoplasmosis, one bacterial sepsis, one bacterial pneumonia, one salmonellosis, one varicella). A grade 2–3 mucositis was observed in 6/28 pts (21%). CR was obtained in 21/28 pts (75%) and PR in 2/28 pts (7%). With a median follow up of 24 months, only 2 pts have relapsed (9%). OS and TTF at 2 years are 86% and 68%, respectively.Conclusions: Our preliminary data demonstrate that VEBEP regimen in combination with HAART is feasible and active in pts with HD-HIV. This study was supported by ISS grants.

Slower fibrosis progression in HIV/HCV-coinfected patients with successful HIV suppression using antiretroviral therapy

HIV/HCV-coinfected patients reportedly have a faster fibrosis progression rate (FPR) than HCV-monoinfected patients. This study examined whether HIV suppression through highly active antiretroviral therapy (HAART) attenuates this accelerated fibrosis progression. In two hepatitis C centers, a retrospective analysis identified 656 consecutive treatment-naïve HCV-infected patients who had undergone a liver biopsy, had a presumed date of HCV infection, and had been tested for HIV, 274 of them HIV-positive (95.2% on HAART) and 382 HIV-negative. The primary outcome measure was the FPR, defined as Ishak fibrosis score [0-6] over estimated duration of HCV infection. Among HIV/HCV-coinfected patients, 51.2% had undetectable HIV RNA (< 400 copies/mL). There was no difference in FPR between HIV/HCV-coinfected and HCV-monoinfected patients (0.136 vs. 0.128 Ishak fibrosis units/year, P=0.29). However, HIV/HCV-coinfected patients with any detectable HIV viral load >400 copies/mL had a faster FPR (0.151) than HCV-monoinfected patients (0.128, P=0.015) and than HIV/HCV-coinfected patients with undetectable plasma HIV RNA (0.122, P=0.013) who in turn had the same FPR as HCV-monoinfected subjects (0.128, P=0.52). An accelerated FPR in HIV viremic patients was seen with CD4+ cells <500/mm(3) (0.162 vs. 0.123, undetectable HIV RNA, P=0.005) but not with CD4+ cells >500/mm(3) (0.118 vs. 0.121, P=0.89). In multivariable linear regression analysis of HIV/HCV-coinfected patients, log(10) HIV RNA level, necroinflammation, and age at HCV infection were independently correlated to FPR, but not alcohol use or CD4+ cell count (r(2)=0.45 for model). HIV/HCV-coinfected patients with undetectable HIV RNA through HAART have a slower FPR than those with any HIV RNA level and an FPR similar to HCV-monoinfected individuals.

Antigen-specific immune responses and liver histology in HIV and hepatitis C coinfection

To test the hypothesis that antigen-specific interferon (IFN)gamma responses are correlated with milder liver disease in subjects coinfected with HIV-1 and hepatitis C virus (HCV). Cellular immune responses were studied in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy. We measured HCV-specific and recall responses in peripheral blood mononuclear cells using IFNgamma and interleukin (IL)-10 ELISpots, and correlated these immune responses with liver histology. The relationship of immunologic, virologic and clinical variables to inflammation and fibrosis was modeled using recursive partitioning. There were significant negative correlations between inflammatory scores and IFNgamma production in response to the HCV proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also correlated with higher IFNgamma production in response to NS5 and summed HCV proteins. Higher IFNgamma production in response to Candida was significantly associated with lower inflammatory and fibrosis scores. In multivariable models, factors associated with severe fibrosis were lower IFNgamma responses to Candida and summed HCV proteins. Factors associated with severe inflammation were detectable HIV viral load and lower HCV viral load, while predictors of mild inflammation included undetectable HIV viral load and higher IFNgamma response to Candida. In this cohort of subjects coinfected with HIV and HCV, antigen-specific IFNgamma responses are correlated with milder inflammation and fibrosis. Immunological responses best predicted severity of fibrosis, while clinical variables and recall antigen responses best predicted severity of inflammation.

The detection of non-adherence by self-administered questionnaires can be optimized by protease inhibitor plasma concentration determination.

Self-reported adherence and plasma protease inhibitor concentration (PPIC) were assessed in 642 HIV-infected patients at month 4 of a single protease inhibitor-containing regimen. PPIC was below the limit of quantification (LOQ) in 32% of non-adherent patients and in 8% of adherent patients. The relationship between non-adherence and a detectable HIV viral load was enhanced when adherent patients with PPIC below LOQ were considered to be non-adherent. PPIC combined with self-report may more reliably detect non-adherence.

CMVR diagnoses and progression of CD4 cell counts and HIV viral load measurements in HIV patients on HAART

AIMTo assess the impact of highly active antiretroviral therapy (HAART) on the prevalence and progression of CMV retinitis (CMVR) among AIDS patients with baseline CD4 cell counts <100 cells ×...

A pilot trial of indinavir, ritonavir, didanosine, and lamivudine in a once-daily four-drug regimen for HIV infection.

To evaluate the tolerance, pharmacokinetics, and virologic and immunologic outcomes of once-daily indinavir, ritonavir, didanosine, and lamivudine in HIV-seropositive individuals. Open-label 24-week pilot study. Ten HIV-seropositive subjects who were either antiretroviral-naive or minimally experienced with short-term single-or dual-nucleoside therapy provided informed consent and were enrolled. All subjects received didanosine (400 mg) 30 to 60 minutes before a meal followed by indinavir (1200 mg), ritonavir (400 mg), and lamivudine (300 mg) concurrent with the aforementioned meal. Safety laboratory tests, including a complete blood cell count and amylase, lipase, liver transaminase, and nonfasting lipid monitoring as well as plasma HIV viral load and CD4+ lymphocyte count, were carried out at monthly intervals. Genotyping was performed at baseline. Pharmacokinetic studies for indinavir and ritonavir were performed at week 8. Nine of 10 subjects completed 24 weeks of therapy. No subject demonstrated primary protease inhibitor mutations at baseline. Toxicities experienced by subjects were typically mild and consistent with those commonly reported for each of the medications, including two cases of hematuria. By week 24, median nonfasting cholesterol and triglyceride levels increased by 49% and 108%, respectively. Median baseline plasma HIV viral load and CD4+ lymphocyte count were 29,292 (4.47 log10) copies/ml and 224 cells/mm3, respectively. Eight of 10 subjects had a plasma HIV viral load of <50 copies/ml by week 12. The 2 subjects with a detectable HIV viral load reached <50 copies/ml by week 28. Median CD4+ lymphocyte counts increased by 193 cells/mm3 at week 24. Indinavir and ritonavir plasma concentrations remained above respective inhibitory and effective concentrations (IC95 and EC50) (uncorrected for protein binding) throughout the 24-hour dosing interval for 6 of 10 and 8 of 10 subjects, respectively. Our pilot study demonstrates excellent virologic suppression despite low minimum protease inhibitor concentrations during a dosing interval in some patients and is supportive of further study.

Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease.

New treatments for HIV can improve immune functioning and decrease mortality. However, lapses in adherence may render these complex regimens ineffective. Sixty-three men and 9 women on highly active antiretroviral therapy completed measures of medication adherence, psychological characteristics, and barriers to adherence. HIV viral load, a health outcome measure of virus amount present in blood, was also obtained. The sample was 36% African American and 56% Caucasian, with 35% reporting disability. Nearly one third of patients had missed medication doses in the past 5 days, and 18% had missed doses weekly over the past 3 months. Frequency of missed doses was strongly related to detectable HIV viral loads. Depression, side-effect severity, self-efficacy, and social support distinguished patients with good and poor adherence. Barriers also varied with adherence level. Implications for interventions promoting HIV treatment adherence are discussed.