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Brief Report: Apparent Antiretroviral Overadherence by Pill Count is Associated With HIV Treatment Failure in Adolescents.

ABSTRACT: Pill counts with calculated adherence percentages are used in many settings to monitor adherence, but can be undermined by patients discarding pills to hide nonadherence. Pill counts suggesting that >100% of prescribed doses were taken can signal "pill dumping." We defined "overadherence" among a cohort of 300 HIV-infected adolescents as having greater than one-third of pill counts with >100% adherence during a year of follow-up. Apparent overadherence was more common in those with virologic failure than in those with suppressed viral loads (33% vs 13%, ?(2) P = 0.001). Pill count adherence repeatedly >100% may identify HIV-infected adolescents at increased risk of treatment failure.

SUBMITTER: Okatch H

PROVIDER: S-EPMC4942380 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Adherence to antiretroviral treatment among children and adolescents in Tanzania: Comparison between pill count and viral load outcomes in a rural context of Mwanza region.

Project description:Background and objectivesAdherence to antiretroviral treatment is a key challenge for paediatric HIV care. Among children and adolescents living with HIV, lower levels of adherence have been reported compared to adults. Individual, caregiver-, health services-related and sociocultural factors were shown to impact on these outcomes. Study objectives were to assess adherence in a paediatric population in rural Tanzania comparing two measurement methods, and to investigate the association between virologic suppression and demographic, clinical, drug- and family-related factors.MethodsThis cross-sectional study was conducted among children and adolescents enrolled in Bukumbi HIV Care and Treatment Clinic (Misungwi district, Mwanza region) in the north of Tanzania, where the HIV prevalence is 7.2%. Adherence was measured through viral load and pill count. Kappa statistics assessed the level of agreement between the methods; bivariate and multivariable analyses identified factors independently associated with virologic suppression.ResultsN = 72 participants (n = 49 children; n = 23 adolescents) with a median age of eight years were enrolled. 62.5% and 65.3% of the individuals presented an optimal adherence according to viral load and pill count respectively, but among 40% viral load results diverged from the pill count method. In multivariable analysis, living outside Misungwi district and having CD4 counts above 500/μl were significantly associated with optimal adherence.ConclusionChildren and adolescents living with HIV in Mwanza show high rates of suboptimal adherence. The poor agreement between pill count and viral load results raises concerns about the interpretation of these measurements in clinical practice.

| S-EPMC6428300 | biostudies-literature

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

Project description:Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

| S-EPMC4911290 | biostudies-literature

Brief Report: Highly Active Antiretroviral Therapy Mitigates Liver Disease in HIV Infection.

Project description:To determine the impact of highly active antiretroviral therapy (HAART) on liver disease, we analyzed changes in the aspartate aminotransferase to platelet ratio index (APRI) pre- and post-HAART initiation among 441 HIV-monoinfected and 53 HIV-viral hepatitis-coinfected men. Before HAART, APRI increased 17% and 34% among the HIV-monoinfected and coinfected men, respectively. With HAART initiation, APRI decreased significantly in men who achieved HIV RNA of <500 copies per milliliter: 16% for HIV-monoinfected and 22% for coinfected men. Decreases in APRI were dependent on HIV suppression. This protective effect of HAART decreased after 2 years, particularly in the HIV-monoinfected men.

| S-EPMC4911239 | biostudies-literature

Brief Report: Changes in Levels of Inflammation After Antiretroviral Treatment During Early HIV Infection in AIDS Clinical Trials Group Study A5217.

Project description:BackgroundWe evaluated the changes in the levels of soluble biomarkers of inflammation and coagulation and T-cell activation among participants of AIDS Clinical Trials Group Study A5217 who were started on antiretroviral therapy (ART) within the first 6 months of HIV infection.MethodsCryopreserved specimens were obtained pre-ART (week 0), at the time of virologic suppression (week 36), and at 36 weeks after treatment interruption (week 72). Levels of D-dimer, C-reactive protein (CRP), and soluble CD14 (sCD14) were measured in plasma, whereas T-cell activation levels, defined as the frequencies of CD4 and CD8 T cells coexpressing HLA-DR and CD38, were measured in peripheral blood mononuclear cells.ResultsD-dimer levels were significantly lower at viral suppression (P = 0.031), whereas CRP and sCD14 levels remained similar to pre-ART levels. At viral suppression, levels of the soluble markers did not correlate with each other. CD4 T-cell counts pre-ART tended to modestly correlate with levels of D-dimer (r = 0.35; P = 0.058) and CRP (r = 0.33; P = 0.078). At 36 weeks after treatment interruption (week 72), D-dimer levels returned back to pre-ART levels. However, CD8 T-cell activation was significantly lower than pre-ART levels (35.8% at week 0 vs 28.9% at week 72; P = 0.004).ConclusionsAmong the A5217 participants who started ART within the first 6 months of HIV infection, high levels of sCD14 and CRP remain similar to pre-ART levels, suggesting that immune damage occurring in the initial stages of infection persists despite short-term virologic suppression.

| S-EPMC5393630 | biostudies-literature

Brief Report: Cofactors of Mortality Among Hospitalized HIV-Infected Children Initiating Antiretroviral Therapy in Kenya.

Project description:OBJECTIVES:Identifying factors associated with mortality among acutely ill HIV-infected children presenting with advanced HIV disease may help clinicians optimize care for those at highest risk of death. DESIGN:Using data from a randomized controlled trial (NCT02063880), we determined baseline sociodemographic, clinical, and laboratory cofactors of mortality among HIV-infected children in Kenya. METHODS:We enrolled hospitalized, HIV-infected, antiretroviral therapy-naive children (0-12 years), initiated antiretroviral therapy, and followed up them for 6 months. We used Cox proportional hazards regression to estimate hazard ratios (HRs) for death and 95% confidence intervals (CIs). RESULTS:Of 181 enrolled children, 39 (22%) died. Common diagnoses at death were pneumonia or suspected pulmonary tuberculosis [23 (59%)] and gastroenteritis [7 (18%)]. Factors associated with mortality in univariate analysis included age <2 years [HR 3.08 (95% CI: 1.50 to 6.33)], orphaned or vulnerable child (OVC) [HR 2.05 (95% CI: 1.09 to 3.84)], weight-for-age Z score <-2 [HR 2.29 (95% CI: 1.05 to 5.00)], diagnosis of pneumonia with hypoxia [HR 5.25 (95% CI: 2.00 to 13.84)], oral thrush [HR 2.17 (95% CI: 1.15 to 4.09)], persistent diarrhea [HR 3.81 (95% CI: 1.89 to 7.69)], and higher log10 HIV-1 viral load [HR 2.16 (95% CI: 1.35 to 3.46)] (all P < 0.05). In multivariable analysis, age <2 years and OVC status remained significantly associated with mortality. CONCLUSIONS:Young age and OVC status independently predicted mortality. Hypoxic pneumonia, oral thrush, and persistent diarrhea are important clinical features that predict mortality. Strategies to enhance early diagnosis in children and improve hospital management of critically ill HIV-infected children are needed.

| S-EPMC6609091 | biostudies-literature

Brief Report: Impact of Early Antiretroviral Therapy on the Performance of HIV Rapid Tests and HIV Incidence Assays.

Project description:BackgroundAntiretroviral therapy (ART) can downregulate antibody responses to HIV infection. We evaluated the impact of early vs. delayed ART on the performance of HIV diagnostic and incidence assays.MethodsSamples were obtained from 207 participants in the HPTN 052 trial, who were stably suppressed on ART for ≥4 years [Malawi sites; pre-ART CD4 cell count 350-550 cells/mm (early ART arm, N = 180) or <250 cells/mm or an AIDS-defining illness (delayed ART arm, N = 27)]. Samples were tested with 2 HIV rapid tests and 2 HIV incidence assays; selected samples were also tested with two fourth-generation immunoassays and a Western blot (WB) assay. A pre-ART sample was analyzed if the follow-up sample had a false-negative or weakly-reactive rapid test result, or had an incidence assay result indicative of recent infection (false-recent result).ResultsTen (4.8%) samples had a nonreactive or weakly-reactive rapid test result (7/180 early ART arm, 3/27 delayed ART arm, P = 0.13); one sample had nonreactive fourth-generation assay results and 3 had indeterminate WBs. Forty (18.9%) samples had a false-recent incidence assay result; 16 (7.8%) had false-recent results with both incidence assays. Baseline samples had stronger rapid test and WB bands, higher fourth-generation assay signal-to-cutoff values, and fewer HIV incidence assay results indicative of recent infection.ConclusionsFalse-negative/weakly-reactive HIV rapid tests and false-recent HIV incidence assay results were observed in virally-suppressed individuals, regardless of pre-ART CD4 cell count. Downregulation of the antibody response to HIV infection in the setting of ART may impact population-level surveys of HIV prevalence and incidence.

| S-EPMC5499248 | biostudies-literature

Determinants of Viral Resuppression or Persistent Virologic Failure After Initial Failure With Second-Line Antiretroviral Treatment Among Asian Children and Adolescents With HIV.

Project description:Of 56 children with perinatally acquired human immunodeficiency virus (HIV) who had been prescribed second-line protease inhibitor-based antiretroviral therapy and had ≥1 previous episode of viral failure (HIV RNA, ≥1000 copies/mL), 46% had ≥1, 34% had ≥2, and 23% had ≥3 consecutive episodes of viral failure during the 2 years of follow-up. Two of these children experienced a major protease inhibitor mutation.

| S-EPMC7368343 | biostudies-literature

Brief Report: HIV Antibodies Decline During Antiretroviral Therapy but Remain Correlated With HIV DNA and HIV-Specific T-Cell Responses.

Project description:BackgroundIn people with HIV on antiretroviral therapy (ART), the relationship between HIV-specific immune responses and measures of HIV persistence is uncertain.MethodsWe evaluated 101 individuals on suppressive ART in the AIDS Clinical Trials Group A5321 cohort. Cell-associated (CA) HIV DNA and RNA levels and HIV antibody concentrations and avidity to Env/p24 were measured longitudinally at years 1, 4, and 6-15 after ART initiation. Plasma HIV RNA by single copy assay and T-cell responses (IFN-γ ELISPOT) against multiple HIV antigens were measured at the last time point.ResultsHIV antibody levels declined significantly with increasing time on ART (19%/year between year 1 and 4). HIV antibody levels correlated with T-cell responses to HIV Pol (r = 0.28, P = 0.014) and to Nef/Tat/Rev (r = 0.34; P = 0.002). HIV antibody and T-cell responses were positively associated with HIV DNA levels; for example, at the last time point (median 7 years on ART), r = 0.35 for antibody levels and HIV DNA (P < 0.001); r = 0.23 for Nef/Tat/Rev-specific T-cell responses and HIV DNA (P = 0.03). Neither antibody nor T-cell responses correlated with cell-associated HIV RNA or plasma RNA by single copy assay.ConclusionsIn individuals on long-term ART, HIV-specific antibody and T-cell responses correlate with each other and with HIV DNA levels. The positive correlation between HIV immune responses and HIV DNA implies that the immune system is sensing, but not clearing, infected cells, perhaps because of immune dysfunction. Measuring immune responses to HIV antigens may provide insight into the impact of reservoir-reducing strategies.

| S-EPMC6625873 | biostudies-literature

Brief Report: Circulating Markers of Immunologic Activity Reflect Adiposity in Persons With HIV on Antiretroviral Therapy.

Project description:BACKGROUND:Obesity alters adipose tissue immunology, and these changes may be reflected in circulating soluble inflammatory biomarker and T-cell subset profiles measured in HIV research studies. METHODS:We recruited 70 adults with HIV (50% obese) on efavirenz, tenofovir, and emtricitabine, virologic suppression for >2 years, and no rheumatologic or other known inflammatory conditions. We measured fasting plasma levels of several markers of innate immunity and major CD4 and CD8 T-cell subsets. We assessed relationships between measurements of total adiposity [body mass index (BMI), dual-energy X-ray absorptiometry-quantified fat mass index (FMI), and plasma leptin] and the immunologic parameters using covariate-adjusted Spearman's rank correlations. RESULTS:The cohort was 43% women, 54% nonwhite, and median age was 45 years. Higher BMI, FMI, and plasma leptin were consistently associated with higher C-reactive protein, serum amyloid A, and interleukin-6 (P < 0.01 for all), but lower interleukin-10 (P ? 0.02 for all). BMI and FMI were positively associated with soluble tumor necrosis factor-? receptor 1 levels (P ? 0.02 for both), and a positive correlation approached significance for all 3 body composition measurements with soluble CD163 (P ? 0.09 for all). Higher BMI and FMI were associated with lower CD38 expression on CD4 T cells (P ? 0.04 for both), but higher CD69 expression (P ? 0.01 for BMI and FMI, P = 0.07 for leptin). CONCLUSIONS:Greater adiposity is associated with alterations in a limited set of circulating immune markers, potentially reflecting changes known to occur in adipose tissue with treated HIV infection. Measuring total fat mass radiographically did not yield substantively different results compared with BMI.

| S-EPMC6092237 | biostudies-literature

Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya.

Project description:We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds.

| S-EPMC5907858 | biostudies-other

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