Evaluation of a practical method to assess antiretroviral adherence in HIV-infected Thai children.

The objective of this study was to evaluate a practical method to assess adherence to antiretroviral therapy by observing virological and immunological responses. We conducted a 12-month longitudinal cohort study of 162 HIV-infected Thai children. Adherence was assessed using 5 methods (self reporting calendar, records of missed doses, pill counts, physician assessment, and an interview questionnaire). CD4 count, percentage and viral load were performed at baseline and at 12 months. Mean adherence rates at 2, 6, and 12 months were 98, 100, and 99% by the calendar method; 98, 100, and 100% by recording missed doses; 96, 96, and 92% by pill count; and 90, 94, and 97% by physician assessment. Poor agreement (kappa < or = 0.1) was found among the methods. There was a statistically significant difference (p = 0.05) in virological response between participants with > or = 95% adherence (0.8 log10) and those with < 95% adherence (0.2 log10) when pill counts were used to assess adherence. In conclusion, despite poor agreement among these tools, a pill count appeared to be the only practical, validated method to differentiate the virological outcome between those who were fully and partially adhere to the treatment regimen.

New antiretroviral drugs in clinical use.

The advent of combination antiretroviral therapy for the treatment of human immunodeficiency virus (HIV) infection has dramatically changed the prognosis and quality of life of HIV-infected adults and children. To date, there are 21 antiretroviral agents available with only 11 agents being approved for the use in young children less than 6 years of age. The currently available antiretroviral agents belong to four different classes; nucleoside/nucleotide reverse transcriptase inhibitors (NRTI, NtRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), and a new class of fusion inhibitors (FI). It is recommended that the treatment regimen should be a combination of at least 3 drugs from different drug classes as this has been shown to slow disease progression, improve survival, and result in better virologic and immunologic responses. Treatment with antiretroviral agents is frequently complicated by the issues of adherence, tolerability, long term toxicity and drug resistance. Many efforts have been made to develop new antiretroviral agents with greater potency, higher tolerability profiles and better convenience. Some new agents are also effective against drug-resistant strains of HIV. Since 2001, there were 7 new antiretroviral agents and 2 fixed-dose multidrug formulations being approved for the treatment of HIV infection, most are approved only for use in adults. In this article, we will review new antiretroviral agents including emtricitabine, tenofovir disoproxil fumarate, atazanavir, fosamprenavir, tipranavir and enfuvirtide. Pediatric information on these drugs will be provided when available.

Antibiotics for treatment of resistant gram-positive coccal infections.

Vancomycin is considered the workhorse for the treatment of most drug-resistant gram-positive bacterial infections. However, concerns have been raised regarding the increasing rates of vancomycin-resistant enterococci and the clinical shortcomings of vancomycin in the treatment of invasive Staphylococcus aureus infections. Resources have been committed to the development of antimicrobial agents with activity against these organisms. This review will focus on the newer antibacterial agents that have been developed for the treatment of resistant gram-positive pathogens. Included in this review are the agents: quinupristin-dalfopristin, linezolid, daptomycin, telithromycin, and tigecycline.

New antiviral agents.

During the last three decades, a better understanding of viral replication and disease states caused by viral infections have led to the development of newer antiviral agents with enhanced activity and better tolerability. This review focuses on newer systemic and topical antiviral agents that are used in treatment of herpes viruses including herpes simplex type-1 (HSV-1) and type-2 (HSV-2), varicella-zoster virus (VZV) and cytomegalovirus CMV) as well as the human papilloma virus (HPV). Included in this article are the agents famciclovir, penciclovir, valganciclovir, imiquimod, docosanole and brivudin.

Effect of antiretroviral therapy in human immunodeficiency virus-infected children.

BACKGROUND: The appropriate timing of antiretroviral (ARV) therapy initiation in children with human immunodeficiency virus (HIV) infection has been uncertain. There was evidence of poorer outcome in adults who initiated treatment at lower baseline CD4 cell count. However, early initiation may not be possible in resource-limited setting and would increased risk of long term side effects and non-adherence. OBJECTIVE: To elucidate the outcome of HIV-infected children who ARV treatment was initiated at different disease stages. MATERIAL AND METHOD: Data from medical records of HIV-infected children who had been followed at Infectious Disease Division, Department of Pediatric Siriraj Hospital were retrospectively reviewed. Clinical response and outcome data were analyzed. RESULTS: From September 1996 to March 2004, there were 200 patients with a median age at treatment initiation of 38 (2-175) months. The median duration of follow up period was 26 (1-91) months. The median baseline CD4 cell count was 545 (2-5016) cells/mm3. The median baseline CD4 percentage was 14.25 (0.11-60). Monotherapy or dual nucleoside reverse transcriptase inhibitor (NRTI) regimens were initiated in 134 (67%), and HAARTwas initiated in 66 (33%) patients. The survival rate in patients who initiated with HAART tended to be better than those initiated with dual NRTI regimens but salvaged appropriately (p=0.2377). The survival rate in those initiated treatment at baseline CD4 > or = 15% was better than those initiated at baseline CD4 < 15% (p=0.0471). CONCLUSION: Initiation of ARV treatment at CD4 more than 15% resulted in a better survival rate than at CD4 below 15%. Initiation with HAART regimen tended to improve survival and resulted in higher CD4 gain especially in cases with baseline CD4< 15%.

Dyslipidemia and lipodystrophy in HIV-infected Thai children on highly active antiretroviral therapy (HAART).

BACKGROUND: Previous cross sectional studies revealed that dyslipidemia occurs in 50-70% of children receiving highly active antiretroviral therapy (HAART). However, there is no information in children in developing countries where children may have a different nutritional status. OBJECTIVE: To evaluate the incidence and associated risk factors of dyslipidemia following HAART in HIV-infected Thai children. The occurrence of clinical lipodystrophy among these children was also evaluated. MATERIAL AND METHOD: Twenty-three HIV-infected children who initiated HAART from "Access to Care Program" sponsored by MOPH around October 2001. Non-fasting blood tests for lipid profile were performed at enrollment and every 6 months. Triglyceride level was not analysed due to a non-fasting condition. The assessment of clinical lipodystrophy was done every 1-2 months. RESULTS. As of October 2003, 19 (83%) children experienced dyslipidemia. There were 10, 13, 5, and 8 children who had dyslipidemia at 6, 12, 18, and 24 months of HAART The mean total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL) tended to increase over time while the children were on HAART: There was a correlation of elevated total cholesterol and CD4 percentage gain particularly at 18-24 months of treatment (r = 0.596, p = 0.007). Two children developed peripheral lipoatrophy. There were no dyslipidemia-associated risk factors identified. Most of the children had transient abnormal lipid profile. There were only 3 children that had persistent abnormality throughout the 24 months of HAART CONCLUSION: Dyslipidemia was found from 6-12 months of HAART and were mostly transient over time. Peripheral lipoatrophy were found in 2 children. Further follow-up will elucidate the long-term incidence, the association factors, and clinical consequences.

Modified boosted – p24 antigen can predict HIV-1 RNA viral load (Ampiclor HIV-1 Monitor).

Objective : To evaluate the prediction of HIV-1 RNA viral load (Ampiclor) in log_copies per ml by each level of modified boosted-p24 antigen in log_ fg per ml. , Methods : 283 plasma samples were collected and blindly determined the HIV-1 RNA Amplicor Monitor, Roche as standard test with modified boosted p24 antigen assay. Likelihood ratio positive analyses of multiple levels of p24 were calculated as well as the post-test probability in predicting the amount of virus (log_copies/ ml). Results: Subject were between 18 to 73 years old with the range of virus 1.75 to 5.92 log-copies per ml. By the calculation of likelihood ratio positive and positive predictive value, it was demonstrated that modified boosted p24 antigen (Ag in log-fg per ml) might predict the viral load (VL in log-copies per ml) as follow. Ag 2.0-3.0 log-fg per ml corresponding to 2.0 or lower log-copies per ml VL Ag 3.0-3.5 log-fg per ml corresponding to 2.5 or lower log-copies per ml VL Ag 3.5-4.0 log-fg per ml corresponding to 3.5 or lower log-copies per ml VL Ag 4.0-over log-fg per ml corresponding to 4.5 or lower log-copies per ml VL Conclusions: In countries with limited financial resources, the modified p24 antigen may be clinically applied in antiretroviral management programmes, instead of the HIV-1 RNA Amplicor Monitor, Roche.