Thai national guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2010.

In Thailand, more than 150,000 patients are currently treated with antiretroviral drugs under the support of the National AIDS Program (NAP). The appointed Adults and Adolescents Committee consisted of 28 members who are experts in HIV research, patient care or health care policy. Relevant published literature, guidelines, and the most recent relevant clinical trials presented internationally were reviewed. Several peer review and clinical studies conducted in Thailand were included in the review process. Special considerations for patients with co-infection of tuberculosis or hepatitis B were incorporated. Appropriate cut-off of CD4+ T-cell counts when to commence ART among Thai patients have been considered. It is now recommended to start ART at CD4+ T-cell count <350 cells/mm3. For treatment-naive patients, the preferred initial therapy is a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen containing lamivudine plus zidovudine or tenofovir. Stavudine will be phased out in a two-year plan at the national program level. Viral load and CD4+ T-cell counts should be monitored at least once and twice a year. To achieve long-term treatment success, enhancing adherence together with the proper management of antiretroviral-related toxicity is critical. In summary, the major changes from the Thai 2008 guidelines include commencing ART earlier. ART is recommended regardless of CD4+ T cell count if patients have an indication to treat their HBV co-infection. Preferred first regimen uses AZT or TDF, not d4T as the NRTI-backbone. Furthermore, efavirenz is now considered a preferred NNRTI, along with nevirapine.

Incidence and risk factors for non-nucleoside reverse transcriptase inhibitors (NNRTI)-related rash in Thai children with HIV infection.

The present study evaluated the incidence and risk factors that correlated with the development of non-nucleoside reverse transcriptase inhibitor (NNRTI) related rash in 69 Thai children followed prospectively. The overall incidence of NNRTI-related rash was 16% (22% for NVP and 4% for EFV rash). The only significant predictive factor that correlated with the development of NNRTI-related rash in a multivariate logistic regression model was a CD4% decrease at week 12.

Cost savings by reagent reduction in flow cytometry-based CD4+ T cell counts: an approach to improve accessibility for HIV management.

In Thailand, the cost of antiretrovirals has recently been reduced more than 10 fold. Likewise strategies for a cost reduction in laboratory monitoring are warranted. This study was designed to explore if the most expensive reagent in flow cytometry based CD4+ cell monitoring, the CD4+/CD8+ monoclonal antibodies, can be reduced without a loss of accuracy. Blood samples from 55 HIV seronegative (HIV-) and 76 HIV+ subjects were analyzed for %CD4+ and %CD8+ T cells using a two color monoclonal antibody panel (BD Biosciences, CA, USA) with 3 different amounts of the recommended reagents for staining: 1) standard, 2) half, and 3) one-fourth. A significant Spearman correlation of 0.987 was shown for the % CD4+ T cell test results for one half as well as one-fourth of the recommended amount compared to the standard staining according to the manufacturer's instruction (p < 0.0001). For the % CD8+ T cell test results, the correlation between the standard and the half or one-fourth reduced staining was 0.972 (p < 0.0001). Bland-Altman analysis showed no significant bias between the results from one half or one-fourth of the recommended amount versus the standard. The sensitivity and specificity of the two methods at the CD4+ T cell count cut-off of 200 cells/microl were 93% and 100%; and 96% and 99%, respectively. Our study indicates that a reduction of the reagents to half or one-fourth of the amount recommended by the manufacturer was still able to generate reliable results for CD4+ and CD8+ T cell counts. Such an approach will significantly reduce the cost of CD4+ monitoring for resource limited settings where a flow cytometer is available.

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

No effect of interleukin-2 on IgE levels given in addition to antiretroviral therapy in HIV-infected adults with CD4 >300 cells/mm3.

HIV-infected patients may have frequent atopy caused by an imbalance of Th1 and Th2 cytokines. The objective of the present study was to investigate whether IL-2 given in addition to antiretrovirals (ARV) would result in lower IgE levels and less allergic symptoms. Patients naive to IL-2 (n=28) began IL-2 plus ARV and were followed for 12 months. IgE, eosinophil and CD4 counts, HIV RNA, symptom scoring, PFT and skin prick test (SPT) were performed. It was found that the baseline median CD4 and IgE were 386.5 cells/mm3 and 63.5 IU/ml, respectively. Four patients had allergic rhinitis (AR) and 61% had a positive SPT to at least 1 antigen. At month 12, patients had higher CD4 counts (p < 0.001) compared to the baseline; however, there were no differences in IgE levels, allergic symptom scores or HIV RNA. The eosinophil count was higher after IL-2 administration. It was concluded that IL-2 plus ARV resulted in higher CD4 counts but had no effect on atopy.

Construction and immunogenicity study of a 297-bp humanized HIV V3 DNA of an approximated last common ancestor in mice.

DNA immunization represents one of the promising HIV-1 vaccine approaches. To overcome the obstacle of genetic variation, we used the last common ancestor (LCA) or "center-of-the-tree" approach to study a DNA fragment of the HIV-1 envelope surrounding the V3 region. A humanized codon of the 297-bp consensus ancestral sequence of the HIV-1 envelope (codons 291-391) was derived from the 80 most recent HIV-1 isolates from the 8 circulating HIV-1 subtypes worldwide. This 297-bp humanized "multi-clade" V3 DNA was amplified by a PCR-based technique. The PCR product was well expressed in vitro whereas the corresponding non-humanized V3 DNA (subtype A/E) could not be expressed. However, both V3 DNA constructs as well as the full-length HIV-1 envelope construct (A/E) were found to be immunogenic in mice by the footpad-swelling assay. Moreover, intracellular and extracellular interferon-gamma could be detected upon in vitro stimulation of spleen cells although the response was relatively weak. Further improvement of our humanized V3 DNA is needed.

Significant differences between plasma HIV-1 RNA assays in HIV-1 subtype E infected patients treated with antiretroviral therapy.

A total of 72 HIV-1 infected Thai patients treated with didanosine (ddI) or stavudine (d4T) plus ddI at the time of interim analysis were analyzed. Sixty patients (83%) carried subtype E documented by HIV-1 V3 serotyping. HIV-1 RNA levels were measured using three commercial viral load assays. At baseline (n = 57), Quantiplex 2.0 and NucliSens 2.0 showed mean log10 HIV-1 RNA of 0.7 log10 or 5 fold lower than Amplicor 1.5 (mean 4.29 versus 5.0 log10, respectively, p < 0.001). At week 20 of treatment (n = 29), HIV-1 RNA levels were detected in 55.2%, 31%, and 33.5% of subjects tested by Amplicor 1.5, Quantiplex 2.0, and NucliSens 2.0, respectively. In conclusion: plasma HIV-1 RNA analyses showed comparable values with Quantiplex 2.0 and NucliSens 2.0 assays. In contrast, Amplicor 1.5 resulted in approximately 5 folds higher HIV-1 RNA levels and a 25% higher rate of detection of plasma HIV-1 RNA as compared to the other two assays. As the current goal of therapy is to suppress plasma viral load below the detection limit of the assays, the significant differences between the assays may influence antiretroviral efficacy evaluation and management.