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Background:Antiretroviral therapy (ART), especially with tenofovir disoproxil fumarate (TDF), has been associated with accelerated bone turnover and leads to significant bone loss.Objective:We aimed to determine the effect of vitamin D2 and calcium on bone mineral density (BMD) in HIV-infected patients receiving TDF/emtricitabine (FTC)/efavirenz (EFV).Methods:A prospective, open-label, randomized controlled study was conducted. Eligible patients were ART naïve HIV individuals who initiated TDF/FTC/EFV. The study group received supplementation with vitamin D2 and calcium carbonate, whereas the control group was administered only ART. The primary outcome was the percentage change in total hip BMD at week 24 compared with baseline.Results:A total of 18 patients were randomized (9 in each group). The mean (standard deviation; SD) total hip BMD significantly decreased from baseline in both groups, from 0.96 (0.14) g/cm2 to 0.93 (0.13) g/cm2 in the study group (p = 0.006) and from 0.87 (0.11) g/cm2 to 0.84 (0.11) g/cm2 in the control group (p = 0.004). The mean (SD) lumbar spine BMD significantly decreased from baseline in both groups, from 1.00 (0.13) g/cm2 to 0.97 (0.13) g/cm2 (p = 0.004) in the study group and from 0.90 (0.09) g/cm3 to 0.86 (0.08) g/cm2 in the control group (p = 0.006). At week 24, the mean (SD) lumbar spine BMD was significantly greater in the study group than in the control group (p = 0.042). However, there were no significant differences in the percentage change of total hip, lumbar spine, and femoral neck BMD between both groups. No adverse events were reported. In conclusion, as early as 24 weeks after TDF initiation, a significant decline in BMD was detected.Conclusion:Vitamin D2 and calcium supplements should be considered for HIV-infected patients receiving TDF/FTC/EFV in a resource-limited setting where there are limited ART options (Clinicaltrials. gov NCT0287643).

Although hepatitis B serology screening has been recommended for HIV care, it has not been routinely performed. We aimed to assess compliance and timing of hepatitis B serology screening among HIV-infected patients in a resource-limited setting. A cross-sectional study was conducted in Thailand. Compliance, timing of hepatitis B serology screening, and factors associated with no HBsAg screening were determined. A total of 416 HIV-infected patients with 61% males were enrolled. Median (range) age at HIV diagnosis was 34 (16-75) years and 92% had heterosexual risk. Proportion of HBsAg screening and prevalence of positive HBsAg were 69.2% and 9.0%, respectively. There was no difference in the proportion of no HBsAg screening during the period 1990-2008 (p = 0.865). Proportion of anti-HBs and anti-HBc screening were 40.9% and 21.2%, respectively. HBsAg was screened before or on the day of anti-HIV testing in 9.1% and before antiretroviral therapy (ART) initiation in 27.2%. By Kaplan-Meier analysis, median time from anti-HIV testing to HBsAg screening was 55.9 (95% confidence interval [CI] 43.9, 68.3) months. By multivariate logistic regression, duration of HIV infection (odds ratio [OR] 1.14; 95% CI 1.07, 1.21), no anti-HBs screening (OR 1.65; 95% CI 1.4-2.63), and no anti-HCV screening (OR 2.60; 95% CI 1.62, 4.17) were associated with no HBsAg screening before ART initiation. In conclusion, compliance with hepatitis B serology screening was relatively low and late. Educational program regarding hepatitis B serology screening, identification of barriers, and interventions to eliminate these barriers in resource-limited settings are crucial to improve HIV care.

Objectives: We aimed at determining the incidence and factors for tenofovir disoproxil fumarate (TDF)- associated renal function decline among Thai HIV-infected patients. Methods: Retrospective and prospective cohort studies were conducted. We enrolled HIV-infected adults who had initiated TDF. Renal function decline was defined by a decrease of 25% in glomerular filtration rate (GFR) from the baseline. Factors associated with the renal function decline were determined. Results: A total of 405 patients with a median (interquartile range, IQR) body weight of 56.5 (50.5-65.0) kg were enrolled. All but four (99%) were antiretroviral treatment-experience patients. A median (IQR) duration of receiving TDF was 16 (8-21) months. Of these, 78 (19.3%) patients had a 25% decrease in GFR with the incidence rate of 16.2 per 100 person- years. By Kaplan-Meier survival analysis, median time to a 25% decrease in GFR was 28 [95% confidence interval (CI) 25.2-30.8] months. By multiple logistic regression, lower body weight [odds ratio (OR) 1.15 per 5 kg, 95% CI 1.00-1.33], lower body mass index (BMI) (OR 2.26 per 1 kg/m2, 95% CI 1.74-2.94), baseline GFR (OR 1.62 per 10 ml/min/1.73m2, 95% CI 1.39-1.88), protease inhibitor (OR 2.12, 95% CI 1.15-3.92), and nephrotoxic drug (OR 3.16, 95% CI 1.44-6.98) were statistically significant factors associated with a 25% decrease in GFR. Conclusions: The study revealed high incidence of TDF-associated renal function decline among patients with low-body weight and BMI. Additional risk factors were baseline GFR, receiving protease inhibitor, and nephrotoxic drugs. Close monitoring of renal function is warranted among patients with these risk factors.

Antiretroviral therapy for HIV/AIDS patients are used globally including in resource-limited settings. Successful outcomes are not always observed and HIV resistance to antiretroviral agents is a major cause of treatment failure. Both primary and secondary drug resistance have been described and reported worldwide. Primary resistance, which presumably means that individuals are infected with drug-resistant virus and secondary resistance typically, means a result of treatment failure. Pathogenesis of resistance of each antiretroviral drugs class differs and depends on the mechanism of action of the drugs. Three main laboratory investigations for diagnosis of treatment failure and HIV drug resistance are HIV RNA level, CD4 cell count, and HIV resistance testing. Management concepts for patients with HIV drug resistance are discussed. Strategies for prevention of HIV resistance emergence include finding cases with acute HIV infection, early detection of virological failure, and behavioral interventions such as adherence and condom usage.

Nevirapine (NVP) is commonly used as a component of first-line antiretroviral therapy in resource-limited countries. We aimed to determine the risk factors for NVP-associated rash among HIV-infected patients who were initiated NVP at low CD4 cell counts in a resource-limited setting. A case-control study was conducted in HIV-infected patients who developed rash after taking NVP (case) and those who did not have rash (control). A total of 357 patients with a mean (SD) age of 36.4 (7.5) years and 52.1% male were included in the study. Mean body weight (SD) was 55.5 (10.5) kg. Of all, 179 (49.0%) patients had a history of AIDS-defining illness and 57 (16.0%) patients had history of drug allergy. Median (IQR) CD4 cell counts at the time of NVP initiation was 95 (31-226) cells/mm(3). There were 115 patients in case group and 242 patients in control group. In case group, 43.0%, 54.4%, and 2.6% of patients developed grade 2, 3, and 4 of rash, respectively. Median time to develop rash was 12 (95%CI, 10.5-13.5) days. By logistic regression, history of drug allergy (OR, 3.41; 95%CI, 1.79-6.52), body weight (OR, 1.22 per each 5 kg decrement; 95%CI, 1.08-1.38), CD4 cells counts (OR, 1.20 per each 50 cells/mm(3) increment; 95%CI, 1.12-1.30), and AIDS-defining illness (OR, 0.42; 95%CI, 0.25-0.70) were significantly associated with rash. In resource-limited settings where patients were initiated NVP at low CD4 cell counts, history of drug allergy, lower body weight, and higher CD4 cell count are the risk factors for NVP-associated rash. Initiation of NVP in patients with these risks needs closed monitoring.

Increasing prevalence of thyroid function abnormality has been reported in HIV-infected patients. We aim to evaluate the prevalence and assess risk factors of thyroid dysfunction in Thai HIV-infected patients. A cross-sectional study was conducted. Serum thyroid hormone concentrations (FT4, FT3, and TSH) and thyroid autoantibodies (TgAb and TPOAb) were measured by electrochemiluminescence immunoassay. A total of 200 HIV-infected outpatients were included. Ninety-seven patients (48.5%) were men (mean age of 36.3 +/- 8.3 years). Duration of HIV infection was 49.6 +/- 35.1 months and 53% had previous opportunistic infections (OI). Mean CD4 cell count was 340.6 +/- 173.1 cells/mm(3). Of these, 167 patients (83.5%) received antiretroviral therapy (ARV). Abnormal thyroid function test was detected in 32 patients (16%). Twenty-seven patients (13.5%) had decreased thyroid function (primary hypothyroidism 3, subclinical hypothyroidism 12, and low FT4 with low or normal TSH 12) whereas 5 patients had increased thyroid function (overt hyperthyroidism 1, subclinical hyperthyroidism 1, and isolated high FT3 3). None had clinical features of thyroid hormone dysfunction. Thirteen patients (6.5%) had thyroid antibody positive. Patients who received ARV had higher mean FT3 levels than those who were naïve to ARV (p = 0.017). History of previous OI was found to be an independently significant risk factor for decreased thyroid function with the odds ratio of 3.28 (95% CI =1.183-9.099; p = 0.022). Hypothyroidism was common among Thai HIV-infected patients, especially in those who had history of previous OI. It is therefore suggested that screening and/or monitoring of thyroid hormone in HIV-infected patients should be considered.

Etravirine demonstrates activity against NNRTI-resistant HIV-1 but its efficacy depends on the number of etravirine resistance-associated mutations (RAMs). This study aimed to evaluate the role of etravirine in the second regimen in a resource-limited setting. Genotype resistance assay was conducted in a cohort of HIV-infected patients who experienced virological failure from an initial NNRTI-based regimen. We focused on etravirine-RAMs previously described: V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, and G190A/S. Frequency and predicting factors for 2 etravirine- RAMs were evaluated. There were 158 patients with a median duration of ART prior to failure of 22 months. The median CD4 cell count and HIV-1 RNA at the time of virological failure were 173 cells/mm3 and 4.1 log copies/mL, respectively. Of all, 75.3% of patients were predicted to have 2 etravirine-RAMs. From logistic regression, there was no clinical factor to predict etravirine susceptibility. Patients with 2 etravirine-RAMs had lower rates of K65R (3.4% vs 17.9%, p=0.005), Q151M (5.9% vs 20.5%, p=0.012), and multi-NRTI resistance mutations (16.8% vs 48.7%, p 2 etravirine-RAMs. Etravirine may have activity for using in the second regimen in most patients in resource-limited setting who fail an initial NNRTI-based regimen. Genotype testing is needed to identify this group. Some of these patients, indicated by genotype results, may be able to use etravirine plus 2 active NRTIs for second ART regimen. This strategy may be an option for patients who cannot afford or tolerate protease inhibitor. Prospective study to evaluate this strategy should be conducted in resource-limited setting.

Etravirine demonstrates activity against NNRTI-resistant HIV-1 but its efficacy depends on the number of etravirine resistance-associated mutations (RAMs). This study aimed to evaluate the role of etravirine in the second regimen in a resource-limited setting. Genotype resistance assay was conducted in a cohort of HIV-infected patients who experienced virological failure from an initial NNRTI-based regimen. We focused on etravirine-RAMs previously described: V90I, A98G, L100I, K101E/P, V106I, V179D/F, Y181C/I/V, and G190A/S. Frequency and predicting factors foror=2 etravirine-RAMs were evaluated. There were 158 patients with a median duration of ART prior to failure of 22 months. The median CD4 cell count and HIV-1 RNA at the time of virological failure were 173 cells/mm(3) and 4.1 log copies/mL, respectively. Of all, 75.3% of patients were predicted to haveor=2 etravirine-RAMs. From logistic regression, there was no clinical factor to predict etravirine susceptibility. Patients withor=2 etravirine-RAMs had lower rates of K65R (3.4% vs 17.9%, p=0.005), Q151M (5.9% vs 20.5%, p=0.012), and multi-NRTI resistance mutations (16.8% vs 48.7%, p0.001) when compared to patients with2 etravirine-RAMs. Etravirine may have activity for using in the second regimen in most patients in resource-limited setting who fail an initial NNRTI-based regimen. Genotype testing is needed to identify this group. Some of these patients, indicated by genotype results, may be able to use etravirine plus 2 active NRTIs for second ART regimen. This strategy may be an option for patients who cannot afford or tolerate protease inhibitor. Prospective study to evaluate this strategy should be conducted in resource-limited setting.

Cryptococcosis is an opportunistic infection with morbidity and mortality in HIV-infected patients. Impact of antiretroviral therapy (ART) on the relapse of cryptococcosis and survival of HIV-infected patients with cryptococcosis has not been well established.A retrospective cohort study of HIV-infected patients with cryptococcosis during 1997-2005 was conducted. Relapse and survival rates with corresponding risk factors were determined.There were 149 patients with a mean age of 33.5+/-7.4 years and 57% were male. Median CD4 cell count was 22 cells/mm(3). After exclusion of patients who died or were lost to follow-up during the first two weeks, 127 patients were eligible for the analysis of the effect of ART on relapse and survival rates. Of 127 patients, 52 received ART. The demographic data between the two groups were similar. Median time of ART initiation after cryptococcal diagnosis was 2.6 months. The most frequent ART used was NNRTI-based regimen (88.4%). Median CD4 change at six months of ART was 97 cells/mm(3) and 87.9% achieved undetectable HIV-RNA. The cumulative 75% survival (free) from relapse duration was 10.4 months in no-ART group and 41.9 months in ART group (P0.01). The 75% survival from cryptococcal-related mortality in no-ART group was 6.4 months whereas54 months for ART group (P0.01). In Cox proportional hazards model, ART was the only factor that associated with lower relapse and mortality rate (P0.01).ART significantly reduced relapse and mortality rate from cryptococcosis in HIV-infected patients. ART is strongly recommended in this population and should not be delayed.