Renal impairment in HIV-1 infected patients receiving antiretroviral regimens including tenofovir in a resource-limited setting.

A retrospective cohort study was conducted among HIV-1 infected patients taking tenofovir as part of an anti-HIV drug regimen in a resource-limited setting in Thailand. One hundred thirty patients with a mean_SD age of 39.7+/-7.4 years, of whom 55% were male, were included in the study. Fifty-eight (45%), 48 (37%), and 24 (18%) patients concurrently received nevirapine-based, efavirenz-based, and protease inhibitor (PI)-based regimens, respectively. The median (IQR) value for serum creatinine was 0.8 (0.6-0.9) mg/dl, for eGFR was 103 (96-120) ml/min/1.73 m2 and for CD4 was 302 (194-511) cells/mm3 at the time of tenofovir initiation. At 3-6 months, the median (IQR) eGFR was 100 (88-117) ml/min/1.73 m2 (p=0.002, compared to baseline). The proportions of patients with an estimated glomerular filtration rate (eGFR)<30 ml/min/1.73 m2 at baseline and 3-6 months were 0% and 2%, respectively (p<0.001). At 6-months follow-up, 2 patients (1.4%) were diagnosed with acute renal failure at 3 weeks and 9 weeks after tenofovir use, respectively. Both patients received a boosted PI in the regimen. Overall, the incidence of acute renal failure was 0.26 per 100 person-months. Renal function progressed to irreversible renal failure in one patient. In summary, tenofovir-associated renal impairment is not uncommon in a real-life practice. This report highlights the potentially irreversible adverse effect of this agent, particularly in patients with vulnerable kidneys and concomitant use of tenofovir and boosted PI.

Single-Boosted Protease Inhibitor versus Double-Boosted Protease Inhibitors for the Salvage Therapy in HIV-Infected Patients.

OBJECTIVE: To compare treatment outcomes between the regimens of single-boosted protease inhibitor (PI) and double-boosted PIs for the salvage therapy in patients who failed nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. METHODS: A total of 64 patients from 2 cohorts, 40 in twice daily ritonavir-boosted lopinavir (LPV/r) at 400/100 mg plus lamivudine (3TC) and 24 in once daily ritonavir-boosted atazanavir and saquinavir (ATV/SQV/r) at 300/1600/100 mg/d, were studied. RESULTS: At 48 weeks, 30 (75%) patients in LPV/r group and 20 (83%) patients in ATV/SQV/r group achieved HIV-1 RNA at <400 copies/mL (P = .790). In all, 24 (60%) and 16 (67%) achieved HIV-1 RNA at <50 copies/mL (P = .541). Low-level viral rebound (51-400 copies/mL) was found in 6 (15%) in LPV/r group and 4 (17%) in ATV/SQV/r group (P = 1.000). Medians CD4 counts were 336 cells/mm(3) and 330 cells/mm(3) in the corresponding groups (P = 0.937). CONCLUSION: No additional benefit is found with double-boosted PIs compared to single-boosted PI in terms of treatment responses in HIV-infected patients failing NNRTI-based regimen.

Treatment outcomes of patients co-infected with HIV and tuberculosis who received a nevirapine-based antiretroviral regimen: a four-year prospective study.

BACKGROUND: The concurrent use of nevirapine-based antiretroviral therapy (ART) and rifampin-containing anti-tuberculosis regimens for the treatment of HIV and tuberculosis (TB) is common in resource-limited countries. Long-term outcomes of this concurrent treatment are unknown. METHODS: Seventy HIV-infected patients receiving rifampin for active TB (TB group) and 70 HIV-mono-infected patients (control group) were enrolled to receive nevirapine 400mg/day-based ART. All were followed through 4 years of ART. Plasma HIV-1 RNA and CD4 cell counts were monitored every 12 weeks until 96 weeks, and every 24 weeks thereafter. RESULTS: Of the 140 patients, the median (interquartile range (IQR)) CD4 count was 31 (14-79) cells/mm(3) and median (IQR) plasma HIV-1 RNA was 5.6 (5.2-5.9) log copies/ml at baseline . Thirty-nine (55.7%) patients in the TB group were diagnosed with extrapulmonary/disseminated TB. The median duration of concurrent administration of nevirapine and rifampin was 5.4 (4.6-6.1) months. By intention-to-treat analysis, the percentage of patients who achieved HIV-1 RNA <50 copies/ml was 52.9% in the TB group and 50% in control group (p=0.866; odds ratio 1.121, 95% confidence interval 0.578-2.176); median (IQR) CD4 counts were 352 (271-580) cells/mm(3) and 425 (308-615) cells/mm(3) in the corresponding groups (p=0.238). The proportion of ART discontinuation due to any reason at 1, 2, 3, and 4 years was 21%, 34%, 37%, and 46% in the TB group and 21%, 36%, 43%, and 49% in the control group, respectively (p=0.651). The 4-year mortality rate was 6.4% in both groups. CONCLUSIONS: Nevirapine-based ART is an option for HIV-infected patients who receive rifampin in resource-limited countries or those who cannot tolerate efavirenz.

Successful viral suppression with subsequent efavirenz-based regimen in HIV-1-infected patients who stop nevirapine prior to discontinuation of the NRTI backbone.

OBJECTIVE: To study antiviral response of efavirenz (EFV)-based antiretroviral therapy (ART) in HIV-1-infected patients who had previously discontinued nevirapine (NVP) and continued the nucleoside reverse transcriptase inhibitor (NRTI) backbone for 7 to 14 days after stopping NVP. METHODS: A retrospective cohort study was conducted in patients who discontinued NVP. CD4 count and plasma HIV-1 RNA levels were monitored through 48 weeks of EFV-based regimen. RESULTS: Forty-five patients were eligible with a mean +/- SD age of 37 +/- 11 years; 60% were males. Median (interquartile range [IQR]) baseline CD4 count was 43 (19-150) cells/mm³ and median (IQR) plasma HIV-1 RNA was 5.7 (5.3-5.9) log copies/mL. Median (IQR) duration from stopping NVP to initiating EFV was 13 (7-18) days. At 48 week, 33 (73.3%) of 45 patients achieved plasma HIV-1 RNA <50 copies/mL. At week 12, 24, and 48, median CD4 counts were 193, 238, and 268 cells/mm³, respectively (P < .05). No studied risk factor was associated with achieving HIV-1 RNA <50 copies/mL at 48 weeks (P > .05). CONCLUSION: The strategy of extended short half-life NRTIs in the regimen after discontinuation of NVP is justified.

Temporary external lumbar drainage for reducing elevated intracranial pressure in HIV-infected patients with cryptococcal meningitis.

The aim of this study was to investigate safety and impact of temporary external lumbar drainage for continuous release of cerebrospinal fluid among patients with HIV-associated cryptococcal meningitis and elevated intracranial pressure (ICP). We conducted a retrospective cohort study among patients with cryptococcal meningitis in whom temporary external lumbar drains were placed to reduce intractable elevated ICP between January 2002 and December 2005. Patients were followed for three months after the procedure. Among 601 HIV-infected patients with cryptococcal meningitis, 54 (8.9%) underwent lumbar drain placement. Of these patients, mean age was 33 years and 80% were males. The median duration of an indwelling lumbar drain was seven days. There were 61 placement procedures among 54 patients, totalling to 473 device-days of observation. Overall incidence of secondary bacterial infections was 6.3 per 1000 device-days, and three (4.9%) of 61 catheters became secondarily infected with nosocomially acquired bacteria. All three drains were removed and appropriate antibiotics were given. There was no difference in median duration of placement between infected and uninfected drains (six days vs. seven days, P=0.572). The overall mortality rate was 5.6% in this cohort of 54 patients. In conclusion, the incidence of nosocomial infection of external lumbar drains is low. In resource-limited settings, the use of temporary external lumbar drainage is a safe and effective management strategy for intractable elevated ICP in HIV-infected patients with cryptococcal meningitis.

Incidence and risk factors of nevirapine-associated severe hepatitis among HIV-infected patients with CD4 cell counts less than 250 cells/microL.

OBJECTIVES: To determine incidence and risk factors of nevirapine (NVP)-associated severe hepatitis that led to NVP discontinuation among HIV-infected patients with CD4 < 250 cells/microL. MATERIAL AND METHOD: A retrospective cohort study was conducted among antiretroviral-naïve HIV-infected patients who had baseline CD4 < 250 cells/microL and were initiated NVP-based antiretroviral therapy (ART) between January 2003 and October 2005. All patients were categorized to group A: occurred clinical hepatitis and group B: did not occur clinical hepatitis. All were followed until 6 months after ART. RESULTS: There were 910 patients with a mean age of 35.4 years, 57% were males and median (IQR) CD4 cell count was 27 (9-80) cells/microL; contributing 5,006 person-months of observations. Ten (1.1%) patients were in group A and 900 (98.9%) patients were in group B. Incidence of clinical hepatitis was 2 per 1,000 person-months. Probabilities of clinical hepatitis at 0.5, 1, 2, 3 and 6 months after ART were 0.2%, 0.5%, 0.7%, 0.8% and 1.1%, respectively. By Cox regression analysis, baseline AST > or = 1.5 times of upper limit was associated with higher incidence of clinical hepatitis (p = 0.019, HR = 5.83, 95% CI = 1.33-25.51). CONCLUSION: Incidence of NVP-associated severe hepatitis that lead to NVP discontinuation among HIV-infected patients with baseline CD4 < 250 cells/microL is low. The higher baseline AST is also associated with a higher risk of severe hepatitis.

Risk factors for mortality in symptomatic hyperlactatemia among HIV-infected patients receiving antiretroviral therapy in a resource-limited setting.

OBJECTIVES: To determine the mortality rate and risk factors after experiencing symptomatic hyperlactatemia in HIV-infected patients receiving antiretroviral therapy (ART). METHODS: A retrospective cohort study was conducted among patients who were diagnosed with symptomatic hyperlactatemia (lactate >2.5mmol/l) between January 2004 and April 2006. All patients were followed until 3 months after the diagnosis. RESULTS: One hundred and twenty-five patients were included in the study. The mean+/-standard deviation (SD) age was 39.9+/-10.1 years and body weight was 58.2+/-16.9kg; 60.8% were male. Symptomatic hyperlactatemia in 114 (91.2%) was associated with receiving d4T, in five (4.0%) with d4T+ddI, in four (3.2%) with ZDV+ddI, and in two (1.6%) with ddI (d4T, stavudine; ddI, didanosine; ZDV, zidovudine). The median duration of ART was 13 months. Nine (7.2%) patients died. Patients who died had a higher mean lactate level (8.0 vs. 5.1mmol/l) and mean alanine aminotransferase (ALT; 164 vs. 48U/l) at the time of diagnosis when compared to those who survived (p<0.05). Patients who died had a lower mean weight than those who survived (48 vs. 59kg, p=0.008). By logistic regression, mortality was associated with patients whose body weight was <45kg (p=0.014, odds ratio (OR) 9.090, 95% confidence interval (CI) 1.575-52.632) and whose serum lactate was >10mmol/l (p=0.004, OR 20.372, 95% CI 2.610-159.001). CONCLUSIONS: The mortality rate of symptomatic hyperlactatemia among HIV-infected patients receiving ART is substantial. Almost all patients received d4T. Patients who have a low body weight and high serum lactate level are at a higher risk of mortality.

Incidence and risk factors of nevirapine-associated skin rashes among HIV-infected patients with CD4 cell counts <250 cells/microL.

The objective of the study was to determine cumulative incidence and risk factors of nevirapine (NVP)-associated rashes that lead to NVP discontinuation among HIV-infected patients with CD4 <250 cells/microL. A retrospective cohort study was conducted among antiretroviral-naïve HIV-infected patients who had baseline CD4 <250 cells/microL and were initiated NVP-based antiretroviral therapy (ART) between January 2003 and October 2005. There were 910 patients with a mean age of 35.4 years and 43% were women. Median CD4 cell count was 27 cells/microL and median HIV RNA was 5.5 log copies/mL. Cumulative incidences of rashes at 0.5, 1, 2, 3 and 6 months after ART were 3.7%, 6.2%, 8.1%, 8.5% and 8.5%, respectively. By Kaplan-Meier analysis, the higher baseline CD4 cell counts had a higher probability of NVP-associated rashes (log-rank test, P=0.041). By Cox regression analysis, higher baseline CD4 cell count was associated with a higher incidence of rashes (hazard ratio=1.244, 95% confidence interval=1.045-1.482, for every 50 cells/microL increment of baseline CD4 stratum). In conclusion, NVP-associated skin rashes that lead to NVP discontinuation are common among HIV-infected patients with baseline CD4 <250 cells/microL. Despite the low baseline in this population, the higher number of baseline CD4 cells is continuously associated with a higher risk for skin rashes.

Safety and efficacy of a generic fixed-dose combination of stavudine, lamivudine and nevirapine antiretroviral therapy between HIV-infected patients with baseline CD4 <50 versus CD4 > or = 50 cells/mm3.

BACKGROUND: Antiretroviral therapy (ART) with a generic fixed-dose combination (FDC) of stavudine (d4T)/lamivudine (3TC)/nevirapine (NVP) is widely used in developing countries. The clinical data of this FDC among very advanced HIV-infected patients is limited. METHODS: A retrospective cohort study was conducted among ART-naïve HIV-infected patients who were initiated a generic FDC of d4T/3TC/NVP between May 2004 and October 2005. Patients were categorized into 2 groups according to the baseline CD4 (group A: <50 cell/mm3 and group B: > or = 50 cell/mm3). RESULTS: There were 204 patients with a mean +/- SD age of 37.1 +/- 8.9 years, 120 (58.8%) in group A and 84 (41.2%) in group B. Median (IQR) CD4 cell count was 6 (16-29) cells/mm3 in group A and 139 (92-198) cells/mm3 in group B. Intention-to-treat analysis at 48 weeks, 71.7% (86/120) of group A and 75.0% (63/84) of group B achieved plasma HIV RNA <50 copies/ml (P = 0.633). On-treatment analysis, 90.5% (87/96) in group A and 96.9% (63/65) in group B achieved plasma HIV RNA <50 copies/ml (P = 0.206). At 12, 24, 36 and 48 weeks of ART, mean CD4 were 98, 142, 176 and 201 cells/mm3 in group A and 247, 301, 336 and 367 cells/mm3 in group B, respectively. There were no differences of probabilities to achieve HIV RNA <50 copies/ml (P = 0.947) and CD4 increment at 48 weeks between the two groups (P = 0.870). Seven (9.6%) patients in group A and 4 (8.5%) patients in group B developed skin reactions grade II or III (P = 1.000). ALT at 12 weeks was not different from that at baseline in both groups (P > 0.05). CONCLUSION: Initiation of FDC of d4T/3TC/NVP in HIV-infected patients with CD4 <50 and > or = 50 cells/mm3 has no different outcomes in terms of safety and efficacy. FDC of d4T/3TC/NVP can be effectively used in advance HIV-infected patients with CD4 <50 cells/mm3.