ABSTRACT
BACKGROUND: Optimal timing for initiation of antiretroviral therapy (ART) among HIV-infected patients with tuberculosis (TB) is not well established. METHODS: HIV/TB-coinfected patients were randomized to initiate tenofovir/lamivudine/efavirenz at 4 weeks (4-week group) or 12 weeks (12-week group) of TB treatment. The primary outcome was 1-year all-cause mortality. RESULTS: Of 156 patients, 79 were in 4-week group and 77 in 12-week group. Overall, median (interquartile range) CD4 was 43 (47-106) cells per cubic millimeter and median (interquartile range) HIV-1 RNA was 5.8 (5.4-6.3) log copies per milliliter. Eleven (7%) mortalities occurred in a total follow-up period of 137 patient-years. Seven percent (6/79, 8.76 per 100 patient-years) mortalities were in 4-week group, and 6% (5/77, 7.25 per 100 person-years) mortalities were in 12-week group [relative risk (RR) = 0.845, 95% confidence interval (CI) = 0.247 to 2.893]. Twenty-eight (35%) patients in 4-week group and 25 (32%) patients in 12-week group were hospitalized (RR = 1.142, 95% CI = 0.588 to 2.217). Grade 2-4 adverse events were 39% (31/79) in 4-week group and 34% (26/77) in 12-week group (RR = 1.267, 95% CI = 0.659 to 2.435). In multivariate analysis, "low albumin" (RR = 2.695, 95% CI = 1.353 to 5.475) and "low baseline CD4 count" (RR = 4.878, 95% CI = 1.019 to 23.256) were the independent predictors of mortality. Immune reconstitution inflammatory syndrome was more frequent in 4-week group with an incidence of 8.86 versus 5.02 per 100 person-months in 12-week group over the first 6 months of ART (P = 0.069). CONCLUSIONS: In middle-income countries where ART is initiated at CD4 count of <350 cells per cubic millimeter, immediate initiation of ART in HIV-infected patients with active TB was not associated with survival advantage when compared to initiation of ART at 12 weeks.
Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , Antitubercular Agents/administration & dosage , HIV Infections/drug therapy , Tuberculosis/drug therapy , Adolescent , Adult , Aged , CD4 Lymphocyte Count , Coinfection/drug therapy , Coinfection/mortality , Female , HIV Infections/mortality , Humans , Male , Middle Aged , Survival Analysis , Time Factors , Treatment Outcome , Tuberculosis/mortality , Young AdultSubject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , Lamivudine/administration & dosage , Lipid Metabolism/drug effects , Organophosphonates/administration & dosage , Stavudine/administration & dosage , Adenine/administration & dosage , Adenine/adverse effects , Adult , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Cohort Studies , Female , Humans , Lamivudine/adverse effects , Male , Middle Aged , Organophosphonates/adverse effects , Prospective Studies , Stavudine/adverse effects , Tenofovir , Treatment OutcomeABSTRACT
BACKGROUND: During stavudine phase-out plan in developing countries, tenofovir is used to substitute stavudine. However, knowledge regarding whether there is any difference of the frequency of renal injury between tenofovir/lamivudine/efavirenz and tenofovir/lamivudine/nevirapine is lacking. METHODS: This prospective study was conducted among HIV-infected patients who were switched NRTI from stavudine/lamivudine to tenofovir/lamivudine in efavirenz-based (EFV group) and nevirapine-based regimen (NVP group) after two years of an ongoing randomized trial. All patients were assessed for serum phosphorus, uric acid, creatinine, estimated glomerular filtration rate (eGFR), and urinalysis at time of switching, 12 and 24 weeks. RESULTS: Of 62 patients, 28 were in EFV group and 34 were in NVP group. Baseline characteristics and eGFR were not different between two groups. At 12 weeks, comparing mean ± SD measures between EFV group and NVP group were: phosphorus of 3.16 ± 0.53 vs. 2.81 ± 0.42 mg/dL (P = 0.005), %patients with proteinuria were 15% vs. 38% (P = 0.050). At 24 weeks, mean ± SD phosphorus and median (IQR) eGFR between the corresponding groups were 3.26 ± 0.78 vs. 2.84 ± 0.47 mg/dL (P = 0.011) and 110 (99-121) vs. 98 (83-112) mL/min (P = 0.008). In NVP group, comparing week 12 to time of switching, there was a decrement of phosphorus (P = 0.007) and eGFR (P = 0.034). By multivariate analysis, 'receiving nevirapine', 'old age' and 'low baseline serum phosphorus' were associated with hypophosphatemia at 24 weeks (P < 0.05). Receiving nevirapine and low baseline eGFR were associated with lower eGFR at 24 weeks (P < 0.05). CONCLUSION: The frequency of tenofovir-associated renal impairment was higher in patients receiving tenofovir/lamivudine/nevirapine compared to tenofovir/lamivudine/efavirenz. Further studies regarding patho-physiology are warranted.
