Generic and low dose antiretroviral therapy in adults and children: implication for scaling up treatment in resource limited settings

Abstract

Although access to antiretroviral therapy (ART) for the treatment of HIV has increased during the last decade, many patients are still in need of treatment. With limited funds to provide ART to millions of patients worldwide, there is a need for alternative ways to scale up ART in resource limited settings. This review provides an overview of pharmacokinetic, safety and efficacy studies of generic and reduced dose ART. The production of generic ART has greatly influenced the decline in drug prices and the increased in ART access. Generic ART has good pharmacokinetic profile, safety and efficacy. Toxicity is however the main cause for ART discontinuation. Several dose reduction studies have shown adequate pharmacokinetic parameters and short term efficacy with reduced dose ART. Ethnicity may affect drug metabolism; several pharmacokinetic studies have confirmed higher plasma ART concentration in Asians. Randomized efficacy trial of reduced versus standard ART is warranted.

Differences in implementation of HIV/AIDS clinical research in developed versus developing world: an evidence-based review on protease inhibitor use among women and minorities

“…24 Thai patients, on the contrary, in a study evaluating tenofovir/emtricitabine (TDF/FTC) plus EFV had lower rate of EFV-related neuropsychiatric disturbances than those reported in developed countries, while renal toxicity due to TDF was higher than in the published literature. 25 As reported also by others, 26 a low proportion of women enrolled in registrative trials was observed in the present analysis (19.2%); although it is interesting that a higher percentage of women was enrolled in multicentre trials conducted in at least one developing than in those conducted only in developing country. Women account for half of all people living with HIV worldwide, and nearly 60% of HIV infections in sub-Saharan Africa, 9 and it is therefore noteworthy that women be adequately represented in clinical trials, particularly in those regions where they account for the majority of patients.…”

Pharmacokinetics of Darunavir/Ritonavir in Asian HIV-1-Infected Children Aged ≥7 Years

“…The numbers of children in the three darunavir/ritonavir weight band twicedaily dosing groups were 12 children for 375/100 mg (20 to <30 kg), 2 children for 450/100 mg (30 to <40 kg) and 5 children for 600/100 mg (≥40 kg). The median (IQR) duration on darunavir/ritonavir was 11 months (6)(7)(8)(9)(10)(11)(12)(13). Other antiretroviral drugs in the regimen were tenofovir (63%), zidovudine (58%), abacavir (5%), lamivudine (95%) and etravirine (42%).…”

“…There were two patients on anticonvulsants for >10 months prior to the pharmacokinetics sampling. One child (body weight 20.3 kg, 375/100 mg dosing) was on phenytoin 100 mg once daily and had an AUC 0-12 of 210 h×mg/l and C 12…”

“…Both children were adherent to the anticonvulsant and ART. Table 2 shows the geometric mean AUC 0-12 , C max and C 12 in Thai children from this study compared with non-Asian children in the DELPHI study. All Thai children received 100 mg ritonavir boosting regardless of weight band, whereas the DELPHI children received <100 mg of ritonavir if they weighed <40 kg.…”

Pharmacokinetics of and Short-Term Virologic Response to Low-Dose 400-Milligram Once-Daily Raltegravir Maintenance Therapy

“…Antiretroviral dose reduction has been one of the options used in Thailand to decrease cost and increase access. Several studies have shown that Thai adults and children on low-dose antiretroviral regimens achieve comparable pharmacokinetic parameters and treatment outcomes to those of Westerners on standard doses (2,3,6,13,17). Therefore, we conducted this study to evaluate the pharmacokinetics of low-dose, once-daily raltegravir (400 mg QD) in HIV-1-infected Thai adults.…”