The HIV drug optimization agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV

Abstract

Introduction Most clinical trials for new antiretroviral (ARV) agents are conducted among narrowly defined adult populations. Only after safety and efficacy have been clearly demonstrated among adults living with HIV are trials including adolescents, children and infants conducted. This approach contributes to significant delays in the availability of optimal new ARV regimens for infants, children and adolescents. This commentary discusses issues related to the inclusion of adolescents aged 12 to 18 years in initial HIV clinical phase 3 trials of novel antiretrovirals (ARVs) or conducting parallel phase 3 clinical trials among adolescents. Discussion The absorption, metabolic and excretion or elimination pathways for drugs do not significantly differ between adolescents and adults. In fact, dosing recommendations for ARVs are the same for adults and adolescents who meet the age and weight criteria. Although conducting clinical trials among adolescents present special challenges (e.g. consenting minors and concerns about trial completion and contraception), these challenges can be addressed to obtain high‐quality trial results. Importantly, new agents and optimized combinations have more favourable dosing schedules and side‐effect profiles and are more effective ARV agents with higher HIV drug resistance thresholds, which would be extremely beneficial to improve outcomes among HIV‐positive adolescents. Conclusions Adolescents may not present with significantly different pharmacokinetic characteristics from those in adults. Including HIV‐positive adolescents in phase 3 ARV clinical trials, either with adults or in specific adolescent studies conducted in parallel, would allow adolescents to access promising, more effective treatment for HIV years earlier than with the current stepwise approach.

Incidence and Predictors of Treatment Failure Among Children Receiving First-Line Antiretroviral Therapy in East Gojjam, Ethiopia: A Fifteen-year Retrospective Cohort Study

“…The most common type of failure was virological failure, followed by clinical and immunological failure. These results were greater than those reported for the different regions of Ethiopia, including Addis Ababa (14.1%) [21], the Amhara Regional State (12.19%) [20], and Jimma University Hospital (11.5%) [22]; moreover, the pooled prevalence of treatment failure was 15.3% [22]. Moreover, ART treatment failure among children reported in other parts of Ethiopia, including University of Gondar Hospital (18.2%), [23] Black Lion Hospital (22.6%) [24], and Fiche and Kuyu Hospitals (18.9%) [23], is consistent with these ndings.…”

“…This could be because stunted children may have had poorer baseline health and ART compliance than normal children. In reality, HIV affects nutritional status on its own, increasing susceptibility to the virus and hastening disease progression in malnourished children [21,35]. Furthermore, stunted children may have had a simultaneous opportunistic infection that caused them to miss out on receiving their medications [36].…”

Survival rate and predictors of mortality among TB/HIV co-infected adult patients: retrospective cohort study

“…Additionally, the current study discovered that patients with TB/HIV co-infection who were receiving INH had a 0.310 times lower mortality rate than those who were not receiving INH. Individuals with HIV and drug-susceptible TB should get standard anti-TB therapy, which includes 2 months of isoniazid (INH), rifampin, pyrazinamide, and ethambutol (intensive phase), followed by 4 months of isoniazid (INH) and rifampin (continuation phase) 50 . Studies from various parts of the world reported CPT as a significant predictor of mortality among patients co-infected with TB and HIV.…”

Pharmacokinetics and Safety of Ainuovirine/Lamivudine/Tenofovir Combination Tablets in Young and Elderly Patients with Human Immunodeficiency Virus-1 Infection

“…By 2022, a total of 39.0 million people were living with HIV-1 [ 3 , 4 ]. Current guidelines recommend that people with HIV-1 infection receive antiretroviral therapy (ART) immediately after they are diagnosed [ 5 , 6 ]. ART has improved the survival and quality of life of HIV-1-infected patients, but also poses challenges such as drug resistance, toxicity, and poor adherence [ 7 , 8 ].…”