METHODS: We performed a comprehensive search in several databases published until April 2022. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year on any biologic therapies as an add-on treatment for moderate to severe asthma in patients of all ages. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were pooled across studies using a random-effects model, stratified by country income level (high-income countries (HICs) and low- and middle-income countries (LMICs)) and perspectives (health care or payer perspective (HCPP) and societal perspective (SP)) and age group (>12 years and 6-11 years). Heterogeneity was assessed using the I2 statistic.

RESULTS: A total of 32 comparisons from 25 studies were included. Pooled INB indicated that the use of omalizumab as an add-on treatment to standard therapy in those aged >12 years was not cost-effective in HICs from the HCPP (n = 8, INB, -6,341 (95% CI, -$25,000 to $12,210), I2=86.18%) and SP (n = 5, -$14,000 (-$170,000 to $140,000), I2=75.64%). A similar finding was observed in those aged 6-11 years from the HCPP in LMICs (n = 2, -$45,000 (-$73,000 to $17,000), I2=00.00%). Subgroup analyses provided no explanations of the potential sources of heterogeneity.

METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.