Lancet Hiv最新文献

Background: The eastern European and central Asian (EECA) region has the fastest growing HIV epidemic globally. We aimed to identify how HIV resources could be allocated for maximum health impact.

Methods: Between Aug 1 and Dec 23, 2022, allocative efficiency analyses were undertaken for 12 countries in the EECA region (Albania, Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kosovo, Kyrgyzstan, Moldova, Serbia, Tajikistan, and Uzbekistan) using HIV epidemic models developed with Optima HIV. Country models were calibrated to demographic, epidemiological, and programmatic data and validated by national teams. Three scenarios were projected from 2023 to 2030: status quo (continued 2021 spending on HIV programmes); optimised allocation of different spending envelopes to minimise HIV infections and deaths; and achieving 95-95-95 UNAIDS targets by 2030.

Findings: Aggregated across the 12 models, HIV infections attributable to sexual transmission were estimated to surpass those attributable to transmission through injecting drugs in 2018, with male-to-male sexual transmission accounting for a continuously increasing share. In the status quo scenario, there were an estimated 111 520 (95% CI 28 960-208 270) new HIV infections and 34 530 (17 280-57 410) HIV-related deaths between 2023 and 2030. Aggregated optimisation results suggest that 35 860 (32%) of 111 520 new HIV infections and 9170 (27%) of 34 530 HIV-related deaths could be averted from 2023 to 2030 compared with the status quo, by prioritising antiretroviral therapy and targeted key population programmes. For ten countries, achieving 95% diagnosis was projected to not be possible with the current budget envelope, and for seven countries, this target could require more than three times the current spending. Compared with the status quo, achieving 95-95-95, or as close as possible, could avert 70 880 (64%) of 111 520 new HIV infections and 18 890 (55%) of 34 530 HIV-related deaths from 2023 to 2030.

Interpretation: Targeted key population programmes should remain high priorities in the EECA region. Achieving 95-95-95 will require more emphasis on implementing appropriate modes of service delivery that reduce the gap in diagnosis and treatment coverage for people living with HIV.

Funding: The Global Fund to Fight AIDS, Tuberculosis and Malaria.

Translation: For the Russian translation of the summary see Supplementary Materials section.

Background: Both efavirenz and dolutegravir have been associated with neuropsychiatric side-effects and cognitive impairment. Furthermore, cerebrospinal fluid (CSF) HIV RNA escape has not been comprehensively studied in African populations. We aimed to examine changes in cognition, neuropsychiatric symptoms, and CSF viral control associated with the widespread switch from efavirenz-based to dolutegravir-based antiretroviral therapy (ART).

Methods: This prospective cohort study of people with HIV and people without HIV recruited adults with HIV (aged 18-55 years) from the Gugulethu Community Health Centre in a low-income periurban area of Cape Town, South Africa. Eligible participants had been receiving efavirenz-based ART for at least 1 year and were identified by the clinic to switch to dolutegravir-based ART as part of the national programmatic switch. Participants were studied at baseline and followed up at 1 year after switch to dolutegravir. People without HIV were recruited from the same area, matched for age and gender, and followed up at the same time interval. People with HIV and people without HIV underwent comprehensive cognitive testing over seven domains and measures of functioning, mood, anxiety, and sleep. People with HIV had CSF sampling for HIV RNA quantification.

Findings: Between Aug 12, 2019, and Sept 16, 2022, we recruited 178 people with HIV and 95 people without HIV. 145 (81%) of 178 people with HIV and 40 (66%) of 60 people without HIV who were offered underwent follow-up. Global cognitive performance was 2·57 T score points lower in people with HIV than in people without HIV at baseline (p=0·0008). At follow-up, cognition in people with HIV improved more than practice effects observed in people without HIV (coefficient 1·40, 95% CI 0·48-2·32, p=0·0028) and no significant difference in cognitive performance between groups was apparent (51·43 vs 52·73; p=0·22). Sleep quality improved following the switch (risk ratio 0·90, 95% CI 0·84-0·95; p=0·0002), driven mainly by indicators of disturbed sleep. There were nine incident cases of depression, although baseline differences were present. There was one case (1%) of CSF escape at baseline and three cases (4%) at follow-up; all were at low levels or resolved with repeated sampling.

Interpretation: Improvements in cognition and sleep are probably related to switching from efavirenz. However, the possible increase in depression warrants further examination. Cognitive performance in virally supressed African people with HIV receiving dolutegravir-based therapy is similar to people without HIV. CSF escape is uncommon on both efavirenz-based and dolutegravir-based therapy.

Funding: South African Medical Research Council and UK Medical Research Council, Newton Fund.

Analytical treatment interruption (ATI) is widely acknowledged as an essential component of studies to advance our understanding of HIV cure, but discussion has largely been focused on adults. To address this gap, we reviewed evidence related to the safety and utility of ATI in paediatric populations. Three randomised ATI trials using CD4 T-cell and clinical criteria to guide restart of antiretroviral therapy (ART) have been conducted. These trials found low risks associated with ATI in children, including reassuring findings pertaining to neurocognitive outcomes. Similar to adults treated during acute infection, infants treated early in life have shifts in virological and immunological parameters that increase their likelihood of achieving ART-free viral control. Early ART limits the size and diversity of the viral reservoir and shapes effective innate and HIV-specific humoral and cellular responses. Several cases of durable ART-free viral control in early treated children have been reported. We recommend that, where appropriate for the study question and where adequate monitoring is available, ATI should be integrated into ART-free viral control research in children living with HIV. Paediatric participants have the greatest likelihood of benefiting and potentially the most years to prospectively realise those benefits. Excluding children from ATI trials limits the evidence base and delays access to interventions.

Large randomised studies of new long-acting medications for the prevention and treatment of HIV have shown high effectiveness and acceptability. Although modelling studies indicate these agents could be fundamental in HIV elimination, coordination of their entry into health-care markets is crucial, especially in low-income and middle-income countries with high HIV prevalence, where coordination is low despite UNAIDS flagging that global HIV targets will not be met. Research and implementation projects are tightly controlled by originator pharmaceutical companies, with only a small percentage of eligible people living with or affected by HIV benefiting from these projects. WHO, financial donors, manufacturers, and governments need to consider urgent coordinated action from stakeholders worldwide, akin to the successful introduction of dolutegravir into treatment programmes across low-income and middle-income countries. Without this immediate coordination, large-scale access to long-acting agents for HIV will be delayed, potentially extending into the 2030s. This delay is unacceptable considering the established global HIV targets.