Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV.

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform ('Policy1-Cervix-HIV') to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7-33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3-5 years.

The hard part we often forget: providing care to children and adolescents with advanced HIV disease.

INTRODUCTION: Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized. DISCUSSION: The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infections, diarrhoeal disease and severe acute malnutrition. In contrast to adults, cryptococcal meningitis is rare in children under 5 years of age but increases in adolescence. In 2021, the World Health Organizations (WHO) consolidated guidelines for managing HIV disease and rapid ART included recommendations for children and adolescents. In addition, a WHO technical brief released in 2020 highlighted the various interventions that are specifically related to children and adolescents with advanced HIV disease (AHD). We discuss the common clinical presentations of children and adolescents with AHD with a focus on diagnosis, prevention and treatment, highlight some of the challenges in the implementation of the existing package of care, and emphasize the importance of additional research to address the needs of children and adolescents with AHD. CONCLUSIONS: There are limited data informing these recommendations and an urgent need for further research on how to implement optimal strategies to ensure tailored approaches to prevent and treat AHD in children and adolescents. Holistic care that goes beyond a simple choice of ART regimen should be provided to all children and adolescents with AHD.

Advanced HIV disease and health-related suffering-exploring the unmet need of palliative care.

With more than 38 million people living with HIV worldwide, the scale-up of antiretroviral therapy ensures nearly 28 million of them receive regular treatment. However, a substantial number of deaths still occur every year from AIDS-related complications, with approximately 680 000 deaths in 2021. Of the estimated 56·8 million people globally in need of palliative care in 2020, only 7 million can access services. Providing palliative care services can help alleviate health-related suffering, such as pain and disease-related symptoms, and improve wellbeing. This Viewpoint discusses the unrealised potential of palliative care in individuals with advanced HIV disease. Key areas of training for health-care workers include appropriate sensitisation, training in palliative care, and effective communication. Advance care planning supports both the individual and their family and is therefore of crucial importance. Integration of palliative care in HIV programmes is needed to address health-related suffering, particularly for advanced HIV disease.

Implementation research to accelerate scale-up of national screen and treat strategies towards the elimination of cervical cancer.

BACKGROUND: Cervical cancer is a significant public health problem, with 570,000 new cases and 300,000 deaths of women per year globally, mostly in low- and middle-income countries. In 2018 the WHO Director General made a call to action for the elimination of cervical cancer as a public health problem. MAIN BODY: New thinking on programmatic approaches to introduce emerging technologies and screening and treatment interventions of cervical precancer at scale is needed to achieve elimination goals. Implementation research (IR) is an important yet underused tool for facilitating scale-up of evidence-based screening and treatment interventions, as most research has focused on developing and evaluating new interventions. It is time for countries to define their specific IR needs to understand acceptability, feasibility, and cost-effectiveness of interventions as to design and ensure effective implementation, scale-up, and sustainability of evidence-based screening and treatment interventions. WHO convened an expert advisory group to identify priority IR questions for HPV-based screening and treatment interventions in population-based programmes. Several international organizations are supporting large scale introduction of screen-and-treat approaches in many countries, providing ideal platforms to evaluate different approaches and strategies in diverse national contexts. CONCLUSION: For reducing cervical cancer incidence and mortality, the readiness of health systems, the reach and effectiveness of new technologies and algorithms for increasing screening and treatment coverage, and the factors that support sustainability of these programmes need to be better understood. Answering these key IR questions could provide actionable guidance for countries seeking to implement the WHO Global Strategy towards cervical cancer elimination.

Current and future priorities for the development of optimal HIV drugs.

PURPOSE OF REVIEW: To summarize global efforts to accelerate access to simpler, safer and more affordable antiretroviral drugs and how this has shaped HIV treatment policy over the last decade, and outline future priorities. Several expert consultations aimed at aligning opportunities for optimization of antiretroviral drugs have been convened by WHO in partnership with academic institutions, international agencies, innovators and manufacturers. The increased access to lifelong treatment for people living with HIV also brings about new challenges in the long-term use of antiretrovirals (ARVs). RECENT FINDINGS: The article describes the evolution of global research agenda on ARV optimization ascribing the characteristics of a target product profile, the importance of sequencing of first-line and second-line regimens, the role of programmatic data when looking at policy transition for new ARVs, inclusion of more subpopulations living with HIV, as well as the challenges in identifying what improvements can be made in an era where drugs are already safe, tolerable and efficacious. SUMMARY: Within a framework of evolving treatment harmonization and simplification, future therapeutic options in development must take into consideration safety and efficacy across a range of patient populations as well the mode of administration in the context of lifelong therapy.