Summary Background The COVID-19 pandemic could lead to disruptions to provision of HIV services for people living with HIV and those at risk of acquiring HIV in sub-Saharan Africa, where UNAIDS estimated that more than two-thirds of the approximately 38 million people living with HIV resided in 2018. We aimed to predict the potential effects of such disruptions on HIV-related deaths and new infections in sub-Saharan Africa. Methods In this modelling study, we used five well described models of HIV epidemics (Goals, Optima HIV, HIV Synthesis, an Imperial College London model, and Epidemiological MODeling software [EMOD]) to estimate the effect of various potential disruptions to HIV prevention, testing, and treatment services on HIV-related deaths and new infections in sub-Saharan Africa lasting 6 months over 1 year from April 1, 2020. We considered scenarios in which disruptions affected 20%, 50%, and 100% of the population. Findings A 6-month interruption of supply of antiretroviral therapy (ART) drugs across 50% of the population of people living with HIV who are on treatment would be expected to lead to a 1·63 times (median across models; range 1·39–1·87) increase in HIV-related deaths over a 1-year period compared with no disruption. In sub-Saharan Africa, this increase amounts to a median excess of HIV deaths, across all model estimates, of 296 000 (range 229 023–420 000) if such a high level of disruption occurred. Interruption of ART would increase mother-to-child transmission of HIV by approximately 1·6 times. Although an interruption in the supply of ART drugs would have the largest impact of any potential disruptions, effects of poorer clinical care due to overstretched health facilities, interruptions of supply of other drugs such as co-trimoxazole, and suspension of HIV testing would all have a substantial effect on population-level mortality (up to a 1·06 times increase in HIV-related deaths over a 1-year period due to disruptions affecting 50% of the population compared with no disruption). Interruption to condom supplies and peer education would make populations more susceptible to increases in HIV incidence, although physical distancing measures could lead to reductions in risky sexual behaviour (up to 1·19 times increase in new HIV infections over a 1-year period if 50% of people are affected). Interpretation During the COVID-19 pandemic, the primary priority for governments, donors, suppliers, and communities should focus on maintaining uninterrupted supply of ART drugs for people with HIV to avoid additional HIV-related deaths. The provision of other HIV prevention measures is also important to prevent any increase in HIV incidence. Funding Bill & Melinda Gates Foundation.

Growth hormone (GH) action is attenuated during the hepatic acute-phase response (APR). To understand this attenuation, we asked whether GH and cytokine-signaling pathways intersect during an APR. In hypophysectomized rats treated with lipopolysaccharide (LPS), accumulation of activated signal transducer and transcription activator 5 (Stat5) in hepatic nuclei in response to GH and its binding to a GH response element (GHRE) from the serine protease inhibitor (Spi) 2.1 promoter are diminished in a time-dependent manner. Similarly, accumulation of activated Stat3 in hepatic nuclei in response to LPS and its binding to a high-affinity sis-inducible element (SIE) are also diminished by the simultaneous administration of GH. In functional assays with primary hepatocytes, LPS-stimulated monocyte-conditioned medium (MoCM) inhibits the GH response of Stat5-dependent Spi 2.1 reporter activity but induces Stat3-dependent Spi 2.2 reporter activity, as in an APR. Similar results are obtained when hepatocytes are treated with either tumor necrosis factor-alpha (TNF-alpha) or interleukin (IL)-1beta. TNF-alpha, IL-1beta, and IL-6 also inhibit GH-induced Spi 2.1 mRNA expression in hepatocytes. Thus inhibition of the GH signaling pathway during an APR results in reduced expression of GH-responsive genes.

Introduction Heterogeneity of sociodemographics and risk behaviours across the HIV treatment cascade could influence the public health impact of universal ART in sub‐Saharan Africa if those not virologically suppressed are more likely to be part of a risk group contributing to onward infections. Sociodemographic and risk heterogeneity across the treatment cascade has not yet been comprehensively described or quantified and we seek to systematically review and synthesize research on this topic among adults in Africa. Methods We conducted a systematic review of peer‐reviewed literature in Embase and MEDLINE databases as well as grey literature sources published in English between 2014 and 2018. We included studies that included people living with HIV (PLHIV) aged ≥15 years, and reported a 90‐90‐90 outcome: awareness of HIV‐positive status, ART use among those diagnosed or viral suppression among those on ART. We summarized measures of association between sociodemographics, within each outcome, and as a composite measure of population‐wide viral suppression. Results and discussion From 3533 screened titles, we extracted data from 92 studies (50 peer‐reviewed, 42 grey sources). Of included studies, 32 reported on awareness, 53 on ART use, 32 on viral suppression and 23 on population‐wide viral suppression. The majority of studies were conducted in South Africa, Uganda, and Malawi and reported data for age and gender. When stratified, PLHIV ages 15 to 24 years had lower median achievement of the treatment cascade (60‐49‐81), as compared to PLHIV ≥25 years (70‐63‐91). Men also had lower median achievement of the treatment cascade (66‐72‐85), compared to women (79‐76‐89). For population‐wide viral suppression, women aged ≥45 years had achieved the 73% target, while the lowest medians were among 15‐ to 24‐year‐old men (37%) and women (49%). Conclusions Considerable heterogeneity exists by age and gender for achieving the HIV 90‐90‐90 treatment goals. These results may inform delivery of HIV testing and treatment in sub‐Saharan Africa, as targeting youth and men could be a strategic way to maximize the population‐level impact of ART.

Background The rapid scale-up of antiretroviral therapy (ART) towards the UNAIDS 90-90-90 goals over the last decade has sparked considerable debate as to whether universal test and treat can end the HIV-1 epidemic in sub-Saharan Africa. We aimed to develop a network transmission model, calibrated to capture age-specific and sex-specific gaps in the scale-up of ART, to estimate the historical and future effect of attaining and surpassing the UNAIDS 90-90-90 treatment targets on HIV-1 incidence and mortality, and to assess whether these interventions will be enough to achieve epidemic control (incidence of 1 infection per 1000 person-years) by 2030.Methods We used eSwatini (formerly Swaziland) as a case study to develop our model. We used data on HIV prevalence by 5-year age bins, sex, and year from the 2007 Swaziland Demographic Health Survey (SDHS), the 2011 Swaziland HIV Incidence Measurement Survey, and the 2016 Swaziland Population Health Impact Assessment (PHIA) survey. We estimated the point prevalence of ART coverage among all HIV-infected individuals by age, sex, and year. Age-specific data on the prevalence of male circumcision from the SDHS and PHIA surveys were used as model inputs for traditional male circumcision and scale-up of voluntary medical male circumcision (VMMC). We calibrated our model using publicly available data on demographics; HIV prevalence by 5-year age bins, sex, and year; and ART coverage by age, sex, and year. We modelled the effects of five scenarios (historical scale-up of ART and VMMC [status quo], no ART or VMMC, no ART, age-targeted 90-90-90, and 100% ART initiation) to quantify the contribution of ART scale-up to declines in HIV incidence and mortality in individuals aged 15-49 by 2016, 2030, and 2050. Findings Between 2010 and 2016, status-quo ART scale-up among adults (aged 15-49 years) in eSwatini (from 34•0% in 2010 to 74•1% in 2016) reduced HIV incidence by 43•57% (95% credible interval 39•71 to 46•36) and HIV mortality by 56•17% (54•06 to 58•92) among individuals aged 15-49 years, with larger reductions in incidence among men and mortality among women. Holding 2016 ART coverage levels by age and sex into the future, by 2030 adult HIV incidence would fall to 1•09 (0•87 to 1•29) per 100 person-years, 1•42 (1•13 to 1•71) per 100 person-years among women and 0•79 (0•63 to 0•94) per 100 person-years among men. Achieving the 90-90-90 targets evenly by age and sex would further reduce incidence beyond status-quo ART, primarily among individuals aged 15-24 years (an additional 17•37% [7•33 to 26•12] reduction between 2016 and 2030), with only modest additional incidence reductions in adults aged 35-49 years (1•99% [-5•09 to 7•74]). Achieving 100% ART initiation among all people living with HIV within an average of 6 months from infection-an upper bound of plausible treatment effect-would reduce adult HIV incidence to 0•73 infections (0•55 to 0•92) per 100 person-years by 2030 and 0•46 (0•33 to 0•59) per 100 person-years by 2050.Interpretation Scale-up of ART over the last dec...

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