Highlights From CROI, the Conference on Retroviruses and Opportunistic Infections-Postexposure Prophylaxis for Sexually Transmitted Infections, a New Protease Inhibitor for COVID-19, Goals for Preventing HIV Transmission, and More.

This Medical News Q&A discusses research highlights from the recent Conference on Retroviruses and Opportunistic Infections.

The persistent and evolving HIV epidemic in American men who have sex with men.

Men who have sex with men (MSM) in the USA were the first population to be identified with AIDS and continue to be at very high risk of HIV acquisition. We did a systematic literature search to identify the factors that explain the reasons for the ongoing epidemic in this population, using a social-ecological perspective. Common features of the HIV epidemic in American MSM include role versatility and biological, individual, and social and structural factors. The high-prevalence networks of some racial and ethnic minority men are further concentrated because of assortative mixing, adverse life experiences (including high rates of incarceration), and avoidant behaviour because of negative interactions with the health-care system. Young MSM have additional risks for HIV because their impulse control is less developed and they are less familiar with serostatus and other risk mitigation discussions. They might benefit from prevention efforts that use digital technologies, which they often use to meet partners and obtain health-related information. Older MSM remain at risk of HIV and are the largest population of US residents with chronic HIV, requiring culturally responsive programmes that address longer-term comorbidities. Transgender MSM are an understudied population, but emerging data suggest that some are at great risk of HIV and require specifically tailored information on HIV prevention. In the current era of pre-exposure prophylaxis and the undetectable equals untransmittable campaign, training of health-care providers to create culturally competent programmes for all MSM is crucial, since the use of antiretrovirals is foundational to optimising HIV care and prevention. Effective control of the HIV epidemic among all American MSM will require scaling up programmes that address their common vulnerabilities, but are sufficiently nuanced to address the specific sociocultural, structural, and behavioural issues of diverse subgroups.

Breastfeeding inequities in South Africa: Can enforcement of the WHO Code help address them? - A systematic scoping review.

INTRODUCTION: Suboptimal breastfeeding rates in South Africa have been attributed to the relatively easy access that women and families have had to infant formula, in part as a result of programs to prevent maternal-to-child transmission (MTCT) of HIV. This policy may have had an undesirable spill-over effect on HIV-negative women as well. Thus, the aims of this scoping review were to: (a) describe EBF practices in South Africa, (b) determine how EBF has been affected by the WHO HIV infant feeding policies followed since 2006, and (c) assess if the renewed interest in The Code has had any impact on breastfeeding practices in South Africa. METHODS: We applied the Joanna Briggs Institute guidelines for scoping reviews and reported our work in compliance with the PRISMA Extension (PRISMA-ScR). Twelve databases and platforms were searched. We included all study designs (no language restrictions) from South Africa published between 2006 and 2020. Eligible participants were women in South Africa who delivered a healthy live newborn who was between birth and 24 months of age at the time of study, and with known infant feeding practices. RESULTS: A total of 5431 citations were retrieved. Duplicates were removed in EndNote and by Covidence. Of the 1588 unique records processed in Covidence, 179 records met the criteria for full-text screening and 83 were included in the review. It was common for HIV-positive women who initiated breastfeeding to stop doing so prior to 6 months after birth (1-3 months). EBF rates rapidly declined after birth. School and work commitments were also reasons for discontinuation of EBF. HIV-positive women expressed fear of HIV MTCT transmission as a reason for not breastfeeding. CONCLUSION: The Review found that while enforcing the most recent WHO HIV infant feeding guidelines and the WHO Code may be necessary to improve breastfeeding outcomes in South Africa, they may not be sufficient because there are additional barriers that impact breastfeeding outcomes. Mixed-methods research, including in-depth interviews with key informants representing different government sectors and civil society is needed to prioritize actions and strategies to improve breastfeeding outcomes in South Africa.

Similarities and differences between HIV and SARS-CoV-2.

In the last 50 years we have experienced two big pandemics, the HIV pandemic and the pandemic caused by SARS-CoV-2. Both pandemics are caused by RNA viruses and have reached us from animals. These two viruses are different in the transmission mode and in the symptoms they generate. However, they have important similarities: the fear in the population, increase in proinflammatory cytokines that generate intestinal microbiota modifications or NETosis production by polymorphonuclear neutrophils, among others. They have been implicated in the clinical, prognostic and therapeutic attitudes.

Network centrality for the identification of biomarkers in respondent-driven sampling datasets.

Networks science techniques are frequently used to provide meaningful insights into the populations underlying medical and social data. This paper examines SATHCAP, a dataset related to HIV and drug use in three US cities. In particular, we use network measures such as betweenness centrality, closeness centrality, and eigenvector centrality to find central, important nodes in a network derived from SATHCAP data. We evaluate the attributes of these important nodes and create an exceptionality score based on the number of nodes that share a particular attribute. This score, along with the underlying network itself, is used to reveal insight into the attributes of groups that can be effectively targeted to slow the spread of disease. Our research confirms a known connection between homelessness and HIV, as well as drug abuse and HIV, and shows support for the theory that individuals without easy access to transportation are more likely to be central to the spread of HIV in urban, high risk populations.

AIDS and COVID-19 in southern Africa.

By the end of the first year of the COVID-19 pandemic, in February 2021, the numbers of cases and deaths in southern Africa were low in absolute and relative numbers. The BBC ran a story (which was later retracted) headlined "Coronavirus in Africa: Could poverty explain mystery of low death rate?". A heading in the New York Post said: "Scientists can't explain puzzling lack of coronavirus outbreaks in Africa". Journalist Karen Attiah concluded: "It's almost as if they are disappointed that Africans aren't dying en masse and countries are not collapsing". We wondered if the knowledge that southern African countries have acquired in their struggle against AIDS has contributed to a more effective approach against COVID-19. The viral origins of the diseases through zoonotic events are similar; neither has a cure, yet. In both diseases, behaviour change is an important prevention tool, and there are specific groups that are more vulnerable to infection. Equally, there are important differences: most people with COVID-19 will recover relatively quickly, while people living with HIV will need lifelong treatment. COVID-19 is extremely infectious, while HIV is less easily transmitted.

Design and challenges of a large HIV prevention clinical study on mother-to-child transmission: ANRS 12397 PROMISE-EPI study in Zambia and Burkina Faso.

Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols.

The impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.

INTRODUCTION: The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China, over a one- and five-year time horizon. METHODS: Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of all sexual partners (62%) and consistency of condom use (25%), but initial data indicated no change in viral suppression. A mathematical model of HIV transmission/treatment among MSM was used to estimate the impact of disruptions on HIV infections/HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over one and five years for 3/4/6-month disruption periods, starting from 1 January 2020. RESULTS: Our model predicted new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions (25% virally suppressed MSM stop taking ART) for a three-month period increasing HIV infections by 5% to 14% over one year and deaths by 7% to 12%. Observed reductions in condom use increased HIV infections by 5% to 14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility HIV testing and ART initiation, but reduced partner numbers resulted in 11% to 23% fewer infections and 0.4% to 1.0% fewer deaths. Longer disruption periods (4/6 months) amplified the impact of disruption scenarios. When realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections occurred over one year (3% to 17%), but not for five years (1% increase to 4% decrease), whereas deaths mostly increased over one year (1% to 2%) and five years (1.2 increase to 0.3 decrease). CONCLUSIONS: The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19-related disruption on HIV transmission and control among MSM in China.

Potential and demonstrated impacts of the COVID-19 pandemic on sexually transmissible infections: Republication.

PURPOSE OF REVIEW: This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission. RECENT FINDINGS: COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities. SUMMARY: In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response. VIDEO ABSTRACT: http://links.lww.com/COID/A31.

The potential effect of COVID-19-related disruptions on HIV incidence and HIV-related mortality among men who have sex with men in the USA: a modelling study.

BACKGROUND: During the COVID-19 pandemic, men who have sex with men (MSM) in the USA have reported similar or fewer sexual partners and reduced HIV testing and care access compared with before the pandemic. Pre-exposure prophylaxis (PrEP) use has also declined. We aimed to quantify the potential effect of COVID-19 on HIV incidence and HIV-related mortality among US MSM. METHODS: We used a calibrated, deterministic, compartmental HIV transmission model for MSM in Baltimore (MD, USA) and available data on COVID-19-related disruptions to HIV services to predict effects of reductions in sexual partners (0%, 25%, 50%), condom use (5%), HIV testing (20%), viral suppression (10%), PrEP initiations (72%), PrEP adherence (9%), and antiretroviral therapy (ART) initiations (50%). In our main analysis, we modelled disruptions due to COVID-19 starting Jan 1, 2020, and lasting 6 months. We estimated the median change in cumulative new HIV infections and HIV-related deaths among MSM over 1 and 5 years, compared with a base case scenario without COVID-19-related disruptions. FINDINGS: A 25% reduction in sexual partners for 6 months among MSM in Baltimore, without HIV service changes, could reduce new HIV infections by median 12·2% (95% credible interval 11·7 to 12·8) over 1 year and median 3·0% (2·6 to 3·4) over 5 years. In the absence of changes in sexual behaviour, the 6-month estimated reductions in condom use, HIV testing, viral suppression, PrEP initiations, PrEP adherence, and ART initiations combined are predicted to increase new HIV infections by median 10·5% (5·8 to 16·5) over 1 year, and by median 3·5% (2·1 to 5·4) over 5 years. Disruptions to ART initiations and viral suppression are estimated to substantially increase HIV-related deaths (ART initiations by median 1·7% [0·8 to 3·2], viral suppression by median 9·5% [5·2 to 15·9]) over 1 year, with smaller proportional increases over 5 years. The other individual disruptions (to HIV testing, PrEP and condom use, PrEP initiation, and partner numbers) were estimated to have little effect on HIV-related deaths (<1% change over 1 or 5 years). A 25% reduction in sexual partnerships is estimated to offset the effect of the combined service disruptions on new HIV infections (change over 1 year: median -3·9% [-7·4 to 1·0]; over 5 years: median 0·0% [-0·9 to 1·4]), but not on HIV deaths (change over 1 year: 11·0% [6·2 to 17·7]; over 5 years: 2·6% [1·5 to 4·3]). INTERPRETATION: Maintaining access to ART and adherence support is of the utmost importance to maintain viral suppression and minimise excess HIV-related mortality due to COVID-19 restrictions in the USA, even if disruptions to services are accompanied by reductions in sexual partnerships. FUNDING: National Institutes of Health.

Why Are Viruses Spiked?

Many viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and human immunodeficiency virus (HIV), have a structure consisting of spikes protruding from an underlying spherical surface. Research in biological and colloidal sciences has revealed secrets of why spikes exist on virus surfaces. Specifically, the spikes favor virus attachment on surfaces via receptor-specific interactions (RSIs), mediate the membrane fusion, and determine or change viral tropism. The spikes also facilitate viruses to approach surfaces before attachment and subsequently escape back to the environment if RSIs do not occur (i.e., easy come and easy go). Therefore, virus spikes create the paradox of having a large capacity for binding with cells (high infectivity) and meanwhile great mobility in the environment. Such structure-function relationships have important implications for the fabrication of virus-like particles and analogous colloids (e.g., hedgehog- and raspberry-like particles) for applications such as the development of antiviral vaccines and drug delivery.

Potential and demonstrated impacts of the COVID-19 pandemic on sexually transmissible infections.

PURPOSE OF REVIEW: This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission. RECENT FINDINGS: COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities. SUMMARY: In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response. VIDEO ABSTRACT: http://links.lww.com/COID/A31.

Management of Viral Complications of Pregnancy: Pharmacotherapy to Reduce Vertical Transmission.

Viral infections are common complications of pregnancy. Although some infections have maternal sequelae, many viral infections can be perinatally transmitted to cause congenital or chronic infection in fetuses or infants. Treatments of such infections are geared toward reducing maternal symptoms and complications and toward preventing maternal-to-child transmission of viruses. The authors review updates in the treatment of herpes simplex virus, cytomegalovirus, hepatitis B and C viruses, human immunodeficiency virus, and COVID-19 during pregnancy.

Rho GTPases and the emerging role of tunneling nanotubes in physiology and disease.

Tunneling nanotubes (TNTs) emerged as important specialized actin-rich membrane protrusions for cell-to-cell communication. These structures allow the intercellular exchange of material, such as ions, soluble proteins, receptors, vesicles and organelles, therefore exerting critical roles in normal cell function. Indeed, TNTs participate in a number of physiological processes, including embryogenesis, immune response, and osteoclastogenesis. TNTs have been also shown to contribute to the transmission of retroviruses (e.g., human immunodeficiency virus-1, HIV-1) and coronaviruses. As with other membrane protrusions, the involvement of Rho GTPases in the formation of these elongated structures is undisputable, although the mechanisms involved are not yet fully elucidated. The tight control of Rho GTPase function by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) strongly suggests that localized control of these Rho regulators may contribute to TNT assembly and disassembly. Deciphering the intricacies of the complex signaling mechanisms leading to actin reorganization and TNT development would reveal important information about their involvement in normal cellular physiology as well as unveil potential targets for disease management.

The WetNet: What the Oral Polio Vaccine Hypothesis Exposes about Globalized Interspecies Fluid Bonds.

The author analyzes the aftermath of Edward Hooper's suggestion that the trial of an oral polio vaccine (OPV) in the Belgian colonies of Africa engendered the pandemic form of the AIDS virus, HIV-1. In response to Hooper's book, The River (1999), the Royal Society in London held a conference to debate the origins of HIV. Examination of the quick dismissal of the OPV theory opens a space for legitimately challenging the widely held belief that the vaccine contamination question was convincingly resolved. This article interrogates the relationship between historiography and the making of scientific facts and history, suggesting that historians have been too credulous of scientists' testimony. The further result of the lack of a thorough analysis of the evidence backing the OPV hypothesis has resulted in a missed opportunity to read The River as one of the few detailed accounts of the immense social, political, technological, and interspecies infrastructure constituted by Cold War vaccine production. This biomedical infrastructure dramatically changed the geographic and interspecies mobility of viruses in ways that may be impossible to reconstruct. Yet these potential transmission routes remain crucial to acknowledge. The COVID-19 pandemic draws attention to the critical importance of studying The WetNet, a concept coined by the author to name the conceptual and material infrastructures of inter- and intraspecies fluid bonding.