Perceptions of door-to-door HIV counselling and testing in Botswana

Prevalence of HIV infection in Botswana is among the highest in the world, at 23.9% of 15 - 49-year-olds. Most HIV testing is conducted in voluntary counselling and testing centres or medical settings. Improved access to testing is urgently needed. This qualitative study assessed and documented community perceptions about the concept of door-to-door HIV counselling and rapid testing in two of the highest-prevalence districts of Botswana. Community members associated many positive benefits with home-based, door-to-door HIV testing, including convenience, confidentiality, capacity to increase the number of people tested, and opportunities to increase knowledge of HIV transmission, prevention and care through provision of correct information to households. Community members also saw the intervention as increasing opportunities to engage and influence family members and to role model positive behaviours. Participants also perceived social risks and dangers associated with home-based testing including the potential for conflict, coercion, stigma, and psychological distress within households. Community members emphasised the need for individual and community preparation, including procedures to protect confidentiality, provisions for psychological and social support, and links to appropriate services for HIV-positive persons

Acceptability of Carraguard Vaginal Microbicide Gel among HIV-Infected Women in Chiang Rai, Thailand

Background: Few studies of microbicide acceptability among HIV-infected women have been done. We assessed CarraguardH vaginal gel acceptability among participants in a randomized, controlled, crossover safety trial in HIV-infected women in Thailand. Methodology/Principal Findings: Participants used each of 3 treatments (Carraguard gel, methylcellulose placebo gel, and no product) for 7 days, were randomized to one of six treatment sequences, and were blinded to the type of gel they received in the two gel-use periods. After both gel-use periods, acceptability was assessed by face-to-face interview. Responses were compared to those of women participating in two previous Carraguard safety studies at the same study site. Sixty women enrolled with a median age of 34 years; 25 % were sexually active. Self-reported adherence (98%) and overall satisfaction rating of the gels (87% liked ‘‘somewhat’ ’ or ‘‘very much’’) were high, and most (77%) considered the volume of gel ‘‘just right.’ ’ For most characteristics, crossover trial participants evaluated the gels more favorably than women in the other two trials, but there were few differences in the desired characteristics of a hypothetical microbicide. Almost half (48%) of crossover trial participants noticed a difference between Carraguard and placebo gels; 33 % preferred Carraguard while 12 % preferred placebo (p=0.01). Conclusions/Significance: Daily Carraguard vaginal gel use was highly acceptable in this population of HIV-infecte

Advancing detection and response capacities for emerging and re-emerging pathogens in Africa

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa

Contact Tracing and the COVID-19 Response in Africa: Best Practices, Key Challenges, and Lessons Learned from Nigeria, Rwanda, South Africa, and Uganda.

Most African countries have recorded relatively lower COVID-19 burdens than Western countries. This has been attributed to early and strong political commitment and robust implementation of public health measures, such as nationwide lockdowns, travel restrictions, face mask wearing, testing, contact tracing, and isolation, along with community education and engagement. Other factors include the younger population age strata and hypothesized but yet-to-be confirmed partially protective cross-immunity from parasitic diseases and/or other circulating coronaviruses. However, the true burden may also be underestimated due to operational and resource issues for COVID-19 case identification and reporting. In this perspective article, we discuss selected best practices and challenges with COVID-19 contact tracing in Nigeria, Rwanda, South Africa, and Uganda. Best practices from these country case studies include sustained, multi-platform public communications; leveraging of technology innovations; applied public health expertise; deployment of community health workers; and robust community engagement. Challenges include an overwhelming workload of contact tracing and case detection for healthcare workers, misinformation and stigma, and poorly sustained adherence to isolation and quarantine. Important lessons learned include the need for decentralization of contact tracing to the lowest geographic levels of surveillance, rigorous use of data and technology to improve decision-making, and sustainment of both community sensitization and political commitment. Further research is needed to understand the role and importance of contact tracing in controlling community transmission dynamics in African countries, including among children. Also, implementation science will be critically needed to evaluate innovative, accessible, and cost-effective digital solutions to accommodate the contact tracing workload

Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission

The vast majority of new HIV infections result from relatively inefficient transmission of the virus across mucosal surfaces during sexual intercourse. A consequence of this inefficiency is that small numbers of transmitted founder viruses initiate most heterosexual infections. This natural bottleneck to transmission has stimulated efforts to develop interventions that are aimed at blocking this step of the infection process. Despite the promise of this strategy, clinical trials of preexposure prophylaxis have had limited degrees of success in humans, in part because of lack of adherence to the recommended preexposure treatment regimens. In contrast, a number of existing vaccines elicit systemic immunity that protects against mucosal infections, such as the vaccines for influenza and human papilloma virus. We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV in humanized mice using broadly neutralizing antibodies. Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse HIV strains despite repeated exposures. Moreover, animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain, suggesting that VIP may be effective in preventing vaginal transmission of HIV between humans

An Antiretroviral/Zinc Combination Gel Provides 24 Hours of Complete Protection against Vaginal SHIV Infection in Macaques

Repeated use, coitus-independent microbicide gels that do not contain antiretroviral agents also used as first line HIV therapy are urgently needed to curb HIV spread. Current formulations require high doses (millimolar range) of antiretroviral drugs and typically only provide short-term protection in macaques. We used the macaque model to test the efficacy of a novel combination microbicide gel containing zinc acetate and micromolar doses of the novel non-nucleoside reverse transcriptase inhibitor MIV-150 for up to 24 h after repeated gel application.Rhesus macaques were vaginally challenged with SHIV-RT up to 24 h after repeated administration of microbicide versus placebo gels. Infection status was determined by measuring virologic and immunologic parameters. Combination microbicide gels containing 14 mM zinc acetate dihydrate and 50 µM MIV-150 afforded full protection (21 of 21 animals) for up to 24 h after 2 weeks of daily application. Partial protection was achieved with the MIV-150 gel (56% of control at 8 h after last application, 11% at 24 h), while the zinc acetate gel afforded more pronounced protection (67% at 8-24 h). Marked protection persisted when the zinc acetate or MIV-150/zinc acetate gels were applied every other day for 4 weeks prior to challenge 24 h after the last gel was administered (11 of 14 protected). More MIV-150 was associated with cervical tissue 8 h after daily dosing of MIV-150/zinc acetate versus MIV-150, while comparable MIV-150 levels were associated with vaginal tissues and at 24 h.A combination MIV-150/zinc acetate gel and a zinc acetate gel provide significant protection against SHIV-RT infection for up to 24 h. This represents a novel advancement, identifying microbicides that do not contain anti-viral agents used to treat HIV infection and which can be used repeatedly and independently of coitus, and underscores the need for future clinical testing of their safety and ability to prevent HIV transmission in humans

Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series

<p>Abstract</p> <p>Background</p> <p>We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis – a point of substantial importance to the VA, which is the largest provider of HIV care in the United States.</p> <p>Methods</p> <p>Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA.</p> <p>Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide <it>decision support</it>; audit/feedback as a <it>clinical information system</it>, and appropriate changes in <it>delivery system design</it>. These activities are complemented by academic detailing and social marketing interventions to achieve <it>provider activation</it>.</p> <p>Results</p> <p>Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3–5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations.</p> <p>Discussion</p> <p>This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4).</p

Molecular Characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and Impact of T-Cell Epitope Mutations on HLA Recognition (ANRS 12159)

To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution. The aim of this study was to describe HIV-1 strains circulating in an unexplored area of Mekong Delta, Vietnam, and to assess the impact of optimal epitope mutations on HLA binding.We recruited 125 chronically antiretroviral-naive HIV-1-infected subjects from five cities in the Mekong Delta. We performed high-resolution DNA typing of HLA class I alleles, sequencing of Gag and RT-Prot genes and phylogenetic analysis of the strains. Epitope mutations were analyzed in patients bearing the HLA allele restricting the studied epitope. Optimal wild-type epitopes from the Los Alamos database were used as reference. T-cell epitope recognition was predicted using the immune epitope database tool according to three different scores involved in antigen processing (TAP and proteasome scores) and HLA binding (MHC score). with a Vietnamese specificity held by two different haplotypes. The percentage of homology between Mekong and B consensus HIV-1 sequences was above 85%. Divergent epitopes had TAP and proteasome scores comparable with wild-type epitopes. MHC scores were significantly lower in divergent epitopes with a mean of 2.4 (±0.9) versus 2 (±0.7) in non-divergent ones (p<0.0001).Our study confirms the wide predominance of CRF01_AE in the Mekong Delta where patients harbor a specific HLA pattern. Moreover, it demonstrates the lower MHC binding affinity among divergent epitopes. This weak immune pressure combined with a narrow genetic diversity favors immune escape and could explain why CRF01_AE is still predominant in Vietnam, particularly in the Mekong area

Vaginally Administered PEGylated LIF Antagonist Blocked Embryo Implantation and Eliminated Non-Target Effects on Bone in Mice

Female-controlled contraception/HIV prevention is critical to address health issues associated with gender inequality. Therefore, a contraceptive which can be administered in tandem with a microbicide to inhibit sexually transmitted infections, is desirable. Uterine leukemia inhibitory factor (LIF) is obligatory for blastocyst implantation in mice and associated with infertility in women. We aimed to determine whether a PEGylated LIF inhibitor (PEGLA) was an effective contraceptive following vaginal delivery and to identify non-uterine targets of PEGLA in mice