HLA-A*23 Is Associated With Lower Odds of Acute Retroviral Syndrome in Human Immunodeficiency Virus Type 1 Infection: A Multicenter Sub-Saharan African Study.

The role of human leukocyte antigen (HLA) class I and killer immunoglobulin-like receptor molecules in mediating acute retroviral syndrome (ARS) during human immunodeficiency virus type 1 (HIV-1) infection is unclear. Among 72 sub-Saharan African adults, HLA-A*23 was associated with lower odds of ARS (adjusted odds ratio, 0.10 [95% confidence interval, .01-.48]; P = .009), which warrants further studies to explore its role on HIV-1-specific immunopathogenesis.

Success in vaccination programming through community health workers: a qualitative analysis of interviews and focus group discussions from Nepal, Senegal and Zambia.

OBJECTIVES: Community health workers are essential to front-line health outreach throughout low-income and middle-income countries, including programming for early childhood immunisation. Understanding how community health workers are engaged for successful early childhood vaccination among countries who showed success in immunisation coverage would support evidence-based policy guidance across contexts. DESIGN: We employed a multiple case study design using qualitative research methods. SETTING: We conducted research in Nepal, Senegal and Zambia. PARTICIPANTS: We conducted 207 interviews and 71 focus group discussions with 678 participants at the national, regional, district, health facility and community levels of the health systems of Nepal, Senegal and Zambia, from October 2019 to April 2021. We used thematic analysis to investigate contributing factors of community health worker programming that supported early childhood immunisation within each country and across contexts. RESULTS: Implementation of vaccination programming relied principally on the (1) organisation, (2) motivation and (3) trust of community health workers. Organisation was accomplished by expanding cadres of community health workers to carry out their roles and responsibilities related to vaccination. Motivation was supported by intrinsic and extrinsic incentives. Trust was expressed by communities due to community health worker respect and value placed on their work. CONCLUSION: Improvements in immunisation coverage was facilitated by community health worker organisation, motivation and trust. With the continued projection of health worker shortages, especially in low-income countries, community health workers bridged the equity gap in access to vaccination services by enabling wider reach to underserved populations. Although improvements in vaccination programming were seen in all three countries-including government commitment to addressing human resource deficits, training and remuneration; workload, inconsistency in compensation, training duration and scope, and supervision remain major challenges to immunisation programming. Health decision-makers should consider organisation, motivation and trust of community health workers to improve the implementation of immunisation programming.

Female Genital Schistosomiasis Lesion Resolution Post-Treatment with Praziquantel in Zambian Adults.

We evaluated changes in female genital schistosomiasis (FGS) 6 to 12 months after praziquantel treatment among 43 adult Zambian women. Most women (60%) experienced decreased FGS severity and 23% experienced complete lesion resolution. This is the first study to demonstrate a meaningful effect of praziquantel treatment of FGS in adult women.

Developing a diversity, equity and inclusion compass to guide scientific capacity strengthening efforts in Africa.

Diversity, equity and inclusion (DEI) in science is vital to improve the scientific process and ensure societal uptake and application of scientific results. DEI challenges include a full spectrum of issues from the lack of, and promotion of, women in science, to the numerous barriers in place that limit representation of African scientists in global scientific efforts. DEI principles in African science remain relatively underdeveloped, with limited engagement and discussion among all stakeholders to ensure that initiatives are relevant to local environments. The Sub-Saharan African Network for TB/HIV research Excellence (SANTHE) is a network of African-led research in HIV, tuberculosis (TB), associated co-morbidities, and emerging pathogens, now based in eight African countries. Our aim, as a scientific capacity strengthening network, was to collaboratively produce a set of DEI guidelines and to represent them visually as a DEI compass. We implemented a consortium-wide survey, focus group discussions and a workshop where we were able to identify the key DEI challenges as viewed by scientists and support staff within the SANTHE network. Three thematic areas were identified: 1. Conquering Biases, 2. Respecting the Needs of a Diverse Workforce (including mental health challenges, physical disability, career stability issues, demands of parenthood, and female-specific challenges), and 3. Promotion of African Science. From this we constructed a compass that included proposed steps to start addressing these issues. The use of the compass metaphor allows 're-adjustment/re-positioning' making this a dynamic output. The compass can become a tool to establish an institution's DEI priorities and then to progress towards them.

High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope.

A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks. Diversification and expansion of many B cell clonotypes occurred broadly in the absence of serum neutralization. However, in one animal that developed neutralization, two neutralizing B cell clonotypes arose from the same immunoglobulin germline and were tracked longitudinally. Early antibody variants with high identity to germline neutralized the autologous virus while later variants acquired somatic hypermutation and increased neutralization potency. The early engagement of precursors capable of neutralization with little to no SHM followed by prolonged affinity maturation allowed the two neutralizing lineages to successfully persist despite many other antigen specific B cells. The findings provide new insight into B cells responding to HIV-1 envelope during heterologous prime and boost immunization in rhesus macaques and the development of selected autologous neutralizing antibody lineages.

Critical success factors for high routine immunisation performance: a qualitative analysis of interviews and focus groups from Nepal, Senegal, and Zambia.

OBJECTIVES: Vaccination averts an estimated 2-3 million deaths annually. Although vaccine coverage improvements across Africa and South Asia have remained below global targets, several countries have outperformed their peers with significant increases in coverage. The objective of this study was to examine these countries' vaccination programmes and to identify and describe critical success factors that may have supported these improvements. DESIGN: Multiple case study design using qualitative research methods. SETTING: Three countries with high routine immunisation rates: Nepal, Senegal, and Zambia. PARTICIPANTS: We conducted 207 key informant interviews and 71 focus group discussions with a total of 678 participants. Participants were recruited from all levels, including government officials, health facility staff, frontline workers, community health workers, and parents. Participants were recruited from both urban and rural districts in Nepal, Senegal, and Zambia. RESULTS: Our data revealed that the critical success factors for vaccination programmes relied on the cultural, historical, and statutory context in which the interventions were delivered. In Nepal, Senegal, and Zambia, high immunisation coverage was driven by (1) strong governance structures and healthy policy environments; (2) adjacent successes in health system strengthening; (3) government-led community engagement initiatives, and (4) adaptation considering contextual factors at all levels of the health system. CONCLUSIONS: Throughout this project, our analysis returned to the importance of defining and understanding the context, governance, financing, and health systems within a country, rather than focusing on any one intervention. This paper augments findings from existing literature by highlighting how contextual factors impact implementation decisions that have led to improvements in childhood vaccine delivery. Findings from this research may help identify transferable lessons and support actionable recommendations to improve national immunisation coverage in other settings.

Drivers of early childhood vaccination success in Nepal, Senegal, and Zambia: a multiple case study analysis using the Consolidated Framework for Implementation Research.

INTRODUCTION: The fundamental components of a vaccine delivery system are well-documented, but robust evidence is needed on how the related processes and implementation strategies - including the facilitators and barriers - contribute to improvements in childhood vaccination coverage. The purpose of this study was to identify critical facilitators and barriers to the implementation of common interventions across three countries that have dramatically increased coverage of early childhood vaccination over the past 20 years, and to qualify common or divergent themes in their success. METHODS: We conducted 278 key informant interviews and focus group discussions with public health leaders at the regional, district, and local levels and community members in Nepal, Senegal, and Zambia to identify intervention activities and the facilitators and barriers to implementation. We used thematic analysis grounded in the Consolidated Framework for Implementation Research (CFIR) constructs of inner and outer settings to identify immunization program key facilitators and barriers. RESULTS: We found that the common facilitators to program implementation across the countries were the CFIR inner setting constructs of (1) networks and communications, (2) goals and feedback, (3) relative priority, and (4) readiness for implementation and outer setting constructs of (5) cosmopolitanism and (6) external policies and mandates. The common barriers were incentives and rewards, available resources, access to knowledge and information, and patients' needs and resources. Critical to the success of these national immunization programs were prioritization and codification of health as a human right, clear chain of command and shared ownership of immunization, communication of program goals and feedback, offering of incentives at multiple levels, training of staff central to vaccination education, the provision of resources to support the program, key partnerships and guidance on implementation and adoption of vaccination policies. CONCLUSION: Adequate organizational commitment, resources, communication, training, and partnerships were the most critical facilitators for these countries to improve childhood vaccination.

Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis1, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa2, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV3. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.3 log10-transformed copies per ml lower set-point viral load per minor allele copy and is specific to populations of African descent. The top associated variant is intergenic and lies between a long intergenic non-coding RNA (LINC00624) and the coding gene CHD1L, which encodes a helicase that is involved in DNA repair4. Infection assays in iPS cell-derived macrophages and other immortalized cell lines showed increased HIV-1 replication in CHD1L-knockdown and CHD1L-knockout cells. We provide evidence from population genetic studies that Africa-specific genetic variation near CHD1L associates with HIV replication in vivo. Although experimental studies suggest that CHD1L is able to limit HIV infection in some cell types in vitro, further investigation is required to understand the mechanisms underlying our observations, including any potential indirect effects of CHD1L on HIV spread in vivo that our cell-based assays cannot recapitulate.

Use of "Strengthening Our Vows" Video Intervention to Encourage Negotiated Explicit Sexual Agreements in Zambian Heterosexual HIV Seroconcordant-Negative Couples.

Negotiating sexual agreements in combination with couples' voluntary HIV counseling and testing (CVCT) may help further reduce HIV transmission in Zambian concordant HIV-negative couples (CNC). Though CVCT has been shown to reduce HIV transmission in CNC by 47%, approximately half of residual infections occur in this group. We developed a "Strengthening Our Vows" video session to foster communication and negotiation of explicit sexual agreements to reduce concurrent sexual exposures and prevent HIV transmission to the spouse due to unprotected, extramarital sex. CNC were recruited through CVCT services at five clinics in Lusaka and Ndola in 2016. Enrolled CNC attending the facilitated group video sessions were encouraged to discuss sexual agreements at home and return 1-2 weeks later for follow-up assessment. One-fourth of the 580 CNC returning reported a history of extramarital partners and/or a sexually transmitted infection (STI) prior to enrollment. More than 95% reported a friendly, supportive 15-60 min negotiation culminating in an agreement to remain monogamous or disclose sexual contacts and use condoms together until a repeat HIV test 30 days after an outside sexual exposure. Two-thirds of participants identified at least one threat to adherence of their agreements including alcohol use, financial pressures, travel, discord in the home, and post-partum or menstrual abstinence. CNC negotiated explicit sexual agreements to avoid exposure to HIV through concurrent partnerships and protect the spouse in the event of an outside sexual contact. Open communication was a consistent theme to facilitate mutual protective efforts. Long-term follow-up of HIV/STI incidence is ongoing to assess the impact of these agreements.Trial registration This sub-study is part of a trial retrospectively registered on ClinicalTrials.gov (Identifier: NCT02744586) on April 20, 2016.

Cohort-Specific Peptide Reagents Broaden Depth and Breadth Estimates of the CD8 T Cell Response to HIV-1 Gag Potential T Cell Epitopes.

An effective HIV vaccine will need to stimulate immune responses against the sequence diversity presented in circulating virus strains. In this study, we evaluate breadth and depth estimates of potential T-cell epitopes (PTEs) in transmitted founder virus sequence-derived cohort-specific peptide reagents against reagents representative of consensus and global sequences. CD8 T-cells from twenty-six HIV-1+ PBMC donor samples, obtained at 1-year post estimated date of infection, were evaluated. ELISpot assays compared responses to 15mer consensus (n = 121), multivalent-global (n = 320), and 10mer multivalent cohort-specific (n = 300) PTE peptides, all mapping to the Gag antigen. Responses to 38 consensus, 71 global, and 62 cohort-specific PTEs were confirmed, with sixty percent of common global and cohort-specific PTEs corresponding to consensus sequences. Both global and cohort-specific peptides exhibited broader epitope coverage compared to commonly used consensus reagents, with mean breadth estimates of 3.2 (global), 3.4 (cohort) and 2.2 (consensus) epitopes. Global or cohort peptides each identified unique epitope responses that would not be detected if these peptide pools were used alone. A peptide set designed around specific virologic and immunogenetic characteristics of a target cohort can expand the detection of CD8 T-cell responses to epitopes in circulating viruses, providing a novel way to better define the host response to HIV-1 with implications for vaccine development.

Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV.

Background: Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants. Methods: We used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses. Results: Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn't significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity. Conclusion: Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous.

Critical success factors for routine immunization performance: A case study of Zambia 2000 to 2018.

Introduction: The essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies prove effective at driving coverage is not well-established. To address this gap, we identified critical success factors associated with advancing key policies and programs that may have led to the substantial changes in routine childhood immunization coverage in Zambia between 2000 and 2018. Methods: We identified Zambia as an exemplar in the delivery of childhood vaccines through analysis of DTP1 and DTP3 coverage data. Through interviews and focus group discussions at the national and subnational levels, we investigated factors that contributed to high and sustained vaccination coverage. We conducted a thematic analysis through application of implementation science frameworks to determine critical success factors. We triangulated these findings with quantitative analyses using publicly available data. Results: The following success factors emerged: 1) the Inter-agency Coordinating Committee was strengthened for long-term engagement which, complemented by the Zambia Immunization Technical Advisory Group, is valued by the government and integrated into national-level decision-making; 2) the Ministry of Health improved the coordination of data collection and review for informed decision-making across all levels; 3) Regional multi-actor committees identified development priorities, strategies, and funding, and iteratively adjusted policies to account for facilitators, barriers, and lessons learned; 4) Vaccine messaging was disseminated through multiple channels, including the media and community leaders, increasing trust in the government by community members; 5) The Zambia Ministry of Health and Churches Health Association of Zambia formalized a long-term organizational relationship to leverage the strengths of faith-based organizations; and 6) Neighborhood Health Committees spearheaded community-driven strategies via community action planning and ultimately strengthened the link between communities and health facilities. Conclusion: Broader health systems strengthening and strong partnerships between various levels of the government, communities, and external organizations were critical factors that accelerated vaccine coverage in Zambia. These partnerships were leveraged to strengthen the overall health system and healthcare governance.

A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.

Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T/F Env sequences from two human subjects, one of whom developed potent and broad neutralizing antibodies (Z1800M) while the other developed little to no neutralizing antibody responses (R66M) during HIV-1 infection. Using a DNA/MVA/protein immunization protocol, 10 RM were immunized with each T/F Env. Within each T/F Env group, the protein boosts were administered as either monomeric gp120 or stabilized trimeric gp140 protein. All vaccination regimens elicited high titers of antigen-specific IgG, and two animals that received monomeric Z1800M Env gp120 developed autologous neutralizing activity. Using early Env escape variants isolated from subject Z1800M as guides, the serum neutralizing activity of the two immunized RM was found to be dependent on the gp120 V5 region. Interestingly, the exact same residues of V5 were also targeted by a neutralizing monoclonal antibody (nmAb) isolated from the subject Z1800M early in infection. Glycan profiling and computational modeling of the Z1800M Env gp120 immunogen provided further evidence that the V5 loop is exposed in this T/F Env and was a dominant feature that drove neutralizing antibody targeting during infection and immunization. An expanded B cell clonotype was isolated from one of the neutralization-positive RM and nmAbs corresponding to this group demonstrated V5-dependent neutralization similar to both the RM serum and the human Z1800M nmAb. The results demonstrate that neutralizing antibody responses elicited by the Z1800M T/F Env in RM converged with those in the HIV-1 infected human subject, illustrating the potential of using immunogens based on this or other T/F Envs with well-defined immunogenicity as a starting point to drive breadth.

Measles immunity gap among reproductive-age women participating in a simulated HIV vaccine efficacy trial in Zambia.

Measles is a vaccine-preventable viral disease whose vaccination coverage remains low in Zambia, where the target group for vaccination is children aged 9 to 18 months. In addition to inadequate measles vaccination coverage among children, few studies address potential resultant immunity gaps among adults. We analyzed data from a simulated HIV vaccine efficacy trial (SiVET) conducted from 2015-2017 among adult Zambian women of childbearing age to determine measles antibody seroprevalence before and after vaccination with the measles, mumps and rubella (MMR) vaccine. We used MMR vaccine as a substitute for an experimental HIV vaccine as part of a simulation exercise to prepare for an HIV vaccine efficacy trial. We found that 75% of women had measles antibodies prior to receiving MMR, which increased to 98% after vaccination. In contrast, mumps and rubella antibody prevalence was high before (93% and 97%, respectively) and after (99% and 100%, respectively) vaccination. The low baseline measles seropositivity suggests an immunity gap among women of childbearing age. We recommend that measles vaccination programs target women of childbearing age, who can pass antibodies on to neonates. Moreover, administering the MMR vaccine to clinical trial candidates could prevent measles, mumps or rubella-related adverse events during actual trials.

Exemplars in vaccine delivery protocol: a case-study-based identification and evaluation of critical factors in achieving high and sustained childhood immunisation coverage in selected low-income and lower-middle-income countries.

INTRODUCTION: Increases in global childhood vaccine delivery have led to decreases in morbidity from vaccine-preventable diseases. However, these improvements in vaccination have been heterogeneous, with some countries demonstrating greater levels of change and sustainability. Understanding what these high-performing countries have done differently and how their decision-making processes will support targeted improvements in childhood vaccine delivery. METHODS AND ANALYSIS: We studied three countries-Nepal, Senegal, Zambia-with exemplary improvements in coverage between 2000 and 2018 as part of the Exemplars in Global Health Programme. We apply established implementation science frameworks to understand the 'how' and 'why' underlying improvements in vaccine delivery and coverage. Through mixed-methods research, we will identify drivers of catalytic change in vaccine coverage and the decision-making process supporting these interventions and activities. Methods include quantitative analysis of available datasets and in-depth interviews and focus groups with key stakeholders in the global, national and subnational government and non-governmental organisation space, as well as community members and local health delivery system personnel. ETHICS AND DISSEMINATION: Working as a multinational and multidisciplinary team, and under oversight from all partner and national-level (where applicable) institutional review boards, we collect data from participants who provided informed consent. Findings are disseminated through a variety of forms, including peer-reviewed manuscripts related to country-specific case studies and vaccine system domain-specific analyses, presentations to key stakeholders in the global vaccine delivery space and narrative dissemination on the Exemplars.Health website.

Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study.

BACKGROUND: People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. RESULTS: We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28-42) years and 31(25-36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465-702.5 cells/mm3] vs 345 [157-483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827-23,686 pg/ml] vs. 9,508 [5,514-15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990-24,206 pg/ml] vs 9,505 [5,400-15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087-22,584 pg/ml] vs 10,413 [7,397-14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36-0.72; p < 0.0001) and r = 0.48 (95% CI 0.15-0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0-0.28] vs 0.007 [0-0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. CONCLUSIONS: This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.

A comparison of vitamin D and cathelicidin (LL-37) levels between patients with active TB and their healthy contacts in a high HIV prevalence setting: a prospective descriptive study.

BACKGROUND: Studies from Asia and Europe indicate an association between vitamin D deficiency and susceptibility to TB. We performed an observational case-control study to determine vitamin D and cathelicidin (LL-37) levels and their association with active TB in newly diagnosed and microbiologically confirmed adult TB patients in Zambia, a high HIV prevalence setting. METHODS: Both total vitamin D and LL-37 were measured using ELISA from serum and supernatant isolated from cultured whole blood that was stimulated with heat-killed Mycobacterium tuberculosis. Statistical analysis was performed using STATA statistical software version 12. RESULTS: The median vitamin D in TB patients and healthy contacts was 28.7 (19.88-38.64) and 40.8 (31.2-49.44) ng/ml, respectively (p<0.001). The median LL-37 in TB patients compared with healthy contacts was 1.87 (2.74-8.93) and 6.73 (5.6-9.58) ng/ml, respectively (p=0.0149). Vitamin D correlation with LL-37 in healthy contacts was R2=0.7 (95% CI 0.566 to 0.944), p<0.0001. Normal vitamin D significantly predicted a healthy status (OR 4.06, p=0.002). CONCLUSIONS: Significantly lower levels of vitamin D and LL-37 are seen in adults with newly diagnosed active TB. Longitudinal studies across various geographical regions are required to accurately define the roles of vitamin D and LL-37 in preventive and TB treatment outcomes.

Evolution of Condom Use Among a 5-Year Cohort of Female Sex Workers in Zambia.

Observing sexual behaviour change over time could help develop behavioural HIV prevention interventions for female sex workers in Zambia, where these interventions are lacking. We investigated the evolution of consistent condom use among female sex workers and their clients and steady partners. Participants were recruited into an HIV incidence cohort from 2012 to 2017. At each visit, women received HIV counselling and testing, screening for sexually transmitted infections (STIs) and free condoms. Our outcome was reported consistent (100%) condom use in the previous month with steady partners, repeat clients, and non-repeat clients. Consistent condom use at baseline was highest with non-repeat clients (36%) followed by repeat clients (27%) and steady partners (17%). Consistent condom use between baseline and Month 42 increased by 35% with steady partners, 39% with repeat clients and 41% with non-repeat clients. Access to condoms, HIV/STI counselling and testing promoted positive sexual behaviour change.

A cluster randomized trial to reduce HIV risk from outside partnerships in Zambian HIV-Negative couples using a novel behavioral intervention, "Strengthening Our Vows": Study protocol and baseline data.

BACKGROUND: Heterosexual couples contribute to most new HIV infections in areas of generalized HIV epidemics in sub-Saharan Africa. After Couples' Voluntary HIV Counseling and Testing (CVCT), heterosexual concordant HIV negative couples (CNC) in cohabiting unions contribute to approximately 47% of residual new infections in couples. These infections are attributed to concurrent sexual partners, a key driver of the HIV epidemic in Zambia. METHODS/DESIGN: Ten Zambian government clinics in two of the largest cities were randomized in matched pairs to a Strengthening Our Vows (SOV) intervention or a Good Health Package (GHP) comparison arm. SOV addressed preventing HIV infection from concurrent partners and protecting spouses after exposures outside the relationship. GHP focused on handwashing; water chlorination; household deworming; and screening for hypertension, diabetes and schistosomiasis. CNC were referred from CVCT services in government clinics. Follow-up includes post-intervention questionnaires and outcome assessments through 60 months. Longitudinal outcomes of interest include self-report and laboratory markers of condomless sex with outside partners and reported sexual agreements. We present baseline characteristics and factors associated with study arm and reported risk using descriptive statistics. RESULTS: The mean age of men was 32 and 26 for women. On average, couples cohabited for 6 years and had 2 children. Baseline analyses demonstrated some failures of randomization by study arm which will be considered in future primary analyses of longitudinal data. An HIV/STI risk factor composite was not different in the two study arms. Almost one-quarter of couples had an HIV risk factor at baseline. DISCUSSION: In preparation for future biomedical and behavioral interventions in sub-Saharan Africa, it is critical to understand and decrease HIV risk within CNC.