Motivations and barriers to uptake and use of female-initiated, biomedical HIV prevention products in sub-Saharan Africa: an adapted meta-ethnography

Abstract: Background: Women bear a disproportionate burden of HIV throughout the world prompting extensive research into HIV prevention products for women which has met with varied success. With an aim of informing future policy and programming, this review examines the barriers and motivations to the uptake and use of female initiated products in sub-Saharan countries. Methods: We conducted a systematic review as an adapted meta-ethnography of qualitative data focused on actual use of products. After deduplication, 10,581 and 3861 papers in the first and second round respectively were screened. Following the PRISMA guidance, 22 papers were selected and synthesized using Malpass’s definitions of first, second, and third order constructs. First order constructs, consisting of participant data published in the selected papers, were extracted and categorised by second and third order constructs for analysis. A weight of evidence review was conducted to compare and assess quality across the papers. Results: The 22 papers selected span 11 studies in 13 countries. We derived 23 s order constructs that were translated into seven overarching third order constructs: Sexual Satisfaction, Trust, Empowerment and Control, Personal Well-being, Product use in the social-cultural environment, Practical Considerations, Risk Reduction, and Perceptions of Efficacy. Relationships and trust were seen to be as or more important for product use as efficacy. These constructs reveal an inherent inter-relationality where decision making around HIV prevention uptake and use cannot be binary or mono-faceted, but rather conducted on multiple levels. We developed a framework illustrating the central and proximal natures of constructs as they relate to the decision-making process surrounding the use of prevention products. Conclusions: Health systems, structural, and individual level HIV prevention interventions for women should adopt a holistic approach. Interventions should attend to the ways in which HIV prevention products can serve to reduce the likelihood of HIV transmission, as well as help to protect partnerships, enhance sexual pleasure, and take into account woman’s roles in the social environment. Stigma, as well as sexuality, is likely to continue to influence product uptake and use and should be prominently taken into account in large-scale interventions. Trial registration: Not applicable

The integrin α4β7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1

Both activated and resting CD4+ T cells in mucosal tissues play important roles in the earliest phases of infection after sexual transmission of HIV-1, a process that is inefficient. HIV-1 gp120 binds to integrin α4β7 (α4β7), the gut mucosal homing receptor. We find that α4β7high CD4+ T cells are more susceptible to productive infection than are α4β7low-neg CD4+ T cells in part because this cellular subset is enriched with metabolically active CD4+ T cells. α4β7high CD4+ T cells are CCR5high and CXCR4low; on these cells, α4β7 appears in a complex with CD4. The specific affinity of gp120 for α4β7 provides a mechanism for HIV-1 to target activated cells that are critical for efficient virus propagation and dissemination following sexual transmission

Optimizing Viable Leukocyte Sampling from the Female Genital Tract for Clinical Trials: An International Multi-Site Study

<div><p>Background</p><p>Functional analysis of mononuclear leukocytes in the female genital mucosa is essential for understanding the immunologic effects of HIV vaccines and microbicides at the site of HIV exposure. However, the best female genital tract sampling technique is unclear.</p><p>Methods and Findings</p><p>We enrolled women from four sites in Africa and the US to compare three genital leukocyte sampling methods: cervicovaginal lavages (CVL), endocervical cytobrushes, and ectocervical biopsies. Absolute yields of mononuclear leukocyte subpopulations were determined by flow cytometric bead-based cell counting. Of the non-invasive sampling types, two combined sequential cytobrushes yielded significantly more viable mononuclear leukocytes than a CVL (p<0.0001). In a subsequent comparison, two cytobrushes yielded as many leukocytes (∼10,000) as one biopsy, with macrophages/monocytes being more prominent in cytobrushes and T lymphocytes in biopsies. Sample yields were consistent between sites. In a subgroup analysis, we observed significant reproducibility between replicate same-day biopsies (r = 0.89, p = 0.0123). Visible red blood cells in cytobrushes increased leukocyte yields more than three-fold (p = 0.0078), but did not change their subpopulation profile, indicating that these leukocytes were still largely derived from the mucosa and not peripheral blood. We also confirmed that many CD4⁺ T cells in the female genital tract express the α4β7 integrin, an HIV envelope-binding mucosal homing receptor.</p><p>Conclusions</p><p>CVL sampling recovered the lowest number of viable mononuclear leukocytes. Two cervical cytobrushes yielded comparable total numbers of viable leukocytes to one biopsy, but cytobrushes and biopsies were biased toward macrophages and T lymphocytes, respectively. Our study also established the feasibility of obtaining consistent flow cytometric analyses of isolated genital cells from four study sites in the US and Africa. These data represent an important step towards implementing mucosal cell sampling in international clinical trials of HIV prevention.</p></div

Comparison of immune cell yield and distribution in endocervical cytobrush (CB) and ectocervical biopsy samples.

<p>(<b>A</b>) Representative gates for identification of CD45⁺ leukocytes from cytobrush and biopsy samples. (<b>B</b>) Numbers of CD45⁺ leukocytes, CD4⁺ T cells, CD8⁺ T cells, CD19⁺ B cells, CD14⁺ macrophages, and CD19^neg/HLA-DQ⁺ DC enumerated from cytobrush and biopsy samples. Cell numbers were log₁₀ transformed, and plotted per site (Chicago, red dots; Nairobi, blue dots; Seattle, black dots). Horizontal bars indicate median values for each site. (<b>C</b>) Percentage contribution of each cell subset, as well as of cells that do not fit one of the described populations (“unknown”), to the total CD45⁺ population from cytobrush and biopsy samples. Data are averaged across sites. P values are listed in the text, and median and IQR in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085675#pone-0085675-t002" target="_blank">Table 2</a>.</p

Inter-site variability and sample reproducibility from female genital tract immune cell sampling techniques.

<p>(<b>A</b>) Percentage contribution of each immune cell population to the total CD45⁺ population recovered from CVL, cytobrush, and biopsy samples collected at the Seattle, Chicago, and Nairobi study sites. (<b>B</b>) Numbers of CD45⁺ leukocytes recovered from cytobrush samples collected from all women recruited in Chicago. Filled circles and connecting lines indicate women participating in both Part 1 and Part 2 of the study (n = 12). Open circles indicate women sampled only in one part of the study. Boxes indicate median, interquartile range and total range. (<b>C</b>) Scatterplot of cell numbers from the twelve women sampled in both Part 1 (x axis) and Part 2 (y axis) of the study. (<b>D</b>) Scatterplot of cell numbers from replicate biopsies collected at the same clinic visit in seven participants at the Nairobi study site. Biopsies were taken from upper left and upper right quadrants of the ectocervix.</p

Median (IQR) numbers of leukocyte subpopulations in endocervical cytobrushes (CB) and ectocervical biopsies.

<p>CD4, helper T lymphocytes; CD8, cytotoxic T lymphocytes; B, B lymphocytes; MΦ, macrophages; DC, dendritic cells.</p

Median (IQR) numbers of leukocyte subpopulations in endocervical cytobrushes (CB) and cervicovaginal lavages (CVL).

<p>CD4, helper T lymphocytes; CD8, cytotoxic T lymphocytes; B, B lymphocytes; MΦ, macrophages; DC, dendritic cells.</p

Percentages of α4β7⁺ immune cells isolated from cytobrush (CB) and biopsy samples at the Seattle (black dots) and Chicago (red dots) study sites.

<p>Percent α4β7 expression on CD4⁺ T cells, CD8⁺ T cells, CD19⁺ B cells and CD19^neg/HLA-DQ⁺ DC. Samples are only shown if more than 50 cells were acquired for the indicated population. Horizontal bars indicate median values for each site.</p