Annabelle Gourlay

Barriers and facilitating factors to the uptake of antiretroviral drugs for prevention of mother-to-child transmission of HIV in sub-Saharan Africa:a systematic review

To investigate and synthesize reasons for low access, initiation and adherence to antiretroviral drugs by mothers and exposed babies for prevention of mother‐to‐child transmission (PMTCT) of HIV in sub‐Saharan Africa.

“It Is Like That, We Didn't Understand Each Other”: Exploring the Influence of Patient-Provider Interactions on Prevention of Mother-To-Child Transmission of HIV Service Use in Rural Tanzania

Interactions between patients and service providers frequently influence uptake of prevention of mother-to-child transmission (PMTCT) HIV services in sub-Saharan Africa, but this process has not been examined in depth. This study explores how patient-provider relations influence PMTCT service use in four government facilities in Kisesa, Tanzania. Qualitative data were collected in 2012 through participatory group activities with community members (3 male, 3 female groups), in-depth interviews with 21 women who delivered recently (16 HIV-positive), 9 health providers, and observations in antenatal clinics. Data were transcribed, translated into English and analysed with NVIVO9 using an adapted theoretical model of patient-centred care. Three themes emerged: decision-making processes, trust, and features of care. There were few examples of shared decision-making, with a power imbalance in favour of providers, although they offered substantial psycho-social support. Unclear communication by providers, and patients not asking questions, resulted in missed services. Omission of pre-HIV test counselling was often noted, influencing womens ability to opt-out of HIV testing. Trust in providers was limited by confidentiality concerns, and some HIV-positive women were anxious about referrals to other facilities after establishing trust in their original provider. Good care was recounted by some women, but many (HIV-positive and negative) described disrespectful staff including discrimination of HIV-positive patients and scolding, particularly during delivery; exacerbated by lack of materials (gloves, sheets) and associated costs, which frustrated staff. Experienced or anticipated negative staff behaviour influenced adherence to subsequent PMTCT components. Findings revealed a pivotal role for patient-provider relations in PMTCT service use. Disrespectful treatment and lack of informed consent for HIV testing require urgent attention by PMTCT programme managers. Strategies should address staff behaviour, emphasizing ethical standards and communication, and empower patients to seek information about available services. Optimising provider-patient relations can improve uptake of maternal health services more broadly, and ART adherence.

Using vignettes in qualitative research to explore barriers and facilitating factors to the uptake of prevention of mother-to-child transmission services in rural Tanzania: a critical analysis

BackgroundVignettes are short stories about a hypothetical person, traditionally used within research (quantitative or qualitative) on sensitive topics in the developed world. Studies using vignettes in the developing world are emerging, but with no critical examination of their usefulness in such settings. We describe the development and application of vignettes to a qualitative investigation of barriers to uptake of prevention of mother-to-child transmission (PMTCT) HIV services in rural Tanzania in 2012, and critique the successes and challenges of using the technique in this setting.MethodsParticipatory Learning and Action (PLA) group activities (3 male; 3 female groups from Kisesa, north-west Tanzania) were used to develop a vignette representing realistic experiences of an HIV-infected pregnant woman in the community. The vignette was discussed during in-depth interviews with 16 HIV-positive women, 3 partners/relatives, and 5 HIV-negative women who had given birth recently. A critical analysis was applied to assess the development, implementation and usefulness of the vignette.ResultsThe majority of in-depth interviewees understood the concept of the vignette and felt the story was realistic, although the story or questions needed repeating in some cases. In-depth interviewers generally applied the vignette as intended, though occasionally were unsure whether to steer the conversation back to the vignette character when participants segued into personal experiences. Interviewees were occasionally confused by questions and responded with what the character should do rather than would do; also confusing fieldworkers and presenting difficulties for researchers in interpretation. Use of the vignette achieved the main objectives, putting most participants at ease and generating data on barriers to PMTCT service uptake. Participants’ responses to the vignette often reflected their own experience (revealed later in the interviews).ConclusionsParticipatory group research is an effective method for developing vignettes. A vignette was incorporated into qualitative interview discussion guides and used successfully in rural Africa to draw out barriers to PMTCT service use; vignettes may also be valuable in HIV, health service use and drug adherence research in this setting. Application of this technique can prove challenging for fieldworkers, so thorough training should be provided prior to its use.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges

Summary Definitions for a 4-stage continuum of HIV care were standardized and applied to HIV surveillance and national cohort data in 11 European Union countries. These countries are nearing the UNAIDS 90-90-90 target, although reducing the proportion undiagnosed remains challenging.

Viral genetic variation accounts for a third of variability in HIV-1 set-point viral load in Europe.

HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%–43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical “Brownian motion” model and another model (“Ornstein–Uhlenbeck”) that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%–43%) is consistent with other studies based on regression of viral load in donor–recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation.

Factors associated with uptake of services to prevent mother-to-child transmission of HIV in a community cohort in rural Tanzania

Objectives This study aimed to identify factors associated with access to HIV care and antiretroviral (ARV) drugs for prevention of mother-to-child transmission (PMTCT) of HIV among HIV-positive pregnant women in a community cohort in rural Tanzania (Kisesa). Methods Kisesa-resident women who tested HIV-positive during HIV serosurveillance and were pregnant (while HIV-positive) between 2005 and 2012 were eligible. Community cohort records were linked to PMTCT and HIV clinic data from four facilities (PMTCT programme implemented in 2009; referrals to city-based hospitals since 2005) to ascertain service use. Factors associated with access to HIV care and ARVs during pregnancy were analysed using logistic regression. Results Overall, 24% of women accessed HIV care and 12% accessed ARVs during pregnancy (n=756 pregnancies to 420 women); these proportions increased over time. In multivariate analyses for 2005–2012, being married, prior voluntary counselling and testing, increasing age, increasing year of pregnancy and increasing duration of infection were independently associated with access to care and ARVs. Residence in roadside areas was an independent predictor of access to care but not ARVs. There was no evidence of an interaction with time period. Conclusions Access to PMTCT services was low in this rural setting but improved markedly over time. There were fairly few sociodemographic differentials although support for young women and those without partners may be needed. Further decentralisation of HIV services to more remote areas, promotion of voluntary counselling and testing and implementation of Option B+ are likely to improve uptake and may bring women into care and treatment sooner after infection.

Easy and Accurate Reconstruction of Whole HIV Genomes from Short-Read Sequence Data

Next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of rapid between- and within-host evolution may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions. De novo assembly avoids this bias by effectively aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the tool shiver to preprocess reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We use shiver to reconstruct the consensus sequence and minority variant information from paired-end short-read data produced with the Illumina platform, for 65 existing publicly available samples and 50 new samples. We show the systematic superiority of mapping to shiver’s constructed reference over mapping the same reads to the standard reference HXB2: an average of 29 bases per sample are called differently, of which 98.5% are supported by higher coverage. We also provide a practical guide to working with imperfect contigs.

A Phylogenetic Analysis of HIV-1 Sequences in Kiev: Findings among Key Populations.

Background The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013-March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56-7.50]); risk group (OR, 5.65 [95% CI, 3.27-9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64-4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07-3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10-3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31-.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions Our findings suggest high levels of transmission and bridging between risk groups.

Towards standardized definitions for monitoring the continuum of HIV care in Europe

The continuum of HIV care is a simple conceptual framework for monitoring HIV programmes, comprising a series of stages that people living with HIV (PLHIV) pass through to access antiretroviral treatment (ART) and achieve viral suppression [1,2]. Individual benefits of suppression include reduced risk of morbidity and mortality. At the population level, viral suppression reduces the risk of onward transmission and enables epidemic containment [3]. Transmission risk may be further reduced by lowering the number of undiagnosed PLHIV [4,5]. Complete continua are, therefore, constructed beginning with the total number of PLHIV in a given population and ending with the number virally suppressed. Intervening stages have included the numbers diagnosed, linked to HIV care, retained in care, eligible for ART, on ART and adhering to ART. Although people can move between stages, the continuum is typically conceptualized as a ‘snapshot’ at one time-point. As the Joint United Nations Programme on HIV and AIDS (UNAIDS) announced the target of reaching ‘90-90-90’ by 2020, which envisions 90% of PLHIV diagnosed, 90% of those diagnosed on ART and 90% of those on ART virally suppressed [6], interest in constructing HIV care continua to inform national programmes and policies has grown [7–11]. However, there has been limited consistency in the methods used to construct these measures and the stages presented in publications. Key stages are often missing or continua entirely absent for many countries, including in Europe, particularly the Eastern region [7,8,11–15]. Drawing from a review of recent literature and expert opinion, we highlight the methodological inconsistencies, the challenges associated with constructing each stage and recommend a standardized way forward for monitoring the continuum of HIV care in Europe.

Risk factors for service use and trends in coverage of different HIV testing and counselling models in northwest Tanzania between 2003 and 2010

To investigate the relative effectiveness of different HIV testing and counselling (HTC) services in improving HIV diagnosis rates and increasing HTC coverage in African settings.