Articles tagged as "Uganda"

Mixed methods in biomedical intervention trials yield rich data – the VOICE-D qualitative study

How presentation of drug detection results changed reports of product adherence in South Africa, Uganda and Zimbabwe.

Musara P, Montgomery ET, Mgodi NM, Woeber K, Akello CA, Hartmann M, Cheng H, Levy L, Katz A, Grossman CI, Chirenje ZM, van der Straten A, Mensch B. AIDS Behav. 2017 Jan 21. doi: 10.1007/s10461-017-1685-x. [Epub ahead of print]

Accurate estimates of study product use are critical to understanding and addressing adherence challenges in HIV prevention trials. The VOICE trial exposed a significant gap between self-reported adherence and drug detection. The VOICE-D qualitative study was designed to better understand non-adherence during VOICE, and was conducted in 2 stages: before (stage 1) and after (stage 2) drug detection results were provided to participants. Transcripts from 44 women who participated in both stages were analysed to understand the effect of presenting drug detection data on narratives of product use. Thirty-six women reported high adherence in stage 1, yet admitted non-use in stage 2, three reported high adherence in both stages (contrary to their drug detection results) and five had consistent responses across both stages and drug results. Presenting objective measures of use may facilitate more accurate product use reporting and should be evaluated in future prevention trials.

Abstract access  

Editor’s notes: The VOICE trial looked at the effectiveness of PrEP and vaginal microbicides in women in three African countries. One of the findings of the study was low product adherence among some women, based on retrospective drug level testing. In this paper, the authors compare data on product adherence from before and after participants were given plasma drug detection results. The findings are revealing, not least because many of women interviewed explained why they had claimed to be adhering to the drug, when they were not. Women gave many reasons for not being open about taking their medicines/use of the microbicide. It is interesting that a few women continued to say that they were good adherers, even when presented with drug plasma data, which suggested otherwise. This, the authors note, requires further investigation. 

The findings provide valuable evidence of the shortcomings of collecting self-reported adherence data. The use of biomedical markers to reveal drug plasma levels is important. However, the qualitative research, which documented the discussion around those findings, is both fascinating and extremely useful. Perhaps in future there will be an even greater willingness to fund good qualitative research as a key component of trials?

Africa
South Africa, Uganda, Zimbabwe
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Violence and sex work in Uganda

Policing the epidemic: high burden of workplace violence among female sex workers in conflict-affected northern Uganda.

Muldoon KA, Akello M, Muzaaya G, Simo A, Shoveller J, Shannon K. Glob Public Health. 2017 Jan;12(1):84-97. Epub 2015 Oct 27.

Sex workers in sub-Saharan Africa experience a high burden of HIV with a paucity of data on violence and links to HIV risk among sex workers, and even less within conflict-affected environments. Data are from a cross-sectional survey of female sex workers in Gulu, northern Uganda (n = 400). Logistic regression was used to determine the specific association between policing and recent physical/sexual violence from clients. A total of 196 (49.0%) sex workers experienced physical/sexual violence by a client. From those who experienced client violence the most common forms included physical assault (58.7%), rape (38.3%), and gang rape (15.8%) Police harassment was very common, a total of 149 (37.3%) reported rushing negotiations with clients because of police presence, a practice that was significantly associated with increased odds of client violence (adjusted odds ratio: 1.61, 95% confidence intervals: 1.03-2.52). Inconsistent condom use with clients, servicing clients in a bar, and working for a manager/pimp were also independently associated with recent client violence. Structural and community-led responses, including decriminalisation, and engagement with police and policy stakeholders, remain critical to addressing violence, both a human rights and public health imperative.

Abstract access  

Editor’s notes: Sex workers are at increased risk of HIV and of violence from multiple perpetrators. There is a paucity of research examining violence among sex workers in conflict-affected areas. Sex work in Uganda is illegal. A police presence can reduce sex workers ability to screen for dangerous clients, negotiate sex acts, price and condom use. This study is from northern Uganda. The site, now at peace, has experienced 20 years of war. A quarter of sex workers are living with HIV. The paper examines the prevalence of client violence, police arrest and other factors, and how they interrelate.

Participants in the study were usually young (median age 21 years), poorly educated and had ≥1 child. One third had been abducted into the Lord’s Resistance Army and two thirds had lived in an Internal Displacement Camp. Some 49% had experienced recent physical or sexual violence from clients.  Eight percent had been gang raped in the past six months. Policing, inconsistent condom use, having sex in a bar and working for a manager or pimp were significantly associated with client violence. Sex workers in this survey face a high prevalence of violence and HIV. Decriminalisation of sex work is vital if sex workers are to access labour and human rights protection and to reduce the high prevalence of violence and HIV

Africa
Uganda
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Peer support: not a panacea for poor adherence

Use of peers to improve adherence to antiretroviral therapy: a global network meta-analysis.

Kanters S, Park JJ, Chan K, Ford N, Forrest J, Thorlund K, Nachega JB, Mills EJ. J Int AIDS Soc. 2016 Nov 30;19(1):21141. doi: 10.7448/IAS.19.1.21141. eCollection 2016.

Introduction: It is unclear whether using peers can improve adherence to antiretroviral therapy (ART). To construct the World Health Organization's global guidance on adherence interventions, we conducted a systematic review and network meta-analysis to determine the effectiveness of using peers for achieving adequate adherence and viral suppression.

Methods: We searched for randomized clinical trials of peer-based interventions to promote adherence to ART in HIV populations. We searched six electronic databases from inception to July 2015 and major conference abstracts within the last three years. We examined the outcomes of adherence and viral suppression among trials done worldwide and those specific to low- and middle-income countries (LMIC) using pairwise and network meta-analyses.

Results and discussion: Twenty-two trials met the inclusion criteria. We found similar results between pairwise and network meta-analyses, and between the global and LMIC settings. Peer supporter+Telephone was superior in improving adherence than standard-of-care in both the global network (odds-ratio [OR]=4.79, 95% credible intervals [CrI]: 1.02, 23.57) and the LMIC settings (OR=4.83, 95% CrI: 1.88, 13.55). Peer support alone, however, did not lead to improvement in ART adherence in both settings. For viral suppression, we found no difference of effects among interventions due to limited trials.

Conclusions: Our analysis showed that peer support leads to modest improvement in adherence. These modest effects may be due to the fact that in many settings, particularly in LMICs, programmes already include peer supporters, adherence clubs and family disclosures for treatment support. Rather than introducing new interventions, a focus on improving the quality in the delivery of existing services may be a more practical and effective way to improve adherence to ART.

Abstract  Full-text [free] access 

Editor’s notes: Sustained adherence to antiretroviral therapy (ART) is critical to ensure successful treatment outcomes and prevent drug resistance, AIDS-associated illness, death and onward transmission of HIV infection. In recent years, there has been much enthusiasm for use of peer support as a programme to improve adherence. Most high HIV prevalence settings have limited resources. Stigma influences adherence to treatment, and peer-based support may be a practical solution both in terms of being low cost and a mechanism for addressing stigma.

In this systematic review, the authors evaluated the effectiveness of peer-supporter programmes alone or in combination with other activities, namely telephone calls, device reminders or cognitive behavioural therapy (CBT), globally and in low and middle-income countries (LMIC). The systematic review findings were used to inform the 2015 World Health Organization HIV treatment guidelines.

The study demonstrates that peer support alone did not have any impact on adherence or on viral suppression. It did demonstrate modest improvements on adherence when combined with telephone activities. Several factors need to be considered in interpreting these findings. Firstly, adherence was assessed using a variety of methods including pill counts and the Medication Event Monitoring System (MEMS), which may have introduced heterogeneity. Secondly, few trials (particularly in LMICs) used HIV viral load as an outcome and therefore there may not have been adequate statistical power to detect an effect. Thirdly, populations included in the review were heterogeneous e.g. ART-naïve and experienced, people who inject drugs, non-adherent individuals. Notably, only one trial included children and adolescents among whom adherence is typically poorer. 

Importantly, in many settings particularly in LMICs, programmes already include treatment supporters and adherence clubs and therefore additional peer support would likely not add additional impact. The findings of this study suggest that programmes should focus on improving the quality of existing services rather than introduce new programmes. The review also highlights the need to standardise adherence measures and the need for robust research on adherence, particularly among children.         

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Thymidine analogue mutations associated with extensive resistance in African people failing on tenofovir

Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub-Saharan Africa: a retrospective multi-centre cohort study.

Gregson J, Kaleebu P, Marconi VC, van Vuuren C, Ndembi N, Hamers RL, Kanki P, Hoffmann CJ, Lockman S, Pillay D, de Oliveira T, Clumeck N, Hunt G, Kerschberger B, Shafer RW, Yang C, Raizes E, Kantor R, Gupta RK. Lancet Infect Dis. 2016 Nov 30. pii: S1473-3099(16)30469-8. doi: 10.1016/S1473-3099(16)30469-8. [Epub ahead of print]

Background: HIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART.

Methods: We retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs.

Findings: Of 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60.5 cells per µL [IQR 21.0-128.0] in patients with TAMS vs 95.0 cells per µL [37.0-177.0] in patients without TAMs; p=0.007) and were more likely to have tenofovir resistance (93 [81%] of 115 patients with TAMs vs 352 [59%] of 597 patients without TAMs; p<0.0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0.0001), and cytosine analogue resistance (100 [87%] vs 378 [63%]; p=0.0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0.64 (p<0.0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1.29 (1.13-1.47; p<0.0001)

Interpretation: TAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains.

Abstract  Full-text [free] access 

Editor’s notes: Since 2012, WHO has recommended that tenofovir should be included in first-line antiretroviral therapy, in place of the thymidine analogues, zidovudine and stavudine, which have more significant adverse effects. When therapy fails to maintain virologic control, tenofovir is associated with characteristic resistance mutations that are different from the thymidine analogue mutations (TAMs) associated with the older drugs. This study looked at the resistance patterns of people in Africa with virologic failure after starting on WHO recommended first-line combination including tenofovir and a non-nucleoside reverse transcriptase inhibitor (NNRTI).  TAMs were surprisingly common (16%) for a group who were not known to have received thymidine analogues. This is not what would be expected from this drug combination. The implication is that TAMs may have been present before tenofovir-containing treatment was started, possibly because of undeclared previous therapy. It is well known that TAMs make subsequent therapy with an NNRTI and nucleoside analogues very much more likely to fail. The presence of TAMs was associated with more extensive resistance to other drugs including lamivudine and NNRTIs, some of which may also have been present before the tenofovir based treatment.

Only people with treatment failure were studied. The total number entering into treatment is not recorded. However, based on other reports in Africa the authors speculate a failure rate of 15 to 35% and that they may therefore have found TAMs in two to six percent of people who started treatment. That seems a realistic figure for undeclared prior treatment and gives some perspective to the scale of this problem.

There is continuing concern about drug resistance in low- and middle-income countries.  As the thymidine analogues are phased out, people receiving them may be switched to tenofovir. In situations where there is no access to viral load monitoring, some people will have unrecognised virologic failure and may have developed resistance including TAMs. They are then likely to fail on tenofovir with additional resistance. Realistic strategies are necessary for the prompt detection of treatment failure.

Africa
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Home-based HIV testing more effective than community testing, but fewer linked to care

A comparison of home-based versus outreach event-based community HIV testing in Ugandan fisherfolk communities.

Bogart LM, Wagner GJ, Musoke W, Naigino R, Linnemayr S, Maistrellis E, Klein DJ, Jumamil RB, Mukasa B, Bassett IV, Giordano TP, Wanyenze RK. AIDS Behav. 2016 Nov 29. [Epub ahead of print]

We compared two community-based HIV testing models among fisherfolk in Lake Victoria, Uganda. From May to July 2015, 1364 fisherfolk residents of one island were offered (and 822 received) home-based testing, and 344 fisherfolk on another island were offered testing during eight community mobilization events (outreach event-based testing). Of 207 home-based testing clients identified as HIV-positive (15% of residents), 82 were newly diagnosed, of whom 31 (38%) linked to care within 3 months. Of 41 who screened positive during event-based testing (12% of those tested), 33 were newly diagnosed, of whom 24 (75%) linked to care within 3 months. Testing costs per capita were similar for home-based ($45.09) and event-based testing ($46.99). Compared to event-based testing, home-based testing uncovered a higher number of new HIV cases but was associated with lower linkage to care. Novel community-based test-and-treat programs are needed to ensure timely linkage to care for newly diagnosed fisherfolk.

Abstract access  

Editor’s notes: Regular and reliable HIV testing is necessary to ensure that people who need antiretroviral treatment know their status. When someone tests positive for HIV, it is critical that they are linked to care. This study compares two different types of HIV testing among fisherfolk in Uganda – home-based and community event-based testing. The authors find that home-based testing uncovered more people living with HIV than community event-based testing, but a lower proportion of people were successfully linked to care. The costs of both types of testing were similar. Fewer new people living with HIV were identified through community event-based testing. People who know that they are HIV positive are perhaps more likely to attend such events than people who have not sought to be tested recently, or who are HIV negative. Home-based testing requires less effort from persons receiving a test, and therefore may reach people less likely to test independently. This study further emphasises that linkage to care is a critical step in the HIV treatment cascade.

HIV testing
Africa
Uganda
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At the halfway mark? Community viral suppression in East Africa

Population levels and geographical distribution of HIV RNA in rural Ugandan and Kenyan communities, including serodiscordant couples: a cross-sectional analysis.

Jain V, Petersen ML, Liegler T, Byonanebye DM, Kwarisiima D, Chamie G, Sang N, Black D, Clark TD, Ladai A, Plenty A, Kabami J, Ssemmondo E, Bukusi EA, Cohen CR, Charlebois ED, Kamya MR, Havlir DV. Lancet HIV. 2016 Dec 15. pii: S2352-3018(16)30220-X. doi: 10.1016/S2352-3018(16)30220-X. [Epub ahead of print]

Background: As sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa.

Methods: The Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged 15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603.

Findings: Between April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90.3%), of whom 132 030 (48.2%) were adults. Of these, 117 711 (89.2%) had their HIV status established, of whom 11 964 (10.2%) were HIV positive. Of these, we measured viral load in 8828 (73.8%) people. Viral suppression occurred in 3427 (81.6%) of 4202 HIV-positive adults on ART and 4490 (50.9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48.2%) of 1827 people in west Uganda, 516 (45.0%) of 1147 in east Uganda, and 3093 (52.8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2.9%) of 16 874 couples were serodiscordant: in 287 (58.3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14.0%], viral load was >100 000 copies per mL). In Kenya, 859 (10.0%) of 8616 couples were serodiscordant: in 445 (53.0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL).

Interpretation: Before the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions.

Abstract access  

Editor’s notes: Half of all people living with HIV with a valid viral load measurement in these East African communities had viral suppression (<500 copies/mL) at the start of this cluster randomised trial in 2013-14. These results already provided good evidence of the effectiveness and impact of antiretroviral programmes in East Africa. However, at the AIDS conference in July 2016 the study group presented updated results following two years of a universal test and treat (UTT) strategy with expansion of community-based HIV testing services (access abstract here). By this point, the UNAIDS 90-90-90 treatment target had been exceeded in the study communities and, overall, 82% of people living with HIV had viral suppression. 

These results highlight the role of community viral load metrics as indicators of programme impact. What gives rise to more debate is the role of these metrics in estimating the risk of ongoing HIV transmission in the community. Consensus seems to be emerging that the population prevalence of viraemia may be the metric best suited for this purpose. In this study, the estimated population prevalence of viraemia varied quite widely from 0.5 to 14.1% at the level of local communities (of between around 500 and 5000 people). This measure was also used to define several transmission hotspots, based on an arbitrary cut-off of five percent prevalence of viraemia.

Additional research is necessary in different epidemiological contexts to understand the association between these metrics and risk of HIV transmission. There is also some way to go to understand if such metrics can have practical public health implications for HIV prevention. Whether revealing such heterogeneity in transmission risk within generalized epidemics can inform the application of geographically focussed programmes is a question that now should be addressed.

Africa
Kenya, Uganda
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A step forward for HIV prevention in women

Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women.

Nel A, van Niekerk N, Kapiga S, Bekker LG, Gama C, Gill K, Kamali A, Kotze P, Louw C, Mabude Z, Miti N, Kusemererwa S, Tempelman H, Carstens H, Devlin B, Isaacs M, Malherbe M, Mans W, Nuttall J, Russell M, Ntshele S, Smit M, Solai L, Spence P, Steytler J, Windle K, Borremans M, Resseler S, Van Roey J, Parys W, Vangeneugden T, Van Baelen B, Rosenberg Z; Ring Study Team. N Engl J Med. 2016 Dec;375(22):2133-2143.

Background: The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda.

Methods: In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion.

Results: A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P=0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P=0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified.

Conclusions: Among women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo. (Funded by the International Partnership for Microbicides; ClinicalTrials.gov number, NCT01539226 .).

Abstract  Full-text [free] access

Editor’s notes: The need to develop safe, effective tools for women, particularly young women and adolescent girls, remains a high priority in sub-Saharan Africa. Self-inserted vaginal rings, which provide sustained release of antiretroviral drugs over time, offer an option that women can initiate themselves. Two large randomised trials have been conducted to assess the efficacy and safety of a vaginal ring containing dapivirine in preventing HIV infection in women. This trial is published in the same issue of the New England Journal of Medicine as the trial by Baeten et al. (reviewed by HIV This Month in March 2016). Both trials were conducted in eastern and southern Africa where the incidence of HIV remains high.

As in the Baeten trial, this trial found a moderate reduction in HIV infection (31% lower) among women using the dapivirine vaginal ring compared with placebo. In both trials, protection was higher among women older than 21 years of age, although, unlike the Baeten trial, the difference in efficacy between the two age groups in this trial was not statistically significant. Baeten et al noted that biological measurement of adherence was higher among women older than 21 years (more than 70% overall) which may partly explain the higher protection observed. The investigators of both trials note that the genital tract of younger women may make them more susceptible to HIV infection. This warrants further investigation. Differences in the frequency of vaginal and/or anal sex across different age groups may also be important. In an editorial to accompany publication of these two important trials, Adimora notes that “providers and women must ensure that the HIV interventions that women adopt match their sexual behaviours and needs. Different women – and women at different life stages – will require different types of HIV prevention.”  

Africa
South Africa, Uganda
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Lies in clinical trials – the truth about data accuracy

Misreporting of product adherence in the MTN-003/VOICE trial for HIV prevention in Africa: participants' explanations for dishonesty.

Montgomery ET, Mensch B, Musara P, Hartmann M, Woeber K, Etima J, van der Straten. AIDS Behav. 2016 Nov 17. [Epub ahead of print]

Consistent over-reporting of product use limits researchers' ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that participants understood the importance of daily product use and honest reporting, yet acknowledged that research participants typically lie. Participants cited multiple reasons for misreporting adherence, including human nature, self-presentation with study staff, fear of repercussions (study termination resulting in loss of benefits and experience of HIV-related stigma), a permissive environment in which it was easy to get away with misreporting, and avoiding inconvenient additional counseling. Some participants also reported mistrust of the staff and reciprocal dishonesty about the study products. Many suggested real-time blood-monitoring during trials would encourage greater fidelity to product use and honesty in reporting. Participants at all sites understood the importance of daily product use and honesty, while also acknowledging widespread misreporting of product use. Narratives of dishonesty may suggest a wider social context of hiding products from partners and distrust about research, influenced by rumors circulating in clinic waiting-rooms and surrounding communities. Prevailing power hierarchies between staff and participants may exacerbate misreporting. Participants recognized and suggested that objective, real-time feedback is needed to encourage honest reporting.

Abstract access  

Editor’s notes: The authors of this insightful paper set out the reasons women gave in a trial of vaginal and oral programmes for inaccurately reporting their behaviour during the trial.  The authors could conduct this study because biologic/pharmacokinetic data were available which showed evidence of product use. These data were shared with individual women. None of the reasons women gave for not telling the truth is surprising. They lied to avoid additional questioning from research staff.  They feared telling the truth would result in being removed from the trial. They feared beingreprimanded. Overall, not telling the truth about product use helped them save face and time. The findings do highlight the power difference between researchers and researched, something that is hard to avoid in many areas of research. This difference was exacerbated in some circumstances by the (reported) harsh behaviour of staff towards women. The ease with which women could manipulate pill counts or product use checks, by discarding unused product is also not surprising.  The perception by some women that the researchers had lied, because of changes in the trial part way through, is important to note. This highlights the importance of clear information when a trial is explained as it begins. It also points to the importance of continuous explanations and checking participant understanding. It cannot be assumed that there is a shared understanding between researcher and researched. This is something that is easily overlooked as a trial progresses and routine visits are established. The authors highlight the value of objective measures on product use.  They also observe that some participants suggested objective, real-time feedback, during trials.  However, the authors also note that for many women lying about aspects of their lives to partners and family, was a way of managing their lives. It could be that ‘real time feedback’ would act as a deterrent to participation for some in such circumstances.  No system of data collection is perfect.  It is, however, very useful to have a timely reminder that no interview data, however collected, can be assumed to be wholly accurate.    

Africa
South Africa, Uganda, Zimbabwe
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Improving ART adherence: what works?

Interventions to improve adherence to antiretroviral therapy: a systematic review and network meta-analysis.

Kanters S, Park JJ, Chan K, Socias ME, Ford N, Forrest JI, Thorlund K, Nachega JB, Mills EJ. Lancet HIV. 2017 Jan;4(1):e31-e40. doi: 10.1016/S2352-3018(16)30206-5. Epub 2016 Nov 16.

Background: High adherence to antiretroviral therapy is crucial to the success of HIV treatment. We evaluated comparative effectiveness of adherence interventions with the aim of informing the WHO's global guidance on interventions to increase adherence.

Methods: For this systematic review and network meta-analysis, we searched for randomised controlled trials of interventions that aimed to improve adherence to antiretroviral therapy regimens in populations with HIV. We searched Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for reports published up to July 16, 2015, and searched major conference abstracts from Jan 1, 2013, to July 16, 2015. We extracted data from eligible studies for study characteristics, interventions, patients' characteristics at baseline, and outcomes for the study populations of interest. We used network meta-analyses to compare adherence and viral suppression for all study settings (global network) and for studies in low-income and middle-income countries only (LMIC network).

Findings: We obtained data from 85 trials with 16 271 participants. Short message service (SMS; text message) interventions were superior to standard of care in improving adherence in both the global network (odds ratio [OR] 1.48, 95% credible interval [CrI] 1.00-2.16) and in the LMIC network (1.49, 1.04-2.09). Multiple interventions showed generally superior adherence to single interventions, indicating additive effects. For viral suppression, only cognitive behavioural therapy (1.46, 1.05-2.12) and supporter interventions (1.28, 1.01-1.71) were superior to standard of care in the global network; none of the interventions improved viral response in the LMIC network. For the global network, the time discrepancy (whether the study outcome was measured during or after intervention was withdrawn) was an effect modifier for both adherence to antiretroviral therapy (coefficient estimate -0.43, 95% CrI -0.75 to -0.11) and viral suppression (-0.48; -0.84 to -0.12), suggesting that the effects of interventions wane over time.

Interpretation: Several interventions can improve adherence and viral suppression; generally, their estimated effects were modest and waned over time.

Abstract access  

Editor’s notes: Maintaining adherence to self-administered medications is difficult. On average, people who are prescribed medications for chronic diseases take fewer than half the prescribed doses. Evidence suggests that in most settings adherence to antiretroviral therapy (ART) is better than this, but there will always be people that struggle to maintain the high levels of adherence required for durable virologic suppression. In this analysis, there was some evidence that specific activities or combinations of activities improved virologic suppression. However, the effect sizes were small and when the analysis was confined to studies in low-income and middle-income countries, there was no evidence to suggest an effect on virologic suppression. Overall the evidence to support any particular activity or combination of activities was not compelling.     

Findings from this analysis have been incorporated into most recent consolidated ART guidelines from the World Health Organization. Trying to summarize complex evidence in this way creates many challenges. Trials were conducted in different populations. Some with all people starting ART, others with people considered to have high risk of suboptimal adherence, and others with people who already had adherence problems. The trials also naturally would have differed in content and quality of the usual package of care to support adherence (the comparator for most programme). 60% of the trials were conducted exclusively in the United States, while others were conducted across different settings.

These are just some of the things that make it difficult to synthesize this evidence into guidance that can be applicable to people living with HIV worldwide. HIV programmes in countries have to decide whether or not to adopt any of these activities that are recommended by WHO on the basis of relatively weak evidence. Would we expect activities aimed at improving adherence to be generalizable across different settings? One might argue probably not. Adherence is a multifactorial, dynamic process and there is unlikely to be a ‘one size fits all’ approach to supporting adherence. In the absence of better evidence for any specific activity, we should perhaps focus on improving the quality of the basic package of adherence support offered to all people receiving ART, while also developing better ways to identify when certain people might benefit from enhanced support.        

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How to keep HIV prevalence low in refugee populations

Predictors of HIV infection: a prospective HIV screening study in a Ugandan refugee settlement.

O'Laughlin KN, Rabideau DJ, Kasozi J, Parker RA, Bustamante ND, Faustin ZM, Greenwald KE, Walensky RP, Bassett IV. BMC Infect Dis. 2016 Nov 23;16(1):695.

Background: The instability faced by refugees may place them at increased risk of exposure to HIV infection. Nakivale Refugee Settlement in southwestern Uganda hosts  68 000 refugees from 11 countries, many with high HIV prevalence. We implemented an HIV screening program in Nakivale and examined factors associated with new HIV diagnosis.

Methods: From March 2013-November 2014, we offered free HIV screening to all clients in the Nakivale Health Center while they waited for their outpatient clinic visit. Clients included refugees and Ugandan nationals accessing services in the settlement. Prior to receiving the HIV test result, participants were surveyed to obtain demographic information including gender, marital status, travel time to reach clinic, refugee status, and history of prior HIV testing. We compared variables for HIV-infected and non-infected clients using Pearson's chi-square test, and used multivariable binomial regression models to identify predictors of HIV infection.

Results: During the HIV screening intervention period, 330 (4%) of 7766 individuals tested were identified as HIV-infected. Refugees were one quarter as likely as Ugandan nationals to be HIV-infected (aRR 0.27 [0.21, 0.34], p < 0.0001). Additionally, being female (aRR 1.43 [1.14, 1.80], p = 0.002) and traveling more than 1 h to the clinic (aRR 1.39 [1.11, 1.74], p = 0.003) increased the likelihood of being HIV-infected. Compared to individuals who were married or in a stable relationship, being divorced/separated/widowed increased the risk of being HIV-infected (aRR 2.41 [1.88, 3.08], p < 0.0001), while being single reduced the risk (aRR 0.60 [0.41, 0.86], p < 0.0001). Having been previously tested for HIV (aRR 0.59 [0.47, 0.74], p < 0.0001) also lowered the likelihood of being HIV-infected.

Conclusions: In an HIV screening program in a refugee settlement in Uganda, Ugandan nationals are at higher risk of having HIV than refugees. The high HIV prevalence among clients seeking outpatient care, including Ugandan nationals and refugees, warrants enhanced HIV screening services in Nakivale and in the surrounding region. Findings from this research may be relevant for other refugee settlements in sub-Saharan Africa hosting populations with similar demographics, including the 9 other refugee settlements in Uganda.

Abstract  Full-text [free] access 

Editor’s notes: The 4% prevalence seen among refugees in this study warrants the introduction of a routine offer of HIV testing and counselling, provider-initiated testing and counselling (PITC), in the outpatient services provided at this refugee settlement in Uganda. Although 7766 people accepted the offer of HIV testing and counselling (HTC), the real extent of the acceptability of this service is unclear because routine service delivery records document simply encounters (23 016 during the study period) rather than unique individuals. There may be challenges in defining and using unique identifiers in refugee settlement health care services but this is one example of their potential utility in helping understand the true burden of disease in these settings. HIV prevalence in refugees accepting testing was not significantly different from that in the general population in their countries of origin. For example, Rwanda 2.3% versus 2.9% and Burundi 1.4% versus 1.0%. The exception was the Democratic Republic of Congo (DRC) with 1.9% of Congolese refugees being HIV-positive compared to 0.8% in the DRC general population, warranting further study to understand this increased HIV risk.

This study reveals lower HIV prevalence among refugees (2%) than among Ugandan nationals availing themselves of the settlement health services (9%). The Ugandans included both refugees and people living in surrounding communities. Ugandans freely come and go from the settlement for job-associated or personal reasons. People testing positive for HIV were more likely to live outside the settlement. The extent of sexual mixing between local Ugandans and refugees from other countries in Nakivale is unknown but providing prevention and treatment services to both populations could help reduce the risk of HIV transmission within the settlement. This study was conducted when the 2010 WHO guidelines of 350 cells/mm3 or WHO stage III/IV for treatment initiation were in effect and antiretroviral therapy was free of charge. However, data are not presented in this paper on the important question of the extent of linkage to care and antiretroviral therapy. These data are now being used worldwide to track progress towards the UNAIDS 90-90-90 treatment target. Refugee settlements in sub-Saharan Africa provide fertile settings for a routine offer of HIV testing and immediate offer of antiretroviral therapy to people found to be HIV-positive, as per current WHO guidelines. This would benefit not only these individuals clinically but would help keep HIV transmission as low as possible in refugee settlements.

Africa
Uganda
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