Articles tagged as "Kenya"

Cost-effectiveness analysis of home-based HIV testing and education for pregnant women and their male partners in Kenya

Modeling the cost-effectiveness of home-based HIV testing and education (HOPE) for pregnant women and their male partners in Nyanza Province, Kenya.

Sharma M, Farquhar C, Ying R, Krakowiak D, Kinuthia J, Osoti A, Asila V, Gone M, Mark J, Barnabas RV. J Acquir Immune Defic Syndr. 2016 Aug 1;72 Suppl 2:S174-80. doi: 10.1097/QAI.0000000000001057.

Introduction: Women in sub-Saharan Africa face a 2-fold higher risk of HIV acquisition during pregnancy and postpartum and the majority do not know the HIV status of their male partner. Home-based couple HIV testing for pregnant women can reduce HIV transmission to women and infants while increasing antiretroviral therapy (ART) coverage in men. However, the cost-effectiveness of this program has not been evaluated.

Methods: We modeled the health and economic impact of implementing a home-based partner education and HIV testing (HOPE) intervention for pregnant women and their male partners in a region of Western Kenya (formally Nyanza Province). We used data from the HOPE randomized clinical trial conducted in Kisumu, Kenya, to parameterize a mathematical model of HIV transmission. We conducted an in-country microcosting of the HOPE intervention (payer perspective) to estimate program costs as well as a lower cost scenario of task-shifting to community health workers.

Results: The incremental cost of adding the HOPE intervention to standard antenatal care was $31-37 and $14-16 USD per couple tested with program and task-shifting costs, respectively. At 60% coverage of male partners, HOPE was projected to avert 6987 HIV infections and 2603 deaths in Nyanza province over 10 years with an incremental cost-effectiveness ratio (ICER) of $886 and $615 per disability-adjusted life year averted for the program and task-shifting scenario, respectively. ICERs were robust to changes in intervention coverage, effectiveness, and ART initiation and dropout rates.

Conclusions: The HOPE intervention can moderately decrease HIV-associated morbidity and mortality by increasing ART coverage in male partners of pregnant women. ICERs fall below Kenya's per capita gross domestic product ($1358) and are therefore considered cost-effective. Task-shifting to community health workers can increase intervention affordability and feasibility.

Abstract access

Editor’s notes: HIV remains one of the most serious public health and economic challenges in sub-Saharan Africa. In this study, a deterministic mathematical model was used to assess the cost-effectiveness of providing home-based partner education and HIV testing to couples as a part of routine antenatal care in western Kenya. Detailed cost and effectiveness data were obtained from home-based partner education and an HIV testing programme in Kisumu, Kenya. The model was parameterised using data from that region. The model was analysed for two scenarios; the status quo (with no activity) and the activity scenario in which home-based partner education and HIV testing was added to the status quo with 60% coverage of male partners of pregnant women. Sensitivity analysis was conducted to ascertain the robustness of key model assumption on the study findings.  The authors found home-based partner education and HIV testing activities to be a cost-effective method to reduce HIV disease prevalence in Kenya as it increases ART coverage in male partners of pregnant women. This is a very interesting study which confirms previous findings that community-based HIV counselling and testing is cost-effective. 

Africa
Kenya
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Antiretroviral therapy dramatically reduces transmission of HIV to sexual partners

Antiretroviral therapy for the prevention of HIV-1 transmission.

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR. N Engl J Med. 2016 Jul 18. [Epub ahead of print]

Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.

Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.

Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

Abstract access

Editor’s notes: The HPTN 052 trial has been a landmark study in establishing antiretroviral therapy as a strategy for preventing onward transmission of HIV. It was a study of more than 800 couples. More than half of the couples were in African countries. In each couple, one sexual partner was HIV positive and the other HIV negative.  The participants living with HIV were randomised either to receive immediate antiretroviral therapy or to delay until their CD4 count fell to 350, an approved approach at that time. The HIV negative partners were then monitored for acquisition of HIV.  When new HIV infections occurred, the virus was studied for genetic similarity to the virus of the known positive partner. The interim analysis was published in 2011.  It illustrated the programme to be so effective that the randomisation was ended and all the participants living with HIV were offered antiretroviral therapy. 

This article presents data after five years of follow-up, and if anything the results are even more remarkable. In more than 10 000 person-years of follow up, there were only eight transmissions of genetically linked virus from participants receiving antiretroviral therapy. Of these transmissions, four occurred early in treatment when the viral load would not be expected to be suppressed.  The other four occurred after treatment failure. In this enormous study, there were therefore no linked transmissions from participants who were stable on treatment without detectable viraemia. The study provides powerful support for the UNAIDS 90-90-90 treatment target.  The widest possible effective use of antiretroviral therapy will not only improve the health of people treated but could have a dramatic effect on new HIV infections.

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Demand-side activities are essential for achieving population level impact of HIV prevention tools

Interventions to strengthen the HIV prevention cascade: a systematic review of reviews.

Krishnaratne S, Hensen B, Cordes J, Enstone J, Hargreaves JR. Lancet HIV. 2016 Jul;3(7):e307-17. doi: 10.1016/S2352-3018(16)30038-8.

Background: Much progress has been made in interventions to prevent HIV infection. However, development of evidence-informed prevention programmes that translate the efficacy of these strategies into population effect remain a challenge. In this systematic review, we map current evidence for HIV prevention against a new classification system, the HIV prevention cascade.

Methods: We searched for systematic reviews on the effectiveness of HIV prevention interventions published in English from Jan 1, 1995, to July, 2015. From eligible reviews, we identified primary studies that assessed at least one of: HIV incidence, HIV prevalence, condom use, and uptake of HIV testing. We categorised interventions as those seeking to increase demand for HIV prevention, improve supply of HIV prevention methods, support adherence to prevention behaviours, or directly prevent HIV. For each specific intervention, we assigned a rating based on the number of randomised trials and the strength of evidence.

Findings: From 88 eligible reviews, we identified 1964 primary studies, of which 292 were eligible for inclusion. Primary studies of direct prevention mechanisms showed strong evidence for the efficacy of pre-exposure prophylaxis (PrEP) and voluntary medical male circumcision. Evidence suggests that interventions to increase supply of prevention methods such as condoms or clean needles can be effective. Evidence arising from demand-side interventions and interventions to promote use of or adherence to prevention tools was less clear, with some strategies likely to be effective and others showing no effect. The quality of the evidence varied across categories.

Interpretation: There is growing evidence to support a number of efficacious HIV prevention behaviours, products, and procedures. Translating this evidence into population impact will require interventions that strengthen demand for HIV prevention, supply of HIV prevention technologies, and use of and adherence to HIV prevention methods.

Abstract  Full-text [free] access

Editor’s notes: Demand, supply and use of programmes are crucial for the uptake and effective use of HIV prevention strategies. This paper presents an impressive undertaking in which the authors conducted a review of systematic reviews on the evidence for the effectiveness of HIV prevention programmes across the multiple steps in an HIV prevention cascade. This particular prevention cascade allocates programmes into demand-side, supply-side, adherence, and direct HIV prevention technologies. This was published in a separate paper in conjunction with this review. The review found that there is strong evidence with regards to which direct HIV prevention technologies are efficacious, as well as maps where adherence and supply-side programmes have been effective. A primary gap was noted on the demand-side of the cascade (e.g. information, education and communication, and peer-based activities to increase demand for medical male circumcision) where studies have not resulted in reducing HIV incidence or prevalence. There remains a need to understand why, despite supply, there is low uptake of some HIV prevention strategies, and for evaluation of novel activities to increase demand.  

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Immediate initiation of HIV treatment is cost-effective, but needs a large portion of health system spending

Changing HIV treatment eligibility under health system constraints in sub-Saharan Africa: Investment needs, population health gains, and cost-effectiveness.

Hontelez JA, Chang AY, Ogbuoji O, Vlas SJ, Barnighausen T, Atun R. AIDS. 2016 Jun 29. [Epub ahead of print]

Objective: We estimated the investment need, population health gains, and cost-effectiveness of different policy options for scaling-up prevention and treatment of HIV in the 10 countries that currently comprise 80% of all people living with HIV in sub-Saharan Africa (Ethiopia, Kenya, Malawi, Mozambique, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe).

Design: We adapted the established STDSIM model, to capture the health system dynamics: demand-side and supply-side constraints in the delivery of antiretroviral treatment (ART).

Methods: We compared different scenarios of supply-side (i.e. health system capacity) and demand-side (i.e. health seeking behavior) constraints, and determined the impact of changing guidelines to ART eligibility at any CD4 cell count within these constraints.

Results: Continuing current scale-up would require US$178 billion by 2050. Changing guidelines to ART at any CD4 cell count is cost-effective under all constraints tested in the model, especially in demand-side constrained health systems because earlier initiation prevents loss to follow-up of patients not yet eligible. Changing guidelines under current demand-side constraints would avert 1.8 million infections at US$208 per life-year saved.

Conclusions: Treatment eligibility at any CD4 cell count would be cost-effective, even under health system constraints. Excessive loss to follow up and mortality in patients not eligible for treatment can be avoided by changing guidelines in demand-side constrained systems. The financial obligation for sustaining the AIDS response in sub-Saharan Africa over the next 35 years is substantial, and requires strong, long-term commitment of policy makers and donors to continue to allocate substantial parts of their budgets.

Abstract access

Editor’s notes: Recent WHO guidelines recommend that everyone who is diagnosed as HIV positive should be allowed to start treatment immediately, a change to the former guideline where their CD4 count (a measure of disease progression) was the main criteria for starting treatment. This paper uses a model to look at the costs and benefits of changing to this immediate treatment regimen in the sub-Saharan African countries most affected by the epidemic. The authors find that allowing all HIV people living with HIV to access treatment is cost-effective, and this finding does not change when the model assumptions are varied. However, the impact of this change on the health system budgets in these countries is very substantial, and the authors suggest that a large commitment is necessary from policymakers and donors to sustain this response as short-term spending will not be enough to make an impact.

Africa
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Women are successful in promoting HIV self-testing in Kenyan men

Promoting male partner HIV testing and safer sexual decision making through secondary distribution of self-tests by HIV-negative female sex workers and women receiving antenatal and post-partum care in Kenya: a cohort study.

Thirumurthy H, Masters SH, Mavedzenge SN, Maman S, Omanga E, Agot K. Lancet HIV. 2016 Jun;3(6):e266-74. doi: 10.1016/S2352-3018(16)00041-2. Epub 2016 Apr 8.

Background: Increased uptake of HIV testing by men in sub-Saharan Africa is essential for the success of combination prevention. Self-testing is an emerging approach with high acceptability, but little evidence exists on the best strategies for test distribution. We assessed an approach of providing multiple self-tests to women at high risk of HIV acquisition to promote partner HIV testing and to facilitate safer sexual decision making.

Methods: In this cohort study, HIV-negative women aged 18-39 years were recruited at two sites in Kisumu, Kenya: a health facility with antenatal and post-partum clinics and a drop-in centre for female sex workers. Participants gave informed consent and were instructed on use of oral fluid based rapid HIV tests. Participants enrolled at the health facility received three self-tests and those at the drop-in centre received five self-tests. Structured interviews were conducted with participants at enrolment and over 3 months to determine how self-tests were used. Outcomes included the number of self-tests distributed by participants, the proportion of participants whose sexual partners used a self-test, couples testing, and sexual behaviour after self-testing.

Findings: Between Jan 14, 2015, and March 13, 2015, 280 participants were enrolled (61 in antenatal care, 117 in post-partum care, and 102 female sex workers); follow-up interviews were completed for 265 (96%). Most participants with primary sexual partners distributed self-tests to partners: 53 (91%) of 58 participants in antenatal care, 91 (86%) of 106 in post-partum care, and 64 (75%) of 85 female sex workers. 82 (81%) of 101 female sex workers distributed more than one self-test to commercial sex clients. Among self-tests distributed to and used by primary sexual partners of participants, couples testing occurred in 27 (51%) of 53 in antenatal care, 62 (68%) of 91 from post-partum care, and 53 (83%) of 64 female sex workers. Among tests received by primary and non-primary sexual partners, two (4%) of 53 tests from participants in antenatal care, two (2%) of 91 in post-partum care, and 41 (14%) of 298 from female sex workers had positive results. Participants reported sexual intercourse with 235 (62%) of 380 sexual partners who tested HIV-negative, compared with eight (18%) of 45 who tested HIV-positive (p<0.0001); condoms were used in all eight intercourse events after positive results compared with 104 (44%) after of negative results (p<0.0018). Four participants reported intimate partner violence as a result of self-test distribution: two in the post-partum care group and two female sex workers. No other adverse events were reported.

Interpretation: Provision of multiple HIV self-tests to women at high risk of HIV infection was successful in promoting HIV testing among their sexual partners and in facilitating safer sexual decisions. This novel strategy warrants further consideration as countries develop self-testing policies and programmes.

Abstract access

Editor’s notes: This paper presents a novel approach to promoting HIV self-testing strategies among men and couples, by distributing self-tests through social and sexual networks of women. Women attending antenatal clinics, post-partum care, and sex workers were briefly trained on how to use the Ora-Quick self-test kit, and then given five kits to take with them and give to people in their networks. This strategy allowed women and their partners to choose when and where they tested, often together and in the comfort of their own environments. The majority of women reported having distributed self-test kits to partners/clients and undertaking couples testing. Further, according to participant’s report, 58% of people testing positive linked to HIV care (and linkage was unknown in 35%). Interestingly, the on-the-spot, or point-of-sex testing allowed individuals to decide whether to continue with sexual encounters according to status, which reportedly proved to be especially useful to the female sex workers. There were four reported cases of violence resulting from test use, and this should be closely watched in future research. This is the first study to assess the potential for secondary distribution of HIV self-test kits by multiple populations of women to promote HIV testing in their male partners, and overall, the results indicate that this model is a promising strategy for promoting further HIV-testing, leading the field closer to the UNAIDS 90-90-90 treatment target and improved HIV prevention as well. 

Africa
Kenya
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Increased adolescent testing

Increased adolescent HIV testing with a hybrid mobile strategy in Uganda and Kenya.

Kadede K, Ruel T, Kabami J, Ssemmondo E, Sang N, Kwarisiima D, Bukusi E, Cohen CR, Liegler T, Clark TD, Charlebois ED, Petersen ML, Kamya MR, Havlir DV, Chamie G, SEARCH team. AIDS. 2016 Jun 1. [Epub ahead of print]

Objective: We sought to increase adolescent HIV testing across rural communities in east Africa and identify predictors of undiagnosed HIV.

Design: Hybrid mobile testing.

Methods: We enumerated 116 326 adolescents (10-24 years) in 32 communities of Uganda and Kenya (SEARCH: NCT01864603): 98 694 (85%) reported stable (≥6 months of prior year) residence. In each community we performed hybrid testing: 2- week multi-disease community health campaign (CHC) that included HIV testing, followed by home-based testing of CHC non-participants. We measured adolescent HIV testing coverage and prevalence, and determined predictors of newly-diagnosed HIV among HIV+ adolescents using multivariable logistic regression.

Results: 86 421 (88%) stable adolescents tested for HIV; coverage was 86%, 90%, and 88% in early (10-14), mid (15-17) and late (18-24) adolescents, respectively. Self- reported prior testing was 9%, 26%, and 55% in early, mid and late adolescents tested, respectively. HIV prevalence among adolescents tested was 1.6% and 0.6% in Ugandan women and men, and 7.1% and 1.5% in Kenyan women and men, respectively. Prevalence increased in mid-adolescence for women, and late adolescence for men. Among HIV+ adolescents, 58% reported newly-diagnosed HIV. In multivariate analysis of HIV+ adolescents, predictors of newly-diagnosed HIV included male gender (OR = 1.97 [95%CI: 1.42-2.73]), Ugandan residence (OR = 2.63 [95%CI: 2.08-3.31]), and single status (OR = 1.62 [95%CI: 1.23-2.14] vs. married).

Conclusions: The SEARCH hybrid strategy tested 88% of stable adolescents for HIV, a substantial increase over the 28% reporting prior testing. The majority (57%) of HIV+ adolescents were new diagnoses. Mobile HIV testing for adults should be leveraged to reach adolescents for HIV treatment and prevention.

Abstract access 

Editor’s notes: Ending the AIDS epidemic requires much greater focus on adolescents, among whom HIV associated deaths is a leading cause of death in sub-Saharan Africa. Critical behaviours that are likely to impact on future health, such as risky sexual behaviour, often begin in adolescence. However, it is estimated that less than a third of adolescents in sub-Saharan Africa have been tested for HIV. In this paper, the authors report the impact of a hybrid community-based mobile testing approach to increase HIV testing among adolescents in rural communities in East Africa. This model, which does not rely on accessing schools or clinics, is very suitable for this age group, given the low rates of school attendance among female adolescents and the low use of clinic-based services by adolescents. A high rate of HIV testing was achieved, and testing for HIV in a multi-disease context may have enabled adolescents to access testing without fear of being stigmatised. However, uptake of testing is only the first stage in the HIV prevention and treatment cascade, and further data on the proportion of people testing positive who link to care and start treatment, and people testing negative who link to prevention services, are necessary. 

Africa
Kenya, Uganda
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Changing norms: lessons from HIV advocacy for NCDs prevention

Ability of HIV advocacy to modify behavioral norms and treatment impact: a systematic review.

Sunguya BF, Munisamy M, Pongpanich S, Yasuoka J, Jimba M. Am J Public Health. 2016 Aug;106(8):e1-e8. Epub 2016 Jun 16.

Background: HIV advocacy programs are partly responsible for the global community's success in reducing the burden of HIV. The rising wave of the global burden of noncommunicable diseases (NCDs) has prompted the World Health Organization to espouse NCD advocacy efforts as a possible preventive strategy. HIV and NCDs share some similarities in their chronicity and risky behaviors, which are their associated etiology. Therefore, pooled evidence on the effectiveness of HIV advocacy programs and ideas shared could be replicated and applied during the conceptualization of NCD advocacy programs. Such evidence, however, has not been systematically reviewed to address the effectiveness of HIV advocacy programs, particularly programs that aimed at changing public behaviors deemed as risk factors.

Objectives: To determine the effectiveness of HIV advocacy programs and draw lessons from those that are effective to strengthen future noncommunicable disease advocacy programs.

Search methods: We searched for evidence regarding the effectiveness of HIV advocacy programs in medical databases: PubMed, The Cumulative Index to Nursing and Allied Health Literature Plus, Educational Resources and Information Center, and Web of Science, with articles dated from 1994 to 2014.

Search criteria. The review protocol was registered before this review. The inclusion criteria were studies on advocacy programs or interventions. We selected studies with the following designs: randomized controlled design studies, pre-post intervention studies, cohorts and other longitudinal studies, quasi-experimental design studies, and cross-sectional studies that reported changes in outcome variables of interest following advocacy programs. We constructed Boolean search terms and used them in PubMed as well as other databases, in line with a population, intervention, comparator, and outcome question. The flow of evidence search and reporting followed the standard Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

Data collection and analysis: We selected 2 outcome variables (i.e., changing social norms and a change in impact) out of 6 key outcomes of advocacy interventions. We assessed the risk of bias for all selected studies by using the Cochrane risk-of-bias tool for randomized studies and using the Risk of Bias for Nonrandomized Observational Studies for observational studies. We did not grade the collective quality of evidence because of differences between the studies, with regard to methods, study designs, and context. Moreover, we could not carry out meta-analyses because of heterogeneity and the diverse study designs; thus, we used a narrative synthesis to report the findings.

Main results: A total of 25 studies were eligible, of the 1463 studies retrieved from selected databases. Twenty-two of the studies indicated a shift in social norms as a result of HIV advocacy programs, and 3 indicated a change in impact. We drew 6 lessons from these programs that may be useful for noncommunicable disease advocacy: (1) involving at-risk populations in advocacy programs, (2) working with laypersons and community members, (3) working with peer advocates and activists, (4) targeting specific age groups and asking support from celebrities, (5) targeting several, but specific, risk factors, and (6) using an evidence-based approach through formative research.

Author conclusions: HIV advocacy programs have been effective in shifting social norms and facilitating a change in impact.

Public health implications: The lessons learned from these effective programs could be used to improve the design and implementation of future noncommunicable disease advocacy programs.

Abstract access

Editor’s notes: This article presents the results of a systematic review to answer a question about the effectiveness of HIV advocacy in changing social norms and changing impact among key populations. The review was conducted to learn from effective HIV advocacy and apply similar strategies for the prevention and reduction of the global burden of non-communicable diseases. The review included quantitative research only. After searching 3320 articles, 25 articles met the inclusion criteria. The HIV advocacy activities reviewed ranged from local and mass campaigns using a variety of media, to social marketing, celebrities, drama, promotional activities and counselling. Changes in social norms were assessed using six specific variables, for example testing behaviour change or HIV-associated stigma. Changes in impact were analysed in two aspects, changes in HIV transmission and in adherence to antiretroviral therapy. The review has found significant evidence of the effect of HIV advocacy on the outcomes of interest. The authors highlight lessons from HIV advocacy that might be useful for future non-communicable diseases advocacy. These included the vital role of peer-educator and of lay members of the community and the involvement of key populations in programmes that focus on them.  In addition, there is a need to tailor programmes to specific (rather than multiple) risks using local and salient evidence. 

Africa, Northern America, Oceania
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Oral PrEP reduces risk of HIV and does not result in riskier sex

Effectiveness and safety of oral HIV pre-exposure prophylaxis (PrEP) for all populations: A systematic review and meta-analysis.

Fonner VA, Dalglish SL, Kennedy CE, Baggaley R, O'Reilly K R, Koechlin FM, Rodolph M, Hodges-Mameletzis I, Grant RM. AIDS. 2016 May 5. [Epub ahead of print]

Objective: Pre-exposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate (TDF) as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes.

Design: Rigorous systematic review and meta-analysis.

Methods: A comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis.

Results: Eighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared to placebo. Trials with PrEP use >70% demonstrated the highest PrEP effectiveness (RR = 0.30, 95% CI: 0.21-0.45, p < 0.001) compared to placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness.

Conclusion: PrEP is protective against HIV infection across populations, presents few significant safety risks, and no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV-risk.

Abstract access

Editor’s notes: This systematic review is the first to aggregate data from across oral pre-exposure prophylaxis (PrEP) studies, including randomized control trials and observational studies, to present clear evidence on the effectiveness of oral PrEP use. The findings confirm that oral PrEP significantly reduces the risk of acquiring HIV if taken consistently and correctly across populations, countries, and most age groups. Differences in efficacy directly correlate with adherence, which accounts for the lower efficacy seen in some subgroups. Perhaps two of the most compelling analyses presented in this paper relate to resistance and behavioural disinhibition. The risk of resistance was shown to be quite low, and study participants exhibiting resistant HIV either enrolled in the studies during an acute infection stage or acquired resistant strains during the course of the research. Regarding behavioural disinhibition, indicators measured such as rates of sexually transmitted infections revealed that PrEP use in the efficacy trials was not associated with behavioural disinhibition and in some studies, resulted in even safer sexual behaviour than what was reported at baseline. Recently completed demonstration projects have reported increased rates of STIs among gay men and other men who have sex with men. However, in the open-label extensions included in this review, where counselling was more intensive, safer sex practices were maintained, thus suggesting that counselling can be effective in preventing behavioural disinhibition. 

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Intimate partner violence is a challenge to PrEP adherence

Intimate partner violence and adherence to HIV pre-exposure prophylaxis (PrEP) in African women in HIV serodiscordant relationships: a prospective cohort study.

Roberts ST, Haberer J, Celum C, Mugo N, Ware NC, Cohen CR, Tappero JW, Kiarie J, Ronald A, Mujugira A, Tumwesigye E, Were E, Irungu E, Baeten JM. J Acquir Immune Defic Syndr. 2016 May 26. [Epub ahead of print]

Background: Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP).

Methods: We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV-serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence.

Results: 16% of women reported IPV during a median of 34.8 months of follow-up (IQR 27.0 - 35.0). Overall, 7% of visits had pill count coverage <80% and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted RR 1.49, 95% CI 1.17-1.89) and by plasma tenofovir (adjusted RR 1.51, 95% CI 1.06-2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away.

Conclusion: Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP non-adherence in the context of IPV should be evaluated.

Abstract access

Editor’s notes: The high rates of HIV infection in women underscore persistent gender inequalities, in particular that of violence against women. Intimate partner violence (IPV) puts women at increased risk of HIV infection. Further, among women living with HIV, IPV has also been associated with lower rates of treatment uptake and adherence to antiretroviral therapy (ART). The interaction between IPV and HIV is complex, and includes biological, socio-economic and cultural mechanisms. This is the first study to examine the association between IPV and adherence to HIV pre-exposure prophylaxis (PrEP).  Women who had experienced IPV in the past three months were 50% more likely than women who had never experienced IPV to have poor adherence, as measured by both pills counts and drug levels in the blood.  Recent IPV was also associated with an increase in the risk of HIV infection.  Women in the study were in stable, serodiscordant relationships, had enrolled in the study together with their partners, and were using PrEP with their partner’s consent. The proportion of women reporting IPV during the study was much lower than national estimates in the region.  These findings are thus of concern for PrEP demonstration projects focusing on key populations at high risk of HIV, who may experience higher rates of IPV and be less likely to have partner support. 

PrEP is a key element of combination HIV prevention strategies in high-risk populations, but requires high adherence in order to be effective. Programmes focusing on promoting PrEP adherence in women who have experienced violence are urgently needed.  More broadly, HIV prevention programmes should be expanded to integrate IPV prevention as an important component to reducing women’s risk of HIV.

Africa
Kenya, Uganda
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Role for LAM test in TB diagnosis among the sickest people living with HIV

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults.

Shah M, Hanrahan C, Wang ZY, Dendukuri N, Lawn SD, Denkinger CM, Steingart KR. Cochrane Database Syst Rev. 2016 May 10;5:CD011420. doi: 10.1002/14651858.CD011420.pub2.

Background: Rapid detection of tuberculosis (TB) among people living with human immunodeficiency virus (HIV) is a global health priority. HIV-associated TB may have different clinical presentations and is challenging to diagnose. Conventional sputum tests have reduced sensitivity in HIV-positive individuals, who have higher rates of extrapulmonary TB compared with HIV-negative individuals. The lateral flow urine lipoarabinomannan assay (LF-LAM) is a new, commercially available point-of-care test that detects lipoarabinomannan (LAM), a lipopolysaccharide present in mycobacterial cell walls, in people with active TB disease.

Objectives: To assess the accuracy of LF-LAM for the diagnosis of active TB disease in HIV-positive adults who have signs and symptoms suggestive of TB (TB diagnosis). To assess the accuracy of LF-LAM as a screening test for active TB disease in HIV-positive adults irrespective of signs and symptoms suggestive of TB (TB screening).

Search methods: We searched the following databases without language restriction on 5 February 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE (PubMed,1966); EMBASE (OVID, from 1980); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926) (all three using the Web of Science platform; MEDION; LILACS (BIREME, from 1982); SCOPUS (from 1995); the metaRegister of Controlled Trials (mRCT); the search portal of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); and ProQuest Dissertations & Theses A&l (from 1861).

Selection criteria: Eligible study types included randomized controlled trials, cross-sectional studies, and cohort studies that determined LF-LAM accuracy for TB against a microbiological reference standard (culture or nucleic acid amplification test from any body site). A higher quality reference standard was one in which two or more specimen types were evaluated for TB, and a lower quality reference standard was one in which only one specimen type was evaluated for TB. Participants were HIV-positive people aged 15 years and older.

Data collection and analysis: Two review authors independently extracted data from each included study using a standardized form. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We evaluated the test at two different cut-offs: (grade 1 or 2, based on the reference card scale of five intensity bands). Most analyses used grade 2, the manufacturer's currently recommended cut-off for positivity. We carried out meta-analyses to estimate pooled sensitivity and specificity using a bivariate random-effects model and estimated the models using a Bayesian approach. We determined accuracy of LF-LAM combined with sputum microscopy or Xpert(R) MTB/RIF. In addition, we explored the influence of CD4 count on the accuracy estimates. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results: We included 12 studies: six studies evaluated LF-LAM for TB diagnosis and six studies evaluated the test for TB screening. All studies were cross-sectional or cohort studies. Studies for TB diagnosis were largely conducted among inpatients (median CD4 range 71 to 210 cells per µL) and studies for TB screening were largely conducted among outpatients (median CD4 range 127 to 437 cells per µL). All studies were conducted in low- or middle-income countries. Only two studies for TB diagnosis (33%) and one study for TB screening (17%) used a higher quality reference standard LF-LAM for TB diagnosis (grade 2 cut-off): meta-analyses showed median pooled sensitivity and specificity (95% credible interval (CrI)) of 45% (29% to 63%) and 92% (80% to 97%), (five studies, 2313 participants, 35% with TB, low quality evidence). The pooled sensitivity of a combination of LF-LAM and sputum microscopy (either test positive) was 59% (47% to 70%), which represented a 19% (4% to 36%) increase over sputum microscopy alone, while the pooled specificity was 92% (73% to 97%), which represented a 6% (1% to 24%) decrease from sputum microscopy alone (four studies, 1876 participants, 38% with TB). The pooled sensitivity of a combination of LF-LAM and sputum Xpert(R) MTB/RIF (either test positive) was 75% (61% to 87%) and represented a 13% (1% to 37%) increase over Xpert(R) MTB/RIF alone. The pooled specificity was 93% (81% to 97%) and represented a 4% (1% to 16%) decrease from Xpert(R) MTB/RIF alone (three studies, 909 participants, 36% with TB). Pooled sensitivity and specificity of LF-LAM were 56% (41% to 70%) and 90% (81% to 95%) in participants with a CD4 count of less than or equal to 100 cells per µL (five studies, 859 participants, 47% with TB) versus 26% (16% to 46%) and 92% (78% to 97%) in participants with a CD4 count greater than 100 cells per µL (five studies, 1410 participants, 30% with TB). LF-LAM for TB screening (grade 2 cut-off): for individual studies, sensitivity estimates (95% CrI) were 44% (30% to 58%), 28% (16% to 42%), and 0% (0% to 71%) and corresponding specificity estimates were 95% (92% to 97%), 94% (90% to 97%), and 95% (92% to 97%) (three studies, 1055 participants, 11% with TB, very low quality evidence). There were limited data for additional analyses. The main limitations of the review were the use of a lower quality reference standard in most included studies, and the small number of studies and participants included in the analyses. The results should, therefore, be interpreted with caution.

Authors' conclusions: We found that LF-LAM has low sensitivity to detect TB in adults living with HIV whether the test is used for diagnosis or screening. For TB diagnosis, the combination of LF-LAM with sputum microscopy suggests an increase in sensitivity for TB compared to either test alone, but with a decrease in specificity. In HIV-positive individuals with low CD4 counts who are seriously ill, LF-LAM may help with the diagnosis of TB.

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Editor’s notes: Tuberculosis (TB) remains a leading cause of death among people living with HIV. Diagnostic tests for TB are suboptimal, and a test for TB with adequate performance which could be used by nurses in primary care clinics would be a great advance. Lipoarabinomannam (LAM) is a component of mycobacterial cell wall which can be found in urine. A lateral flow assay to detect LAM in urine is commercially available at low cost, and can be used in primary care settings without the need for laboratory equipment. However the test is insensitive, such that it has no useful role among HIV-negative people, but has better sensitivity among people living with HIV, leading to questions concerning its role in TB diagnostic pathways.

This systematic review puts together data concerning the performance of the LAM lateral flow assay when used either as a screening test or for diagnosis of TB among people living with HIV. Assessment is made more complicated because the recommended reference cut-off for the test has been changed, with relatively few studies performed after the recommended cut off became what is referred to here as the “higher quality” reference standard (grade two test band intensity, rather than grade one as was previously recommended). Based on the grade two cut–off, the pooled estimate of sensitivity of the test was 45%. As expected, sensitivity was better for individuals with low CD4 counts.

This review informed WHO recommendations on the use of the LAM assay, suggesting that its use should be restricted to assisting with TB diagnosis in people living with HIV with low CD4 counts who are seriously ill. This is consistent with the results of the recent trial (PMID: 26970721) comparing management of hospitalised HIV-positive people reporting one or more TB symptoms with routine testing of urine for LAM compared to standard diagnostic tests, which found that the addition of LAM testing resulted in a small reduction in eight-week mortality.

Overall, LAM is inadequate as a single test for TB, and an accurate diagnostic test that could be used in-session for TB diagnosis in primary care clinics remains a pressing priority.

Comorbidity, HIV testing
Africa
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