Articles tagged as "Zimbabwe"

Moving from facility to community-based models of HIV care - will it work?

Community-based interventions to improve and sustain antiretroviral therapy adherence, retention in HIV care and clinical outcomes in low- and middle-income countries for achieving the UNAIDS 90-90-90 targets.

Nachega JB, Adetokunboh O, Uthman OA, Knowlton AW, Altice FL, Schechter M, Galarraga O, Geng E, Peltzer K, Chang LW, Van Cutsem G, Jaffar SS, Ford N, Mellins CA, Remien RH, Mills EJ. Curr HIV/AIDS Rep. 2016 Oct;13(5):241-55. doi: 10.1007/s11904-016-0325-9.

Little is known about the effect of community versus health facility-based interventions to improve and sustain antiretroviral therapy (ART) adherence, virologic suppression, and retention in care among HIV-infected individuals in low- and middle-income countries (LMICs). We systematically searched four electronic databases for all available randomized controlled trials (RCTs) and comparative cohort studies in LMICs comparing community versus health facility-based interventions. Relative risks (RRs) for pre-defined adherence, treatment engagement (linkage and retention in care), and relevant clinical outcomes were pooled using random effect models. Eleven cohort studies and eleven RCTs (N = 97 657) were included. Meta-analysis of the included RCTs comparing community- versus health facility-based interventions found comparable outcomes in terms of ART adherence (RR = 1.02, 95 % CI 0.99 to 1.04), virologic suppression (RR = 1.00, 95 % CI 0.98 to 1.03), and all-cause mortality (RR = 0.93, 95 % CI 0.73 to 1.18). The result of pooled analysis from the RCTs (RR = 1.03, 95 % CI 1.01 to 1.06) and cohort studies (RR = 1.09, 95 % CI 1.03 to 1.15) found that participants assigned to community-based interventions had statistically significantly higher rates of treatment engagement. Two studies found community-based ART delivery model either cost-saving or cost-effective. Community- versus facility-based models of ART delivery resulted in at least comparable outcomes for clinically stable HIV-infected patients on treatment in LMICs and are likely to be cost-effective.

Abstract access  

Editor’s notes: The remarkable global scale-up of antiretroviral therapy (ART) programmes, while much-needed and impressive, has had inevitable consequences. These include overcrowding of health facilities, longer waiting times, reduced time for counselling and care of newly-enrolled people and restricted capacity to provide support for people who do not remain engaged with care. Furthermore, the UNAIDS 90-90-90 treatment target for 2020 to have 90% of people living with HIV know their HIV status, 90% of all diagnosed individuals receiving ART and 90% of people living with HIV on ART to be virally suppressed, will now require an additional 20 million people living with HIV to start treatment.

Community-based programmes to complement facility-based model of HIV care delivery are increasingly being recognised as an important and sustainable approach to address the growing numbers of people accessing care in high-HIV prevalence settings. This review compared outcomes of community-based versus facility-based models of ART delivery and treatment support. There was no statistical difference in optimal ART adherence, virologic suppression or all-cause mortality between participants assigned to community-based ART and facility-based ART in randomised controlled trials (RCTs). When data from RCTs and cohort studies were pooled, participants assigned to community-based ART appeared to have higher rates of retention in care at the end of the follow-up period. Notably, the few studies that did examine cost-effectiveness found community-based programmes to be cost-saving.

The findings demonstrate that community-level programmes are certainly not inferior to facility-based programmes. However, it is important to note some key limitations. Firstly, many of the studies are subject to selection bias, i.e. people at risk of poorer outcomes e.g. sicker people or people with a history of poor adherence may be excluded from receiving community-based programmes. The authors also highlight a high risk of “other forms of bias” in the cohort studies, but these are not specified. Secondly, adherence measures based on self-report may not be reliable. Thirdly, the review compared a heterogeneous set of programmes. Fourthly, as with other systematic reviews, publication bias is highly likely.   

Notwithstanding these limitations, this study suggests that community-based programmes have promise in supporting fragile and overcrowded facility-based healthcare systems in providing HIV care to a growing number of people. There may even be potential for integrating HIV care with care for other chronic conditions.

Well-designed studies are necessary, given the ambitious targets we have set ourselves, to explore the effectiveness and cost-effectiveness of community-based programmes. This is particularly important in under-represented groups with disproportionately poor outcomes such as children, adolescents and pregnant women. Further, for community-based programmes to be effective, it will be critical to ensure that adequate training and mentorship and ongoing monitoring for quality assurance is in place.      

Africa, Asia, Latin America
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Improving programmes: a thematic synthesis of qualitative studies of treatment adherence programmes

Barriers and facilitators of interventions for improving antiretroviral therapy adherence: a systematic review of global qualitative evidence.

Ma Q, Tso LS, Rich ZC, Hall BJ, Beanland R, Li H, Lackey M, Hu F, Cai W, Doherty M, Tucker JD. J Int AIDS Soc. 2016 Oct 17;19(1):21166. doi: 10.7448/IAS.19.1.21166. eCollection 2016.

Introduction: Qualitative research on antiretroviral therapy (ART) adherence interventions can provide a deeper understanding of intervention facilitators and barriers. This systematic review aims to synthesize qualitative evidence of interventions for improving ART adherence and to inform patient-centred policymaking.

Methods: We searched 19 databases to identify studies presenting primary qualitative data on the experiences, attitudes and acceptability of interventions to improve ART adherence among PLHIV and treatment providers. We used thematic synthesis to synthesize qualitative evidence and the CERQual (Confidence in the Evidence from Reviews of Qualitative Research) approach to assess the confidence of review findings.

Results: Of 2982 references identified, a total of 31 studies from 17 countries were included. Twelve studies were conducted in high-income countries, 13 in middle-income countries and six in low-income countries. Study populations focused on adults living with HIV (21 studies, n=1025), children living with HIV (two studies, n=46), adolescents living with HIV (four studies, n=70) and pregnant women living with HIV (one study, n=79). Twenty-three studies examined PLHIV perspectives and 13 studies examined healthcare provider perspectives. We identified six themes related to types of interventions, including task shifting, education, mobile phone text messaging, directly observed therapy, medical professional outreach and complex interventions. We also identified five cross-cutting themes, including strengthening social relationships, ensuring confidentiality, empowerment of PLHIV, compensation and integrating religious beliefs into interventions. Our qualitative evidence suggests that strengthening PLHIV social relationships, PLHIV empowerment and developing culturally appropriate interventions may facilitate adherence interventions. Our study indicates that potential barriers are inadequate training and compensation for lay health workers and inadvertent disclosure of serostatus by participating in the intervention.

Conclusions: Our study evaluated adherence interventions based on qualitative data from PLHIV and health providers. The study underlines the importance of incorporating social and cultural factors into the design and implementation of interventions. Further qualitative research is needed to evaluate ART adherence interventions.

Abstract  Full-text [free] access 

Editor’s notes: This is a review of studies using qualitative methods to explore the experiences of people living with HIV and healthcare providers involved in programmes to support antiretroviral treatment adherence. The thematic synthesis is presented in two ways. First, the reviewed studies are categorised by types of adherence programmes, such as task shifting, education, or directly observed therapy. Secondly, the authors present themes that are common across all reviewed studies. These include: the benefits and challenges of employing lay healthcare workers; the need to maintain confidentiality in adherence programmes; the benefits of supporting empowerment and social relationships for people living with HIV; and the need for culturally appropriate information and practice. Overall the review illustrates that adherence programmes can have more impact if they address confidentiality, strengthen social ties among people living with HIV and their communities; provide adequate compensation and training for lay healthcare workers; and sensitively reflect local social, cultural and religious norms and beliefs. 

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Standard methods underestimate the effect of HIV on fertility

The effects of HIV on fertility by infection duration: evidence from African population cohorts before ART availability: fertility by duration of HIV infection.

Marston M, Nakiyingi-Miiro J, Kusemererwa S, Urassa M, Michael D, Nyamukapa C, Gregson S, Zaba B, Eaton JW. AIDS. 2016 Oct 20. [Epub ahead of print]

Objectives: To estimate the relationship between HIV natural history and fertility by duration of infection in East and Southern Africa before the availability of antiretroviral therapy, and assess potential biases in estimates of age-specific sub-fertility when using retrospective birth histories in cross-sectional studies.

Design: Pooled analysis of prospective population-based HIV cohort studies in Masaka (Uganda) Kisesa (Tanzania), and Manicaland (Zimbabwe).

Methods: Women aged 15-49 who had ever tested for HIV were included. Analyses were censored at antiretroviral treatment roll out. Fertility rate ratios were calculated to see the relationship of duration of HIV infection on fertility, adjusting for background characteristics. Survivorship and misclassification biases on age-specific subfertility estimates from cross-sectional surveys were estimated by reclassifying person time from the cohort data to simulate cross-sectional surveys and comparing fertility rate ratios to true cohort results.

Results: HIV negative and positive women contributed 15 440 births and 86 320 person years; and 1236 births and 11 240 thousand person years respectively to the final dataset. Adjusting for age, study site and calendar year, each additional year since HIV sero conversion was associated with a 0.02 (95%CI 0.01-0.03) relative decrease in fertility for HIV-positive women. Survivorship and misclassification biases in simulated retrospective birth histories resulted in modest underestimates of sub-fertility by 2-5% for age groups 20-39y.

Conclusion: Longer duration of infection is associated with greater relative fertility reduction for HIV-positive women. This should be considered when creating estimates for HIV prevalence among pregnant women and PMTCT need over the course of the HIV epidemic and ART scale-up.

Abstract access 

Editor’s notes: HIV prevalence among antenatal clinic attenders is used to help estimate population HIV prevalence. It is known that figures must be adjusted upwards to reflect the fact HIV reduces fertility, especially in older women. However, older women are also likely to have been living with HIV for longer. The authors investigated whether length of infection changes the effect of HIV on fertility. Using three prospective longitudinal cohorts, they found that time since seroconversion was associated with reduced fertility, even after adjusting for age and age at seroconversion. This result is important because as the epidemic matures and the majority of women living with HIV are not recently infected, the effect of HIV on suppressing fertility will increase. This will cause measurements of HIV prevalence in pregnancy to underestimate the true population prevalence even if they adjust for age. Conversely, women who have been living with HIV for longer are more likely to be taking ART, which increases fertility relative to women who have been diagnosed more recently. Therefore, within an age-group, pregnancy data is likely to overestimate the proportion of HIV positive women on ART. The usual way to measure the age-specific effects of HIV on fertility is to compare the three-year reported fertility of women living with HIV, and women without HIV in a cross-sectional survey. The authors used longitudinal data to simulate a survey and showed that surveys slightly underestimate the size of the fertility effect, for two reasons. Firstly, if women acquire HIV during the three years any pregnancies before infection are misattributed to HIV. Secondly, there is excess mortality of HIV positive women with low fertility who therefore do not appear in the survey.

The reasons for the age-dependent effect of HIV on fertility are both biological and social (older women living with HIV are more likely to be widowed or divorced) and the relationship is not fixed over time. It shifts according to demographic factors, the stage of the epidemic and, availability of treatment. Assumptions must be continually tested as the epidemic evolves. 

Epidemiology
Africa
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Improving retention in HIV care

Barriers and facilitators to interventions improving retention in HIV care: a qualitative evidence meta-synthesis.

Hall BJ, Sou KL, Beanland R, Lacky M, Tso LS, Ma Q, Doherty M, Tucker JD. AIDS Behav. 2016 Aug 31. [Epub ahead of print]

Retention in HIV care is vital to the HIV care continuum. The current review aimed to synthesize qualitative research to identify facilitators and barriers to HIV retention in care interventions. A qualitative evidence meta-synthesis utilizing thematic analysis. Prospective review registration was made in PROSPERO and review procedures adhered to PRISMA guidelines. Nineteen databases were searched to identify qualitative research conducted with individuals living with HIV and their caregivers. Quality assessment was conducted using CASP and the certainty of the evidence was evaluated using CERQual. A total of 4419 citations were evaluated and 11 were included in the final meta-synthesis. Two studies were from high-income countries, 3 from middle-income countries, and 6 from low-income countries. A total of eight themes were identified as facilitators or barriers for retention in HIV care intervention: (1) stigma and discrimination, (2) fear of HIV status disclosure, (3) task shifting to lay health workers, (4) human resource and institutional challenges, (5) mobile health (mHealth), (6) family and friend support, (7) intensive case management, and, (8) relationships with caregivers. The current review suggests that task shifting interventions with lay health workers were feasible and acceptable. mHealth interventions and stigma reduction interventions appear to be promising interventions aimed at improving retention in HIV care. Future studies should focus on improving the evidence base for these interventions. Additional research is needed among women and adolescents who were under-represented in retention interventions.

Abstract access 

Editor’s notes: Retention in HIV care is defined as the continued engagement in health services from enrolment in care to discharge or death of an individual living with HIV. There is strong evidence for the clinical and public health benefits of early antiretroviral therapy initiation. Individuals retained in care have lower mortality and a higher likelihood of viral suppression. Universal test and treat strategies are dependent on successful retention in HIV care.

A qualitative evidence meta-synthesis utilising thematic analysis was conducted. Some 11 studies were ultimately included in the review. Task shifting to non-specialist community caregivers was the most common activity identified in the review. Other programmes included home-based care, case management, primary HIV medical care, counselling, and mHealth.

The findings of the meta-synthesis highlight eight themes that were identified as facilitators or barriers for retention in HIV care programmes. This offers important insights for improving retention in care. However, more research is necessary to understand the experience of important sub populations including pregnant women, children and adolescents and key populations including gay men and other men who have sex with men.  The authors also emphasise the need for studies to provide particular emphasis on the perspectives of individuals living with HIV and providers involved in programme delivery. This, they argue, would greatly enhance subsequent implementation and development of tailored programmes to retain individuals living with HIV in care.

Africa, Northern America
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Systematic review finds that the evidence for the impact of HCT on HIV acquisition is limited but scale-up remains vital to facilitate other proven interventions

The effect of HIV counselling and testing on HIV acquisition in sub-Saharan Africa: a systematic review.

Rosenberg NE, Hauser BM, Ryan J, Miller WC. Sex Transm Infect. 2016 Aug 16. pii: sextrans-2016-052651. doi: 10.1136/sextrans-2016-052651. [Epub ahead of print]

Objectives: Annually, millions of people in sub-Saharan Africa (SSA) receive HIV counselling and testing (HCT), a service designed to inform persons of their HIV status and, if HIV uninfected, reduce HIV acquisition risk. However, the impact of HCT on HIV acquisition has not been systematically evaluated. We conducted a systematic review to assess this relationship in SSA.

Methods: We searched for articles from SSA meeting the following criteria: an HIV-uninfected population, HCT as an exposure, longitudinal design and an HIV acquisition endpoint. Three sets of comparisons were assessed and divided into strata: sites receiving HCT versus sites not receiving HCT (Strata A), persons receiving HCT versus persons not receiving HCT (Strata B) and persons receiving couple HCT (cHCT) versus persons receiving individual HCT (Strata C).

Results: We reviewed 1635 abstracts; eight met all inclusion criteria. Strata A consisted of one cluster randomised trial with a non-significant trend towards HCT being harmful: incidence rate ratio (IRR): 1.4. Strata B consisted of five observational studies with non-significant unadjusted IRRs from 0.6 to 1.3. Strata C consisted of two studies. Both displayed trends towards cHCT being more protective than individual HCT (IRRs: 0.3-0.5). All studies had at least one design limitation.

Conclusions: In spite of intensive scale-up of HCT in SSA, few well-designed studies have assessed the prevention impacts of HCT. The limited body of evidence suggests that individual HCT does not have a consistent impact on HIV acquisition, and cHCT is more protective than individual HCT.

Abstract access  

Editor’s notes: Although it is plausible that knowing that you are HIV-negative might be an incentive for safer behaviour and thus reduce the risk of HIV acquisition, previous studies have not been conclusive.  HIV counselling and testing (HCT) is an integral part of other prevention and treatment activities (e.g. voluntary medical male circumcision (VMMC) or pre-exposure prophylaxis (PreP)). The findings from this systematic review suggest that with the available evidence individual HCT does not consistently have a protective or harmful effect on HIV acquisition. Couples’ HCT may be protective but the authors caution against a simplistic interpretation, reminding us of limited evidence including imprecise estimates and possibilities of bias. There were just two studies on couples’ HCT and convincing evidence of benefit was only seen in the study which compared couples’ HCT with individual HCT. There could be systematic differences between people who sought couples’ versus individual HCT (who may be unable or unwilling to take up a couples programme). While couples’ HCT may be suited to some people and be protective for them, the wider applicability may be more limited. The authors describe the methodological challenges of measuring the impact of an HCT activity on HIV acquisition, including the fact that large cohorts need to be effectively followed for long periods. In addition, randomised comparisons with no HCT are not possible because of ethical barriers to withholding HCT. Another challenge the authors cite is that both the primary exposure (HCT) and the primary outcome (HIV acquisition) require an HIV test. Arguably, this could be circumvented by offering anonymised remote (eg laboratory) HIV testing to determine HIV acquisition, rather than point-of-care tests where results would be immediately available. The final message from this paper is that although convincing evidence for reduction in HIV acquisition from HCT is not apparent, it’s scale-up must continue. HCT is the gateway to other proven activities for both prevention and treatment.

HIV testing
Africa
Rwanda, South Africa, Uganda, Zimbabwe
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The power of soccer to increase voluntary medical male circumcision uptake in adolescents

A sport-based intervention to increase uptake of voluntary medical male circumcision among adolescent male students: results from the MCUTS 2 cluster-randomized trial in Bulawayo, Zimbabwe.

Kaufman ZA, DeCelles J, Bhauti K, Hershow RB, Weiss HA, Chaibva C, Moyo N, Mantula F, Hatzold K, Ross DA. J Acquir Immune Defic Syndr. 2016 Aug 15;72 Suppl 4:S292-8. doi: 10.1097/QAI.0000000000001046.

Background: Mathematical models suggest that 570 000 HIV infections could be averted between 2011 and 2025 in Zimbabwe if the country reaches 80% voluntary medical male circumcision (VMMC) coverage among 15- to 49-year-old male subjects. Yet national coverage remains well below this target, and there is a need to evaluate interventions to increase the uptake.

Methods: A cluster-randomized trial was conducted to assess the effectiveness of Make-The-Cut-Plus (MTC+), a single, 60-minute, sport-based intervention to increase VMMC uptake targeting secondary school boys (14-20 years). Twenty-six schools in Bulawayo, Zimbabwe, were randomized to either receive MTC+ at the start (intervention) or end (control) of a 4-month period (March to June 2014). VMMC uptake over these 4 months was measured via probabilistic matching of participants in the trial database (n = 1226 male participants; age, 14-20 years; median age, 16.2 years) and the registers in Bulawayo's 2 free VMMC clinics (n = 5713), using 8 identifying variables.

Results: There was strong evidence that the MTC+ intervention increased the odds of VMMC uptake by approximately 2.5 fold (odds ratio = 2.53; 95% confidence interval, 1.21 to 5.30). Restricting to participants who did not report being already circumcised at baseline, MTC+ increased VMMC uptake by 7.6% (12.2% vs 4.6%, odds ratio = 2.65; 95% confidence interval, 1.19 to 5.86). Sensitivity analyses related to the probabilistic matching did not change these findings substantively. The number of participants who would need to be exposed to the demand creation intervention to yield one additional VMMC client was 22.7 (or 13.2 reporting not already being circumcised). This translated to approximately US dollar 49 per additional VMMC client.

Conclusions: The MTC+ intervention was an effective and cost-effective strategy for increasing VMMC uptake among school-going adolescent male subjects in Bulawayo.

Abstract access  

Editor’s notes: WHO and UNAIDS have stressed the importance of focusing on schools and sports to increase uptake of voluntary medical male circumcision (VMMC) among adolescent males. Adolescents have the maximum potential gain from VMMC in terms of prevented infections, and the paper illustrates that the soccer-based ‘Make The Cut’ programme significantly increased VMMC in school-based adolescents. This follows an earlier trial of the programme in adult men in which the proportion accepting VMMC was 4.8% compared with 0.5% in the control arm.

The programme was designed to be brief and low cost. A trained, recently circumcised young male ‘coach’ led a one hour soccer-themed session in school. After the session the coach contacted participants who expressed an interest in VMMC, and arranged transport to a VMMC clinic. The trial team faced the common problem that the clinics where they collected outcome data used a handwritten register rather than electronic records. To address this, the team linked the clinic records to trial participants using probabilistic matching of names and contact details.

Both the prevalence and background incidence of circumcision were higher than expected. Almost half of participants (48%) said they were already circumcised at the beginning of the trial (the authors anticipated 20%), reflecting the recent increased uptake in VMMC in Zimbabwe. Although the trial illustrates significant increase in VMMC, the absolute uptake remained relatively low in the programme arm (12.2%), and a combination of successful VMMC demand creation activities (for example including monetary or non-monetary incentives) are necessary to reach global targets. 

Africa
Zimbabwe
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Updated evidence that DMPA increases HIV risk among women

Update on hormonal contraceptive methods and risk of HIV acquisition in women: a systematic review of epidemiological evidence, 2016.

Polis CB, Curtis KM, Hannaford PC, Phillips SJ, Chipato T, Kiarie JN, Westreich DJ, Steyn PS. AIDS. 2016 Aug 5. [Epub ahead of print]

Objective and design: Some studies suggest that specific hormonal contraceptive (HC) methods (particularly depot medroxyprogesterone acetate [DMPA]) may increase women's HIV acquisition risk. We updated a systematic review to incorporate recent epidemiological data.

Methods: We searched for articles published between 1/15/2014-1/15/2016, and hand-searched reference lists. We identified longitudinal studies comparing users of a specific HC method against either (1) non-users of HC, or (2) users of another specific HC method. We added newly identified studies to those in the previous review, assessed study quality, created forest plots to display results, and conducted a meta-analysis for data on DMPA versus no HC.

Results: We identified ten new reports: five were considered "unlikely to inform the primary question". We focus on the other five reports, along with 9 from the previous review, considered "informative but with important limitations". The preponderance of data for oral contraceptive pills, injectable norethisterone enanthate (NET-EN), and levonorgestrel implants do not suggest an association with HIV acquisition, though data for implants are limited. The new, higher-quality studies on DMPA (or non-disaggregated injectables), which had mixed results in terms of statistical significance, had hazard ratios (HR) between 1.2 and 1.7, consistent with our meta-analytic estimate for all higher-quality studies of HR 1.4.

Conclusions: While confounding in these observational data cannot be excluded, new information increases concerns about DMPA and HIV acquisition risk in women. If the association is causal, the magnitude of effect is likely ≤HR 1.5. Data for other hormonal contraceptive methods, including NET-EN, are largely reassuring.

Abstract access

Editor’s notes: For several years there has been debate about whether the risk of HIV acquisition in women may be increased by the use of hormonal contraception. A systematic review published in 2014 included a meta-analysis of data from 22 studies, and this paper adds 10 new studies to the analysis. While these new papers carried some of the previous review’s limitations which cannot be ignored, the new data also lends further strength to the evidence and renewed analysis. The authors found some encouraging results which suggest that there is no significant increased risk of HIV with the use of oral contraceptives and the NET-EN injectable. However, this analysis does suggest that there is an increased risk of 1.4-1.5 of HIV with the use of DMPA. This is particularly concerning given the widespread use of this product throughout the world, and especially in areas where high rates of new HIV infections continue to persist, such as sub-Saharan Africa. Studies continue to explore this association of risk, and will hopefully produce evidence in the near future to definitively provide guidance as to how clinicians should direct the use of DMPA in women at risk of HIV. 

Africa, Northern America
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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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The HIV prevention cascade – a new approach to guide HIV prevention programmes

Providing a conceptual framework for HIV prevention cascades and assessing feasibility of empirical measurement with data from east Zimbabwe: a case study.

Garnett GP, Hallett TB, Takaruza A, Hargreaves J, Rhead R, Warren M, Nyamukapa C, Gregson S. Lancet HIV. 2016 Jul;3(7):e297-306. doi: 10.1016/S2352-3018(16)30039-X.

Background: The HIV treatment cascade illustrates the steps required for successful treatment and is a powerful advocacy and monitoring tool. Similar cascades for people susceptible to infection could improve HIV prevention programming. We aim to show the feasibility of using cascade models to monitor prevention programmes.

Methods: Conceptual prevention cascades are described taking intervention-centric and client-centric perspectives to look at supply, demand, and efficacy of interventions. Data from two rounds of a population-based study in east Zimbabwe are used to derive the values of steps for cascades for voluntary medical male circumcision (VMMC) and for partner reduction or condom use driven by HIV testing and counselling (HTC).

Findings: In 2009 to 2011 the availability of circumcision services was negligible, but by 2012 to 2013 about a third of the population had access. However, where it was available only 12% of eligible men sought to be circumcised leading to an increase in circumcision prevalence from 3.1% to 6.9%. Of uninfected men, 85.3% did not perceive themselves to be at risk of acquiring HIV. The proportions of men and women tested for HIV increased from 27.5% to 56.6% and from 61.1% to 79.6%, respectively, with 30.4% of men tested self-reporting reduced sexual partner numbers and 12.8% reporting increased condom use.

Interpretation: Prevention cascades can be populated to inform HIV prevention programmes. In eastern Zimbabwe programmes need to provide greater access to circumcision services and the design and implementation of associated demand creation activities. Whereas, HTC services need to consider how to increase reductions in partner numbers or increased condom use or should not be considered as contributing to prevention services for the HIV-negative adults.

Abstract  Full-text [free] access 

Editor’s notes: UNAIDS has set an ambitious goal of reducing new adult HIV infections below 500 000 per year by 2020. Achieving this goal relies on increased coverage of primary HIV prevention programmes, including pre-exposure prophylaxis and voluntary medical male circumcision (VMMC). The HIV treatment cascade is a well known tool to monitor the performance of services for people living with HIV, and to identify gaps in care. An HIV prevention cascade could provide a similarly useful tool to inform prevention programmes. The tool would define the steps necessary for an effective HIV prevention programme, estimating the proportion of people lost at each step, and hence identifying the barriers to effective HIV prevention in populations. The authors propose a framework for HIV prevention cascades, differentiating between availability, uptake, adherence, and efficacy.  The framework would estimate the proportion of the population protected by a given strategy or combination of strategies. Population survey data from rural Zimbabwe are used to illustrate the prevention cascade for VMMC and behaviour change driven by HIV testing and counselling (HTC). These data are used to highlight the barriers impacting on reducing HIV incidence. As the authors acknowledge, there are limitations to the cascade approach for HIV prevention. The cascade is more difficult to define and to estimate for HIV prevention than for HIV treatment. In order for the cascade to be useful, it is necessary to have a good understanding of who is at risk of acquiring HIV.  However, the prevention needs of HIV negative adults change over time as people move in and out of risk. Although the authors illustrate the use of the cascade for an individual programme, it is more difficult to assess the combined effect of several prevention strategies. Still, the cascade approach may provide a useful tool to help guide HIV prevention efforts, by identifying gaps and prioritising areas for action.

Africa
Zimbabwe
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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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