Articles tagged as "South Africa"

Invasive cervical cancers preventable by HPV vaccines: a comparison of HIV-positive and negative women

Effect of HIV infection on human papillomavirus types causing invasive cervical cancer in Africa.

Clifford GM, de Vuyst H, Tenet V, Plummer M, Tully S, Franceschi S. J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):332-339.

Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type.

Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa.

Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR).

Results: HPV detection was similar in 770 HIV-positive (91.2%) and 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV.

Conclusions: HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection.

Abstract access  

Editor’s notes: Invasive cervical cancer (ICC) is one of the most common cancers in low and middle income countries. In the African region the prevalence of both ICC and HIV are high. Compared to HIV-negative women, HIV-positive women are at increased risk of oncogenic high-risk (HR) human papillomavirus (HPV) incidence and persistence, and cervical lesion incidence and progression. Current HPV vaccines offer potential for cervical cancer prevention by targeting the HR-HPV types associated with ICC. Although there is no data yet available on HPV vaccine efficacy among HIV-positive persons, HPV vaccines have been reported to be safe and immunogenic in HIV-positive children, female adolescents and adults. 

This systematic review compared the HPV type distribution and the HPV vaccine type distribution in ICC biopsy and cervical cell specimens of 770 HIV-positive and 3846 HIV-negative women from 21 studies in 12 African countries.

The authors report that the fraction of ICC attributable to the HPV types included in the current bivalent (HPV16/18) and nonavalent (HPV16/18/31/33/45/52/58) vaccines was similar among HIV-positive and HIV-negative women (bivalent: 61.7% and 67.3%; nonavalent: 88.9% and 89.5%, respectively). However, a non-negligible proportion of ICC from both HIV-positive and HIV-negative women were infected with non-vaccine types in the absence of any of the vaccine types (7.0% and 7.9% of ICC from HIV-positive and HIV-negative women, respectively), and this was highest for HPV35.

These findings confirm that the currently available HPV vaccines could prevent a similar proportion of ICC cases in HIV-positive as in HIV-negative women. ICC remains an important co-morbidity among HIV-positive women even in the antiretroviral era. Given that HIV-positive women are at greater risk of HR-HPV persistence and cervical lesion incidence and faster progression to high-grade cervical lesions, primary prevention of HPV infection through vaccination could reduce HPV infection and HPV-associated disease in Africa. However, cervical cancer screening will continue to remain important for both HIV-positive and HIV-negative women as there remain a proportion of ICC cases that may not be preventable by currently available vaccines. 

Comorbidity, Epidemiology
Africa
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School-based HIV prevention programmes appear ineffective

School-based interventions for preventing HIV, sexually transmitted infections, and pregnancy in adolescents.

Mason-Jones AJ, Sinclair D, Mathews C, Kagee A, Hillman A, Lombard C. Cochrane Database Syst Rev. 2016 Nov 8;11:CD006417.

Background: School-based sexual and reproductive health programmes are widely accepted as an approach to reducing high-risk sexual behaviour among adolescents. Many studies and systematic reviews have concentrated on measuring effects on knowledge or self-reported behaviour rather than biological outcomes, such as pregnancy or prevalence of sexually transmitted infections (STIs).

Objectives: To evaluate the effects of school-based sexual and reproductive health programmes on sexually transmitted infections (such as HIV, herpes simplex virus, and syphilis), and pregnancy among adolescents.

Search methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for published peer-reviewed journal articles; and ClinicalTrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform for prospective trials; AIDS Education and Global Information System (AEGIS) and National Library of Medicine (NLM) gateway for conference presentations; and the Centers for Disease Control and Prevention (CDC), UNAIDS, the WHO and the National Health Service (NHS) centre for Reviews and Dissemination (CRD) websites from 1990 to 7 April 2016. We hand searched the reference lists of all relevant papers.

Selection criteria: We included randomized controlled trials (RCTs), both individually randomized and cluster-randomized, that evaluated school-based programmes aimed at improving the sexual and reproductive health of adolescents.

Data collection and analysis: Two review authors independently assessed trials for inclusion, evaluated risk of bias, and extracted data. When appropriate, we obtained summary measures of treatment effect through a random-effects meta-analysis and we reported them using risk ratios (RR) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.

Main results: We included eight cluster-RCTs that enrolled 55,157 participants. Five trials were conducted in sub-Saharan Africa (Malawi, South Africa, Tanzania, Zimbabwe, and Kenya), one in Latin America (Chile), and two in Europe (England and Scotland). Sexual and reproductive health educational programmes. Six trials evaluated school-based educational interventions. In these trials, the educational programmes evaluated had no demonstrable effect on the prevalence of HIV (RR 1.03, 95% CI 0.80 to 1.32, three trials; 14 163 participants; low certainty evidence), or other STIs (herpes simplex virus prevalence: RR 1.04, 95% CI 0.94 to 1.15; three trials, 17 445 participants; moderate certainty evidence; syphilis prevalence: RR 0.81, 95% CI 0.47 to 1.39; one trial, 6977 participants; low certainty evidence). There was also no apparent effect on the number of young women who were pregnant at the end of the trial (RR 0.99, 95% CI 0.84 to 1.16; three trials, 8280 participants; moderate certainty evidence). Material or monetary incentive-based programmes to promote school attendance. Two trials evaluated incentive-based programmes to promote school attendance. In these two trials, the incentives used had no demonstrable effect on HIV prevalence (RR 1.23, 95% CI 0.51 to 2.96; two trials, 3805 participants; low certainty evidence). Compared to controls, the prevalence of herpes simplex virus infection was lower in young women receiving a monthly cash incentive to stay in school (RR 0.30, 95% CI 0.11 to 0.85), but not in young people given free school uniforms (data not pooled, two trials, 7229 participants; very low certainty evidence). One trial evaluated the effects on syphilis and the prevalence was too low to detect or exclude effects confidently (RR 0.41, 95% CI 0.05 to 3.27; one trial, 1291 participants; very low certainty evidence). However, the number of young women who were pregnant at the end of the trial was lower among those who received incentives (RR 0.76, 95% CI 0.58 to 0.99; two trials, 4200 participants; low certainty evidence). Combined educational and incentive-based programmes. The single trial that evaluated free school uniforms also included a trial arm in which participants received both uniforms and a programme of sexual and reproductive education. In this trial arm herpes simplex virus infection was reduced (RR 0.82, 95% CI 0.68 to 0.99; one trial, 5899 participants; low certainty evidence), predominantly in young women, but no effect was detected for HIV or pregnancy (low certainty evidence).

Authors' conclusions: There is a continued need to provide health services to adolescents that include contraceptive choices and condoms and that involve them in the design of services. Schools may be a good place in which to provide these services. There is little evidence that educational curriculum-based programmes alone are effective in improving sexual and reproductive health outcomes for adolescents. Incentive-based interventions that focus on keeping young people in secondary school may reduce adolescent pregnancy but further trials are needed to confirm this.

Abstract  Full-text [free] access 

Editor’s notes: School-based HIV prevention programmes are widespread worldwide. These programmes use educational institutions as a venue to reach a population that is entering sexual maturity. Several systematic reviews have found beneficial effects of these programmes on HIV-associated knowledge and behaviours, though a subsequent effect of reduced HIV incidence remains unconfirmed. In this systematic review and meta-analysis, the authors included eight randomized controlled trials from sub-Saharan Africa, Europe, and Latin America. Whether using a curriculum- or incentive-based programme, the trials did not provide evidence of an effect of school-based programmes on reducing HIV infection. Nor was there compelling evidence of an effect of these programmes on reducing sexually transmitted infection or pregnancy. This paper highlights the difficulty of translating knowledge and reported behaviors into reductions in HIV infection and other biological outcomes. Further thought is necessary to deliver effective sexual and reproductive health programmes in schools – possibly including incentives, which show some promise but need further evidence on effectiveness. 

Africa, Europe, Latin America
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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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Migrations, even over short distances, substantially increase the risk of HIV acquisition in rural South Africa

Space-time migration patterns and risk of HIV acquisition in rural South Africa: a population-based cohort study.

Dobra A, Barnighausen T, Vandormael A, Tanser F. AIDS. 2016 Oct 14. [Epub ahead of print]

Objective: To quantify the space-time dimensions of human mobility in relationship to the risk of HIV acquisition.

Methods: We used data from the population cohort located in a high HIV-prevalence, rural population in KwaZulu-Natal, South Africa (2000 - 2014). We geolocated 8006 migration events (representing 1 028 782 km travelled) for 17 743 individuals (≥15 years of age) who were HIV-negative at baseline and followed-up these individuals for HIV acquisition (70 395 person-years). Based on the complete geolocated residential history of every individual in this cohort, we constructed two detailed time-varying migration indices. We then used interval-censored Cox proportional hazards models to quantify the relationship between the migration indices and the risk of HIV acquisition.

Results: 17.4% of participants migrated at least once outside the rural study community during the period of observation (median migration distance = 107.1 km, IQR 18.9-387.5). The two migration indices were highly predictive of hazard of HIV acquisition (p < 0.01) in both men and women. Holding other factors equal, the risk of acquiring HIV infection increased by 50% for migration distances of 40 km (men) and 109 km (women). HIV acquisition risk also increased by 50% when participants spent 44% (men) and 90% (women) of their respective time outside the rural study community.

Conclusion: This in-depth analysis of a population cohort in a rural sub-Saharan African population has revealed a clear non-linear relationship between distance migrated and HIV acquisition. Our findings show that even relatively short distance migration events confer substantial additional risk of acquisition.

Abstract access  

Editor’s notes: Many studies in sub-Saharan African settings have illustrated that migrants have a greater risk of HIV infection and subsequent HIV-associated mortality than their non-migrant peers. The causal mechanisms underlying this enhanced risk and the temporal sequence of the migration and HIV acquisition events are less well understood. This study conducted in rural KwaZulu-Natal in South Africa is a longitudinal analysis linking data on migration episodes and the results of repeated HIV tests for individuals who were HIV negative at baseline. The two places of residence associated with the migration event were geo-coded, enabling the associations between spatiotemporal aspects of the migration and the risk of HIV acquisition to be explored. Two migration indices were calculated - one measuring the length of time spent outside the home residence and the other measuring the sum of the distances associated with the migrations. Both migration indices were significantly associated the risk of HIV acquisition. The association with distance was non-linear, with the risk of acquisition increasing by 50% at relatively short distances (approximately 55km), and the rates of increase of risk declined as the distance of migration increased further. The magnitude of this effect was similar for both sexes. By contrast the effect of time spent away from home on the risk of acquisition of HIV was significantly greater for men than women.

There are likely to be a number of mechanisms explaining the increased risks for migrants. These include an increase in the number of sexual partners, adoption of higher risk sexual behaviour and a detachment from the social support networks that exist in the home community. Further qualitative studies are necessary to explore these more fully. The authors also recommend that such studies are replicated in other settings to assess the generalisability of the findings. Having established these causal pathways, novel HIV prevention approaches focused towards these highly vulnerable migrant populations will need to be developed as part of efforts to achieve the UNAIDS 90:90:90 treatment target.

Africa
South Africa
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Voluntary male circumcision still a cost-effective intervention in the era of 90-90-90

Impact and cost of scaling up voluntary medical male circumcision for HIV prevention in the context of the new 90-90-90 HIV treatment targets.

Kripke K, Reed J, Hankins C, Smiley G, Laube C, Njeuhmeli E. PLoS One. 2016 Oct 26;11(10):e0155734. doi: 10.1371/journal.pone.0155734. eCollection 2016.

Background: The report of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for World AIDS Day 2014 highlighted a Fast-Track Strategy that sets ambitious treatment and prevention targets to reduce global HIV incidence to manageable levels by 2020 and end the AIDS epidemic by 2030. The 90-90-90 treatment targets for 2020 call for 90% of people living with HIV to know their HIV status, 90% of people who know their status to receive treatment, and 90% of people on HIV treatment to be virally suppressed. This paper examines how scale-up of voluntary medical male circumcision (VMMC) services in four priority countries in sub-Saharan Africa could contribute to ending the AIDS epidemic by 2030 in the context of concerted efforts to close the treatment gap, and what the impact of VMMC scale-up would be if the 90-90-90 treatment targets were not completely met.

Methods: Using the Goals module of the Spectrum suite of models, this analysis modified ART (antiretroviral treatment) scale-up coverage from base scenarios to reflect the 90-90-90 treatment targets in four countries (Lesotho, Malawi, South Africa, and Uganda). In addition, a second scenario was created to reflect viral suppression levels of 75% instead of 90%, and a third scenario was created in which the 90-90-90 treatment targets are reached in women, with men reaching more moderate coverage levels. Regarding male circumcision (MC) coverage, the analysis examined both a scenario in which VMMCs were assumed to stop after 2015, and one in which MC coverage was scaled up to 90% by 2020 and maintained at 90% thereafter.

Results: Across all four countries, scaling up VMMC is projected to provide further HIV incidence reductions in addition to those achieved by reaching the 90-90-90 treatment targets. If viral suppression levels only reach 75%, scaling up VMMC leads to HIV incidence reduction to nearly the same levels as those achieved with 90-90-90 without VMMC scale-up. If only women reach the 90-90-90 targets, scaling up VMMC brings HIV incidence down to near the levels projected with 90-90-90 without VMMC scale-up. Regarding cost, scaling up VMMC increases the annual costs during the scale-up phase, but leads to lower annual costs after the MC coverage target is achieved.

Conclusions: The scenarios modeled in this paper show that the highly durable and effective male circumcision intervention increases epidemic impact levels over those of treatment-only strategies, including the case if universal levels of viral suppression in men and women are not achieved by 2020. In the context of 90-90-90, prioritizing continued successful scale-up of VMMC increases the possibility that future generations will be free not only of AIDS but also of HIV.

Abstract  Full-text [free] access 

Editor’s notes: Voluntary medical male circumcision (VMMC) has been shown to reduce the risk of female-to-male HIV transmission by up to 60%. It is a highly cost-effective HIV prevention activity. Since 2007, extensive efforts have been made to scale up VMMC in settings with high HIV prevalence and low levels of male circumcision, with the aim of reaching 80% VMMC coverage in 14 priority countries by 2016.  At the end of 2015, more than 11 million men in east and southern Africa had received VMMC.  In this modelling study, the authors look at the impact of scaling up VMMC to 90% coverage in four priority countries. The paper illustrates that VMMC scale-up can achieve additional reductions in HIV incidence above reductions achieved through testing and treatment alone. In the scenarios where the UNAIDS 90-90-90 treatment target is not completely met, VMMC scale-up can reduce HIV incidence to levels comparable to what would be achieved with the 90-90-90 treatment target. VMMC scale-up also resulted in lower long-term annual programme costs in all four settings. In 2015, UNAIDS set a target of an additional 27 million men in high-HIV prevalence settings receiving VMMC by 2021. Achieving this target will require new service delivery models, and innovative approaches to overcome current barriers that discourage men from accessing health care. VMMC is only one component in combination HIV prevention. It has advantages in being a single event that does not require ongoing adherence, offers men lifelong benefits, and is a valuable entry point for providing a broader range of health services to men including HIV testing. As this study demonstrates, VMMC remains a cost-effective strategy for reducing HIV incidence, even in the context of universal testing and treatment.  

Africa
Lesotho, Malawi, South Africa, Uganda
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Costs for HIV services vary widely across different countries

Costs along the service cascades for HIV testing and counselling and prevention of mother-to-child transmission.

Bautista-Arredondo S, Sosa-Rubi SG, Opuni M, Contreras-Loya D, Kwan A, Chaumont C, Chompolola A, Condo J, Galarraga O, Martinson N, Masiye F, Nsanzimana S, Ochoa-Moreno I, Wamai R, Wang'ombe.  J. AIDS. 2016 Oct 23;30(16):2495-2504. Published online 2016 Sep 28.  doi:  10.1097/QAD.0000000000001208

Objective: We estimate facility-level average annual costs per client along the HIV testing and counselling (HTC) and prevention of mother-to-child transmission (PMTCT) service cascades.

Design: Data collected covered the period 2011-2012 in 230 HTC and 212 PMTCT facilities in Kenya, Rwanda, South Africa, and Zambia.

Methods: Input quantities and unit prices were collected, as were output data. Annual economic costs were estimated from the service providers' perspective using micro-costing. Average annual costs per client in 2013 United States dollars (US$) were estimated along the service cascades.

Results: For HTC, average cost per client tested ranged from US$5 (SD US$7) in Rwanda to US$31 (SD US$24) in South Africa, whereas average cost per client diagnosed as HIV-positive ranged from US$122 (SD US$119) in Zambia to US$1367 (SD US$2093) in Rwanda. For PMTCT, average cost per client tested ranged from US$18 (SD US$20) in Rwanda to US$89 (SD US$56) in South Africa; average cost per client diagnosed as HIV-positive ranged from US$567 (SD US$417) in Zambia to US$2021 (SD US$3210) in Rwanda; average cost per client on antiretroviral prophylaxis ranged from US$704 (SD US$610) in South Africa to US$2314 (SD US$3204) in Rwanda; and average cost per infant on nevirapine ranged from US$888 (SD US$884) in South Africa to US$2359 (SD US$3257) in Rwanda.

Conclusion: We found important differences in unit costs along the HTC and PMTCT service cascades within and between countries suggesting that more efficient delivery of these services is possible.

Abstract  Full-text [free] access 

Editor’s notes: With resources for HIV prevention and treatment services becoming limited, more focus is being placed on maximising the benefit gain from current service provision. This paper examines the cost of different HIV services in four sub-Saharan African countries to see how costs vary for the provision of different services. The authors find a wide variation in costs across different countries. For example, HIV testing appears to have a relatively high cost in South Africa, however South Africa’s cost per person on ARV treatment is lower than other countries. This variation suggests that a more efficient delivery of HIV services could give greater benefit for the same amount of funding required. 

Africa
Kenya, Rwanda, South Africa, Zambia
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Health care navigators do not improve early outcomes on ART in South Africa

Sizanani: a randomized trial of health system navigators to improve linkage to HIV and TB care in South Africa.

Bassett IV, Coleman SM, Giddy J, Bogart LM, Chaisson CE, Ross D, Jacobsen MM, Robine M, Govender T, Freedberg KA, Katz JN, Walensky RP, Losina E. J Acquir Immune Defic Syndr. 2016 Oct 1;73(2):154-60. doi: 10.1097/QAI.0000000000001025.

Background: A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy (ART). We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis (TB) care among newly diagnosed HIV-infected outpatients in Durban, South Africa.

Methods: We conducted a randomized controlled trial (Sizanani Trial, NCT01188941) among adults (≥18 years) at 4 sites. Participants underwent TB screening and randomization into a health system navigator intervention or usual care. Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months. We assessed 9-month outcomes via medical records and the National Population Registry. Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants.

Results: Four thousand nine hundred three participants were enrolled and randomized; 1899 (39%) were HIV-infected, with 1146 (60%) ART-eligible and 523 (28%) TB coinfected at baseline. In the intervention, 212 (39% of outcome-eligible) reached primary outcome compared to 197 (42%) in usual care (RR 0.93, 95% CI: 0.80 to 1.08). One hundred thirty-one (14%) HIV-infected intervention participants died compared to 119 (13%) in usual care; death rates did not differ between arms (RR 1.06, 95% CI: 0.84 to 1.34). In the as-treated analysis, participants reached for ≥5 navigator calls were more likely to achieve study outcome.

Conclusions: approximately 40% of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis. Low rates of engagement in care, high death rates, and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes.

Abstract access  

Editor’s notes: Early mortality remains high among people starting antiretroviral therapy (ART) in low- and middle-income countries, and tuberculosis is consistently identified as a leading cause. In KwaZulu-Natal province, South Africa, where this study was conducted, tuberculosis incidence is very high, and around two-thirds of people starting tuberculosis treatment are HIV-positive. Previous studies have illustrated gaps between positive test results and linkage to HIV and tuberculosis care. For HIV-positive people with tuberculosis, accessing treatment for both HIV and tuberculosis is made more difficult by a lack of integrated care in many settings. Health care navigators have helped people with HIV link to care in the United States.

This study tested a programme whereby health care navigators helped newly-diagnosed HIV-positive people to link to HIV care, and if necessary also to tuberculosis treatment. The navigators had a counselling role, and also contacted patients by phone or text message reminders. Disappointingly, the programme did not improve outcomes at nine months after enrolment. All-cause mortality was high at around 14% by nine months, and was not reduced by the programme. This is an important result, contrasting with findings from other studies. The SEARCH trial in Uganda illustrated more rapid ART initiation resulting from a complex programme, primarily targeting health system rather than individual barriers. However, the primary outcome of the SEARCH analysis was ART initiation; there was no detectable effect on mortality, which was very low, suggesting a lower-risk study population. In the REMSTART study, a programme including point-of-care testing for cryptococcal antigen plus adherence support from community counsellors (along with routine tuberculosis investigation in both arms) was associated with a reduction in early mortality; the “active ingredient” of this programme was not clearly defined. Ideally, people with HIV need to start ART before they reach the stage of advanced disease. However, given the reality that many people do present with advanced disease, more work is necessary to define which programme could reduce their risk of mortality.

Africa
South Africa
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High mortality persists among people presenting with advanced HIV disease

Mortality in the first 3 months on antiretroviral therapy among HIV-positive adults in low- and middle-income countries: a meta-analysis.

Brennan AT, Long L, Useem J, Garrison L, Fox MP. J Acquir Immune Defic Syndr. 2016 Sep 1;73(1):1-10. doi: 10.1097/QAI.0000000000001112.

Previous meta-analyses reported mortality estimates of 12-month post-antiretroviral therapy (ART) initiation; however, 40%-60% of deaths occur in the first 3 months on ART, a more sensitive measure of averted deaths through early ART initiation. To determine whether early mortality is dropping as treatment thresholds have increased, we reviewed studies of 3 months on ART initiation in low- to middle-income countries. Studies of 3-month mortality from January 2003 to April 2016 were searched in 5 databases. Articles were included that reported 3-month mortality from a low- to middle-income country; nontrial setting and participants were ≥15. We assessed overall mortality and stratified by year using random effects models. Among 58 included studies, although not significant, pooled estimates show a decline in mortality when comparing studies whose enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce early HIV-related mortality at the population level, intensified efforts to increase demand for ART through active testing and facilitated referral should be a priority. Continued financial investments by multinational partners and the implementation of creative interventions to mitigate multidimensional complex barriers of accessing care and treatment for HIV are needed.

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Editor’s notes: Early mortality among people initiating antiretroviral therapy (ART) remains high, presumed to be because many people living with HIV present when already very sick with advanced HIV disease. This systematic review included 43 studies from Africa and 13 from Asia. Its main aim was to see whether the evolution of guidelines recommending ART initiation at progressively higher CD4 counts over this period had reduced early mortality (defined as death within three months of ART start) and, by implication, the proportion of people starting ART who had advanced disease. To investigate this, the authors compared studies where enrolment ended before 2010 with studies that had started later.

Overall early mortality was six percent.  Because of the large numbers lost to follow up this will be an underestimate. The authors attempted to compensate for this, and calculated an adjusted overall figure of more than 10%. There was a fall in early mortality from seven percent to four percent (unadjusted) between the early and late periods but although the trend was consistent the difference was not significant.

In only four of the 58 studies was the median CD4 count at ART initiation above 200x106/l. It seems likely that even when policies to initiate ART at high CD4 counts are adopted, additional efforts will be necessary to promote initiation of ART and retention in care for people who feel well.  This is in order to reduce the number of people starting ART with advanced disease and consequently at very high risk of early death.   

Africa, Asia, Latin America
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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.

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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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