Articles tagged as "HIV testing and treatment"

A cohort-based approach to the HIV treatment cascade finds linkage the major bottleneck

From HIV infection to therapeutic response: a population-based longitudinal HIV cascade-of-care study in KwaZulu-Natal, South Africa.

Haber N, Tanser F, Bor J, Naidu K, Mutevedzi T, Herbst K, Porter K, Pillay D, Barnighausen T. Lancet HIV. 2017 Jan 30. pii: S2352-3018(16)30224-7. doi: 10.1016/S2352-3018(16)30224-7. [Epub ahead of print]

Background: Standard approaches to estimation of losses in the HIV cascade of care are typically cross-sectional and do not include the population stages before linkage to clinical care. We used individual-level longitudinal cascade data, transition by transition, including population stages, both to identify the health-system losses in the cascade and to show the differences in inference between standard methods and the longitudinal approach.

Methods: We used non-parametric survival analysis to estimate a longitudinal HIV care cascade for a large population of people with HIV residing in rural KwaZulu-Natal, South Africa. We linked data from a longitudinal population health surveillance (which is maintained by the Africa Health Research Institute) with patient records from the local public-sector HIV treatment programme (contained in an electronic clinical HIV treatment and care database, ARTemis). We followed up all people who had been newly detected as having HIV between Jan 1, 2006, and Dec 31, 2011, across six cascade stages: three population stages (first positive HIV test, HIV status knowledge, and linkage to care) and three clinical stages (eligibility for antiretroviral therapy [ART], initiation of ART, and therapeutic response). We compared our estimates to cross-sectional cascades in the same population. We estimated the cumulative incidence of reaching a particular cascade stage at a specific time with Kaplan-Meier survival analysis.

Findings: Our population consisted of 5205 individuals with HIV who were followed up for 24 031 person-years. We recorded 598 deaths. 4539 individuals gained knowledge of their positive HIV status, 2818 were linked to care, 2151 became eligible for ART, 1839 began ART, and 1456 had successful responses to therapy. We used Kaplan-Meier survival analysis to adjust for censorship due to the end of data collection, and found that 8 years after testing positive in the population health surveillance, 16% had died. Among living patients, 82% knew their HIV status, 45% were linked to care, 39% were eligible for ART, 35% initiated ART, and 33% had reached therapeutic response. Median times to transition for these cascade stages were 52 months, 52 months, 20 months, 3 months, and 9 months, respectively. Compared with the population stages in the cascade, the transitions across the clinical stages were fast. Over calendar time, rates of linkage to care have decreased and patients presenting for the first time for care were, on average, healthier.

Interpretation: HIV programmes should focus on linkage to care as the most important bottleneck in the cascade. Cascade estimation should be longitudinal rather than cross-sectional and start with the population stages preceding clinical care.

Abstract access  

Editor’s notes: The HIV treatment cascade outlines the stages required to effectively treat HIV, starting with HIV testing and ending with viral suppression. The cascade has become a widely-used framework to evaluate the performance of HIV care programmes, to measure progress towards universal treatment coverage, and to identify gaps in care. However, methods for constructing the HIV treatment cascade vary considerably. The majority of cascade analyses rely on cross-sectional data obtained from different sources. The authors present the first analysis of the HIV treatment cascade that follows individuals longitudinally from the time of HIV infection across all stages of the cascade. By linking data from a demographic surveillance system with electronic clinical records, they are able to describe the cascade for a large population-based cohort of people living with HIV in rural KwaZulu-Natal, South Africa.  They demonstrate that, once people became eligible for ART, the rates of ART initiation, and of viral suppression after initiation, were high. Half of individuals started ART within three months of becoming eligible, and 94% of people on therapy achieved virologic suppression. In addition, retention in care improved over time. However, a key finding is that rates of HIV diagnosis and linkage to care worsened over time, and less than 50% of people had linked to care within eight years of HIV infection, despite 82% being aware of their status. As illustrated by cascade analyses in other settings, increasing linkage to care remains a major challenge for reaching the UNAIDS 90-90-90 treatment target in sub-Saharan Africa.  

In addition to highlighting linkage as the most important bottleneck in the HIV care cascade in this part of rural KwaZulu-Natal, the study illustrates some of the weaknesses in traditional cascade analyses based on cross-sectional data. The cross-sectional cascade is constructed from snapshots of different groups of people in a particular moment in time, rather than describing what happens to the same group of people over time. The authors illustrate how a cross-sectional analysis can give a misleading impression of improvement in the cascade over time, because it fails to take account of changes in the population. The longitudinal cascade, by following the same group of people, provides important insights into the true progression of the cascade over time, and identification of losses along each stage. However, the individual-level longitudinal data necessary for this type of analysis requires a large investment in data collection, and is unlikely to be feasible in most resource-limited settings.

Africa
South Africa
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Treatment of depression at antiretroviral initiation could have a considerable impact on mortality

Depression at antiretroviral therapy initiation and clinical outcomes among a cohort of Tanzanian women living with HIV.

Sudfeld CR, Kaaya S, Gunaratna NS, Mugusi F, Fawzi WW, Aboud S, Smith Fawzi. AIDS. 2017 Jan 14;31(2):263-271. doi: 10.1097/QAD.0000000000001323.

Objective: The objective of the study was to assess the relationship of depression at antiretroviral therapy (ART) initiation with mortality and clinical outcomes among Tanzanian women living with HIV.

Design: We conducted a prospective cohort study of 1487 women who initiated ART in Dar es Salaam, Tanzania.

Methods: Symptoms of depression and anxiety were assessed using a Tanzanian-adapted and validated version of the Hopkins Symptom Checklist. Participants attended monthly clinic visits during the first 2 years of ART and CD4 T-cell counts were assessed every 4 months. Proportional hazard models were used to assess the relationship of depression with mortality and clinical outcomes.

Results: Symptoms consistent with depression were prevalent among 57.8% of women at ART initiation. After multivariate adjustment, including social support and stigma, depression at ART initiation was associated with increased risk of mortality [hazard ratio (HR): 1.92; 95% confidence interval (CI): 1.15-3.20; P = 0.01] and incidence of severe anemia (hemoglobin <8.5 g/dl; HR: 1.59; 95% CI: 1.07-2.37; P = 0.02). Under the assumption of causality, we estimate 36.1% (95% CI: 13.6-55.1%) of deaths among the study cohort were attributable to depression and its consequences. Depression was not significantly associated with trajectory of CD4 T-cell reconstitution or the risk of immunologic failure (P values >0.05).

Conclusion: Elimination of depression may reduce mortality during the first 2 years of ART by one-third in our study cohort. Randomized trials and rigorous implementation studies are needed to evaluate the individual and population-level effects of integrated mental health interventions and HIV treatment approaches in resource-limited settings.

Abstract access  

Editor’s notes: People living with HIV are more than twice as likely to have depression than the general population, in both high- and low-income settings. Many studies in high-income countries have illustrated that depression is associated with poor HIV-associated outcomes. There have been relatively few longitudinal studies on this from low-income settings. This study, among women in Tanzania living with HIV, found that over half had symptoms consistent with depression at ART initiation, and this was associated with a two-fold risk of mortality. The results suggest that effective programmes which address depression, such as problem-solving therapy or cognitive behaviour therapy, at ART initiation, could have a considerable impact on mortality. There is a need to evaluate appropriate mental health programmes integrated with HIV strategies in resource-limited settings that address the specific needs of different populations of people living with HIV, such as children and adolescents   

Africa
United Republic of Tanzania
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Outcomes on ART among children and adolescents in Latin America

Mortality in children with human immunodeficiency virus initiating treatment: a six-cohort study in Latin America.

Luque MT, Jenkins CA, Shepherd BE, Padgett D, Rouzier V, Succi RC, Machado DM, McGowan CC, Vermund SH, Pinto JA. J Pediatr. 2017 Jan 9. pii: S0022-3476(16)31433-0. doi: 10.1016/j.jpeds.2016.12.034. [Epub ahead of print]

Objectives: To assess the risks of and factors associated with mortality, loss to follow-up, and changing regimens after children with HIV infected perinatally initiate combination antiretroviral therapy (cART) in Latin America and the Caribbean.

Study design: This 1997-2013 retrospective cohort study included 1174 antiretroviral therapy-naive, perinatally infected children who started cART when they were younger than 18 years of age (median 4.7 years; IQR 1.7-8.8) at 1 of 6 cohorts from Argentina, Brazil, Haiti, and Honduras, within the Caribbean, Central and South America Network for HIV Epidemiology. Median follow-up was 5.6 years (IQR 2.3-9.3). Study outcomes were all-cause mortality, loss to follow-up, and major changes/interruption/stopping of cART. We used Cox proportional hazards models stratified by site to examine the association between predictors and times to death or changing regimens.

Results: Only 52% started cART at younger than 5 years of age; 19% began a protease inhibitor. At cART initiation, median CD4 count was 472 cells/mm3 (IQR 201-902); median CD4% was 16% (IQR 10-23). Probability of death was high in the first year of cART: 0.06 (95% CI 0.04-0.07). Five years after cART initiation, the cumulative mortality incidence was 0.12 (95% CI 0.10-0.14). Cumulative incidences for loss to follow-up and regimen change after 5 years were 0.16 (95% 0.14-0.18) and 0.30 (95% 0.26-0.34), respectively. Younger children had the greatest risk of mortality, whereas older children had the greatest risk of being lost to follow-up or changing regimens.

Conclusions: Innovative clinical and community approaches are needed for quality improvement in the pediatric care of HIV in the Americas.

Abstract access

Editor’s notes: Despite the dramatic declines in mortality with antiretroviral therapy (ART), mortality rates among children living with HIV still remain substantially higher than in the general paediatric population in high-income settings, such as in the United States of America. Mortality rates after ART initiation are even higher in sub-Saharan Africa, likely because children initiate ART at older ages and at more advanced stages of disease. There are, however, no data available for Latin America and the Caribbean, which has had a mostly stable epidemic with a slowly declining adult HIV incidence over the past decade.

In this retrospective cohort study, the authors investigate mortality, loss-to-follow-up (LTFU) and regimen change among children who acquired HIV in the perinatal period from Argentina, Haiti, Honduras and Brazil. They initiated ART aged below 18 years. About half of all children started ART aged over five years, and a third had clinical AIDS by the time they initiated ART. This would suggest that paediatric HIV programmes in this region face similar challenges to those seen in African programmes, including failure of prevention of mother-to-child HIV transmission (PMTCT) programmes and late diagnosis of children.

As expected, a low baseline CD4 count and clinical AIDS at baseline were both associated with an increased risk of mortality. Importantly, younger age at starting ART was also associated with an increased hazard of death, as was being an adolescent (although the association was weaker). The most likely reason for this is that the youngest children placed on ART may have been initiated following presentation with fast-progressing disease, and would therefore have a higher risk of death than comparatively healthier and stable older children. The higher risk of death among the adolescents likely reflects delayed diagnosis of slow-progressors in adolescence.   

Another important finding was the significantly higher risk of LTFU and regimen change in adolescents compared to younger children. This finding, also noted in African and high-income setting cohorts, highlights the challenges of retaining adolescents in care, addressing treatment fatigue, and possibly increased risk of attrition from care during transitioning from paediatric to adult services. 

In summary, HIV care outcomes in children in Latin America and the Caribbean appear to be similar to those reported in other settings. Together, they highlight the pressing need for strengthening prevention of mother-to-child HIV transmission programmes, particularly follow-up and prompt testing of HIV-exposed infants. It also emphasizes the need for innovative approaches to support children to stay in care and maintain long-term adherence. 

Latin America
Argentina, Brazil, Haiti, Honduras
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HIV Self-testing acceptable to vocational students in South Africa

High acceptability of HIV self-testing among technical vocational education and training college students in Gauteng and North West province: what are the implications for the scale up in South Africa?

Mokgatle MM, Madiba S. PLoS One. 2017 Jan 31;12(1):e0169765. doi: 10.1371/journal.pone.0169765. eCollection 2017.

Background: Although HIV self-testing (HIVST) is globally accepted as an important complement to existing HIV testing approaches, South Africa has lagged behind in its adoption. As a result, data on the acceptability and uptake of HIVST is limited. The study investigated the acceptability of HIVST among students in Technical Vocational Education and Training (TVET) colleges in two provinces in South Africa.

Methods: A cross-sectional survey using a self-administered structured questionnaire was used to collect data among 3662 students recruited from 13 TVET colleges.

Results: The mean age of the students was 21.9 years. The majority (80.9%) were sexually active; while 66.1% reported that they had one sexual partner, and 33.9% had two or more sexual partners in the past year, and 66.5% used condoms during the last sexual act. Three-quarters tested for HIV in the past year but less than half knew about HIVST prior to the survey. The acceptability of HIVST was high; about three-quarters showed a willingness to purchase a self-test kit and a majority would self-test with partners. Acceptability of HIVST was associated with being sexually active (OR = 1.73, p = 0.02, confidence interval (CI): 1.08-2.75), having ever been tested for HIV (OR = 1.74, p = 0.001, CI: 1.26-2.38), and having multiple sexual partners (OR = 0.61, p = 0.01, CI: 0.42-0.88). Three-quarters would confirm test results at a local health facility. In terms of counselling, telephone hotlines were acceptable to only 39.9%, and less than half felt that test-kit leaflets would provide sufficient information to self-test.

Interpretations: The high acceptability of HIVST among the students calls for extensive planning and preparation for the scaling up of HIVST in South Africa. In addition, campaigns similar to those conducted to promote HIV counselling and testing (HCT) should be considered to educate communities about HIVST.

Abstract  Full-text [free] access  

Editor’s notes: The percentage of people living with HIV who know their status (the first 90 of the UNAIDS 90:90:90 treatment target) has been consistently well below the stated target in national HIV treatment cascades. HIV self-testing is an exciting strategy being used to increase the uptake of testing, and has recently been adopted in South Africa. This study had two aims; firstly to assess the participants attitudes to currently available HIV counselling and testing services and secondly to assess the level of acceptability of HIV self-testing. The study population were students in technical and vocational education and training colleges in South Africa.

Among people who had not tested for HIV in the past year, reasons given for non-uptake of testing (other than a low perception of risk) included a fear of stigma associated with a positive test or a lack of comfort with testing in a hospital setting. Less than half of participants had heard of HIV self-testing, but when the concept was explained to them, around 80% expressed a willingness to use it if it was available, and 70% were willing to purchase the self-test kit. These results are consistent with other studies of HIV self-testing uptake and acceptability in sub-Saharan Africa.

The stated willingness of participants to present at a clinic for a confirmatory test is encouraging. However, this may not reflect actual behaviour, especially in a setting where there is currently no plan or system to link people with positive HIV self-test results to a clinic for confirmatory testing. However, the drive to improve counselling and linkage around self-testing needs to be balanced against the fundamental principle for HIV self-testing to allow choice for users to test without the need for a health worker to be present, and the privacy associated with this. Further work may include assessing acceptability of using remote services to complement HIV self-testing such as telephone hotlines or other counselling strategies. 

Africa
South Africa
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Community mobilization programme to increase HIV testing – more work is necessary

Community mobilization for HIV testing uptake: results from a community randomized trial of a theory-based intervention in rural South Africa.

Lippman SA, Neilands TB, MacPhail C, Peacock D, Maman S, Rebombo D, Twine R, Selin A, Leslie HH, Kahn K, Pettifor A. J Acquir Immune Defic Syndr. 2017 Jan 1;74 Suppl 1:S44-S51.

Background: HIV testing uptake in South Africa is below optimal levels. Community mobilization (CM) may increase and sustain demand for HIV testing, however, little rigorous evidence exists regarding the effect of CM interventions on HIV testing and the mechanisms of action.

Methods: We implemented a theory-driven CM intervention in 11 of 22 randomly-selected villages in rural Mpumalanga Province. Cross-sectional surveys including a community mobilization measure were conducted before (n = 1181) and after (n = 1175) a 2-year intervention (2012-2014). We assessed community-level intervention effects on reported HIV testing using multilevel logistic models. We used structural equation models to explore individual-level effects, specifically whether intervention assignment and individual intervention exposure were associated with HIV testing through community mobilization.

Results: Reported testing increased equally in both control and intervention sites: the intervention effect was null in primary analyses. However, the hypothesized pathway, CM, was associated with higher HIV testing in the intervention communities. Every standard deviation increase in village CM score was associated with increased odds of reported HIV testing in intervention village participants (odds ratio: 2.6, P = <0.001) but not control village participants (odds ratio: 1.2, P = 0.53). Structural equation models demonstrate that the intervention affected HIV testing uptake through the individual intervention exposure received and higher personal mobilization scores.

Conclusions: There was no evidence of community-wide gains in HIV testing due to the intervention. However, a significant intervention effect on HIV testing was noted in residents who were personally exposed to the intervention and who evidenced higher community mobilization. Research is needed to understand whether CM interventions can be diffused within communities over time.

Abstract  Full-text [free] access 

Editor’s notes: HIV testing is an integral component of HIV prevention strategies, and essential for achieving the UNAIDS 90-90-90 treatment target. However, testing coverage in many parts of sub-Saharan Africa remains low, particularly among men. Stigma, gender norms, and lack of ‘buy in’ about the benefits of early testing and treatment remain major barriers to testing. 

This cluster-randomised trial of a community mobilization (CM) approach for HIV prevention in South Africa is one of the first to be based around an explicit theoretical model of community change. CM is designed to engage community members and motivate people to achieve a common goal, and has been used successfully in some HIV prevention programmes. The programme focused on young men aged 18-35 years, with an aim to build community support for normative changes that are necessary to tackle social barriers to HIV testing and care. Trial outcomes included gender norms, sexual behaviour and HIV testing uptake. The trial found no overall effect on the uptake of HIV testing – self-reported HIV testing increased significantly in both arms over the two year observation period, with no difference between the programme and control communities. However, CM scores, used to quantify the degree of community engagement, were higher in the programme communities. In addition, individuals with greater exposure to the programme were more likely to report HIV testing. These findings suggest that although the CM programme did have an impact on the individuals exposed to it, the effect did not filter through to the wider community.  

CM strategies are used increasingly in public health programmes, and can be a powerful tool for increasing community awareness and engagement with HIV prevention. The benefit of CM is its ability to diffuse beyond the immediate participants to the community as a whole, to bring about the greatest possible change. However, little is known about why and how these approaches work. As this study illustrates, there is a need to understand more about the underlying mechanisms of change associated with CM, and the factors that contribute to its success.

Africa
South Africa
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High MDR-TB treatment success rates among people on ART

High treatment success rates among HIV-infected multidrug-resistant tuberculosis patients after expansion of antiretroviral therapy in Botswana, 2006-2013.

Shin SS, Modongo C, Boyd R, Caiphus C, Kuate L, Kgwaadira B, Zetola NM. J Acquir Immune Defic Syndr. 2017 Jan 1;74(1):65-71.

Background: Few studies have examined multidrug-resistant (MDR) tuberculosis (TB) treatment outcomes among HIV-infected persons after widespread expansion of antiretroviral therapy (ART). We describe MDR-TB treatment outcomes among HIV-infected and HIV-uninfected patients in Botswana after ART expansion.

Methods: We retrospectively reviewed data from patients who started MDR-TB therapy in Botswana during 2006-2013. Multivariable regression models were used to compare treatment outcomes between HIV-infected and HIV-uninfected patients.

Results: We included 588 MDR-TB patients in the analysis, of whom, 47 (8.0%) and 9 (1.5%) were diagnosed with pre-extensively drug-resistant (XDR)-TB and XDR-TB, respectively. Of the 408 (69.4%) HIV-infected patients, 352 (86.0%) were on ART or started ART during treatment, and median baseline CD4 T-cell count was 234 cells/mm3. Treatment success rates were 79.4% and 73.0% among HIV-uninfected and HIV-infected patients, respectively (P = 0.121). HIV-infected patients with CD4 T-cell count <100 cells/mm3 were more likely to die during treatment compared with HIV-uninfected patients (adjusted risk ratio = 1.890; 95% CI: 1.098 to 3.254).

Conclusions: High rates of treatment success were achieved with programmatic management of MDR-TB and HIV in Botswana after widespread expansion of ART. However, a 2-fold increase in mortality was observed among HIV-infected persons with baseline CD4 <100 cells/mm3 compared with HIV-uninfected persons.

Abstract access  

Editor’s notes: This article describes the treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) among HIV-positive and HIV-negative people in Botswana between 2006 and 2013, after expansion of the antiretroviral therapy (ART) programme. The investigators used programmatic data for their analysis, and the results therefore reflect “real-life” experience of people in the MDR-TB programme.

The authors found very high rates of treatment success. Some 75% of people started on MDR-TB treatment achieved treatment success, and among people living with HIV the success rate was 73%. This is significantly higher than the 57% treatment success reported in a recent systematic review of HIV-positive MDR-TB people. Pre-treatment counselling, strict directly observed therapy, food and transport incentives, follow-up of people who missed their monthly consultations are all aspects of the MDR-TB (and ART programme) that may have contributed to these high success rates. On the other hand, the inclusion of studies done before widespread access to ART may have contributed to the lower success rates reported in the systematic review. 

The reported treatment success of 79% among HIV-negative people was lower than the 84-89% treatment success reported for the new nine-month MDR-TB regimen endorsed by WHO. However, the authors emphasize that additional research is necessary to evaluate the effectiveness of the nine-month regimen in a similar setting as Botswana, where the majority of MDR-TB people are HIV-positive.

In this study, about 70% of MDR-TB people were HIV-positive, and 20% of people had a CD4 count of less than 100 cells/mm3 at the time of MDR-TB treatment initiation. People with a CD4 less than 100 cells/mm3 were almost twice as likely to die during their MDR-TB treatment compared to HIV-negative people. People living with HIV, with CD4<100 cells/mm3 often have co-morbidities, and are at high risk of dying of diseases other than TB, including cryptococcal meningitis and other opportunistic infections. The authors suggest that additional research is necessary to improve the clinical management of MDR-TB people with advanced immunosuppression.

The authors conclude that to reduce mortality from MDR-TB and other causes, increased efforts are necessary to reach all people living with HIV with ART as part of comprehensive HV care. In June 2016, Botswana launched the “Test and Treat” programme, to provide ART to all people living with HIV, which should contribute to this goal. 

Africa
Botswana
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Increased risk of death associated with perceived barriers to care at HIV diagnosis in South Africa

Barriers to care and 1-year mortality among newly-diagnosed HIV-infected people in Durban, South Africa.

Bassett IV, Coleman SM, Giddy J, MfamMed, Bogart LM, Chaisson CE, Ross D, Flash MJ, Govender T, Walensky RP, Freedberg KA, Losina E. J Acquir Immune Defic Syndr. 2017 Apr 1;74(4):432-438.  doi: 10.1097/QAI.0000000000001277. 2016 Dec 30. [Epub ahead of print]

Background: Prompt entry into HIV care is often hindered by personal and structural barriers. Our objective was to evaluate the impact of self-perceived barriers to healthcare on 1-year mortality among newly diagnosed HIV-infected individuals in Durban, South Africa.

Methods: Prior to HIV testing at four outpatient sites, adults (≥18y) were surveyed regarding perceived barriers to care including: 1) service delivery; 2) financial; 3) personal health perception; 4) logistical; and 5) structural. We assessed deaths via phone calls and the South African National Population Register. We used multivariable Cox proportional hazards models to determine the association between number of perceived barriers and death within one year.

Results: 1899 HIV-infected participants enrolled. Median age was 33 years (IQR: 27-41y), 49% were female, and median CD4 count was 192/µl (IQR: 72-346/µl). 1057 participants (56%) reported no, 370 (20%) reported 1-3, and 460 (24%) reported >3 barriers to care. By one year, 250 (13%, 95% CI: 12%, 15%) participants died. Adjusting for age, sex, education, baseline CD4 count, distance to clinic, and TB status, participants with 1-3 barriers (adjusted hazard ratio [aHR]: 1.49, 95% CI: 1.06, 2.08) and >3 barriers (aHR: 1.81, 95% CI: 1.35, 2.43) had higher 1-year mortality risk compared to those without barriers.

Conclusions: HIV-infected individuals in South Africa who reported perceived barriers to medical care at diagnosis were more likely to die within one year. Targeted structural interventions such as extended clinic hours, travel vouchers, and streamlined clinic operations may improve linkage to care and ART initiation for these people.

Abstract access  

Editor’s notes: Mortality among people living with HIV remains high in South Africa. Suboptimal engagement in HIV care is noted to be a significant contributor to this, with many deaths occurring before people have even started antiretroviral therapy. Potential barriers to care range from personal, such as perceived good health therefore believing antiretroviral therapy is not necessary, to logistical, such as a lack of transportation, to structural barriers such as busy clinics and long waits for care. Barriers perceived by the patient may also be different to barriers perceived by providers of care.

This study sought to explore self-perceived barriers to care at the time of testing for HIV and their impact on one-year mortality. This was in the context of a trial testing whether or not health system navigators improved linkage to and retention in care. Between 2010 and 2013, adults attending for HIV testing across four clinics in Durban, South Africa enrolled in this trial, completed a baseline questionnaire. This examined self-perceived barriers to care, their emotional health and social support. Participants found to be HIV positive were followed up via phone within 12 months. Limited clinical data was sought from clinic notes. Any reported deaths were confirmed by a national register.

Some 1887 participants were enrolled and subsequently diagnosed with HIV. Some 250 people died by 12 months post enrollment. A myriad of barriers were reported, the most common being associated with personal health, service delivery and structural issues. However, it was the sum of barriers that was predictive of risk. People with one or more perceived barriers had a higher one-year mortality risk compared to people without perceived barriers. Furthermore, it was illustrated that the greater the number of perceived barriers, the greater the risk of mortality. The risk for people with greater than three perceived barriers was double that of people with three or less barriers (22% versus 11%). Interestingly, there was no significant impact of emotional and social support as reported at baseline.

Limitations noted by the authors include a possible overestimation of deaths attributable to HIV, since there were no specific data on the cause of death. Data on co-morbidities (apart from tuberculosis) were also not collected and their potential impact on mortality is not addressed. However, it may be fair to assume that any barriers to HIV care would also extend to affecting access to other forms of healthcare. Overall, the study highlights perceived barriers at diagnosis as plausible factors to address when shaping programmes to improve retention in care. 

Africa
South Africa
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Assisted partner services a safe, effective strategy to identify undiagnosed HIV cases in sub-Saharan Africa

Assisted partner services for HIV in Kenya: a cluster randomised controlled trial.

Cherutich P, Golden MR, Wamuti B, Richardson BA, Asbjornsdottir KH, Otieno FA, Ng'ang'a A, Mutiti PM, Macharia P, Sambai B, Dunbar M, Bukusi D, Farquhar C. Lancet HIV. 2016 Nov 29. pii: S2352-3018(16)30214-4. doi: 10.1016/S2352-3018(16)30214-4. [Epub ahead of print]

Background: Assisted partner services for index patients with HIV infections involves elicitation of information about sex partners and contacting them to ensure that they test for HIV and link to care. Assisted partner services are not widely available in Africa. We aimed to establish whether or not assisted partner services increase HIV testing, diagnoses, and linkage to care among sex partners of people with HIV infections in Kenya.

Methods: In this cluster randomised controlled trial, we recruited non-pregnant adults aged at least 18 years with newly or recently diagnosed HIV without a recent history of intimate partner violence who had not yet or had only recently linked to HIV care from 18 HIV testing services clinics in Kenya. Consenting sites in Kenya were randomly assigned (1:1) by the study statistician (restricted randomisation; balanced distribution in terms of county and proximity to a city) to immediate versus delayed assisted partner services. Primary outcomes were the number of partners tested for HIV, the number who tested HIV positive, and the number enrolled in HIV care, in those who were interviewed at 6 week follow-up. Participants within each cluster were masked to treatment allocation because participants within each cluster received the same intervention. This trial is registered with ClinicalTrials.gov, number NCT01616420.

Findings: Between Aug 12, 2013, and Aug 31, 2015, we randomly allocated 18 clusters to immediate and delayed HIV assisted partner services (nine in each group), enrolling 1305 participants: 625 (48%) in the immediate group and 680 (52%) in the delayed group. 6 weeks after enrolment of index patients, 392 (67%) of 586 partners had tested for HIV in the immediate group and 85 (13%) of 680 had tested in the delayed group (incidence rate ratio 4.8, 95% CI 3.7-6.4). 136 (23%) partners had new HIV diagnoses in the immediate group compared with 28 (4%) in the delayed group (5.0, 3.2-7.9) and 88 (15%) versus 19 (3%) were newly enrolled in care (4.4, 2.6-7.4). Assisted partner services did not increase intimate partner violence (one intimate partner violence event related to partner notification or study procedures occurred in each group).

Interpretation: Assisted partner services are safe and increase HIV testing and case-finding; implementation at the population level could enhance linkage to care and antiretroviral therapy initiation and substantially decrease HIV transmission.

Abstract access  

Editor’s notes: One of the greatest challenges to achieving goals such as the UNAIDS 90:90:90 treatment target is the development of more effective strategies to enable people undiagnosed living with HIV to be tested and engaged with care. One strategy for achieving this in high-income settings, albeit with a very limited evidence base, is assisted partner services. In this approach, health-care workers identify and attempt to contact the sexual partners of people recently diagnosed with HIV. These partners are then encouraged to be tested and engaged with care. This pragmatic cluster randomised study, conducted in Kenya, aimed to assess whether assisted partner services were feasible in a sub-Saharan African setting and if so, to measure the effectiveness in terms of additional individuals testing for HIV, receiving new HIV diagnoses and engaging with care as a result of the programme.

The results were striking, in that six weeks after enrolment almost five times as many partners of index cases in the immediate group (partners contacted  at enrolment) had been tested for HIV compared to the delayed group (partners contacted  six weeks after enrolment). There were five times as many new HIV diagnoses in the immediate group compared to the delayed group. There were also four times as many partners newly engaged with care in the immediate arm compared to the delayed arm. There was also no evidence that the tracing of sexual partners led to an increase in intimate partner violence.

These results illustrate that assisted partner services can make an important contribution to identifying people living with HIV who are undiagnosed, enabling people to get tested and engaged with care in a low-income setting. A major challenge, identified by the study authors, is whether the human resources would be available in already highly stretched settings to implement this strategy. They suggest that task shifting from professional healthcare providers to a less highly educated cadre of workers would be feasible and point to other areas of care such as safe male circumcision and ART delivery, where this has been successfully achieved. 

Africa
Kenya
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Peer support: not a panacea for poor adherence

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

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

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

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

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

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

Abstract  Full-text [free] access 

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

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

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

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

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

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

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

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

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

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

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

Abstract  Full-text [free] access 

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

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

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

Africa
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