Articles tagged as "Health care delivery"

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. 

South Africa
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Improving education about HIV transmission among health workers could reduce stigmatizing attitudes

Another generation of stigma? Assessing healthcare student perceptions of HIV-positive patients in Mwanza, Tanzania.

Aggarwal S, Lee DH, Minteer WB, Fenning RT, Raja SK, Bernstein ME, Raman KR, Denny SP, Patel PA, Lieber M, Farfel AO, Diamond CA. AIDS Patient Care STDS. 2017 Feb;31(2):87-95. doi: 10.1089/apc.2016.0175. Epub 2017 Jan 18.

HIV-related stigma remains a persistent global health concern among people living with HIV/AIDS (PLWA) in developing nations. The literature is lacking in studies about healthcare students' perceptions of PLWA. This study is the first effort to understand stigmatizing attitudes toward HIV-positive patients by healthcare students in Mwanza, Tanzania, not just those who will be directly treating patients but also those who will be indirectly involved through nonclinical roles, such as handling patient specimens and private health information. A total of 208 students were drawn from Clinical Medicine, Laboratory Sciences, Health Records and Information Management, and Community Health classes at the Tandabui Institute of Health Sciences and Technology for a voluntary survey that assessed stigmatizing beliefs toward PLWA. Students generally obtained high scores on the overall survey instrument, pointing to low stigmatizing beliefs toward PLWA and an overall willingness to treat PLWA with the same standard of care as other patients. However, there are gaps in knowledge that exist among students, such as a comprehensive understanding of all routes of HIV infection. The study also suggests that students who interact with patients as part of their training are less likely to exhibit stigmatizing beliefs toward PLWA. A comprehensive course in HIV infection, one that includes classroom sessions focused on the epidemiology and routes of transmission as well as clinical opportunities to directly interact with PLWA-perhaps through teaching sessions led by PLWA-may allow for significant reductions in stigma toward such patients and improve clinical outcomes for PLWA around the world.

Abstract access 

Editor’s notes: This paper reports on a survey of students who were undergoing training in Clinical Medicine, Laboratory Sciences, Health Records and Information Management, Nursing, and Community Health in Mwanza, Tanzania. The survey aimed to explore attitudes about people living with HIV. The authors report that their results illustrate low stigmatizing beliefs towards people living with HIV. However, around a quarter believed that HIV is a punishment for bad behaviour. A third believed that people who acquired HIV from drug use or sex deserved to become infected. Further to this, nearly three quarters believed that individuals who were HIV positive could have avoided infection if they wanted to. A quarter believed that people living with HIV have been promiscuous. There were no differences in response by gender but students under 24 were more likely to have negative attitudes. The authors suggest that this could be due to lower education levels than the older students, although they had not measured this. Students studying Clinical Medicine were less likely to have negative attitudes. On a positive note the students reported that they would treat people living with HIV as equal with other people.

The students displayed some lack of knowledge about routes of HIV infection beyond sex and drug use, especially mother-to-child HIV transmission. The authors suggest that better education in this area may reduce the negative attitudes about people living with HIV, reported by many of the students. Overall, this survey reveals some gaps in education, that if addressed could reduce stigma by health workers against people living with HIV.

United Republic of Tanzania
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Xpert® for active TB case finding in high prevalence communities

Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial.

Calligaro GL, Zijenah LS, Peter JG, Theron G, Buser V, McNerney R, Bara W, Bandason T, Govender U, Tomasicchio M, Smith L, Mayosi BM, Dheda K. Lancet Infect Dis. 2017 Jan 4. pii: S1473-3099(16)30384-X. doi: 10.1016/S1473-3099(16)30384-X. [Epub ahead of print]

Background: Inadequate case detection results in high levels of undiagnosed tuberculosis in sub-Saharan Africa. Data for the effect of new diagnostic tools when used for community-based intensified case finding are not available, so we investigated whether the use of sputum Xpert®-MTB/RIF and the Determine™ TB LAM urine test in two African communities could be effective.

Methods: In a pragmatic, randomised, parallel-group trial with individual randomisation stratified by country, we compared sputum Xpert®-MTB/RIF, and if HIV-infected, the Determine™ TB LAM urine test (novel diagnostic group), with laboratory-based sputum smear microscopy (routine diagnostic group) for intensified case finding in communities with high tuberculosis and HIV prevalence in Cape Town, South Africa, and Harare, Zimbabwe. Participants were randomly assigned (1:1) to these groups with computer-generated allocation lists, using culture as the reference standard. In Cape Town, participants were randomised and tested at an Xpert®-equipped mobile van, while in Harare, participants were driven to a local clinic where the same diagnostic tests were done. The primary endpoint was the proportion of culture-positive tuberculosis cases initiating tuberculosis treatment in each study group at 60 days. This trial is registered at, number NCT01990274.

Findings: Between Oct 18, 2013, and March 31, 2015, 2261 individuals were screened and 875 (39%) of these met the criteria for diagnostic testing. 439 participants were randomly assigned to the novel group and 436 to the routine group. 74 (9%) of 875 participants had confirmed tuberculosis. If late culture-based treatment initiation was excluded, more patients with culture-positive tuberculosis were initiated on treatment in the novel group at 60 days (36 [86%] of 42 in the novel group vs 18 [56%] of 32 in the routine group). Thus the difference in the proportion initiating treatment between groups was 29% (95% CI 9-50, p=0.0047) and 53% more patients initiated therapy in the novel diagnostic group than in the routine diagnostic group. One culture-positive patient was treated based only on a positive LAM test.

Interpretation: Compared with traditional tools, Xpert®-MTB/RIF for community-based intensified case finding in HIV and tuberculosis-endemic settings increased the proportion of patients initiating treatment. By contrast, urine LAM testing was not found to be useful for intensive case finding in this setting.

Abstract access   

Editor’s notes: Undiagnosed tuberculosis (TB) is the main source of ongoing transmission of Mycobacterium tuberculosis in the community.  Community-based intensified TB case finding strategies in high prevalence settings aim to reduce the prevalence of undiagnosed tuberculosis (TB) and thereby to reduce TB transmission. This is the first randomised trial to date comparing a point of contact diagnostic tool, Xpert® MTB/RIF, with a traditional tool, smear microscopy, for community-based intensive case-finding in sub-Saharan Africa.

The key finding was that a community-based intensified strategy using Xpert® MTB/RIF reduced time-to-treatment and increased the proportion of culture-positive people started on treatment in the first 60 days (when culture-based treatment initiation was not included).  Additional findings included a reduction in the number of people with TB treated empirically and a 50% increase in 60-day detection rate compared with smear microscopy. However, there was no difference by study arm in the proportion of culture-positive people who were retained on TB treatment at six months, and this was suboptimal (69% versus 71% for routine versus novel). The study also demonstrated that it was feasible to undertake community-based screening by minimally trained health-care workers using Xpert® in a mobile van with a generator or on site within a community-based clinic. 

It is interesting to note that there were major differences between study sites. In multivariable analysis, study site was the strongest risk factor for a shorter time-to-treatment initiation among culture-positive cases (Harare versus Cape Town - adjusted hazard ratio 7.18, 95% confidence interval 3.69 – 13.96) with screening method (novel versus routine diagnostics) found to have an adjusted hazard ratio of 2.32 (95% confidence interval 1.35 – 3.97). This finding likely reflects differences in the clinical management of Xpert®-negative and smear-negative people with presumed TB between study sites. In Harare, almost all people with a negative test result (in either arm) were referred for chest radiography, and probably because of this, a much larger proportion of study participants were started on anti-tuberculosis treatment in Harare compared to Cape Town (49% versus 9%). There was also a major difference in retention on treatment at six months among culture-positive people (81% in Harare versus 59% in Cape Town). These results highlight the importance of context, including heterogeneity in patient characteristics and differences in quality of health-care, access and practices between settings, in interpreting study findings associated with TB case-finding strategies.

Whether implementation of community-based intensive case finding using Xpert® in high-prevalence areas actually translates into reduced community TB transmission or improved clinical outcomes remains to be determined. 

South Africa, Zimbabwe
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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, 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. 

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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.

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ART has dramatically improved life expectancy for people living with HIV in KwaZulu-Natal, South Africa

Trends in the burden of HIV mortality after roll-out of antiretroviral therapy in KwaZulu-Natal, South Africa: an observational community cohort study.

Reniers G, Blom S, Calvert C, Martin-Onraet A, Herbst AJ, Eaton JW, Bor J, Slaymaker E, Li ZR, Clark SJ, Barnighausen T, Zaba B, Hosegood V Lancet HIV. 2016 Dec 9. pii: S2352-3018(16)30225-9. doi: 10.1016/S2352-3018(16)30225-9

Background: Antiretroviral therapy (ART) substantially decreases morbidity and mortality in people living with HIV. In this study, we describe population-level trends in the adult life expectancy and trends in the residual burden of HIV mortality after the roll-out of a public sector ART programme in KwaZulu-Natal, South Africa, one of the populations with the most severe HIV epidemics in the world.

Methods: Data come from the Africa Centre Demographic Information System (ACDIS), an observational community cohort study in the uMkhanyakude district in northern KwaZulu-Natal, South Africa. We used non-parametric survival analysis methods to estimate gains in the population-wide life expectancy at age 15 years since the introduction of ART, and the shortfall of the population-wide adult life expectancy compared with that of the HIV-negative population (ie, the life expectancy deficit). Life expectancy gains and deficits were further disaggregated by age and cause of death with demographic decomposition methods.

Findings: Covering the calendar years 2001 through to 2014, we obtained information on 93 903 adults who jointly contribute 535 428 person-years of observation to the analyses and 9992 deaths. Since the roll-out of ART in 2004, adult life expectancy increased by 15.2 years for men (95% CI 12.4-17.8) and 17.2 years for women (14.5-20.2). Reductions in pulmonary tuberculosis and HIV-related mortality account for 79.7% of the total life expectancy gains in men (8.4 adult life-years), and 90.7% in women (12.8 adult life-years). For men, 9.5% is the result of a decline in external injuries. By 2014, the life expectancy deficit had decreased to 1.2 years for men (-2.9 to 5.8) and to 5.3 years for women (2.6-7.8). In 2011-14, pulmonary tuberculosis and HIV were responsible for 84.9% of the life expectancy deficit in men and 80.8% in women.

Interpretation: The burden of HIV on adult mortality in this population is rapidly shrinking, but remains large for women, despite their better engagement with HIV-care services. Gains in adult life-years lived as well as the present life expectancy deficit are almost exclusively due to differences in mortality attributed to HIV and pulmonary tuberculosis.

Abstract access

Editor’s notes: Health and demographic surveillance system (HDSS) sites allow for monitoring of population health through the collection of detailed data on tens of thousands of individuals. Such sites in countries with high HIV prevalence have played an important role in measuring the effects of large-scale programmes, such as the global roll-out of antiretroviral therapy (ART). The data presented in this paper, from the Africa Centre Demographic Information System (ACDIS) in KwaZulu-Natal, South Africa, span 13 years (2001–14) and represent over 93 000 individuals living in an area with extremely high HIV prevalence (29% in adults aged 15–49 years in 2011). At least 15 000 of people studied were HIV-positive, of whom at least 2000 died. ART was first made available to people living with HIV (PLHIV) in this area in 2004.

Among adults aged 15–49 years, the authors report an overall reduction in death rate from 2001–14.  This translates into large increases in life expectancy (i.e., the expected number of years lived from age 15) of 15 and 17 years for men and women, respectively, between 2001 and 2014.  The changes in life expectancy are greater in people who were confirmed HIV-positive: 18 and 21 years for men and women, respectively, from 2007–14.  The large difference in life expectancies between the sexes that still exists (31 versus 44 years in HIV-positive men and women, respectively) are consistent with previously published estimates from Rwanda and Uganda. This study, however, illustrates that HIV-positive men are catching up to their HIV-negative counterparts faster than women are. The ‘deficit’ in 2014 - the gap in life expectancies between HIV-positive and HIV-negative individuals, was 1.2 years in men but still 5.3 years in women.

The authors propose that increased access to ART is the primary driver of the gains in life expectancy seen in this cohort. To further support this, they include data from verbal autopsies (VAs), which suggest that reductions in deaths due to HIV and pulmonary tuberculosis were responsible for 80% and 90% of the increases in life expectancy in men and women, respectively. VAs have limitations, however, particularly in areas of high HIV prevalence, but the overall mortality patterns suggested by these findings are likely to be accurate, even if the precise estimates differ.

The dramatic increases in life expectancy, in only seven years, for HIV-positive individuals in this cohort add to the encouraging observations from other low- and middle-income countries that many people receiving ART can expect to live for nearly as long as HIV-negative individuals.  Of course, people with advanced disease starting ART are still at high risk of death and there remain considerable challenges in getting treatment to all people in need of it. 

South Africa
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Community-based HIV testing for MSM: available at an acceptable cost in Europe

Economic evaluation of HIV testing for men who have sex with men in community-based organizations - results from six European cities.

Perelman J, Rosado R, Amri O, Morel S, Rojas Castro D, Chanos S, Cigan B, Lobnik M, Fuertes R, Pichon F, Slaaen Kaye P, Agusti C, Fernandez-Lopez L, Lorente N, Casabona J. AIDS Care. 2016 Dec 27:1-5. doi: 10.1080/09540121.2016.1271392. [Epub ahead of print]

The non-decreasing incidence of HIV among men who have sex with men (MSM) has motivated the emergence of Community Based Voluntary Counselling and Testing (CBVCT) services specifically addressed to MSM. The CBVCT services are characterized by facilitated access and linkage to care, a staff largely constituted by voluntary peers, and private not-for-profit structures outside the formal health system institutions. Encouraging results have been measured about their effectiveness, but these favourable results may have been obtained at high costs, questioning the opportunity to expand the experience. We performed an economic evaluation of HIV testing for MSM at CBVCT services, and compared them across six European cities. We collected retrospective data for six CBVCT services from six cities (Copenhagen, Paris, Lyon, Athens, Lisbon, and Ljubljana), for the year 2014, on the number of HIV tests and HIV reactive tests, and on all expenditures to perform the testing activities. The total costs of CBVCTs varied from 54 390€ per year (Ljubljana) to 245 803€ per year (Athens). The cost per HIV test varied from to 41€ (Athens) to 113€ (Ljubljana). The cost per HIV reactive test varied from 1966€ (Athens) to 9065€ (Ljubljana). Our results show that the benefits of CBVCT services are obtained at an acceptable cost, in comparison with the literature (values, mostly from the USA, range from 1600$ to 16 985$ per HIV reactive test in clinical and non-clinical settings). This result was transversal to several European cities, highlighting that there is a common CBVCT model, the cost of which is comparable regardless of the epidemiological context and prices. The CBVCT services represent an effective and "worth it" experience, to be continued and expanded in future public health strategies towards HIV.

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Editor’s notes: Although HIV incidence among some key populations in Europe has declined in recent years, new cases among gay men and other men who have sex with men have steadily increased over the last decade. Among those new cases, over a third are reported late, leading to worse health outcomes for the person, as well as an increased risk of onward transmission. As a result, community-based voluntary counselling and testing has been rolled out in European cities to encouraging results in terms of effectiveness.

In that context, the authors of this paper have carried out an economic evaluation of community-based voluntary counselling and testing programmes in six cities across Europe (Athens, Copenhagen, Lisbon, Lyon, Paris and Ljubljana). They collected total annual costs of running the programmes. They found that the cost per HIV test ranged from €41 in Athens to €113 in Ljubljana and the cost per reactive HIV test ranged from €1966 to €9065 in the same two cities. The authors found that these costs are acceptable compared to those found in the literature.

Oddly, one of the more interesting results found in the article, but not discussed within the text, is the cost per reactive HIV test link to care. This varied in absolute terms (€2297- €20 215) likely due to different linkages to care rates, from 100% in Copenhagen to under 40% in Paris. Given the ultimate aims of testing (which ought to be to improve health outcomes and reduce onward transmission) this is a more important figure than the cost per test. Further research therefore should explore the unit costs further down the treatment cascade resulting from these programmes. These would be, for example, cost per person on treatment and cost per person with a suppressed viral load. 

Denmark, France, Greece, Portugal, Slovenia
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Adolescents’ concerns: psychosocial needs of young people living with HIV in Thailand

Psychosocial needs of perinatally HIV-infected youths in Thailand: lessons learnt from instructive counseling.

Manaboriboon B, Lolekha R, Chokephaibulkit K, Leowsrisook P, Naiwatanakul T, Tarugsa J, Durier Y, Aunjit N, Punpanich Vandepitte W, Boon-Yasidhi V. AIDS Care. 2016 Dec;28(12):1615-1622. Epub 2016 Jun 26.

Identifying psychosocial needs of perinatally HIV-infected (pHIV) youth is a key step in ensuring good mental health care. We report psychosocial needs of pHIV youth identified using the "Youth Counseling Needs Survey" (YCS) and during individual counseling (IC) sessions. pHIV youth receiving care at two tertiary-care hospitals in Bangkok or at an orphanage in Lopburi province were invited to participate IC sessions. The youths' psychosocial needs were assessed using instructive IC sessions in four main areas: general health, reproductive health, mood, and psychosocial concerns. Prior to the IC session youth were asked to complete the YCS in which their concerns in the four areas were investigated. Issues identified from the YCS and the IC sessions were compared. During October 2010-July 2011, 150 (68.2%) of 220 eligible youths participated in the IC sessions and completed the YCS. Median age was 14 (range 11-18) years and 92 (61.3%) were female. Mean duration of the IC sessions was 36.5 minutes. One-hundred and thirty (86.7%) youths reported having at least one psychosocial problem discovered by either the IC session or the YCS. The most common problems identified during the IC session were poor health attitude and self-care (48.0%), lack of life skills (44.0%), lack of communication skills (40.0%), poor antiretroviral (ARV) adherence (38.7%), and low self-value (34.7%). The most common problems identified by the YCS were lack of communication skills (21.3%), poor health attitude and self-care (14.0%), and poor ARV adherence (12.7%). Youth were less likely to report psychosocial problems in the YCS than in the IC session. Common psychosocial needs among HIV-infected youth were issues about life skills, communication skills, knowledge on self-care, ARV adherence, and self-value. YCS can identify pHIV youths' psychosocial needs but might underestimate issues. Regular IC sessions are useful to detect problems and provide opportunities for counseling.

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Editor’s notes: The study reports on the psychological needs of young people who acquired HIV in the perinatal period.  The needs were highlighted during counselling sessions and in a survey conducted as part of the Happy-Teen Programme in Thailand. Young people (age 11-18) who have perinatally acquired HIV were recruited in two hospitals and from a service run by an orphanage linked to one of the hospitals. Young people took part in two individual ‘instructive counselling’ sessions, and two survey sessions for a needs-assessment questionnaire. Participants reported higher levels of needs in the counselling sessions compared to the questionnaire. Key areas of need identified included: health attitudes and self-care (e.g., diet, sleep, drug use); issues with sexual risk and difficulties communicating with sexual partners; HIV treatment adherence problems; concerns about HIV-associated stigma; and concerns about peer pressure. The study illustrates the difference in the quality of findings obtained from data collected via the questionnaire in comparison with data collected via sessions with counsellors. The counsellors were people that the young people knew for some time and trusted. The study highlights the importance of counselling with young people to improve self-esteem and health-associated behaviours.  Counsellors are also important to provide referrals for more severe mental health issues. 

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Improving ART adherence: what works?

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

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

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

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

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

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

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

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

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

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