Articles tagged as "HIV Treatment"

Measuring adherence – a promising approach with caregivers of children living with HIV

Improved adherence to antiretroviral therapy observed among HIV-infected children whose caregivers had positive beliefs in medicine in sub-Saharan Africa.

Abongomera G, Cook A, Musiime V, Chabala C, Lamorde M, Abach J, Thomason M, Mulenga V, Kekitiinwa A, Colebunders R, Kityo C, Walker AS, Gibb DM. AIDS Behav. 2017 Feb;21(2):441-449. doi: 10.1007/s10461-016-1582-8.

A high level of adherence to antiretroviral treatment is essential for optimal clinical outcomes in HIV infection, but measuring adherence is difficult. We investigated whether responses to a questionnaire eliciting caregiver beliefs in medicines were associated with adherence of their child (median age 2.8 years), and whether this in turn was associated with viral suppression. We used the validated beliefs in medicine questionnaire (BMQ) to measure caregiver beliefs, and medication event monitoring system caps to measure adherence. We found significant associations between BMQ scores and adherence, and between adherence and viral suppression. Among children initiating antiretroviral therapy (ART), we also found significant associations between BMQ 'necessity' scores, and BMQ 'necessity-concerns' scores, and later viral suppression. This suggests that the BMQ may be a valuable tool when used alongside other adherence measures, and that it remains important to keep caregivers well informed about the long-term necessity of their child's ART.

Abstract  Full-text [free] access 

Editor’s notes: How we measure adherence to antiretroviral therapy has long been a challenge within HIV clinical care. We need to know who is struggling with their HIV treatment so that we can provide support to improve their treatment taking behaviour before treatment resistance and other complex clinical problems take hold. This can be an especially relevant concern for children who will need to take HIV treatment throughout their lives. The analysis within this paper proffers a relatively accessible means to identify families who are more likely to encounter adherence problems. This potentially allows people to receive pre-emptive support before clinical problems arise. 

The authors tested their hypothesis that the children of caregivers who had concerns about the overuse and associated toxicity of medicine and/or had strong beliefs in divine intervention as curative, relative to their belief in the necessity of medicines, would be less likely to be virally suppressed. Such beliefs were measured in a validated ‘belief in medicine’ questionnaire. Although this was used within a clinical trial setting it is potentially simple enough to feasibly be used in more general clinical settings. This measure could identify particular ‘at-risk’ caregiver groups to inform not only the provision of tailored adherence support but also at which critical time points such support should be delivered.

Africa
Uganda, Zambia
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Only a quarter of people living with HIV in South Africa virally suppressed

The continuum of HIV care in South Africa: implications for achieving the second and third UNAIDS 90-90-90 targets.

Takuva S, Brown AE, Pillay Y, Delpech V, Puren AJ. AIDS. 2017 Feb 20;31(4):545-552. doi: 10.1097/QAD.0000000000001340.

Background: We characterize engagement with HIV care in South Africa in 2012 to identify areas for improvement towards achieving global 90-90-90 targets.

Methods: Over 3.9 million CD4 cell count and 2.7 million viral load measurements reported in 2012 in the public sector were extracted from the national laboratory electronic database. The number of persons living with HIV (PLHIV), number and proportion in HIV care, on antiretroviral therapy (ART) and with viral suppression (viral load <400 copies/ml) were estimated and stratified by sex and age group. Modified Poisson regression approach was used to examine associations between sex, age group and viral suppression among persons on ART.

Results: We estimate that among 6 511 000 PLHIV in South Africa in 2012, 3 300 000 individuals (50.7%) accessed care and 32.9% received ART. Although viral suppression was 73.7% among the treated population in 2012, the overall percentage of persons with viral suppression among all PLHIV was 23.8%. Linkage to HIV care was lower among men (38.5%) than among women (57.2%). Overall, 47.1% of those aged 0-14 years and 47.0% of those aged 15-49 years were linked to care compared with 56.2% among those aged above 50 years.

Conclusion: Around a quarter of all PLHIV have achieved viral suppression in South Africa. Men and younger persons have poorer linkage to HIV care. Expanding HIV testing, strengthening prompt linkage to care and further expansion of ART are needed for South Africa to reach the 90-90-90 target. Focus on these areas will reduce the transmission of new HIV infections and mortality in the general population.

Abstract access 

Editor’s notes: To maximise the impact of ART, people living with HIV should be diagnosed early, enrolled and initiated on antiretroviral therapy (ART) and retained in ART care. Long-term adherence to achieve and maintain viral load suppression is the last step in the continuum of HIV care. Engagement along the complete treatment cascade will determine the long-term success of the global response to HIV.

In this manuscript, the authors used a combination of national HIV prevalence estimates and routine data collected through the National Health Laboratory Service to construct and characterize the different stages of the HIV care continuum in South Africa.

They estimate that, despite the expansion of the ART programme in South Africa, only about a quarter of people living with HIV were virally suppressed in 2012, contrasting with recent estimates from Botswana where about 70% of people living with HIV were reported to be virally suppressed. They estimate that only about half of all people living with HIV accessed care, but report that, once in care, the ART programme proves to be effective with three-quarters of people on ART achieving virologic suppression. Not surprisingly they found that men and younger persons have poorer linkage to care. They recommend that HIV testing needs to be expanded, and linkage to care needs to be promoted for people testing HIV-positive, if the UNAIDS 90-90-90 treatment target is to be reached.

This paper illustrates how, in the context of a national public sector laboratory diagnostic service, routine laboratory data can be used to monitor the public health response to HIV at a national level. 

Africa
South Africa
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Adolescents and PMTCT services: where are the gaps?

PMTCT service uptake among adolescents and adult women attending antenatal care in selected health facilities in Zimbabwe.

Musarandega R, Machekano R, Chideme M, Muchuchuti C, Mushavi A, Mahomva A, Guay L. J Acquir Immune Defic Syndr. 2017 Feb 20. doi: 10.1097/QAI.0000000000001327. [Epub ahead of print]

Background: Age-disaggregated analyses of prevention of mother-to-child transmission (PMTCT) program data to assess the uptake of HIV services by pregnant adolescent women are limited but are critical to understanding the unique needs of this vulnerable, high risk population.

Methods: We conducted a retrospective analysis of patient-level PMTCT data collected from 2011 to 2013 in 36 health facilities in 5 districts of Zimbabwe using an electronic database. We compared uptake proportions for PMTCT services between adolescent (< 19 years) and adult (> 19 years) women. Multivariable binomial regression analysis was used to estimate the association of the women's age group with each PMTCT service indicator.

Results: The study analysed data from 22 215 women aged 12 to 50 years (22.5% adolescents). Adolescents were more likely to present to ANC before 14 weeks gestational age compared to older women (adjusted relative risk (aRR)=1.34; 95% confidence interval (CI): 1.22-1.47) with equally low rates of completion of four ANC visits. Adolescents were less likely to present with known HIV status (aRR=0.34; 95% CI: 0.29-0.41) but equally likely to be HIV tested in ANC. HIV prevalence was 5.5% in adolescents versus 20.1% in adults. While > 84% of both HIV-positive groups received ARVs for PMTCT, 44% of eligible adolescents were initiated on ART versus 51.3% of eligible adults, though not statistically significant.

Conclusions: Pregnant adolescents must be a priority for primary HIV prevention services and expanded HIV treatment services among pregnant women to achieve an AIDS-free generation in Zimbabwe and similar high HIV burden countries.

Abstract access  

Editor’s notes: Young women continue to be a key population at risk of acquiring HIV, and contribute approximately one-third of all new infections in sub-Saharan Africa. Young women face multiple legal, economic and social vulnerabilities that place them not only at higher risk of acquiring HIV but may also have an impact on their ability to access antenatal care (ANC) services and programmes to prevent mother-to-child HIV transmission (PMTCT) if they get pregnant. This in turn has implications for the goal of eliminating paediatric HIV infection.

This retrospective study compared the uptake of PMTCT services between adolescents (people aged 19 years and below) and older women accessing ANC in 36 public sector services across Zimbabwe. The study was conducted between 2011 and 2013, when PMTCT guidelines recommended Option A. Option A called for life-long antiretroviral therapy (ART) for women who were ART-eligible based on immunological or clinical criteria; or, for people ineligible, zidovudine monotherapy through pregnancy followed by single dose nevirapine at the onset of labour. It is no longer formally recommended by World Health Organization (WHO), although it is still used in some countries.      

Nearly a quarter of all women were adolescents and over 80% were on their first pregnancy or primigravid. Adolescent women were 34% more likely to attend their first ANC visit by 14 weeks of gestational age compared to adult women. But among both groups, only about 10% attended their first ANC visit in the first trimester and less than 40% attended the four antenatal visits recommended by WHO. Notably, knowledge of HIV status prior to the first ANC attendance was 66% lower in adolescent women, even after adjusting for parity and facility type, with only 3.1% aware of their HIV status. In addition, the proportion of women who were known HIV-positive and taking ART was also lower, although this may be due partly to fewer adolescents being eligible for ART. The uptake of HIV testing (over 95%) and uptake of zidovudine prophylaxis was high among all women. However, there was a suggestion that adolescents were less likely than older women to start ART if they were eligible, although this was not statistically significant. Indeed, several studies in the region have demonstrated lower levels of ART initiation among pregnant adolescents compared to older women.  

Older women would have been more likely to have undergone HIV testing in previous pregnancies. However, even after adjusting for parity, this study demonstrates that adolescents are less likely to have previously accessed HIV testing. Common barriers to testing highlighted by other studies include lack of information, unavailability of HIV testing services, unfriendly HIV testing environments in health facilities and the need for parental consent. Lack of knowledge of HIV status prior to pregnancy is also a missed opportunity for family planning, and initiation of ART prior to pregnancy. The substantial difference in HIV prevalence among adolescents compared to older women highlights the critical need for implementing prevention programmes such as pre-exposure prophylaxis among young women in high HIV prevalence settings. While adolescents are less likely to be tested for HIV in the general population than adults, this study illustrates that when HIV testing is offered in appropriate, supportive environments, uptake is high.

Overall, the uptake of HIV testing and of prophylaxis were high, demonstrating the potential for eliminating infections in children. A major limitation is that this analysis was limited to women who had sought antenatal care. Promoting early ANC attendance is important to allow early ART initiation, to reduce the risk of intrauterine HIV transmission. Following a positive HIV test result, particular attention is necessary to ensure linkage to care and support for sustained adherence to ART.

Africa
Zimbabwe
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Providing HIV treatment in Tanzania costs relatively little, but means a large increase in current health spending

The costs of providing antiretroviral therapy services to HIV-infected individuals presenting with advanced HIV disease at public health centres in Dar es Salaam, Tanzania: Findings from a randomised trial evaluating different health care strategies.

Kimaro GD, Mfinanga S, Simms V, Kivuyo S, Bottomley C, Hawkins N, Harrison TS, Jaffar S, Guinness L, on behalf of the REMSTART trial team. PLoS One. 2017 Feb 24;12(2):e0171917. doi: 10.1371/journal.pone.0171917. eCollection 2017.

Background: Understanding the costs associated with health care delivery strategies is essential for planning. There are few data on health service resources used by patients and their associated costs within antiretroviral (ART) programmes in Africa.

Material and methods: The study was nested within a large trial, which evaluated screening for cryptococcal meningitis and tuberculosis and a short initial period of home-based adherence support for patients initiating ART with advanced HIV disease in Tanzania and Zambia. The economic evaluation was done in Tanzania alone. We estimated costs of providing routine ART services from the health service provider's perspective using a micro-costing approach. Incremental costs for the different novel components of service delivery were also estimated. All costs were converted into US dollars (US$) and based on 2012 prices.

Results: Of 870 individuals enrolled in Tanzania, 434 were enrolled in the intervention arm and 436 in the standard care/control arm. Overall, the median (IQR) age and CD4 cell count at enrolment were 38 [31, 44] years and 52 [20, 89] cells/mm3, respectively. The mean per patient costs over the first three months and over a one year period of follow up following ART initiation in the standard care arm were US$ 107 (95%CI 101-112) and US$ 265 (95%CI 254-275) respectively. ART drugs, clinic visits and hospital admission constituted 50%, 19%, and 19% of the total cost per patient year, while diagnostic tests and non-ART drugs (co-trimoxazole) accounted for 10% and 2% of total per patient year costs. The incremental costs of the intervention to the health service over the first three months was US$ 59 (p<0.001; 95%CI 52-67) and over a one year period was US$ 67(p<0.001; 95%CI 50-83). This is equivalent to an increase of 55% (95%CI 51%-59%) in the mean cost of care over the first three months, and 25% (95%CI 20%-30%) increase over one year of follow up.

Abstract  Full-text [free] access 

Editor’s notes: There are very few data on the cost of providing HIV treatment in sub-Saharan Africa. The authors of this paper analysed cost data from a trial of screening services for opportunistic infections, to estimate the additional costs of HIV treatment to the health service. The most costly part of treatment was the antiretroviral medicines themselves, followed by clinic visits and hospital admissions. Diagnostic tests and treatments for other conditions were relatively inexpensive. The overall costs of treatment to the health system were fairly low in absolute terms. At around US$67 per year this is on the cheaper side of many cost studies. However, HIV treatment increases overall health system costs by a quarter. This could have significant implications for health system funding requirements in Tanzania as treatment is offered to the many people who need it in the UNAIDS 90-90-90 treatment target.

Africa
United Republic of Tanzania
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Anti-malarial effect of HIV protease inhibitors

Effect of antiretroviral therapy on malaria incidence in HIV-infected Ugandan adults.

Kasirye RP, Grosskurth H, Munderi P, Levin J, Anywaine Z, Nunn A, Kamali A, Baisley K. AIDS. 2017 Feb 20;31(4):577-582. doi: 10.1097/QAD.0000000000001344.

Introduction: Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria.

Methods: During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4 at least 250 cells/µl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell. CD4 cell counts were done 6-monthly. Malaria was defined as fever with a positive blood slide. ART regimens were categorized as nucleoside reverse transcriptase inhibitor (NRTI) only, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or protease inhibitor containing. Malaria incidence was calculated using random effects Poisson regression to account for clustering of events.

Results: Malaria incidence in the three ART regimen groups was 9.9 (3.6-27.4), 9.3 (8.3-10.4), and 3.5 (1.6-7.6) per 100 person-years, respectively. Incidence on protease inhibitors was lower than that on the other regimens with the results just reaching significance (adjusted rate ratio 0.4, 95% confidence interval = 0.2-1.0, comparing with NNRTI regimens). Stratification by CTX/placebo use gave similar results, without evidence of an interaction between the effects of CTX/placebo use and ART regimen. There was no evidence of an interaction between ART regimen and CD4 cell count.

Conclusion: There was some evidence that protease inhibitor-containing ART regimens may be associated with a lower clinical malaria incidence compared with other regimens. This effect was not modified by CTX use or CD4 cell count. The antimalarial properties of protease inhibitors may have clinical and public health importance.

Abstract  Full-text [free] access 

Editor’s notes: HIV protease inhibitors (PIs) have been shown to kill various life cycle stages of the malaria parasite both in vitro and in vivo at therapeutic drug levels.  A randomized controlled trial in children previously illustrated that PI-based antiretroviral therapy (ART) was associated with a lower risk of recurrent malaria compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART.

This study is the first to present data illustrating a reduction in clinical malaria incidence in adults on a PI-based regimen. The authors used data from the COSTOP trial, which was originally designed to look at the safety of discontinuing trimethoprim-sulfamethoxazole (TMP-SMX, Septrin) in HIV-positive Ugandan adults with a CD4 cell count ≥250 cells/µL. A limitation is that only 4% of study participants were on a PI-based ART regimen, so numbers are small. In addition, the authors were unable to adjust for potential confounders relating to individual health status. However, this analysis is a useful addition to the evidence base, suggesting that PIs may have antimalarial properties of clinical and public health importance, especially settings with high malaria transmission and moderate to high HIV prevalence.

Comorbidity, HIV Treatment
Africa
Uganda
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Is stool testing the answer to the problem of childhood TB diagnosis?

Stool Xpert® MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis at primary clinics in Zimbabwe.

Chipinduro M, Mateveke K, Makamure B, Ferrand RA, Gomo E. Int J Tuberc Lung Dis. 2017 Feb 1;21(2):161-166. doi: 10.5588/ijtld.16.0357.

Objective: To evaluate the diagnostic performance of Xpert® MTB/RIF on stool samples from children with clinical suspicion of pulmonary tuberculosis (PTB) at primary care clinics.

Design: A cross-sectional diagnostic evaluation enrolling 5-16 year olds from whom one induced sputum (IS) sample was tested for microbiological TB confirmation. Results of a single stool sample tested using Xpert® were compared against microbiologically confirmed TB, defined as a positive result on sputum microscopy and/or culture and/or IS Xpert®.

Results: Of 222 children enrolled, 218 had complete microbiological results. The median age was 10.6 years (interquartile range 8-13). TB was microbiologically confirmed in 19/218 (8.7%) children. Of these, respectively 5 (26%), 9 (47%) and 15 (79%) were smear-, culture- and IS Xpert®-positive. Stool Xpert® was positive in 13/19 (68%) microbiologically confirmed cases and 4/199 (2%) microbiologically negative cases. Stool Xpert® detected 76.9% (10/13) of human immunodeficiency virus (HIV) infected and 50% (3/6) of non-HIV-infected children with microbiologically confirmed TB (P = 0.241).

Conclusion: Stool Xpert® is a potential alternative screening test for children with suspected TB if sputum is unavailable. Strategies to optimise the diagnostic yield of stool Xpert® assay need further study.

Abstract  Full-text [free] access 

Xpert® MTB/RIF on Stool is Useful for the Rapid Diagnosis of Tuberculosis in Young Children with Severe Pulmonary Disease

Walters E, van der Zalm MM, Palmer M, Bosch C, Demers AM, Draper H, Goussard P, Schaaf HS, Friedrich SO, Whitelaw A, Warren R, Gie RP, Hesseling AC. Pediatr Infect Dis J. 2017 Jan 31. doi: 10.1097/INF.0000000000001563. [Epub ahead of print]

Background: Tuberculosis (TB) continues to result in high morbidity and mortality in children from resource-limited settings. Diagnostic challenges, including resource-intense sputum collection methods and insensitive diagnostic tests, contribute to diagnostic delay and poor outcomes in children. We evaluated the diagnostic utility of stool Xpert® MTB/RIF (Xpert) compared with bacteriologic confirmation (combination of Xpert® and culture of respiratory samples).

Methods: In a hospital-based study in Cape Town, South Africa, we enrolled children younger than 13 years of age with suspected pulmonary TB from April 2012- August 2015. Standard clinical investigations included tuberculin skin test, chest radiograph and HIV testing. Respiratory samples for smear microscopy, Xpert® and liquid culture included gastric aspirates, induced sputum, nasopharyngeal aspirates and expectorated sputum. One stool sample per child was collected and tested using Xpert®.

Results: Of 379 children enrolled (median age, 15.9 months, 13.7% HIV-infected), 73 (19.3%) had bacteriologically confirmed TB. The sensitivity and specificity of stool Xpert® vs. overall bacteriologic confirmation were 31.9% (95% CI 21.84-44.50%) and 99.7% (95% CI 98.2-100%) respectively. 23/51 (45.1%) children with bacteriologically confirmed TB with severe disease were stool Xpert® positive. Cavities on chest radiograph were associated with Xpert® stool positivity regardless of age and other relevant factors (OR 7.05; 95% CI 2.16-22.98; p=0.001).

Conclusions: Stool Xpert® can rapidly confirm TB in children who present with radiologic findings suggestive of severe TB. In resource-limited settings where children frequently present with advanced disease, Xpert® on stool samples could improve access to rapid diagnostic confirmation and appropriate treatment.

Abstract access

Editor’s notes: It has been known for a long time that Mycobacterium tuberculosis can be detected in stool specimens in some people with pulmonary TB disease. This is because sputum is often swallowed and M. tuberculosis bacilli can survive transit through the gastrointestinal tract. With the challenges of detecting TB in children, and the introduction of molecular diagnostic tools, there has been renewed interest in using stool specimens to improve TB diagnosis.

These two studies from southern Africa evaluated the diagnostic yield and accuracy of Xpert® MTB/RIF testing on stool specimens in children with symptoms compatible with intrathoracic TB. The study populations were different. The children in the South African study were younger than in the Zimbabwean study (median age 16 months vs. 10 years). In South Africa, only one in seven children was HIV positive whereas half the children were HIV positive in the Zimbabwean study. The South African study was conducted at hospital level whereas the Zimbabwean study was at primary health care clinics.

Despite these differences, the main findings were similar. Stool Xpert® was positive in six percent in South Africa and eight percent in Zimbabwe. Sensitivity of stool Xpert® compared to a single culture from induced sputum was 50% in South Africa and 67% in Zimbabwe. A single Xpert® test on stool was no better than a single Xpert® test on induced sputum. There was some evidence from both studies that sensitivity was higher in HIV positive children. However, in South Africa, sensitivity compared to any bacteriological confirmation was substantially lower (32%), as the reference standard included Xpert® and culture tests on multiple specimens. Sensitivity compared to the clinical decision to treat for TB was even lower (14%). This may have reflected the fact that all children in the South African study had chest X-rays and there were several children with intrathoracic lymph node disease.

What does this tell us about the role of Xpert® testing on stool for TB diagnosis in children? The evidence does not seem to provide strong support for scaling up stool Xpert® testing within standard diagnostic algorithms. As the South African study demonstrated, many of the children with positive Xpert® on stool were older children with more severe pulmonary disease. These are the children that may be more likely to produce sputum, and are the ones where we would want to make every effort to get respiratory specimens. This is especially the case in HIV-positive children, among whom there may be many possible diagnoses. Added to all this is the fact that processing and testing stool in the laboratory is not simple, meaning it might be difficult to scale up within decentralised laboratory systems.

It is encouraging that research groups are now addressing the challenge of TB diagnosis in children. It would seem that testing stool specimens for now does not really address the fundamental challenge in children, that they usually have paucibacillary disease often with little or no involvement of the lung parenchyma. The search must go on for better diagnostic tests for TB in children. 

Comorbidity, HIV Treatment
Africa
South Africa, Zimbabwe
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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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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.

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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.

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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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