Articles tagged as "Africa"

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
South Africa, Zimbabwe
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Psychological distress and HIV after financial meltdown in Zimbabwe

Prevalence and associations of psychological distress, HIV Infection and HIV care service utilization in East Zimbabwe.

Tlhajoane M, Eaton JW, Takaruza A, Rhead R, Maswera R, Schur N, Sherr L, Nyamukapa C, Gregson S. AIDS Behav. 2017 Feb 13. doi: 10.1007/s10461-017-1705-x. [Epub ahead of print]

The correlation between mental health and sexual risk behaviours for HIV infection remains largely unknown in low and middle income settings. The present study determined the prevalence of psychological distress (PD) in a sub-Saharan African population with a generalized HIV epidemic, and investigated associations with HIV acquisition risk and uptake of HIV services using data from a cross-sectional survey of 13,252 adults. PD was measured using the Shona Symptom Questionnaire. Logistic regression was used to measure associations between PD and hypothesized covariates. The prevalence of PD was 4.5% (95% CI 3.9-5.1%) among men, and 12.9% (95% CI 12.2-13.6%) among women. PD was associated with sexual risk behaviours for HIV infection and HIV-infected individuals were more likely to suffer from PD. Amongst those initiated on anti-retroviral therapy, individuals with PD were less likely to adhere to treatment (91 vs. 96%; age- and site-type-adjusted odds ratio = 0.38; 95% CI 0.15, 0.99). Integrated HIV and mental health services may enhance HIV care and treatment outcomes in high HIV-prevalence populations in sub-Saharan Africa.

Abstract access

Editor’s notes: Psychological distress can lead to increased use of alcohol and drugs, sexual risk behaviour, and hence increased risk of HIV acquisition. In rural Manicaland, the fifth survey round of an open population cohort measured psychological distress for the first time in 2009-2011, following the Zimbabwe hyperinflation crisis of 2008-2009.

Psychological distress was highly prevalent, especially among women, as was HIV infection. Overall, HIV prevalence was 12.7% in men and 18.3% in women. Psychological distress and HIV were also clearly associated. Among people with psychological distress HIV prevalence was 18.8% for men and 27.2% for women, compared to 12.4% and 17.1% for men and women respectively without psychological distress.

People living with HIV (identified by anonymous testing) who had psychological distress were more likely to have had an HIV test than people without psychological distress, although this could be reversed to mean that people with HIV who knew their status were more likely to have psychological distress than people who did not. If diagnosed and on antiretroviral therapy, people with psychological distress also had poorer adherence, supporting findings of other studies.

A main challenge to interpreting these results is a lack of information on poverty and how it may have impacted both psychological distress and risk of HIV acquisition. Only one survey round used the Shona Symptom Questionnaire so the study is essentially a cross-sectional survey. Women with psychological distress were more likely to have transactional sex, engage in sex work and not use condoms, but it is not clear that these behaviours were consequences of psychological distress. Instead, both the behaviours and the distress could have been caused by poverty constraints and lack of options. The only economic variables measured were time of year (as a proxy for food availability) and employment status (employed/unemployed). Being employed was associated with lower risk of psychological distress for women, but had no effect for men.

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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   

United Republic of Tanzania
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HIV Self-testing acceptable to vocational students in South Africa

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

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

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

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

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

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

Abstract  Full-text [free] access  

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

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

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

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

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

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

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

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

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

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

Abstract  Full-text [free] access 

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

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

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

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

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

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

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

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

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

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

Abstract access  

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

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

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

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

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

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

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

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

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

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

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

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

Abstract access  

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

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

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

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

South Africa
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Mixed methods in biomedical intervention trials yield rich data – the VOICE-D qualitative study

How presentation of drug detection results changed reports of product adherence in South Africa, Uganda and Zimbabwe.

Musara P, Montgomery ET, Mgodi NM, Woeber K, Akello CA, Hartmann M, Cheng H, Levy L, Katz A, Grossman CI, Chirenje ZM, van der Straten A, Mensch B. AIDS Behav. 2017 Jan 21. doi: 10.1007/s10461-017-1685-x. [Epub ahead of print]

Accurate estimates of study product use are critical to understanding and addressing adherence challenges in HIV prevention trials. The VOICE trial exposed a significant gap between self-reported adherence and drug detection. The VOICE-D qualitative study was designed to better understand non-adherence during VOICE, and was conducted in 2 stages: before (stage 1) and after (stage 2) drug detection results were provided to participants. Transcripts from 44 women who participated in both stages were analysed to understand the effect of presenting drug detection data on narratives of product use. Thirty-six women reported high adherence in stage 1, yet admitted non-use in stage 2, three reported high adherence in both stages (contrary to their drug detection results) and five had consistent responses across both stages and drug results. Presenting objective measures of use may facilitate more accurate product use reporting and should be evaluated in future prevention trials.

Abstract access  

Editor’s notes: The VOICE trial looked at the effectiveness of PrEP and vaginal microbicides in women in three African countries. One of the findings of the study was low product adherence among some women, based on retrospective drug level testing. In this paper, the authors compare data on product adherence from before and after participants were given plasma drug detection results. The findings are revealing, not least because many of women interviewed explained why they had claimed to be adhering to the drug, when they were not. Women gave many reasons for not being open about taking their medicines/use of the microbicide. It is interesting that a few women continued to say that they were good adherers, even when presented with drug plasma data, which suggested otherwise. This, the authors note, requires further investigation. 

The findings provide valuable evidence of the shortcomings of collecting self-reported adherence data. The use of biomedical markers to reveal drug plasma levels is important. However, the qualitative research, which documented the discussion around those findings, is both fascinating and extremely useful. Perhaps in future there will be an even greater willingness to fund good qualitative research as a key component of trials?

South Africa, Uganda, Zimbabwe
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Getting to 80% male circumcision

Obtaining a male circumcision prevalence rate of 80% among adults in a short time: An observational prospective intervention study in the Orange Farm township of South Africa.

Marshall E, Rain-Taljaard R, Tsepe M, Monkwe C, Taljaard D, Hlatswayo F, Xaba D, Molomo T, Lissouba P, Puren A, Auvert B. Medicine (Baltimore). 2017 Jan;96(4):e5328. doi: 10.1097/MD.0000000000005328.

World Health Organization recommends a target for the male circumcision prevalence rate of 80%. This rate will have a substantial impact on the human immunodeficiency virus-acquired immunodeficiency syndrome epidemic in Eastern and Southern Africa. The objective of the study was to assess whether an innovative intervention can lead to an increased voluntary male medical circumcision (VMMC) uptake among adults in a short time. This prospective observational study of a demand generation intervention was conducted in the township of Orange Farm (South Africa) in August to November 2015. In this community male circumcision prevalence rate among adults was stable between 2010 and 2015 at 55% and 57%, despite regular VMMC campaigns at community level and the presence of a VMMC clinic that offered free VMMC. The intervention took place in a random sample of 981 households where 522 men aged 18 to 49 years accepted to participate in the study. Among the 226 uncircumcised men, 212 accepted to be enrolled in the intervention study. A personal male circumcision adviser trained in interpersonal communication skills was assigned to each uncircumcised participant. The male circumcision advisers were trained to explain the risks and benefits of VMMC, and to discuss 24 possible reasons given by men for not being circumcised. Participants were then followed for 9 weeks. Each participant had a maximum of 3 motivational interviews at home. Participants who decided to be circumcised received financial compensation for their time equivalent to 2.5 days of work at the minimum South African salary rate. Among the 212 uncircumcised men enrolled in the intervention, 69.8% (148/212; 95% confidence interval [CI]; 63.4%-75.7%) agreed to be circumcised, which defines the uptake of the intervention. The male circumcision prevalence rate of the sample increased from 56.7% (296/522) to 81.4% (425/522; 77.9%-84.6%), P < 0.001, corresponding to a relative increase of 43.6% (95% CI: 35.4%-53.7%). The reported reasons for accepting circumcision were motivational interviews with the male circumcision adviser (83.1%), and time compensation (39.4%). Increased uptake of VMMC uptake can be obtained in a short time among adult males but requires an intense intervention centered on uncircumcised men at an individual level and time compensation.

Abstract  Full-text [free] access

Editor’s notes: As there are diverse motives for and barriers to voluntary male medical circumcision (VMMC), a range of programmes are required to reach WHO’s target of 80% male circumcision. This demand-creation activity study took place in a setting where, following school talks, street animation, flyers and local radio advertising, circumcision prevalence had risen to 57% by 2010 but had then plateaued. The programme was based on the theory that saturation had not been reached and many men who remained uncircumcised were not opposed to it but needed the right opportunity and circumstances to motivate them. In just over two months the prevalence of adult male circumcision in the study sample increased to over 80%, (WHO goal) as a result of implementing up to three home-based motivational interviews, plus time compensation of half a week’s pay at minimum wage for men who had VMMC.

Uptake was highest among the oldest men (aged 40-49 years), who had the lowest prevalence of circumcision before the study. Possibly previous programmes that were primarily focussed on adolescents were less likely to affect them. The highest rates were achieved in the youngest age group (aged 18-24 years), who were the most likely to already be circumcised before the study. Time to think about their options at home was important to participants. Most men who opted for VMMC said it was very important to have discussed the situation with their partner (80%) and with relatives or friends (78%). The three motivational interviews produced diminishing yield; 112/212 men sought VMMC after the first interview, 28/78 after the second and 8/54 after the third. After one interview plus financial compensation, the male circumcision prevalence in the sample increased to 75%.

The study is an example of a locally developed and setting-appropriate activity, quickly and rigorously tested in a realistic setting. In this manner, research questions can be relevant to the context and the results can be put into practice. 

South Africa
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Benefits of including males living with HIV in voluntary medical male circumcision - modelling analysis

Could circumcision of HIV-positive males benefit voluntary medical male circumcision programs in Africa? Mathematical modeling analysis.

Awad SF, Sgaier SK, Lau FK, Mohamoud YA, Tambatamba BC, Kripke KE, Thomas AG, Bock N, Reed JB, Njeuhmeli E, Abu-Raddad LJ. PLoS One. 2017 Jan 24;12(1):e0170641. doi: 10.1371/journal.pone.0170641. eCollection 2017.

Background: The epidemiological and programmatic implications of inclusivity of HIV-positive males in voluntary medical male circumcision (VMMC) programs are uncertain. We modeled these implications using Zambia as an illustrative example.

Methods and findings: We used the Age-Structured Mathematical (ASM) model to evaluate, over an intermediate horizon (2010-2025), the effectiveness (number of VMMCs needed to avert one HIV infection) of VMMC scale-up scenarios with varying proportions of HIV-positive males. The model was calibrated by fitting to HIV prevalence time trend data from 1990 to 2014. We assumed that inclusivity of HIV positive males may benefit VMMC programs by increasing VMMC uptake among higher risk males, or by circumcision reducing HIV male-to-female transmission risk. All analyses were generated assuming no further antiretroviral therapy (ART) scale-up. The number of VMMCs needed to avert one HIV infection was projected to increase from 12.2 VMMCs per HIV infection averted, in a program that circumcises only HIV-negative males, to 14.0, in a program that includes HIV-positive males. The proportion of HIV-positive males was based on their representation in the population (e.g. 12.6% of those circumcised in 2010 would be HIV-positive based on HIV prevalence among males of 12.6% in 2010). However, if a program that only reaches out to HIV-negative males is associated with 20% lower uptake among higher-risk males, the effectiveness would be 13.2 VMMCs per infection averted. If improved inclusivity of HIV-positive males is associated with 20% higher uptake among higher-risk males, the effectiveness would be 12.4. As the assumed VMMC efficacy against male-to-female HIV transmission was increased from 0% to 20% and 46%, the effectiveness of circumcising regardless of HIV status improved from 14.0 to 11.5 and 9.1, respectively. The reduction in the HIV incidence rate among females increased accordingly, from 24.7% to 34.8% and 50.4%, respectively.

Conclusion: Improving inclusivity of males in VMMC programs regardless of HIV status increases VMMC effectiveness, if there is moderate increase in VMMC uptake among higher-risk males and/or if there is moderate efficacy for VMMC against male-to-female transmission. In these circumstances, VMMC programs can reduce the HIV incidence rate in males by nearly as much as expected by some ART programs, and additionally, females can benefit from the intervention nearly as much as males.

Abstract  Full-text [free] access

Editor’s notes: Evidence from randomised control trials and modelling studies suggest that voluntary male medical circumcision (VMMC) is a cost-effective HIV prevention programme. A deterministic compartmental age structured HIV model was used to assess benefits of including HIV positive males in VMMC programmes. The HIV model was parameterized using HIV biological and behavioural data for sub-Saharan Africa.  The model was fit to HIV prevalence for Zambia in the years between 1990 and 2014. The model used baseline circumcision coverages from Zambia Demographic and Health Survey 2007. The authors analysed the model for three VMMC programme scenarios; circumcising HIV negative males only, circumcising both HIV negative and HIV positive males, and circumcising males regardless of their HIV status. Sensitivity analysis was conducted to ascertain the robustness of key model assumptions on the study findings. The findings from the study suggest that, improving the inclusivity of all males is likely to improve the effectiveness of VMMC programmes.  This will be the case if there is moderate increase in uptake among higher-risk males and/or moderate VMMC efficacy in preventing male-to-female transmission. This is a very interesting modelling study which gives insights to policymakers on factors to consider in designing VMMC programmes. 

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