Articles tagged as "Zimbabwe"

More data needed from routine programme data on antiretroviral therapy cascade outcomes among female sex workers

Antiretroviral therapy uptake, attrition, adherence and outcomes among HIV-infected female sex workers: a systematic review and meta-analysis.

Mountain E, Mishra S, Vickerman P, Pickles M, Gilks C, Boily MC. PLoS One. 2014 Sep 29;9(9):e105645. doi: 10.1371/journal.pone.0105645. eCollection 2014.

Purpose: We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.

Methods: We systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran's Q test and I2 statistic).

Results: 39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%-48%, I2 = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%-94%, I2 = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%-81%, I2 = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%-83%, I2 = 36%, 4 studies), and 57% (95% CI: 46%-68%, I2 = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm3 (4 studies).

Conclusions: Despite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.

Abstract  Full-text [free] access

Editor’s notes: Female sex workers remain a key population for HIV prevention, treatment and care. This is the first paper to systematically review and quantify the HIV treatment cascade among sex workers globally. The review highlights the scarcity of published data on HIV treatment among sex workers. For example, data were identified from only five countries in sub-Saharan Africa (Benin, Burkina Faso, Kenya, Rwanda and Zimbabwe) and a lack of data from routine (non research) settings. Further, most studies presented data on current antiretroviral therapy (ART) or CD4 count at initiation rather than follow-up data on attrition, adherence or viral suppression. The results suggest that research cohorts have been largely successful at enrolling and retaining female sex workers on ART, but there may be an issue with adherence. Adherence, in the few studies where it was measured (usually by self-report or pill counts) was high, and similar to estimates from the general population. But just over half of the participants initiating ART achieved viral suppression in the four studies which looked at this. This indicates scope for improvements in adherence (and adherence measurement) in these populations. This is possibly due to individual-level and structural-level barriers that sex workers face when receiving HIV treatment and care

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Model estimates large global burden of childhood tuberculosis infection and potentially preventable future tuberculosis disease

Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.

Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Lancet Glob Health. 2014 Aug;2(8):e453-9. doi: 10.1016/S2214-109X(14)70245-1. Epub 2014 Jul 8.

Background: Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease.

Methods: Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude.

Findings: The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15 319 701 (IQR 13 766 297-17 061 821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7 591 759 (5 800 053-9 969 780), and 650 977 children (424 871-983 118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53 234 854 (41 111 669-68 959 804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%.

Interpretation: Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment.

Abstract  Full-text [free] access 

Editor’s notes: Estimating the burden of childhood tuberculosis has been largely neglected until recently. Children with tuberculosis rarely transmit and therefore from a control perspective, childhood tuberculosis does not notably contribute to the continuation of the tuberculosis epidemic. This modelling paper attempts to estimate the global burden of childhood tuberculosis infection and disease. Incidence estimates are made by using adult tuberculosis prevalence data to tackle the known limitations of using paediatric notification data. A second model estimates the prevalence of infection in children and household exposure, ignoring exposure outside of the household.  As with all mathematical model predictions, precision of estimates are dependent on the data used as inputs in the model. Despite these limitations, the paper draws attention to the fact that the burden of childhood tuberculosis infection and disease is significant and reflects failure of tuberculosis control in the 22 high-burden countries. The paper also highlights the fact that household contact tracing and preventive therapy in tuberculosis-exposed children could substantially reduce future tuberculosis-related morbidity.

Avoid TB deaths
Comorbidity, Epidemiology
Africa, Asia, Latin America
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How can we improve the UNAIDS modes of transmission model?

The HIV modes of transmission model: a systematic review of its findings and adherence to guidelines.

Shubber Z, Mishra S, Vesga JF, Boily MC. J Int AIDS Soc. 2014 Jun 23;17:18928. doi: 10.7448/IAS.17.1.18928. eCollection 2014.

Introduction: The HIV Modes of Transmission (MOT) model estimates the annual fraction of new HIV infections (FNI) acquired by different risk groups. It was designed to guide country-specific HIV prevention policies. To determine if the MOT produced context-specific recommendations, we analyzed MOT Results by region and epidemic type, and explored the factors (e.g. data used to estimate parameter inputs, adherence to guidelines) influencing the differences.

Methods: We systematically searched MEDLINE, EMBASE and UNAIDS reports, and contacted UNAIDS country directors for published MOT Results from MOT inception (2003) to 25 September 2012.

Results: We retrieved four journal articles and 20 UNAIDS reports covering 29 countries. In 13 countries, the largest FNI (range 26 to 63%) was acquired by the low-risk group and increased with low-risk population size. The FNI among female sex workers (FSWs) remained low (median 1.3%, range 0.04 to 14.4%), with little variability by region and epidemic type despite variability in sexual behaviour. In India and Thailand, where FSWs play an important role in transmission, the FNI among FSWs was 2 and 4%, respectively. In contrast, the FNI among men who have sex with men (MSM) varied across regions (range 0.1 to 89%) and increased with MSM population size. The FNI among people who inject drugs (PWID, range 0 to 82%) was largest in early-phase epidemics with low overall HIV prevalence. Most MOT studies were conducted and reported as per guidelines but data quality remains an issue.

Conclusions: Although countries are generally performing the MOT as per guidelines, there is little variation in the FNI (except among MSM and PWID) by region and epidemic type. Homogeneity in MOT FNI for FSWs, clients and low-risk groups may limit the utility of MOT for guiding country-specific interventions in heterosexual HIV epidemics.

 Abstract  Full-text [free] access

Editor’s notes: In 2002, the HIV Modes of Transmission model (MoT) was developed by UNAIDS to inform and focus, country-specific HIV prevention policies. The idea behind the model was to use simple mathematical modelling approaches, in combination with country specific data, to predict what the distribution of new HIV infection may look like. In this way, countries would be able to better focus their HIV response. Since its development and through 2012, the MoT has been applied in 29 countries, with the findings being used in many settings to shape priorities. In this study, the authors assess the degree to which the MoT produces different outputs in different epidemic contexts. They explore whether there are key parameters in the model that seem to drive similarities and/or differences in projections between countries. Surprisingly, across a broad range of epidemic settings, they found limited variability in the predicted annual fraction of new HIV infections (FNI) acquired by female sex workers (FSW) (0.04-14.4%). There were higher levels of variability between countries in the projected fraction of new HIV infections among men who have sex with men (0.01-89%) and people who inject drugs (0-82%).

The differences in the MoT projections were largely dependent on whether the country in question was categorised as having a concentrated / low-level epidemic, versus generalised epidemic, as defined by UNAIDS. Differences also arose depending upon whether ‘low risk groups’ were also included in the model. Indeed, for 22 of the 25 studies that included a low-risk group, this group was predicted to have a large annual fraction of new HIV infections (11.8-62.9%). This phenomenon arose, not because of high transmission rates in this group (in comparison to others such as MSM or PWIDs) but because these ‘low risk groups’ are large. They are one third of the total population. These findings may be misleading, as the projected high fraction of transmission is dependent on the assumption that everyone in this ‘low risk group’ does have some risk.

It appears that although the MoT was designed to address an important need, it is likely to have limited utility to guide programming in heterosexually driven epidemics.  To address this limitation, UNAIDS is supporting the HIV Modelling Consortium in their development of a revised MoT model that takes into better consideration risk categorization, data constraints and programmatic needs. The revised model is currently undergoing field testing and will be available for country use in 2015.

Africa, Asia, Europe, Latin America
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WHO-recommended second-line ART regimen is safe and effective in Africa

Assessment of second-line antiretroviral regimens for HIV therapy in Africa.

Paton NI, Kityo C, Hoppe A, Reid A, Kambugu A, Lugemwa A, van Oosterhout JJ, Kiconco M, Siika A, Mwebaze R, Abwola M, Abongomera G, Mweemba A, Alima H, Atwongyeire D, Nyirenda R, Boles J, Thompson J, Tumukunde D, Chidziva E, Mambule I, Arribas JR, Easterbrook PJ, Hakim J, Walker AS, Mugyenyi P, EARNEST Trial Team. N Engl J Med. 2014 Jul 17;371(3):234-47. doi: 10.1056/NEJMoa1311274.

Background: The efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs) are uncertain when these agents are used with a protease inhibitor in second-line therapy for human immunodeficiency virus (HIV) infection in resource-limited settings. Removing the NRTIs or replacing them with raltegravir may provide a benefit.

Methods: In this open-label trial in sub-Saharan Africa, we randomly assigned 1 277 adults and adolescents with HIV infection and first-line treatment failure to receive a ritonavir-boosted protease inhibitor (lopinavir-ritonavir) plus clinician-selected NRTIs (NRTI group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of induction therapy with raltegravir in a noninferiority comparison (monotherapy group, 418 patients). The primary composite end point, good HIV disease control, was defined as survival with no new World Health Organization stage 4 events, a CD4+ count of more than 250 cells per cubic millimeter, and a viral load of less than 10 000 copies per milliliter or 10 000 copies or more with no protease resistance mutations at week 96 and was analyzed with the use of imputation of data (</=4%).

Results: Good HIV disease control was achieved in 60% of the patients (mean, 255 patients) in the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P=0.21 for the comparison with the NRTI group; superiority of raltegravir not shown), and 55% of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy not shown, based on a 10-percentage-point margin). There was no significant difference in rates of grade 3 or 4 adverse events among the three groups (P=0.82). The viral load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86% in the raltegravir group (P=0.97), and 61% in the monotherapy group (P<0.001).

Conclusions: When given with a protease inhibitor in second-line therapy, NRTIs retained substantial virologic activity without evidence of increased toxicity, and there was no advantage to replacing them with raltegravir. Virologic control was inferior with protease-inhibitor monotherapy.

Abstract  Full-text [free] access

Editor’s notes: Over the coming years, increasing numbers of individuals taking antiretroviral therapy (ART) in sub-Saharan Africa will develop treatment failure and require second-line treatment.  There is an urgent need to find the most cost-effective, tolerable and safe standardised second-line regimen for this setting.  The Europe-Africa Research Network for Evaluation of Second-Line Therapy (EARNEST) trial set out to assess whether alternative ART regimens (excluding the nucleoside reverse transcriptase inhibitor [NRTI] backbone) are more efficacious and less toxic than the WHO-recommended second-line regimen of a boosted protease inhibitor (PI) and two NRTIs.  The setting of the trial is typical of most antiretroviral programmes in Africa, with no routine viral load monitoring, and the second-line NRTI backbone selected without genotypic resistance testing. 

Participants in this study had extensive NRTI resistance. Despite this, there was substantial residual NRTI activity, and, by week  96, the WHO-recommended regimen of a boosted PI and two NRTIs was as good as the alternative regimen of a boosted PI and raltegravir, and better than PI monotherapy.  It is worth pointing out that although “good HIV disease control” was achieved in only 60% of study participants in the NRTI arm, this composite outcome required study participants to have had a CD4 count ≥250 cells per mm3 at week 96.  The 60% achieving “good HIV disease control” in the NRTI arm therefore reflects the low baseline CD4 cell counts (median CD4 count 72) at the time of switch to second-line therapy rather than treatment efficacy with regard to virologic suppression (VL<400 copies/ml), which was achieved in some 86% of people.

Further research will be needed to determine whether this second-line regimen continues to be effective in maintaining good HIV disease control through virologic suppression in the longer term.  

HIV Treatment
Kenya, Malawi, Uganda, Zambia, Zimbabwe
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Increasing HIV-testing in men: what works?

Systematic review of strategies to increase men's HIV-testing in sub-Saharan Africa

Hensen B, Taoka S, Lewis JJ, Weiss HA, Hargreaves J. AIDS. 2014 Jul; DOI:10.1097/QAD.0000000000000395

Objective: This systematic review summarizes evidence on the effectiveness of strategies to increase men's HIV-testing in sub-Saharan Africa.

Methods: Medline, EmBase, Africa-Wide Information and Global Health were searched. Cluster and individually randomized trials evaluating interventions to increase the proportion of adults (≥15 years) testing for HIV were eligible if they were conducted in sub-Saharan Africa, included men in the study population, and reported HIV-testing data by sex. References were independently screened.

Findings: Of the 1 852 references, 15 papers including 16 trials were eligible. Trials were judged too heterogeneous to combine in meta-analysis. Three interventions invited men to attend antenatal care-based HIV-testing via pregnant partners, of which two showed a significant effect on partner-testing. One intervention invited men to HIV-test through pregnant partners and showed an increase in HIV-testing when it was offered in bars compared with health facilities. A trial of notification to partners of newly diagnosed HIV-positive people showed an increase in testing where notification was by healthcare providers compared with notification by the patient. Three interventions reached men already at health facilities and eight reported the effects of community-based HIV-testing. Mobile-testing had a significant effect on HIV-testing compared with standard voluntary counselling and testing. Home-based testing also had a significant effect, but reached smaller numbers of men than mobile-testing.

Discussion: Interventions to encourage HIV-testing can increase men's levels of HIV-testing. Community-based programmes in particular had a large effect on population levels of HIV-testing. More data on costs and potential population impact of these approaches over different time-horizons would aid policy-makers in planning resource allocation to increase male HIV-testing.

Abstract access 

Editor’s notes: Approaches to increase rates of HIV-testing among men are urgently needed as uptake of HIV-testing in men remains lower than in women across sub-Saharan Africa. This systematic review identified published randomised controlled trials evaluating the impact of programmes to increase HIV-testing among men in sub-Saharan Africa. Few programmes focus on men specifically but some, like mobile testing, can have a substantial effect on HIV testing compared with standard voluntary counselling and testing. In addition, to be of direct benefit to men, increased HIV-testing among men is likely to lead to increased uptake among women and improved adherence to prevention of mother-to-child transmission. To increase men’s HIV-testing at a population level, country and time-specific combinations of available strategies are likely to be required. Along with additional research to determine whether these strategies encourage repeat-testing by high-risk HIV-negative men.

HIV testing
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Integrating HIV, malaria and diarrhoea prevention is far more efficient than vertical programmes

Scaling up integrated prevention campaigns for global health: costs and cost-effectiveness in 70 countries. 

Marseille E, Jiwani A, Raut A, Verguet S, Walson J, Kahn JG. BMJ Open. 2014 Jun 26;4(6):e003987. doi: 10.1136/bmjopen-2013-003987.

Objective: This study estimated the health impact, cost and cost-effectiveness of an integrated prevention campaign (IPC) focused on diarrhoea, malaria and HIV in 70 countries ranked by per capita disability-adjusted life-year (DALY) burden for the three diseases.

Methods: We constructed a deterministic cost-effectiveness model portraying an IPC combining counselling and testing, cotrimoxazole prophylaxis, referral to treatment and condom distribution for HIV prevention; bed nets for malaria prevention; and provision of household water filters for diarrhoea prevention. We developed a mix of empirical and modelled cost and health impact estimates applied to all 70 countries. One-way, multiway and scenario sensitivity analyses were conducted to document the strength of our findings. We used a healthcare payer's perspective, discounted costs and DALYs at 3% per year and denominated cost in 2012 US dollars.

Primary and secondary outcomes: The primary outcome was cost-effectiveness expressed as net cost per DALY averted. Other outcomes included cost of the IPC; net IPC costs adjusted for averted and additional medical costs and DALYs averted.

Results: Implementation of the IPC in the 10 most cost-effective countries at 15% population coverage would cost US$583 million over 3 years (adjusted costs of US$398 million), averting 8.0 million DALYs. Extending IPC programmes to all 70 of the identified high-burden countries at 15% coverage would cost an adjusted US$51.3 billion and avert 78.7 million DALYs. Incremental cost-effectiveness ranged from US$49 per DALY averted for the 10 countries with the most favourable cost-effectiveness to US$119, US$181, US$335, US$1 692 and US$8 340 per DALY averted as each successive group of 10 countries is added ordered by decreasing cost-effectiveness.

Conclusions: IPC appears cost-effective in many settings, and has the potential to substantially reduce the burden of disease in resource-poor countries. This study increases confidence that IPC can be an important new approach for enhancing global health.

Abstract  Full-text [free] access

Editor’s notes: Increasingly governments and policy makers are seeking to identify how to invest resources most effectively, to achieve multiple health and development outcomes. This paper presents a cost-effectiveness analysis of an integrated campaign to prevent diarrhoea, malaria and HIV.  

They developed a model to estimate the cost per disability adjusted life year (DALY) averted by this intervention, across 70 countries with high disease burden, assuming 15% coverage. The authors categorise countries by income level and their opportunity index (i.e. the opportunity to avert DALYs by having a high disease burden). The findings suggest that an integrated prevention campaign (IPC) could cost as little as US$7 per DALY averted in Guinea-Bissau, a low income, high opportunity country. As would be expected, the contribution of the different IPC components varied by country, depending on their relative disease burdens. This suggests that further focusing of activities within countries may further improve efficiency.

The model was also used to consider potential roll out strategies across counties. For this, countries were grouped into blocks of 10, and ordered with increasing incremental-cost effectiveness. The authors suggest that reaching the top 40 countries with IPC, even at just 15% coverage, could achieve far greater health benefits, with a substantially lower budget, than requested under PEPFAR for antiretroviral therapy alone.

This paper provides further evidence of the need for a more integrated approach to improve population health across disease areas.

Africa, Asia, Europe, Latin America
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Scale-up of voluntary medical male circumcision: context matters

Voluntary medical male circumcision (VMMC) in Tanzania and Zimbabwe: service delivery intensity and modality and their influence on the age of clients.

Ashengo TA, Hatzold K, Mahler H, Rock A, Kanagat N, Magalona S, Curran K, Christensen A, Castor D, Mugurungi O, Dhlamini R, Xaba S, Njeuhmeli E. PLoS One. 2014 May 6;9(5):e83642. doi: 10.1371/journal.pone.0083642. eCollection 2014.

Background: Scaling up voluntary medical male circumcision (VMMC) to 80% of men aged 15-49 within five years could avert 3.4 million new HIV infections in Eastern and Southern Africa by 2025. Since 2009, Tanzania and Zimbabwe have rapidly expanded VMMC services through different delivery (fixed, outreach or mobile) and intensity (routine services, campaign) models. This review describes the modality and intensity of VMMC services and its influence on the number and age of clients.

Methods and findings: Program reviews were conducted using data from implementing partners in Tanzania (MCHIP) and Zimbabwe (PSI). Key informant interviews (N = 13 Tanzania; N = 8 Zimbabwe) were conducted; transcripts were analyzed using Nvivo. Routine VMMC service data for May 2009-December 2012 were analyzed and presented in frequency tables. A descriptive analysis and association was performed using the z-ratio for the significance of the difference. Key informants in both Tanzania and Zimbabwe believe VMMC scale-up can be achieved by using a mix of service delivery modality and intensity approaches. In Tanzania, the majority of clients served during campaigns (59%) were aged 10-14 years while the majority during routine service delivery (64%) were above 15 (p<0.0001). In Zimbabwe, significantly more VMMCs were done during campaigns (64%) than during routine service delivery (36%) (p<0.00001); the difference in the age of clients accessing services in campaign versus non-campaign settings was significant for age groups 10-24 (p<0.05), but not for older groups.

Conclusions: In Tanzania and Zimbabwe, service delivery modalities and intensities affect client profiles in conjunction with other contextual factors such as implementing campaigns during school holidays in Zimbabwe and cultural preference for circumcision at a young age in Tanzania. Formative research needs to be an integral part of VMMC programs to guide the design of service delivery modalities in the face of, or lack of, strong social norms.

Abstract  Full-text [free] access 

Editor’s notes: To reach the target of 80% coverage within five years, an estimated 20.3 million voluntary medical male circumcision (VMMC) procedures among men aged 15-49 years need to be performed in eastern and southern Africa. Approximately 6 million VMMCs have been conducted by the end of 2013.  Rapid scale-up is needed, and this paper provides insights into different service delivery strategies for the scale-up. It emphasises the importance of the cultural context in shaping the uptake of VMMC. Delivery modalities include routine service delivery at existing health care facilities and campaign service delivery. Campaigns have high throughput for short periods of time, and may be conducted at a variety of sites. These include mobile sites (temporary structures) and outreach sites (structures temporarily modified for VMMC service provision). The study highlights the need for VMMC programmes to take into account the underlying social context. For example, in Tanzania, there is an underlying cultural perception that male circumcision is most appropriate before or during puberty. This is reflected in the young age of the clients, particularly during campaigns, where boys may be more susceptible to peer pressure. In Zimbabwe, circumcision was not traditionally practised, so uptake of VMMC is more strongly linked with the convenience of service provision. 

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HIV prevalence of HIV among children in Zimbabwe, justifies the need for provider initiated testing and counselling

Barriers to provider-initiated testing and counselling for children in a high HIV prevalence setting: a mixed methods.

Kranzer K, Meghji J, Bandason T, Dauya E, Mungofa S, Busza J, Hatzold K, Kidia K, Mujuru H, Ferrand RA. PLoS Med. 2014 May 27;11(5):e1001649. doi: 10.1371/journal.pmed.1001649. eCollection 2014.

Background: There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children.

Methods and findings: Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2 831 eligible children, 2 151 (76%) were offered PITC, of whom 1 534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive.

Conclusions: The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.

Abstract  Full-text [free] access

Editor’s notes: An estimated 700 infant HIV infections occur every day. In many priority countries, relatively few of these are diagnosed in early infancy. Subsequent diagnosis largely depends on HIV testing in health care facilities during childhood and adolescence. This is the first study examining Provider Initiated Testing and Counselling (PITC) provision among older children, aged six to 15 years. The study shows high prevalence of HIV infection among those attending primary care services in Harare, Zimbabwe, and among their accompanying caregivers. The paper highlights the challenges of implementing PITC to this age-group, including lack of consent from the guardian, especially male guardians, counsellor non-availability or unwillingness to perform the test. Policy implications from this work include the need to develop clear HIV testing policies and guidance around consent and testing of older children, and the need to address supply-side challenges around the PITC process. An example might be by way of task-shifting through use of lay counsellors or opt-out HIV testing.

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Keeping children living with HIV on antiretroviral therapy in Zimbabwe: barriers and facilitators

I don't want financial support but verbal support. How do caregivers manage children's access to and retention in HIV care in urban Zimbabwe?

Busza J, Dauya E, Bandason T, Mujuru H, Ferrand RA. J Int AIDS Soc. 2014 May 9;17:18839. doi: 10.7448/IAS.17.1.18839. eCollection 2014.

Introduction: Children living with HIV experience particular challenges in accessing HIV care. Children usually rely on adult caregivers for access to care, including timely diagnosis, initiation of treatment and sustained engagement with HIV services. The aim of this study was to inform the design of a community-based intervention to support caregivers of HIV-positive children to increase children's retention in care as part of a programme introducing decentralized HIV care in primary health facilities.

Methods: Using an existing conceptual framework, we conducted formative research to identify key local contextual factors affecting children's linkages to HIV care in Harare, Zimbabwe. We conducted semi-structured interviews with 15 primary caregivers of HIV-positive children aged 6-15 years enrolled at a hospital clinic for at least six months, followed by interviews with nine key informants from five community-based organizations providing adherence support or related services.

Results: We identified a range of facilitators and barriers that caregivers experience. Distance to the hospital, cost of transportation, fear of disclosing HIV status to the child or others, unstable family structure and institutional factors such as drug stock-outs, healthcare worker absenteeism and unsympathetic school environments proved the most salient limiting factors. Facilitators included openness within the family, availability of practical assistance and psychosocial support from community members.

Conclusions: The proposed decentralization of HIV care will mitigate concerns about distance and transport costs but is likely to be insufficient to ensure children's sustained retention. Following this study, we developed a package of structured home visits by voluntary lay workers to proactively address other determinants such as disclosure within families, access to available services and support through caregivers' social networks. A randomized controlled trial is underway to assess impact on children's retention in care over two years.

 Abstract   Full-text [free] access

Editor’s notes: Children living with HIV who are taking antiretroviral therapy (ART) are often reliant on adult carers to support them so they can attend appointments, collect their medicine and take it regularly. This study explored the barriers and facilitators experienced by caregivers of children living with HIV in sustaining HIV treatment and care in Zimbabwe.

The study was conducted in 2012 at the Harare Central Hospital clinic, which is where children diagnosed with HIV are referred to for ART eligibility screening, treatment and follow-up care. The study interviewed 12 females including eight mothers, two aunts, one grandmother and one cousin. It also included three male care-givers, all fathers, as well as nine community-based organisation respondents.

A number of barriers were identified in attending appointments: the costs of travel, the loss of income while away from work and the risk of losing their job. Stigma could lead to the disruption of treatment particularly when visitors came to the house and the fear of discrimination of the child and the family if the child’s status was known. Institutional level factors like long queues at HIV clinics; pharmacies with drug stock outs, long waiting times and staff shortages all affect adherence. Further, how a child was treated at school affected adherence to medication, ability to attend appointments and overall well-being.

The authors highlight issues that affect many children living with HIV in Africa.  They suggest that in their study setting the decentralisation of HIV care to primary health clinics together with a volunteer lay worker programme should help overcome these barriers. A randomized control trial will evaluate the effectiveness of these measures in increasing ART uptake and retention among children living with HIV in Harare.

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Fewer clinical events with early antiretroviral therapy in a trial among serodiscordant couples

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial.

Grinsztejn B, Hosseinipour MC, Ribaudo HJ, Swindells S, Eron J, Chen YQ, Wang L, Ou SS, Anderson M, McCauley M, Gamble T, Kumarasamy N, Hakim JG, Kumwenda J, Pilotto JH, Godbole SV, Chariyalertsak S, de Melo MG, Mayer KH, Eshleman SH, Piwowar-Manning E, Makhema J, Mills LA, Panchia R, Sanne I, Gallant J, Hoffman I, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Havlir D, Cohen MS, HPTN 052-ACTG Study Team. Lancet Infect Dis. 2014 Apr;14(4):281-90. doi: 10.1016/S1473-3099(13)70692-3. Epub 2014 Mar 4.

Background: Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes.

Methods: The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat.

Findings: 1 763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373-522) cells per μL in patients assigned to the early treatment group and 428 (357-522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197-249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0.73, 95% CI 0.52-1.03; p=0.074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0.64, 0.43-0.96; p=0.031), tuberculosis developed in 17 versus 34 patients, respectively (0.49, 0.28-0.89, p=0.018), and primary non-AIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24.9 per 100 person-years, 95% CI 22.5-27.5) versus 585 in the delayed treatment group (29.2 per 100 person-years, 26.5-32.1; p=0.025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group.

Interpretation: Early initiation of antiretroviral treatment delayed the time to AIDS events and decreased the incidence of primary and secondary outcomes. The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment.

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Editor’s notes: The HPTN 052 trial has received wide attention for its main result. This shows a large reduction in HIV transmission risk among HIV-serodiscordant couples where HIV-positive partners with CD4 counts between 350 and 550 started immediate antiretroviral therapy (ART). This was compared to deferring treatment until the CD4 count fell below 250 or an AIDS-defining illness occurred. This analysis reports on clinical events in the trial. Despite the trial population having relatively high CD4 counts at baseline, new AIDS-defining events, excluding tuberculosis, were the most common outcome. These were reduced in the early ART arm. Tuberculosis incidence was reduced by half. Non-AIDS events were rare.

For these trial results to translate into population level benefits, more people need to know their HIV status at an early stage, before they develop symptomatic disease. People with positive test results then need to link to care successfully so that treatment can be initiated. Stigma remains a key barrier to testing and accessing care in many settings. Virologic suppression among people in the intervention arm of this trial was very high, implying very good adherence to treatment. Strategies to support excellent adherence and retention are needed as ART programmes expand and include people starting ART earlier.

Comorbidity, HIV Treatment
Africa, Asia, Latin America
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