Articles tagged as "Rwanda"

Improving linkage to pre-antiretroviral therapy care and antiretroviral therapy initiation

Interventions to improve or facilitate linkage to or retention in pre-ART (HIV) care and initiation of ART in low- and middle-income settings--a systematic review.

Govindasamy D, Meghij J, Kebede Negussi E, Clare Baggaley R, Ford N, Kranzer K. J Int AIDS Soc. 2014 Aug 1;17(1):19032. doi: 10.7448/IAS.17.1.19032. eCollection 2014.

Introduction: Several approaches have been taken to reduce pre-antiretroviral therapy (ART) losses between HIV testing and ART initiation in low- and middle-income countries, but a systematic assessment of the evidence has not yet been undertaken. The aim of this systematic review is to assess the potential for interventions to improve or facilitate linkage to or retention in pre-ART care and initiation of ART in low- and middle-income settings.

Methods: An electronic search was conducted on Medline, Embase, Global Health, Web of Science and conference databases to identify studies describing interventions aimed at improving linkage to or retention in pre-ART care or initiation of ART. Additional searches were conducted to identify on-going trials on this topic, and experts in the field were contacted. An assessment of the risk of bias was conducted. Interventions were categorized according to key domains in the existing literature.

Results: A total of 11 129 potentially relevant citations were identified, of which 24 were eligible for inclusion, with the majority (n=21) from sub-Saharan Africa. In addition, 15 on-going trials were identified. The most common interventions described under key domains included: health system interventions (i.e. integration in the setting of antenatal care); patient convenience and accessibility (i.e. point-of-care CD4 count (POC) testing with immediate results, home-based ART initiation); behaviour interventions and peer support (i.e. improved communication, patient referral and education) and incentives (i.e. food support). Several interventions showed favourable outcomes: integration of care and peer supporters increased enrolment into HIV care, medical incentives increased pre-ART retention, POC CD4 testing and food incentives increased completion of ART eligibility screening and ART initiation. Most studies focused on the general adult patient population or pregnant women. The majority of published studies were observational cohort studies, subject to an unclear risk of bias.

Conclusions: Findings suggest that streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives may decrease attrition, but the quality of the current evidence base is low. Few studies have investigated combined interventions, or assessed the impact of interventions across the HIV cascade. Results from on-going trials investigating POC CD4 count testing, patient navigation, rapid ART initiation and mobile phone technology may fill the quality of evidence gap. Further high-quality studies on key population groups are required, with interventions informed by previously reported barriers to care.

 Abstract  Full-text [free] access 

Editor’s notes: To maximise the impact of antiretroviral therapy (ART), people living with HIV should be diagnosed as early as possible, after acquiring HIV infection. They should be enrolled and retained in pre-ART care, initiated on ART and retained in ART care. And at the same time ensuring long-term adherence to achieve and maintain viral load suppression.

This review focuses on the first few steps in the treatment cascade. The authors review the evidence for activities that enhance the linkage from HIV testing to pre-ART care, retain people in pre-ART care and enhance the linkage to ART initiation. Streamlining services to minimize patient visits, providing adequate medical and peer support, and providing incentives appear to decrease attrition between HIV testing and ART initiation. However, the authors point out that most of the included studies looked at the effect of a single activity on a single point, in the continuum of care. There is a gap in evidence of the effect of combined activities and programmes across the continuum of care.

With the clear trend towards the earliest possible initiation of ART, the pre-ART care period will become much shorter. However there will be need for activities to improve immediate linkage from a positive test result, to ART initiation and ART care.

Health care delivery
Africa, Asia
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Mental health concerns similar for HIV-affected and HIV-positive children in Rwanda

HIV and child mental health: a case-control study in Rwanda

Betancourt T, Scorza P, Kanyanganzi F, Fawzi MC, Sezibera V, Cyamatare F, Beardslee W, Stulac S, Bizimana JI, Stevenson A, Kayiteshonga Y. Paediatrics. 2014 Jul 5. [Epub ahead of print]

The global HIV/AIDS response has advanced in addressing the health and well-being of HIV-positive children. Although attention has been paid to children orphaned by parental AIDS, children who live with HIV-positive caregivers have received less attention. This study compares mental health problems and risk and protective factors in HIV-positive, HIV-affected (due to caregiver HIV), and HIV-unaffected children in Rwanda. A case-control design assessed mental health, risk, and protective factors among 683 children aged 10 to 17 years at different levels of HIV exposure. A stratified random sampling strategy based on electronic medical records identified all known HIV-positive children in this age range in 2 districts in Rwanda. Lists of all same-age children in villages with an HIV-positive child were then collected and split by HIV status (HIV-positive, HIV-affected, and HIV-unaffected). One child was randomly sampled from the latter 2 groups to compare with each HIV-positive child per village. HIV-affected and HIV-positive children demonstrated higher levels of depression, anxiety, conduct problems, and functional impairment compared with HIV-unaffected children. HIV-affected children had significantly higher odds of depression (1.68: 95% confidence interval [CI] 1.15-2.44), anxiety (1.77: 95% CI 1.14-2.75), and conduct problems (1.59: 95% CI 1.04-2.45) compared with HIV-unaffected children, and rates of these mental health conditions were similar to HIV-positive children. These results remained significant after controlling for contextual variables. The mental health of HIV-affected children requires policy and programmatic responses comparable to HIV-positive children.

Abstract access

Editor’s notes: The successes of prevention of mother-to-child transmission programmes have led to a substantial increase in the number of HIV-affected children in sub-Saharan Africa. While the physical health trajectory of these children has been the subject of much research, far less is known about their mental health status. In Rwanda investigators found that, relative to HIV-unaffected children, HIV-positive and HIV-affected children both had similarly compromised mental health and functioning. Many of these differences could be explained by the fact that these latter groups were more likely to have experienced the death of a caregiver and not to have their mother as their primary caregiver. These results make us consider not only the need for psychosocial services for the children of HIV-positive adults, but also to consider parity of services regardless of the child’s own HIV status.

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WHO clinical staging misses a significant proportion of antiretroviral therapy eligible individuals

Diagnostic accuracy of the WHO clinical staging system for defining eligibility for ART in sub-Saharan Africa: a systematic review and meta-analysis.

Munthali C, Taegtmeyer M, Garner PG, Lalloo DG, Squire SB, Corbett EL, Ford N, MacPherson P. J Int AIDS Soc. 2014 Jun 12;17:18932. doi: 10.7448/IAS.17.1.18932. eCollection 2014.

Introduction: The World Health Organization (WHO) recommends that HIV-positive adults with CD4 count ≤500 cells/mm3 initiate antiretroviral therapy (ART). In many countries of sub-Saharan Africa, CD4 count is not widely available or consistently used and instead the WHO clinical staging system is used to determine ART eligibility. However, concerns have been raised regarding its discriminatory ability to identify patients eligible to start ART. We therefore reviewed the accuracy of WHO stage 3 or 4 assessment in identifying ART eligibility according to CD4 count thresholds for ART initiation.

Methods: We systematically searched PubMed and Global Health databases and conference abstracts using a comprehensive strategy for studies that compared the Results of WHO clinical staging with CD4 count thresholds. Studies performed in sub-Saharan Africa and published in English between 1998 and 2013 were eligible for inclusion according to our predefined study protocol. Two authors independently extracted data and assessed methodological quality and risk of bias using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) tool. Summary estimates of sensitivity and specificity were derived for each CD4 count threshold and hierarchical summary receiver operator characteristic curves were plotted.

Results: Fifteen studies met the inclusion criteria, including 25 032 participants from 14 countries. Most studies assessed individuals attending ART clinics prior to treatment initiation. WHO clinical stage 3 or 4 disease had a sensitivity of 60% (95% CI: 45-73%, Q=914.26, p<0.001) and specificity of 73% (95% CI: 60-83%, Q=1439.43, p<0.001) for a CD4 threshold of ≤200 cells/mm3 (11 studies); sensitivity and specificity for a threshold of CD4 count ≤350 cells/mm3 were 45% (95% CI: 26-66%, Q=1607.31, p<0.001) and 85% (95% CI: 69-93%, Q=896.70, p<0.001), respectively (six studies). For the threshold of CD4 count ≤500 cells/mm3 sensitivity was 14% (95% CI: 13-15%) and specificity was 95% (95% CI: 94-96%) (one study).

Conclusions: When used for individual treatment decisions, WHO clinical staging misses a high proportion of individuals who are ART eligible by CD4 count, with sensitivity falling as CD4 count criteria rises. Access to accurate, accessible, robust and affordable CD4 count testing methods will be a pressing need for as long as ART initiation decisions are based on criteria other than seropositivity.

Abstract  Full-text [free] access  

Editor’s notes: This study highlights the major shortcomings of WHO clinical staging when identifying antiretroviral therapy (ART) eligible individuals, with decreasing sensitivity of clinical staging for eligibility at higher CD4 thresholds. There remains limited access to CD4 count testing in many settings in sub-Saharan Africa. The individual and public health benefit of earlier ART initiation will not be achieved unless strategies other than WHO clinical staging are implemented. Access to affordable, quality assured CD4 count testing in all ART initiation clinics may never be feasible in the most resource-constrained settings. Universal treatment, removing the need for CD4 count testing, may be the way to ensure that eligible individuals are started on ART in a timely way.

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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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High human papillomavirus prevalence among men in sub-Saharan Africa, especially among individuals living with HIV

Human papillomavirus prevalence among men in sub-Saharan Africa: a systematic review and meta-analysis.

Olesen TB, Munk C, Christensen J, Andersen KK, Kjaer SK. Sex Transm Infect. 2014 May 7. doi: 10.1136/sextrans-2013-051456. [Epub ahead of print]

Background: We performed a systematic review and meta-analysis to summarise the available data on the prevalence of human papillomavirus (HPV) among men in sub-Saharan Africa.

Methods: PubMed and Embase were searched up to 10 March 2014. Random effects meta-analyses were used to calculate a pooled prevalence of any HPV and high-risk (HR) HPV.

Results: A total of 11 studies comprising 9 342 men were identified. We found that HPV is very common among men in sub-Saharan Africa, the prevalence of any HPV ranging between 19.1% and 100%. Using random effects meta-analysis, the pooled prevalence of any HPV was 78.2% (95% CI 54.2 to 91.6) among HIV-positive and 49.4% (95% CI 30.4 to 68.6) among HIV-negative men (p=0.0632). When restricting the analyses to PCR-based studies, the pooled prevalence of any HPV was 84.5% (95% CI 74.2 to 91.2) among HIV-positive and 56.4% (95% CI 49.7 to 62.9) among HIV-negative men (p<0.0001). Of the HPV types included in the nine-valent HPV vaccine, the most common HR HPV types were HPV16 and HPV52, and HPV6 was the most common low-risk HPV type. When examining the prevalence of HPV in relation to age no clear trend was observed.

Conclusions: The prevalence of HPV is high among men in sub-Saharan Africa, which could contribute to the high rates of penile and cervical cancer in this part of the world. Implementation of the prophylactic HPV vaccines could potentially help prevent this large burden of HPV and HPV-associated disease in sub-Saharan Africa.

Abstract access 

Editor’s notes: The majority of cases of penile cancer and ano-genital warts are caused by genotypes of human papillomavirus (HPV) that are included in currently available vaccines. Sub-Saharan Africa has among the highest prevalence of HPV-related infections in the world. This review summarizes HPV prevalence in this region, showing strong evidence of a higher prevalence of HPV in HIV-positive men compared to HIV-negative men. The pooled prevalence of HPV by PCR shows a significant difference in prevalence by HIV status – as is seen for women. The high HPV prevalence may partly explain the higher rate of ano-genital cancer/warts among HIV-positive men. This is important for the consideration of vaccinating men as well as women against HPV in sub-Saharan Africa (although herd immunity through vaccination of women may offer men some protection in the long term). High HPV prevalence among HIV-negative men is also important given that there is some evidence for the association between prevalent penile-HPV and HIV acquisition. The high HPV prevalence may also add to the arguments for rapid scale-up of voluntary medical male circumcision (VMMC) in sub-Saharan Africa, since VMMC has been shown to reduce HPV prevalence and incidence, in addition to HIV incidence.

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Systematic review highlights gaps in depression research in sub-Saharan Africa

Reliability and validity of depression assessment among persons with HIV in sub-Saharan Africa: systematic review and meta-analysis.

Tsai AC. J Acquir Immune Defic Syndr. 2014 May 21. [Epub ahead of print]

Objectives: To systematically review the reliability and validity of instruments used to screen for major depressive disorder or assess depression symptom severity among persons with HIV in sub-Saharan Africa.

Design: Systematic review and meta-analysis.

Methods: A systematic evidence search protocol was applied to seven bibliographic databases. Studies examining the reliability and/or validity of depression assessment tools were selected for inclusion if they were based on data collected from HIV-positive adults in any African member state of the United Nations. Random-effects meta-analysis was employed to calculate pooled estimates of depression prevalence. In a subgroup of studies of criterion-related validity, the bivariate random-effects model was used to calculate pooled estimates of sensitivity and specificity.

Results: Of 1 117 records initially identified, I included 13 studies of 5 373 persons with HIV in 7 sub-Saharan African countries. Reported estimates of Cronbach's alpha ranged from 0.63-0.95, and analyses of internal structure generally confirmed the existence of a depression-like construct accounting for a substantial portion of variance. The pooled prevalence of probable depression was 29.5% (95% CI, 20.5-39.4), while the pooled prevalence of major depressive disorder was 13.9% (95% CI, 9.7-18.6). The Center for Epidemiologic Studies-Depression scale was the most frequently studied instrument, with a pooled sensitivity of 0.82 (95% CI, 0.73-0.87) for detecting major depressive disorder.

Conclusions: Depression screening instruments yielded relatively high false positive rates. Overall, few studies described the reliability and/or validity of depression instruments in sub-Saharan Africa.

Abstract access 

Editor’s notes: This is the first systematic review of depression screening and diagnostic instruments among HIV-positive people in sub-Saharan Africa. The depression treatment gap for people living with HIV in high-income countries is considerable, and is likely to be even greater in sub-Saharan Africa. The eligible studies in this review were geographically concentrated in southern and eastern Africa. Prevalence of depression overall was high, but was substantially lower among people who had initiated HIV treatment than among people who had not. Additionally, depression prevalence estimates were twice as high when using screening tools rather than diagnostic criteria, indicating a high false positivity rate. This systematic review highlights critical areas for future research, particularly in validating depression screening tools and in expanding investigation of HIV and depression co-morbidity beyond South Africa and Uganda.

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Physical as well as sexual partner violence is associated with increased HIV risk

Intimate partner violence and HIV infection among women: a systematic review and meta-analysis

Li Y, Marshall CM, Rees HC, Nunez A, Ezeanolue EE, Ehiri JE. 4 J Int AIDS Soc. 2014 Feb 13;17:18845. doi: 10.7448/IAS.17.1.18845. eCollection 2014.

Introduction: To assess evidence of an association between intimate partner violence (IPV) and HIV infection among women.

Methods: Medline/PubMed, Embase, Web of Science, EBSCO, Ovid, Cochrane HIV/AIDS Group's Specialized Register and Cochrane Central Register of Controlled Trials were searched up to 20 May 2013 to identify studies that examined the association between IPV and HIV infection in women. We included studies on women aged ≥15 years, in any form of sexually intimate relationship with a male partner.

Results: Twenty-eight studies [(19 cross-sectional, 5 cohorts and 4 case-control studies) involving 331 468 individuals in 16 countries - the US (eight studies), South Africa (four studies), East Africa (10 studies), India (three studies), Brazil (one study) and multiple low-income countries (two studies)] were included. Results were pooled using RevMan 5.0. To moderate effect estimates, we analyzed all data using the random effects model, irrespective of heterogeneity level. Pooled results of cohort studies indicated that physical IPV [pooled RR (95% CI): 1.22 (1.01, 1.46)] and any type of IPV [pooled RR (95% CI): 1.28 (1.00, 1.64)] were significantly associated with HIV infection among women. Results of cross-sectional studies demonstrated significant associations of physical IPV with HIV infection among women [pooled OR (95% CI): 1.44 (1.10, 1.87)]. Similarly, results of cross-sectional studies indicated that combination of physical and sexual IPV [pooled OR (95% CI): 2.00 (1.24, 3.22) and any type of IPV [pooled OR (95% CI): 1.41 (1.16, 1.73)] were significantly associated with HIV infection among women.

Conclusions: Available evidence suggests a moderate statistically significant association between IPV and HIV infection among women. To further elucidate the strength of the association between IPV and HIV infection among women, there is a need for high-quality follow-up studies conducted in different geographical regions of the world, and among individuals of diverse racial/cultural backgrounds and varying levels of HIV risks.

Abstract Full-text [free] access

Editor’s notes: Globally, an estimated 30% of partnered women will experience physical and/or sexual violence. As well as being a violation of human rights, there is growing evidence about the different ways in which violence and the fear of violence may limit women’s ability to prevent themselves from acquiring infection, or access services. This paper presents a systematic review and meta-analysis of current evidence on whether exposures to violence by an intimate partner increase women’s HIV risk. Commonly, debates on this issue focus on forced sex. The findings suggest that the issue is more complex – with exposures to physical violence also being associated with increased HIV risk. Exposures to both physical and sexual violence by partners, which is an indicator of more severe partner violence, found stronger effect estimates. The pathways underlying the documented associations may be multiple: as well as forced sex, women may have difficulties negotiating condom use or accessing services. Other studies have suggested that there may also be other characteristics of the relationship.  These are that men who are violent are also more likely to have other risk behaviours such as problematic alcohol use or multiple sexual partners. These result in them being more likely to be HIV positive than non-violent men. The findings suggest that violence prevention activities may reduce HIV risk. They also highlight the need to ensure that HIV services are sensitive to, and able to support, women who have experienced or fear violence.

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CD4 counts at antiretroviral therapy start rising globally, but could do better!

Immunodeficiency at the start of combination antiretroviral therapy in low-,  middle-, and high-income countries.

The IeDEA and ART Cohort Collaborations. J Acquir Immune Defic Syndr 2014 Jan 1;65(1):e8-e16. doi: 10.1097/QAI.0b013e3182a39979.

Objective: To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries.

Methods: Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed.

Results: In total, 379 865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/µL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/µL (76% increase), 88 to 135 cells/µL (53%), and 209 to 274 cells/µL (31%). In 2009, compared with LIC, median counts were 13 cells/µL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/µL (-62 to +18) lower in UMIC, and 112 cells/µL (+75 to +149) higher in HIC. They were 23 cells/µL (95% CI: +18 to +28 cells/µL) higher in women than men. Median counts were 88 cells/µL (95% CI: +35 to +141 cells/µL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage.

Conclusions: Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/µL in LIC and MIC and below 300 cells/µL in HIC. Earlier start of cART will require substantial efforts and resources globally.

Abstract access 

Editor’s notes: In this multi-cohort analysis spanning six continents, median CD4 counts at initiation of combination antiretroviral therapy were substantially higher in high-income compared to low- or middle-income countries. Median CD4 counts at initiation increased between 2002 and 2009 in most countries studied, but these increases were greater in low- and middle-income than high-income countries and were greater among men than women. Baseline CD4 counts in low- and middle-income countries were higher among countries with national antiretroviral therapy coverage of 80% or above. Nevertheless, despite the massive scale-up of antiretroviral therapy in low-income countries since 2002, the increases in median CD4 count at the start of antiretroviral therapy have been modest. Substantial efforts and resources are needed to achieve earlier implementation of antiretroviral therapy globally.

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Poor long-term outcomes among children on antiretroviral therapy underline the need for effective monitoring

Long-term effectiveness of combination antiretroviral therapy and prevalence of HIV drug resistance in HIV-1-infected children and adolescents in Rwanda.

Mutwa PR, Boer KR, Rusine J, Muganga N, Tuyishimire D, Schuurman R, Reiss P, Lange JM, Geelen SP.Pediatr Infect Dis J 2014 Jan;33(1):63-9. doi: 10.1097/INF.0b013e31829e6b9f.

Methods: A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed.

Results: Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1 000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%).

Conclusion: Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations.

Abstract access 

 Editor’s notes: Antiretroviral therapy access in children has been scaled up much more recently than in adults and there are few data on long-term outcomes. This paper reports on outcomes among children taking antiretroviral therapy for a median duration of 3.4 years.

The paper highlights some key issues. Firstly, children achieve good immune reconstitution (or increase in CD4 counts) with antiretroviral therapy and regain weight. However, catch-up linear growth is poor and a third of children remain stunted. Secondly, children who are older or start antiretroviral therapy at lower CD4 counts are less likely to have immunological recovery. Also, children with lower CD4 counts at start of treatment are more likely to experience treatment failure, underscoring the importance of early institution of antiretroviral therapy.

Thirdly, despite an immunologic response, a third of children in this study had virologic failure, a figure that is much higher than that reported for adults.  Despite treatment failure, the vast majority of children remained on first-line treatment. More than 10% of those failing antiretroviral therapy in this study had multi-drug resistance. Finally, neither clinical nor immunological parameters enable timely detection of virologic failure. Therefore, in settings where virologic monitoring is limited, there is a high risk of children remaining for long periods on failing regimens, resulting in an accumulation of resistance.  This is of particular concern due to the high risk of virologic failure in this age-group.

The study highlights the urgent need to scale-up antiretroviral therapy coverage in children, which significantly lags behind that in adults. Earlier identification of HIV-positive children is crucial to enable earlier treatment and ensure robust outcomes. This age-group is at very high risk of treatment failure and paediatric HIV programmes must focus on developing strategies not only to deliver antiretroviral therapy but also to adequately monitor and support treatment long term.  

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Progress in starting antiretroviral treatment earlier in Africa?

Advanced HIV disease at entry into HIV care and initiation of antiretroviral therapy during 2006-2011: findings from four sub-Saharan African countries

Lahuerta M,  Hoffman S, Elul B,  Kulkarni SG,  Remien RH,  Nuwagaba-Biribonwoha H, El-Sadr W,  Nash D. Clin Infect Dis 2013, Dec 4

Background: Timely antiretroviral therapy (ART) initiation requires early diagnosis of human immunodeficiency virus (HIV) infection with prompt enrollment and engagement in HIV care.

Methods:  We examined programmatic data on 334 557 adults enrolling in HIV care, including 149 032 who initiated ART during 2006-2011 at 132 facilities in Kenya, Mozambique, Rwanda, and Tanzania. We examined trends in advanced HIV disease (CD4+ count <100 cells/µL or World Health Organization disease stage IV) and determinants of advanced HIV disease at ART initiation.

Results: Between 2006-2011, the median CD4+ count at ART initiation increased from 125 to 185 cells/µL an increase of 10 cells/year. Although the proportion of patients initiating ART with advanced HIV disease decreased from 42% to 29%, sex disparities widened. In 2011, the odds of advanced disease at ART initiation were higher among men (adjusted odds ratio [AOR], 1.4; 95% CI, 1.3-1.5), those on tuberculosis treatment (AOR, 1.6; 95% CI, 1.3-2.0), and those with a ≥12 month gap in pre-ART care (AOR, 2.0; 95% CI, 1.6-2.6).

Conclusions: Intensified efforts are needed to identify and link HIV-infected individuals to care earlier and to retain them in continuous pre-ART care to facilitate more timely ART initiation.

Abstract access 

Editor’s notes: This large multi-cohort analysis of programmatic data from four sites in eastern and southern  Africa shows slow but steady reductions in the proportions of patients starting antiretroviral treatment (ART) who have CD4 cell count <100 cells/µl, or WHO stage 4 disease. The risk of advanced disease at ART start was increased among men and among individuals with a long gap in pre-ART care, i.e. no clinic visit for a period of 12 or more months between enrolment and ART initiation. This study reiterates the need to strengthen strategies for retention and to reduce losses during the pre-ART cascade of care and the need to focus interventions on men.

HIV Treatment
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