Articles tagged as "15 million accessing treatment"

Simplifying clinical antiretroviral therapy eligibility assessment

A novel community health worker tool outperforms WHO clinical staging for assessment of antiretroviral therapy eligibility in a resource-limited setting.

Macpherson P, Lalloo DG, Thindwa D, Webb EL, Squire SB, Chipungu GA, Desmond N, Makombe SD, Taegtmeyer M, Choko AT, Corbett EL. J Acquir Immune Defic Syndr. 2014 Feb 1;65(2):e74-8. doi: 10.1097/QAI.0b013e3182a20e74.

The accuracy of a novel community health worker antiretroviral therapy eligibility assessment tool was examined in community members in Blantyre, Malawi. Nurses independently performed World Health Organization (WHO) staging and CD4 counts. One hundred ten (55.6%) of 198 HIV-positive participants had a CD4 count of <350 cells per cubic millimeter. The community health worker tool significantly outperformed WHO clinical staging in identifying CD4 count of <350 cells per cubic millimeter in terms of sensitivity (41% vs. 19%), positive predictive value (75% vs. 68%), negative predictive values (53% vs. 47%), and area under the receiver-operator curve (0.62 vs. 0.54; P = 0.017). Reliance on WHO staging is likely to result in missed and delayed antiretroviral therapy initiation.

 Abstract access 

Editor’s notes: Antiretroviral Therapy (ART) eligibility assessment has been identified as one of the bottlenecks in the HIV care cascade that limits and/or delays progression of patients to starting ART. Laboratory-based CD4 count testing requires more than one visit and is unavailable in many settings. WHO staging is difficult and time-consuming for many health care workers to use. Simplified eligibility tools are needed to simplify both facility-based and community-based ART initiation. This study found that a clinical tool incorporating a series of simple questions had greater accuracy than WHO staging, for identifying those eligible for ART, when used by community health care workers in Malawi. 

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Efavirenz dose reduction could help scale up antiretroviral therapy access

Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial.

ENCORE1 Study Group. Lancet. 2014 Feb 7. pii: S0140-6736(13)62187-X. doi: 10.1016/S0140-6736(13)62187-X. [Epub ahead of print]

Background: The optimum dose of key antiretroviral drugs is often overlooked during product development. The ENCORE1 study compared the efficacy and safety of reduced dose efavirenz with standard dose efavirenz in combination with tenofovir and emtricitabine as first-line treatment for HIV infection. An effective and safe reduced dose could yield meaningful cost savings.

Methods: ENCORE1 is a continuing non-inferiority trial in HIV-1-infected antiretroviral-naive adults in 38 clinical sites in 13 countries. Participants (plasma HIV-RNA >1000 log10 copies per mL, CD4 T-cell count 50-500 cells per µL) were randomly assigned by a computer-generated sequence with a blocking factor of four (stratified by clinical site and by screening viral load) to receive tenofovir plus emtricitabine with either a reduced daily dose (400 mg) or a standard dose (600 mg) of efavirenz. Participants, physicians, and all other trial staff were masked to treatment group. The primary endpoint was the difference in proportions of participants with plasma HIV-RNA of less than 200 copies per mL at 48 weeks. Treatment groups were regarded as non-inferior if the lower limit of the 95% CI for the difference in viral load was less than -10% by modified intention-to-treat analysis. Adverse events were summarised by treatment.

Findings: The modified intention-to-treat analysis consisted of 630 patients (efavirenz 400=321; efavirenz 600=309). 32% were women; 37% were African, 33% were Asian, and 30% were white. The mean baseline CD4 cell count was 273 cells per µL (SD 99) and median plasma HIV-RNA was 4.75 log10 copies per mL (IQR 0.88). The proportion of participants with a viral load below 200 copies per mL at week 48 was 94.1% for efavirenz 400 mg and 92.2% for 600 mg (difference 1.85%, 95% CI -2.1 to 5.79). CD4 T-cell counts at week 48 were significantly higher for the 400 mg group than for the 600 mg group (mean difference 25 cells per µL, 95% CI 6-44; p=0.01). We recorded no difference in grade or number of patients reporting adverse events (efavirenz 400=89.1%, efavirenz 600=88.4%; difference 0.75%, 95% CI -4.19 to 5.69; p=0.77). Study drug-related adverse events were significantly more frequent in the 600 mg group than in the 400 mg group (146% [47] vs 118 [37]), difference -10.5%, 95% CI -18.2 to -2.8; p=0.01) and significantly fewer patients with these events stopped treatment (400 mg=6 [2%], 600 mg=18 [6%], difference -3.96%, 95% CI -6.96 to -0.95; p=0.01).

Interpretation: Our findings suggest that a reduced dose of 400 mg efavirenz is non-inferior to the standard dose of 600 mg, when combined with tenofovir and emtricitabine during 48 weeks in ART-naive adults with HIV-1 infection. Adverse events related to the study drug were more frequent with 600 mg efavirenz than with 400 mg. Lower dose efavirenz should be recommended as part of routine care.

Abstract access

Editor’s notes: Nearly 10 million people in low- and middle-income countries were receiving antiretroviral therapy (ART) by the end of 2012, with plans to expand coverage to 15 million by 2015. Several challenges must be overcome if this target is to be achieved. One of the most pertinent of these is how to fund this expansion in the current economic climate. Significant progress has already been made in reducing the cost of first-line drugs. The authors of this paper propose an alternative approach to lowering drug costs, namely dose reduction.

Evidence supporting the 600mg dose of efavirenz used in clinical practice is weak, with no difference found in the proportion of patients achieving viral suppression in the original dose finding trials of 200mg, 400mg and 600mg (unpublished). This trial in ART-naive individuals found that 400mg was non-inferior to 600mg of efavirenz in terms of viral suppression over 48 weeks of follow-up. Findings were similar when stratified by ethnic group (African, Asian, other) and body mass index, both factors which influence drug concentrations. Furthermore, fewer patients on 400mg reported adverse events which were related to efavirenz, and fewer patients with drug-related side effects on this dose stopped efavirenz. These promising results support a dose reduction strategy. However, longer term outcomes need to be evaluated and efficacy studies in patients with tuberculosis are needed before the 400mg dose is recommended for use in routine clinical practice. Certainly, if drug companies agree to manufacture this dose at scale, preferably in fixed-dose combination tablets, cost-savings could be considerable.  

Africa, Asia, Europe, Latin America
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Do text messaging activities promote adherence to antiretroviral therapy?


Text message intervention designs to promote adherence to antiretroviral therapy (ART): a meta-analysis of randomized controlled trials

Finitsis, D. J. P., J. A. Johnson, B. PLoS One. 2014 Feb 5;9(2):e88166. doi: 10.1371/journal.pone.0088166. eCollection 2014.

Background: The efficacy of antiretroviral therapy depends on patient adherence to a daily medication regimen, yet many patients fail to adhere at high enough rates to maintain health and reduce the risk of transmitting HIV. Given the explosive global growth of cellular-mobile phone use, text-messaging interventions to promote adherence are especially appropriate. This meta-analysis synthesized available text messaging interventions to promote antiretroviral therapy adherence in people living with HIV.

Methods: We performed Boolean searches of electronic databases, hand searches of recent year conference abstracts and reverse searches. Included studies (1) targeted antiretroviral therapy adherence in a sample of people living with HIV, (2) used a randomized-controlled trial design to examine a text messaging intervention, and (3) reported at least one adherence measurement or clinical outcome.

Results: Eight studies, including 9 interventions, met inclusion criteria. Text-messaging interventions yielded significantly higher adherence than control conditions (OR = 1.39; 95% CI = 1.18, 1.64). Sensitivity analyses of intervention characteristics suggested that studies had larger effects when interventions (1) were sent less frequently than daily, (2) supported bidirectional communication, (3) included personalized message content, and (4) were matched to participants' antiretroviral therapy dosing schedule. Interventions were also associated with improved viral load and/or CD4+ count (k = 3; OR = 1.56; 95% CI = 1.11, 2.20).

Conclusions: Text-messaging can support antiretroviral therapy adherence. Researchers should consider the adoption of less frequent messaging interventions with content and timing that is individually tailored and designed to evoke a reply from the recipient. Future research is needed in order to determine how best to optimize efficacy.

Abstract Full-text [free] access

Editor’s notes: Adherence to antiretroviral therapy (ART) is crucial for good clinical outcomes and for reducing the risk of onward HIV transmission. In the last decade, there has been a massive increase in cellular phone ownership. This provides a promising and potentially cost-effective approach to improving ART adherence through short messaging services (SMS). The World Health Organization guidelines recommend using SMS as part of a package of activities to support adherence to ART.

This meta-analysis examined how SMS can be optimally used to promote successful adherence. Eight randomised controlled trials from the USA, Brazil, Kenya and Cameroon investigated nine types of SMS activities. Studies used multiple methods to measure adherence including self-report, electronic drug monitoring and pill counts. Overall, text messaging significantly improved the average adherence outcome. Only three of the eight studies used virologic suppression as an outcome measure; importantly these studies did show an improvement in adherence. The study highlighted the components of SMS activities that were associated with the most effect on adherence. These included less frequent messaging than daily, personalised message content, SMS matched to dosing schedules and bidirectional communication between the care provider and the participant.

In summary, SMS is a promising activity for supporting adherence, although the effect on adherence is modest.  Several questions remain to be answered, namely the optimum way of operationalising this as an adherence support activity, its sustainability and its cost-effectiveness (given the modest effect size). Finally, a major limitation of ART adherence studies is the common use of non-biological measures of adherence, which do not always reflect virologic suppression. Virologic suppression is the most persuasive outcome for evaluations of programmes to improve adherence. 

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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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Earlier antiretroviral therapy initiation halves early mortality in South Africa

Reduction in early mortality on antiretroviral therapy for adults in rural South Africa since change in CD4+ cell count eligibility criteria.

Lessells RJ, Mutevedzi PC, Iwuji CC, Newell ML. J Acquir Immune Defic Syndr 2014 Jan 1;65(1):e17-24. doi: 10.1097/QAI.0b013e31829ceb14.65(1).

Objective: To explore the impact of expanded eligibility criteria for antiretroviral therapy (ART) on median CD4 cell count at ART initiation and early mortality on ART.

Methods: Analyses included all adults (≥16 years) initiated on first-line ART between August 2004 and July 2012. CD4 cell count threshold 350 cells per microliter for all adults was implemented in August 2011. Early mortality was defined as any death within 91 days of ART initiation. Trends in baseline CD4 cell count and early mortality were examined by year (August to July) of ART initiation. Competing risks analysis was used to examine early mortality.

Results: A total of 19 080 adults (67.6% female) initiated ART. Median CD4 cell count at ART initiation was 110-120 cells per microliter over the first 6 years, increasing marginally to 145 cells per microliter in 2010-2011 and more significantly to 199 cells per microliter in 2011-2012. Overall, there were 875 deaths within 91 days of ART initiation; early mortality rate was 19.4 per 100 person-years [95% confidence interval (CI) 18.2 to 20.7]. After adjustment for sex, age, baseline CD4 cell count, and concurrent tuberculosis (TB), there was a 46% decrease in early mortality for those who initiated ART in 2011-2012 compared with the reference period 2008-2009 (subhazard ratio, 0.54; 95% CI: 0.41 to 0.71).

Conclusions: Since the expansion of eligibility criteria, there is evidence of earlier access to ART and a significant reduction in early mortality rate in this primary health care programme. These findings provide strong support for national ART policies and highlight the importance of earlier ART initiation for achieving reductions in HIV-related mortality.

Abstract   Full-text [free] access

Editor’s notes: In a rural area of KwaZulu-Natal province in South Africa, the national policy shifted to recommend antiretroviral therapy (ART) for all adults with CD4+ cell count below 350 cells/μL from August 2011 onwards.  This shift has been associated with a significant increase in the median baseline CD4+ cell count among patients initiating ART and a significant reduction in mortality within the first three months of treatment. These findings suggest that linkage to care and treatment leading to earlier antiretroviral therapy initiation is key to achieving further reductions in HIV-related mortality.

South Africa
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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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Late pharmacy refill identifies patients at risk of poor ART outcomes

Short communication: late refills during the first year of antiretroviral therapy predict mortality and program failure among HIV-infected adults in urban Zambia.

Vinikoor MJ, Schuttner L, Moyo C, Li M, Musonda P, Hachaambwa LM, Stringer JS, Chi BH. AIDS Res Hum Retroviruses 2014 Jan;30(1):74-7. doi: 10.1089/AID.2013.0167. Epub 2013 Aug 30.

We evaluated the association of the number of late antiretroviral therapy (ART) refills with patient outcomes in a large public-sector human immunodeficiency virus treatment program in Lusaka, Zambia. Using pharmacy data routinely collected during 2004-2010, we calculated the number of late refills during the initial year of ART. We used multivariable Cox proportional hazard regression to examine the association between the number of late refills and death or program failure (i.e., death, loss to follow-up, or program withdrawal) >12 months after ART initiation, with and without stratification by the medication possession ratio (MPR) during the initial year of ART. Of 53 015 adults who received ART for ≥12 months (median follow-up duration, 86.1 months; interquartile range, 53.2-128.2 months), 26 847 (50.6%) had 0 late refills, 16 762 (31.6%) had 1, 6 505 (12.3%) had 2, and 2,901 (5.5%) had ≥3. Kaplan-Meier analysis revealed that ≥3 late refills was associated with a greater mortality risk than 1 and 2 late refills (p<0.001, by the log-rank test). The mortality risk was greater for patients with 2 late refills [adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI), 0.99-1.38] or ≥3 late refills (adjusted HR, 1.51; 95% CI, 1.23-1.87), compared with that for patients with 0-1 late refills. Program failure was associated with ≥2 late refills. An MPR of <80% was associated with similar increases in mortality risk across late-refill strata. Monitoring late refills during the initial period of ART may help resource- and time-constrained clinics identify patients at risk for program failure.

Abstract access 

Editor’s notes: As antiretroviral therapy roll-out continues and the number of patients being followed up increases, strategies to promote retention in care which are feasible to use in busy clinics will become ever more important. Identifying patients at higher risk of loss to follow-up, who might benefit from more intensive support, is difficult. Adherence measures based on pharmacy refill data are attractive because they are objective, are predictive of virologic outcomes, use routinely-collected data, and do not place an additional burden on clinic staff.

This study covered over 50 000 patients taking antiretroviral therapy for more than 12 months in Zambia. Findings show that an increasing number of late pharmacy refills in the first year on antiretroviral therapy predicted death, and a composite outcome comprising death and loss from programme, measured after 12 months on treatment. These data support the use of pharmacy refill records to identify patients who may need additional support. Further research is needed to establish how best to combine early identification of risk with effective measures to maximise retention in care.

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Point of Care CD4 testing can improve gaps in the treatment cascade

Impact of point-of-care CD4 testing on linkage to HIV care: a systematic review

Wynberg E, Cooke G, Shroufi A, Reid SD, Ford N.J Int AIDS Soc 2014 Jan 20;17(1):18809. doi: 10.7448/IAS.17.1.18809. eCollection 2014.

Introduction: Point-of-care testing for CD4 cell count is considered a promising way of reducing the time to eligibility assessment for antiretroviral therapy (ART) and of increasing retention in care prior to treatment initiation. In this review, we assess the available evidence on the patient and programme impact of point-of-care CD4 testing.

Methods: We searched nine databases and two conference sites (up until 26 October 2013) for studies reporting patient and programme outcomes following the introduction of point-of-care CD4 testing. Where appropriate, results were pooled using random-effects methods.

Results: Fifteen studies, mainly from sub-Saharan Africa, were included for review, providing evidence for adults, adolescents, children and pregnant women. Compared to conventional laboratory-based testing, point-of-care CD4 testing increased the likelihood of having CD4 measured [odds ratio (OR) 4.1, 95% CI 3.5-4.9, n=2] and receiving a CD4 result (OR 2.8, 95% CI 1.5-5.6, n=6). Time to being tested was significantly reduced, by a median of nine days; time from CD4 testing to receiving the result was reduced by as much as 17 days. Evidence for increased treatment initiation was mixed.

Discussion: The results of this review suggest that point-of-care CD4 testing can increase retention in care prior to starting treatment and can also reduce time to eligibility assessment, which may result in more eligible patients being initiated on ART.

Abstract   Full-text [free] access

Editor’s notes: A recent review from sub-Saharan Africa found that one quarter of patients are lost-to-care in the step between testing HIV positive and having a CD4 measurement done. The potential for point-of-care (PoC) CD4 testing to increase access to antiretroviral therapy (ART) is increasingly recognised. However, the effectiveness of PoC tests depends on effective implementation as well as technical accuracy. This comprehensive systematic review was undertaken to evaluate the programmatic impact of point-of-care (PoC) CD4 tests on the treatment cascade. It shows that compared with laboratory CD4 testing, the PoC tests can reduce time to eligibility assessment, retention in care prior to treatment initiation, and in some settings, increased initiation of ART upon eligibility. The review highlights some gaps in research in this area – all the 15 studies included were located in sub-Saharan Africa, only one of the studies included randomization, and few discussed training of staff on how to use the tests. Overall, this review adds to the evidence that PoC CD4 tests have a useful role to play in improving the treatment cascade. In particular, around time to eligibility assessment, but clearly needs to be used in conjunction with additional strategies to ensure successful linkage to care and retention in care.

HIV testing, HIV Treatment
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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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Pre-antiretroviral therapy losses to care: no time to lose

Adults receiving HIV care before the start of antiretroviral therapy in sub-Saharan Africa: patient outcomes and associated risk factors.

Bastard M N, Szumilin N, Balkan E, Poulet E,  Pujades-Rodriguez, M. J Acquir Immune Defic Syndr 2013; 64(5):455-63

Background: Gaining understanding of the period before antiretroviral therapy (ART) is needed to improve treatment outcomes and to reduce HIV transmission. This study describes the cascade of enrollment in HIV care, pre-ART follow-up, and predictors of mortality and lost to follow-up (LTFU) before ART initiation.

Methods: We conducted a cohort study among HIV-infected adult patients not yet started on ART in 4 HIV sub-Saharan African programs. Patient follow-up began at enrollment and ended at the earliest of death, transfer-out, ART initiation, last visit date, or 60 months postenrollment. Risk factors for death and LTFU were investigated during the periods 0-6 and 6-60 months.

Results: A total of 55 789 patients (65.4% women) were included as follows: 44.2% in clinical stage 3 or 4, with median CD4 of 261 cells per microliter [interquartile range (IQR): 125-447]. Patient care started with a median of 3 days (IQR: 0-11) after HIV diagnosis, and 31 104 of 55 789 (55.8%) patients had CD4 counts performed within 1 month of enrollment. Of 47 283 patients with known ART eligibility status at enrollment, 36 969 (78.2%) patients required ART and 27 798 of 36 969 (75.7%) patients initiated therapy. Median follow-up was 2.5 months (IQR: 0.9-13.1). Mortality and LTFU rates were 3.9 per 100 person-years [95% confidence interval (CI): 3.7 to 4.1] and 28.3 per 100 person-years (95% CI: 27.8 to 28.8), respectively. Regardless of period, increased mortality and LTFU were associated with male, lower body mass index, advanced clinical stage, and lower CD4 cell count.

Conclusions: Short delays between HIV testing and care enrollment were observed in our HIV programs, but delays to determine ART eligibility were long. Interventions to initiate ART earlier, specifically targeted to men, are needed to improve patient retention in Africa.

Abstract access 

Editor’s notes: This large study from four sites in east Africa confirms the findings of other studies from sub-Saharan Africa which have documented substantial losses to care among patients during the care cascade, between the time of HIV testing and starting antiretroviral treatment (ART). The proportion of patients lost to follow-up was particularly striking and the strong association with disease stage suggests that this group may include many unascertained deaths. The need to strengthen and expedite each step of the care cascade is clear. 

Health care delivery
Kenya, Malawi, Uganda
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