Articles tagged as "15 million accessing treatment"

Can clinical algorithms be used to detect people with virologic failure?

CD4 criteria improves the sensitivity of a clinical algorithm developed to identify viral failure in HIV-positive patients on antiretroviral therapy.

Evans DH, Fox MP, Maskew M, McNamara L, MacPhail P, Mathews C, Sanne I. J Int AIDS Soc. 2014 Sep 15;17:19139. doi: 10.7448/IAS.17.1.19139. eCollection 2014.

Introduction: Several studies from resource-limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers.

Methods: We analyzed data from HIV-positive adults initiated on antiretroviral therapy (ART) in Johannesburg, South Africa, between April 2004 and February 2010. Viral failure was defined as ≥2 consecutive HIV-RNA viral loads >400 copies/ml following suppression ≤400 copies/ml. We used Cox-proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Weights for each predictor associated with virologic failure were created as the sum of the natural logarithm of the adjusted HR and dichotomized with the optimal cut-off at the point with the highest sensitivity and specificity (i.e. ≤4 vs. >4). We assessed the diagnostic accuracy of predictor scores cut-offs, with and without CD4 criteria (CD4 <100 cells/mm3; CD4 < baseline; >30% drop in CD4), by calculating the proportion with the outcome and the observed sensitivity, specificity, positive and negative predictive value of the predictor score compared to the gold standard of virologic failure.

Results: We matched 919 patients with virologic failure (1:3) to 2756 patients without. Our predictor score included variables at ART initiation (i.e. gender, age, CD4 count <100 cells/mm3, WHO stage III/IV and albumin) and laboratory and clinical follow-up data (drop in haemoglobin, mean cell volume (MCV) <100 fl, CD4 count <200 cells/mm3, new or recurrent WHO stage III/IV condition, diagnosis of new condition or symptom and regimen change). Overall, 51.4% had a score ≥4 and 48.6% had a score <4. A predictor score including CD4 criteria performed better than a score without CD4 criteria and better than WHO clinico-immunological criteria or WHO clinical staging to predict virologic failure (sensitivity 57.1% vs. 40.9%, 25.2% and 20.9%, respectively).

Conclusions: Predictor scores or risk categories, with CD4 criteria, could be used to identify patients at risk of virologic failure in resource-limited settings so that these patients may be targeted for focused interventions to improve HIV treatment outcomes.

Abstract  Full-text [free] access 

Editor’s notes: Monitoring people for antiretroviral treatment failure is challenging in resource-limited settings. Few countries have access to viral load monitoring and instead rely on immunological criteria or World Health Organization (WHO) clinical staging criteria to determine who is failing therapy. Unfortunately these methods have poor sensitivity and specificity for detecting virologic failure leading to late detection of virologic failure (poor sensitivity) and unnecessary switching (poor specificity).

Using electronic capture data from a large antiretroviral therapy (ART) programme in Johannesburg with access to routine viral load monitoring, the authors propose a new algorithm for identifying people at risk of confirmed virologic failure. The strength of their predictive model is that it incorporates simple clinical and laboratory markers measured at the visit, before virologic failure was confirmed. This gave healthcare workers the opportunity to intervene early. Disappointingly, as others have found, the sensitivity and specificity of their predictive model remain sub-optimal, albeit that it performs better than WHO immunological and clinical criteria alone. While clinical algorithms may be needed as an interim measure to ration access to viral load monitoring, the ultimate goal must be to increase access to low-cost viral load monitoring in these settings.

HIV Treatment
South Africa
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Staying on Option B+: why post-partum women are dropping out of HIV care in a Johannesburg clinic

What they wanted was to give birth; nothing else: barriers to retention in option B+ HIV care among postpartum women in South Africa.

Clouse K, Schwartz S, Van Rie A, Bassett J, Yende N, Pettifor A. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):e12-8. doi: 10.1097/QAI.0000000000000263.

Background: Women initiating antiretroviral therapy during pregnancy have high rates of dropout, particularly after delivery. We aimed to identify challenges to postpartum retention in care under Option B+, which expands antiretroviral therapy access to all HIV-positive pregnant women regardless of CD4 count.

Methodology: We performed 2 semi-structured interviews (SSI, n = 50) and 1 focus group discussion (n = 8) with HIV-positive women at Witkoppen Health and Welfare Centre, a primary care facility in Johannesburg, South Africa, that is one of the only clinics offering Option B+ in South Africa.

Results: Fifty women completed the SSI before delivery, and 48 (96%) completed the second SSI within 3 months of delivery. Median age was 28 years (interquartile range: 26-34); most women worked (62%) or had worked in the previous year (18%). Postpartum women attending HIV care perceived that barriers to HIV care after delivery among other women included the belief that mothers care more about the baby's health than their own (29.2%, 14/48), women were "ignorant" or "irresponsible" (16.7%, 8/48), negative clinic staff treatment (12.5%, 6/48), and denial or lack of disclosure of HIV status (10.4% each, 5/48). Experienced barriers included lack of money (18.0%, 9/50), work conflict (6.0%, 3/50), and negative staff treatment (6.0%, 3/50). During the focus group discussion, 3 main themes emerged: conflict with work commitment, negative treatment from health-care workers, and lack of disclosure related to stigma.

Conclusions: We identified a complex set of interconnected barriers to retaining postpartum women in HIV care under Option B+, including structural, personal, and societal barriers. The importance of postpartum HIV care for the mother's own health must be embraced by health-care workers and public health programs.

Abstract access 

Editor’s notes: This paper addresses a key knowledge gap which is, why do post-partum women living with HIV drop out of HIV care, despite having the opportunity to access ongoing HIV care? This paper presents the findings of a qualitative study conducted with women in a Johannesburg clinic who are being offered option B+. Option B+, seeks to initiate all HIV-positive pregnant women on lifelong highly active antiretroviral therapy (ART) regardless of CD4 count. Its success depends on the proportion of women who are retained in care and continue to adhere to treatment.

While the study found that very few women admitted that they themselves would stop taking their ART, they cited multiple reasons for other women to stop doing so. Many of these reasons have been discussed before, such as prioritising the health of their baby and having been harshly treated by healthcare workers during their delivery. A key issue identified in the paper is that once women have given birth they describe no longer having a ‘legitimate’ reason, in this case antenatal care, to continue attending a clinic. So we learn that being pregnant provides a cover to legitimise clinic attendance and women are able to receive HIV care without the risk of arousing suspicion. This is revealing about the ongoing HIV stigma and the challenges that a woman faces in explaining any regular visits to a healthcare facility to partners, family members, employers and others within their community. This illustrates the complex negotiations involved for many women in leaving their work commitments, formal or informal, to regularly attend an HIV clinic.

This paper is valuable because it shows us that unfortunately, even if costs can be waived, access may still be impeded by the persistent constraints involved in the management of non-disclosure. We may also learn a valuable methodological lesson from this study. To access information and opinions about drop-out and disengagement in HIV care, research may be more effective if studies allow individuals to talk about such issues indirectly through other people’s experiences rather than their own. This will address issues of social desirability bias in clinic based research. 

South Africa
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Low retention among HIV-positive adults not yet eligible for antiretroviral therapy

Impact of systematic HIV testing on case finding and retention in care at a primary care clinic in South Africa.

Clouse K, Hanrahan CF, Bassett J, Fox MP, Sanne I, Van Rie A. Trop Med Int Health. 2014 Sep 22. doi: 10.1111/tmi.12387. [Epub ahead of print]

Objective: Systematic, opt-out HIV counselling and testing (HCT) may diagnose individuals at lower levels of immunodeficiency but may impact loss to follow-up (LTFU) if healthier people are less motivated to engage and remain in HIV care. We explored LTFU and patient clinical outcomes under two different HIV testing strategies.

Methods: We compared patient characteristics and retention in care between adults newly diagnosed with HIV by either voluntary counselling and testing (VCT) plus targeted provider-initiated counselling and testing (PITC) or systematic HCT at a primary care clinic in Johannesburg, South Africa.

Results: One thousand one hundred and forty-four adults were newly diagnosed by VCT/PITC and 1124 by systematic HCT. Two-thirds of diagnoses were in women. Median CD4 count at HIV diagnosis (251 vs. 264 cells/µl, P = 0.19) and proportion of individuals eligible for antiretroviral therapy (ART) (67.2% vs. 66.7%, P = 0.80) did not differ by HCT strategy. Within 1 year of HIV diagnosis, half were LTFU: 50.5% under VCT/PITC and 49.6% under systematic HCT (P = 0.64). The overall hazard of LTFU was not affected by testing policy (aHR 0.98, 95%CI: 0.87-1.10). Independent of HCT strategy, males, younger adults and those ineligible for ART were at higher risk of LTFU.

Conclusions: Implementation of systematic HCT did not increase baseline CD4 count. Overall retention in the first year after HIV diagnosis was low (37.9%), especially among those ineligible for ART, but did not differ by testing strategy. Expansion of HIV testing should coincide with effective strategies to increase retention in care, especially among those not yet eligible for ART at initial diagnosis.

Abstract access 

Editor’s notes: Systematic, opt-out HIV counselling and testing of all individuals presenting to care facilities is recommended by World Health Organization in generalized HIV epidemics.

This study describes the results of a before and after study where the clinic switched from focussed, provider-initiated HIV testing to clinic-wide systematic HIV testing. The authors compare the number of people newly-diagnosed with HIV, their level of immunosuppression, and retention in care one year after HIV testing. They compared them to the focussed provider initiated HIV testing to systematic testing. Interestingly, they did not find any significant differences in these outcomes between the testing strategies. The switch to systematic HIV counselling and testing did not automatically increase HIV case finding nor identify cases at earlier stages of HIV disease. Loss to follow-up one year after HIV diagnosis was high (50%), but did not differ by testing strategy.

As the authors note, expansion of HIV testing strategies need to be combined with effective strategies to retain people in HIV care if the benefits of wider testing are to be fully realised.

South Africa
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Low CD4 counts among alcohol-dependent people on antiretroviral therapy – not due to poor adherence

Alcohol dependence and CD4 cell count: is there a relationship?

Malbergier A, Amaral RA, Cardoso LD. AIDS Care. 2014 Sep 1:1-5. [Epub ahead of print]

Alcohol and other drugs use seem to be common among people infected with HIV on antiretroviral treatment (ART). Their effects on HIV progression is still in debate. This study aimed to assess the association between alcohol and drug use and an HIV disease progression biomarker (CD4 cell count) among patients on ART. A cross-sectional study was carried out at an HIV treatment center affiliated with Medical School of the University of Sao Paulo, Brazil. Four hundred and thirty-eight HIV-positive patients on ART were interviewed by trained psychiatrists and psychologists using the following instruments: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Alcohol Use Disorders Identification Test (AUDIT), 17-item Hamilton Rating Scale for Depression, and the Simplified Medication Adherence Questionnaire (SMAQ). In the previous month, 219 (50%) and 41 (9.3%) patients reported use of alcohol and illicit drugs, respectively. Fifty patients (12.6%) were classified as having harmful alcohol use by AUDIT. According to SCID-I, 80 patients (18.3%) were alcohol abusers, 24 (5.5%) alcohol dependents, and 21 (4.2%) had a current depressive disorder. Almost 73% (n = 319-72.8%) of the patients were adherent to ART. Alcohol dependents were nine times (p < 0.01) more likely to have CD4 cell count ≤200/mm3, and this association was independent of ART adherence. In conclusion, alcohol dependence seems to be associated with low CD4 cell count in HIV-positive patients. Based on these data, HIV health care workers should always assess alcohol consumption in the treatment setting, and patients should be advised that alcohol dependence may be linked to low CD4.

Abstract access 

Editor’s notes: The prognosis for people living with HIV who initiate antiretroviral therapy (ART) depends not only on their adherence to ART, but also the presence of co-morbid health conditions. There is now increasing focus on the role mental health disorders have on HIV-related outcomes. In this study of 438 HIV positive people on ART in Brazil, nearly 20% of individuals were found to be abusing alcohol, and five percent were diagnosed as being alcohol dependent. The people who were alcohol dependent were nine times more likely to have CD4 count <200/mm3, an association which was independent of ART adherence, HIV viral load and illicit substance use. As the availability of mental health care in low- and middle-income countries continues to expand, people living with HIV will comprise a key population for these services. Future research must confirm whether the relationship between alcohol dependence and CD4 count persists over time, and how alcohol dependence services can be integrated with HIV care services.

Latin America
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Treatment of HIV-2, where is the evidence?

Antiretroviral therapy response among HIV-2 infected patients: a systematic review.

Ekouevi DK, Tchounga BK, Coffie PA, Tegbe J, Anderson AM, Gottlieb GS, Vitoria M, Dabis F, Eholie SP. BMC Infect Dis. 2014 Aug 26;14:461. doi: 10.1186/1471-2334-14-461.

Methods: Data were extracted from articles that were selected after screening of PubMed/MEDLINE up to November 2012 and abstracts of the 1996-2012 international conferences. Observational cohorts, clinical trials and program reports were eligible as long as they reported data on ART response (clinical, immunological or virological) among HIV-2 infected patients. The determinants investigated included patients' demographic characteristics, CD4 cell count at baseline and ART received.

Results: Seventeen reports (involving 976 HIV-2 only and 454 HIV1&2 dually reactive patients) were included in the final review, and the analysis presented in this report are related to HIV-2 infected patients only in 17 reports. There was no randomized controlled trial and only two cohorts had enrolled more than 100 HIV-2 only infected patients. The median CD4 count at ART initiation was 165 cells /mm3, [IQR; 137-201] and the median age at ART initiation was 44 years (IQR: 42-48 years). Ten studies included 103 patients treated with three nucleoside reverse transcriptase inhibitors (NRTI). Protease inhibitor (PI) based regimens were reported by 16 studies. Before 2009, the most frequent PIs used were Nelfinavir and Indinavir, whereas it was Lopinavir/ritonavir thereafter. The immunological response at month-12 was reported in six studies and the mean CD4 cell count increase was +118 cells /µL (min-max: 45-200 cells/µL).

Conclusion: Overall clinical and immuno-virologic outcomes in HIV-2 infected individuals treated with ART are suboptimal. There is a need of randomized controlled trials to improve the management and outcomes of people living with HIV-2 infection.

Abstract  Full-text [free] access

Editor’s notes: HIV-2 accounts for between 10-20% of HIV infections in West Africa. With a longer asymptomatic period, lower plasma viral load and slower decline in CD4 count, it is often seen as a less aggressive virus than HIV-1. However, people with HIV-2 still experience clinical progression and AIDS-related deaths. WHO recommends initiating a boosted protease inhibitor regimen or a triple nucleoside reverse transcriptase (NRTI)-based regimen in people living with HIV-2 when their CD4 count falls below 500 cells/mm3. However, as clearly demonstrated in this systematic review, the evidence underlying when to start antiretroviral therapy (ART) and the optimal treatment options for people living with HIV-2, is weak. Only 17 observational studies (15 cohort studies and two case series) were identified. Overall immune recovery was sub-optimal and, given the small sample sizes of these studies, there was limited power to detect any differences in outcomes by treatment regimen. Further evidence is urgently needed to guide optimal treatment of people living with HIV-2. 

Africa, Asia, Europe, Northern America
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Cotrimoxazole appears safe in pregnant women living with HIV, despite poor quality evidence

Safety of cotrimoxazole in pregnancy: a systematic review and meta-analysis.

Ford N, Shubber Z, Jao J, Abrams EJ, Frigati L, Mofenson L. J Acquir Immune Defic Syndr. 2014 Aug 15;66(5):512-21. doi: 10.1097/QAI.0000000000000211.

Introduction: Cotrimoxazole is widely prescribed to treat a range of infections, and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review to update the evidence of cotrimoxazole safety in pregnancy.

Methods: Three databases and 1 conference abstract site were searched in duplicate up to October 31, 2013, for studies reporting adverse maternal and infant outcomes among women receiving cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to April 28, 2014. Studies were included irrespective of HIV infection status or the presence of other coinfections. Our primary outcome was birth defects of any kind. Secondary outcomes included spontaneous abortions, terminations of pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity.

Results: Twenty-four studies were included for review. There were 232 infants with congenital anomalies among 4 196 women receiving cotrimoxazole during pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval: 1.8% to 5.1%; τ² = 0.03). Three studies reported 31 infants with neural tube defects associated with first trimester exposure to cotrimoxazole, giving a crude prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29 neural tube defects) coming from a single study. The majority of adverse drug reactions were mild. The quality of the evidence was very low.

Conclusions: The findings of this review support continued recommendations for cotrimoxazole as a priority intervention for HIV-infected pregnant women. It is critical to improve data collection on maternal and infant outcomes.

Abstract access 

Editor’s notes: Cotrimoxazole significantly reduces morbidity and increases survival in people living with HIV (including people on antiretroviral therapy) in resource-limited settings.  However, there is some concern of potential human foetal risk when cotrimoxazole is taken during pregnancy. This systematic review found very limited evaluable data on maternal and infant outcomes associated with cotrimoxazole exposure during pregnancy. Cotrimoxazole is likely to be of most benefit in high HIV burden, low-income settings. In this context, the known benefit of treatment outweighs the potential risk to the foetus, in HIV-positive pregnant women.  Importantly, this paper highlights the need for better pregnancy outcome surveillance in women living with HIV, in resource-poor settings, which includes evaluation of exposure to cotrimoxazole and antiretroviral treatment.  

Africa, Asia, Europe, Northern America, Oceania
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Delayed initiation of antiretroviral therapy among people living with HIV in stable partnerships

Delay of antiretroviral therapy initiation is common in east African HIV-infected individuals in serodiscordant partnerships.

Mujugira A, Celum C, Thomas KK, Farquhar C, Mugo N, Katabira E, Bukusi EA, Tumwesigye E, Baeten JM, Partners PrEP Study Team. J Acquir Immune Defic Syndr. 2014 Aug 1;66(4):436-42. doi: 10.1097/QAI.0000000000000192.

Objective: WHO guidance recommends antiretroviral therapy (ART) initiation for all persons with a known HIV-uninfected partner, as a strategy to prevent HIV transmission. Uptake of ART among HIV-infected partners in serodiscordant partnerships is not known, which we evaluated in African HIV serodiscordant couples.

Design: Prospective cohort study.

Methods: Among HIV-infected persons from Kenya and Uganda who had a known heterosexual HIV-uninfected partner, we assessed ART initiation in those who became ART eligible under national guidelines during follow-up. Participants received quarterly clinical and semi-annual CD4 monitoring, and active referral for ART upon becoming eligible.

Results: Of 1 958 HIV-infected ART-eligible partners, 58% were women, and the median age was 34 years. At the first visit when determined to be ART eligible, the median CD4 count was 273 cells per microliter (interquartile range, 221-330), 77% had WHO stage 1 or 2 HIV disease, and 96% were receiving trimethoprim-sulfamethoxazole prophylaxis. The cumulative probabilities of initiating ART at 6, 12, and 24 months after eligibility were 49.9%, 70.0%, and 87.6%, respectively. Younger age [<25 years; adjusted hazard ratio (AHR), 1.39; P = 0.001], higher CD4 count (AHR, 1.95; P < 0.001 for >350 compared with <200 cells/µL), higher education (AHR, 1.25; P < 0.001), and lack of income (AHR, 1.15; P = 0.02) were independent predictors for delay in ART initiation.

Conclusions: In the context of close CD4 monitoring, ART counseling, and active linkage to HIV care, a substantial proportion of HIV-infected persons with a known HIV-uninfected partner delayed ART initiation. Strategies to motivate ART initiation are needed, particularly for younger persons with higher CD4 counts.

 Abstract access 

Editor’s notes: WHO guidance recommends immediate antiretroviral therapy (ART) initiation, at any CD4 count, for people living with HIV in HIV serodiscordant partnerships. This is included in national HIV strategies in many countries. However, we do not yet know whether individuals will be willing to start ART at a time when they are still asymptomatic, knowing they will have to take the drugs for the rest of their lives. In this study of stable HIV-serodiscordant couples in the Partners PrEP trial, about three-quarters of participants initiated ART during follow-up.  Reasons for non-initiation included higher CD4 count, younger age, and lack of income. The implications of this study for initiating treatment at higher CD4 counts, especially in economically challenged contexts, are important. A better understanding of individuals’ reasons for delaying treatment initiation is needed, including strategies for support. With the move towards higher initiation CD4 thresholds, the success of programming treatment activities may rely heavily on thoroughly understanding the desires and motivations of people who are responsible for taking up treatment. 

Kenya, Uganda
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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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Task shifting for initiation and maintenance of antiretroviral therapy does not decrease quality of care

Task shifting from doctors to non-doctors for initiation and maintenance of antiretroviral therapy.

Kredo T, Adeniyi FB, Bateganya M, Pienaar E. Cochrane Database Syst Rev. 2014 Jul 1;7:CD007331. doi: 10.1002/14651858.CD007331.pub3.

Background: The high levels of healthcare worker shortage is recognised as a severe impediment to increasing peoples’ access to antiretroviral therapy. This is particularly of concern where the burden of disease is greatest and the access to trained doctors is limited. This review aims to better inform HIV care programmes that are currently underway, and those planned, by assessing if task-shifting care from doctors to non-doctors provides both high quality and safe care for all people requiring antiretroviral treatment.

Objectives: To evaluate the quality of initiation and maintenance of HIV/AIDS care in models that task shift care from doctors to non-doctors.

Search methods:  We conducted a comprehensive search to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress) from 1 January 1996 to 28 March 2014, with major HIV/AIDS conferences searched 23 May 2014. We had also contacted relevant organizations and researchers. Key words included MeSH terms and free-text terms relevant to 'task shifting', 'skill mix', 'integration of tasks', 'service delivery' and 'health services accessibility'.

Selection criteria: We included controlled trials (randomised or non-randomised), controlled-before and after studies, and cohort studies (prospective or retrospective) comparing doctor-led antiretroviral therapy delivery to delivery that included another cadre of health worker other than a doctor, for initiating treatment, continuing treatment, or both, in HIV infected patients.

Data collection and analysis: Two authors independently screened titles, abstracts and descriptor terms of the results of the electronic search and applied our eligibility criteria using a standardized eligibility form to full texts of potentially eligible or uncertain abstracts. Two reviewers independently extracted data on standardized data extraction forms. Where possible, data were pooled using random effects meta-analysis. We assessed evidence quality with GRADE methodology.

Main results: Ten studies met our inclusion criteria, all of which were conducted in Africa. Of these four were randomised controlled trials while the remaining six were cohort studies. From the trial data, when nurses initiated and provided follow-up HIV therapy, there was high quality evidence of no difference in death at one year, unadjusted risk ratio was 0.96 (95% CI 0.82 to 1.12), one trial, cluster adjusted n =     2 770. There was moderate quality evidence of lower rates of losses to follow-up at one year, relative risk of 0.73 (95% CI 0.55 to 0.97). From the cohort data, there was low quality evidence that there may be an increased risk of death in the task shifting group, relative risk 1.23 (95% CI 1.14 to 1.33, two cohorts, n = 39 160) and very low quality data reporting no difference in patients lost to follow-up between groups, relative risk 0.30 (95% CI 0.05 to 1.94). From the trial data, when doctors initiated therapy and nurses provided follow-up, there was moderate quality evidence that there is probably no difference in death compared with doctor-led care at one year, relative risk of 0.89 (95% CI 0.59 to 1.32), two trials, cluster adjusted n = 4 332. There was moderate quality evidence that there is probably no difference in the numbers of patients lost to follow-up at one year, relative risk 1.27 (95% CI 0.92 to 1.77), P = 0.15. From the cohort data, there is very low quality data that death at one year may be lower in the task shifting group, relative risk 0.19 (95% CI 0.05 to 0.78), one cohort, n =  2 772, and very low quality evidence that loss to follow-up was reduced, relative risk 0.34 (95% CI 0.18 to 0.66). From the trial data, for maintenance therapy delivered in the community there was moderate quality evidence that there is probably no difference in mortality when doctors deliver care in the hospital or specially trained field workers provide home-based maintenance care and antiretroviral therapy at one year, relative risk 1.0 (95% CI 0.62 to 1.62), 1 trial, cluster adjusted n = 559. There is moderate quality evidence from this trial that losses to follow-up are probably no different at one year, relative risk 0.52 (0.12 to 2.3), P = 0.39. The cohort studies did not report on one year follow-up for these outcomes. Across the studies that reported on virological and immunological outcomes, there was no clear evidence of difference whether a doctor or nurse or clinical officer delivered therapy. Three studies report on costs to patients, indicating a reduction in travel costs to treatment facilities where task shifting was occurring closer to patient’s homes. There is conflicting evidence regarding the relative cost to the health system, as implementation of the strategy may increase costs. The two studies reporting the patient and staff perceptions of the quality of care, report good acceptability of the service by patients, and general acceptance by doctors of the shifting of roles. One trial reported on the time to initiation of antiretroviral therapy, finding no clear evidence of a difference between groups. The same trial reports on new diagnosis of tuberculosis which favours nurse initiation of HIV care for increasing the numbers of diagnoses of tuberculosis made.

Authors' conclusions: Our review found moderate quality evidence that shifting responsibility from doctors to adequately trained and supported nurses or community health workers for managing HIV patients probably does not decrease the quality of care and, in the case of nurse initiated care, may decrease the numbers of patients lost to follow-up.

Abstract   Full-text [free] access 

Editor’s notes: A strategy of decentralisation of HIV care, combined with shifting of tasks from doctors to non-doctors and other cadres of health workers, has been key to improving access to therapy for people living with HIV in high prevalence settings.

This systematic review focuses on shifting HIV care from doctors to non-doctors (“task shifting” or “task sharing”). Task shifting raises concerns that the quality of care may be less good when delivered by less specialised staff. The authors compared quality of care (as measured by mortality rate at one year), loss to follow-up, laboratory parameters and costs among three types of health service models: 1) doctor versus nurse or clinical officer care for initiation and maintenance of antiretroviral therapy; 2) doctor versus nurse or clinical officer for maintenance of antiretroviral therapy; and 3) doctor versus community health workers for maintenance of antiretroviral therapy.

The authors found similar quality of care among the three types of health care models, and interestingly fewer numbers of people lost to follow-up in the model of nurse-initiated care.

This systematic review is a useful summary of the evidence base supporting task shifting from doctors to adequately trained and supported nurses and community health workers.

Health care delivery
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Falling death rates among people in HIV care: AIDS remains common, non-AIDS cancers need attention

Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration.

Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, Kowalska JD, de Wit S, Law M, el Sadr W, Kirk O, Friis-Moller N, Monforte A, Phillips AN, Sabin CA, Lundgren JD, D:A:D Study Group. Lancet. 2014 Jul 19;384(9939):241-8. doi: 10.1016/S0140-6736(14)60604-8.

Background: With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011.

Methods: Individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed up from March, 1999, until death, loss to follow-up, or Feb 1, 2011, whichever occurred first. The D:A:D study is a collaboration of 11 cohort studies following HIV-1-positive individuals receiving care at 212 clinics in Europe, USA, and Australia. All fatal events were centrally validated at the D:A:D coordinating centre using coding causes of death in HIV (CoDe) methodology. We calculated relative rates using Poisson regression.

Findings: 3 909 of the 49 731 D:A:D study participants died during the 308 719 person-years of follow-up (crude incidence mortality rate, 12.7 per 1 000 person-years [95% CI 12.3-13.1]). Leading underlying causes were: AIDS-related (1 123 [29%] deaths), non-AIDS-defining cancers (590 [15%] deaths), liver disease (515 [13%] deaths), and cardiovascular disease (436 [11%] deaths). Rates of all-cause death per 1 000 person-years decreased from 17.5 in 1999-2000 to 9.1 in 2009-11; we saw similar decreases in death rates per 1 000 person-years over the same period for AIDS-related deaths (5.9 to 2.0), deaths from liver disease (2.7 to 0.9), and cardiovascular disease deaths (1.8 to 0.9). However, non-AIDS cancers increased slightly from 1.6 per 1 000 person-years in 1999-2000 to 2.1 in 2009-11 (p=0.58). After adjustment for factors that changed over time, including CD4 cell count, we detected no decreases in AIDS-related death rates (relative rate for 2009-11 vs 1999-2000: 0.92 [0.70-1.22]). However, all-cause (0.72 [0.61-0.83]), liver disease (0.48 [0.32-0.74]), and cardiovascular disease (0.33 [0.20-0.53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 [34%] in 1999-2000 and 141/627 [22%] in 2009-11) and liver-related (40/256 [16%] in 1999-2000 and 64/627 [10%] in 2009-11) decreased over time, whereas non-AIDS cancers increased (24/256 [9%] in 1999-2000 to 142/627 [23%] in 2009-11).

Interpretation: Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement.

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Editor’s notes: Causes of death among people with HIV help to identify priorities for HIV care services. This very large cohort study, including nearly 50 000 HIV-positive people in industrialised country clinics, reports on changes in causes of death since 1999. Effective antiretroviral treatment was widely available for this cohort. All-cause mortality decreased over time, partly explained by effective antiretroviral therapy and increased CD4 cell counts. Death rates due to AIDS declined over time. However, even in 2009-11, AIDS remained a leading cause of death, suggesting that further efforts to diagnose and treat people with HIV earlier are required.

Deaths due to cardiovascular and liver-related causes decreased over time, even after adjustment for other potentially contributing factors. This suggests that people in this cohort were benefitting not only from good management of their HIV disease, but also from other preventive programmes for cardiovascular and other risk factors. By contrast, death rates due to non-AIDS-related cancers have not fallen, suggesting that more attention to prevention and early detection of common malignancies is needed.

Comorbidity, Epidemiology
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