Articles tagged as "Spain"

Antiretroviral therapy decreases risk of clinically significant depression by about half

Risk of clinically significant depression in HIV-infected patients: effect of antiretroviral drugs.

Gutiérrez F, García L, Padilla S, Alvarez D, Moreno S, Navarro G, Gómez-Sirvent J, Vidal F, Asensi V, Masiá M; CoRIS. HIV Med. 2014 Apr;15(4):213-23. doi: 10.1111/hiv.12104. Epub 2013 Nov 11.

Objectives: We aimed to characterize depression in newly diagnosed HIV-infected patients, to determine the effect of antiretroviral therapy (ART) on its incidence, and to investigate whether efavirenz use was associated with a higher risk, compared with non-efavirenz-containing regimens, in the Spanish CoRIS cohort.

Methods: CoRIS is a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naive at entry, launched in 2004. Poisson regression models were used to investigate demographic, clinical and treatment-related factors associated with a higher incidence of clinically significant depression to October 2010.

Results: In total, 5 185 patients (13 089 person-years) participated in the study, of whom 3 379 (65.2%) started ART during follow-up. The incidence rates of depression before and after starting ART were 11.68 [95% confidence interval (CI) 9.01-15.15] and 7.06 (95% CI 5.45-9.13) cases per 1 000 person-years, respectively. After adjustment, there was an inverse association between the occurrence of depression and the initiation of ART [incidence rate ratio (IRR) 0.53; 95% CI 0.28-0.99], while the likelihood of depression increased in patients of age > 50 years (IRR 1.94; 95% CI 1.21-3.12). Longer exposure to ART was associated with a decreased IRR of depression in unadjusted and adjusted analyses. The IRR for patients receiving < 2, 2-4 and > 4 years of ART was 0.72 (95% CI 0.36-1.44), 0.10 (95% CI 0.04-0.25) and 0.05 (95% CI 0.01-0.17), respectively, compared with ART-naive patients. This protective effect was also observed when durations of exposure to nonnucleoside reverse transcriptase inhibitor-based regimens and efavirenz-containing regimens were analysed separately.

Conclusions: The incidence of clinically significant depression was lower among HIV-infected patients on ART. The protective effect of ART was also observed with efavirenz-containing regimens.

Abstract access 

Editor’s notes: There is a need to consider the mental health implications of initiating antiretroviral therapy (ART) particularly as people living with HIV are initiating treatment sooner and living longer. This is the first large-scale cohort study to examine the effect of ART on incidence of depression. The results are striking, with a 50% lower incidence of “clinically significant depression” among participants who had initiated ART, after adjusting for potential confounders. Clinically significant depression is defined as depression requiring drug therapy or suicide attempts. Older age and female sex were also associated with a higher risk of depression. This is consistent with existing literature. The association with ART was stronger among participants who were on treatment for longer periods of time, for both non-nucleoside reverse-transcriptase inhibitors (NNRTI) and efavirenz-containing regimens. There are several potential mechanisms by which ART may reduce incidence of depression, although the specific mechanism remains unclear.  Regardless, this data shows a clear additional benefit of early ART initiation.

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Overcoming logistical barriers to implementing viral load testing


Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis.

Smit PW, Sollis KA, Fiscus S, Ford N, Vitoria M, Essajee S, Barnett D, Cheng B, Crowe SM, Denny T, Landay A, Stevens W, Habiyambere V, Perriens JH, Peeling RW. PLoS One. 2014 Mar 6;9(3):e86461. doi: 10.1371/journal.pone.0086461. eCollection 2014.

Background: Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID.

Methods and findings: Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52-100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78-100% compared to plasma at VL below 1 000 copies/ml, but this increased to 100% at a threshold of 5 000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5 000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies.  

Conclusions: Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation.

Abstract    Full-text [free] access 

Editor’s notes: The World Health Organization recommends that viral load monitoring is used to confirm early infant diagnoses of HIV and to monitor people on antiretroviral therapy for treatment failure. However, viral load monitoring is expensive, technically complex and requires good laboratory infrastructure and highly trained staff. As a result few countries in resource-limited settings have been able to implement these guidelines.

This systematic review evaluates the performance of dried blood spots as compared to plasma for measuring viral load. Dried blood spots (DBS) are an alternative sampling strategy which could be used to overcome some of the logistical barriers to the widespread implementation of viral load testing. They can be performed by lay workers as there is no need for phlebotomy. Whole blood from a finger or heel prick is placed directly onto filter paper and once dried they can be stored with desiccant and transferred to the central laboratory at room temperature. The results of this systematic review confirm that DBS offer a highly sensitive and specific sampling strategy for early infant diagnosis and for detecting virologic failure at a viral load threshold of      >5 000 copies/ml. However, the authors’ stress that in order to compare different methodologies, standardised protocols for sampling, storing and processing samples are needed. DBS do provide a very promising strategy for increasing access to viral load monitoring. However if we are to see an impact on outcomes, the roll out of DBS will need to be accompanied by robust systems to ensure timely turn-around-times for results. Staff training and support to ensure that appropriate action is taken following a raised viral load, are also a must.

Africa, Asia, Europe
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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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Dolutegravir-based regimen superior to efavirenz-based regimen in treatment-naive patients

Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutiérrez F, Hocqueloux L, Maggiolo F, Sandkovsky U, Granier C, Pappa K, Wynne B, Min S, Nichols G; SINGLE Investigators.  N Engl J Med. 2013 Nov 7;369(19):1807-18. doi: 10.1056/NEJMoa1215541.

Background: Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen.

Methods: We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1 000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance.

Results: A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group.

Conclusions: Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine.

Abstract access 

Editor’s notes: In this 48- week double-blind randomized controlled trial in treatment-naive patients, dolutegravir plus abacavir / lamivudine outperformed efavirenz plus tenofovir / emtricitabine in terms of efficacy (viral suppression at 48 weeks and time to viral suppression), immunological recovery and discontinuation of therapy for adverse events. The difference in virologic response was largely due to higher levels of regimen discontinuation for adverse events in the efavirenz arm. The superior virologic response in the dolutegravir arm was consistent regardless of baseline viral load (above or below 100 000 copies/ml). 4% of patients in both arms developed virologic failure (two consecutive viral load measures >50 copies/ml). As expected, non-nucleoside reverse transcriptase inhibitors (NNRTI) mutations and K65R mutations emerged in patients failing the efavirenz-based regimen; however no mutations emerged amongst patients failing the dolutegravir-based regimen.

 Dolutegravir is clearly an attractive future treatment option: its long half-life supports once a day dosing; there are few relevant drug interactions; trials performed to date show that it is well tolerated; and a fixed drug combination tablet of dolutegravir, abacavir and lamivudine is currently being developed. However, until the cost is lowered we are unlikely to see widespread use of this drug.

Europe, Northern America, Oceania
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Explaining the life expectancy deficit of HIV positives in the era of ART

Do people with HIV infection have a normal life expectancy in the era of combination antiretroviral therapy?

Sabin CA. BMC Med. 2013 Nov 27;11(1):251.

There is evidence that the life expectancy (LE) of individuals infected with the human immunodeficiency virus (HIV) has increased since the introduction of combination antiretroviral therapy (cART). However, mortality rates in recent years in HIV-positive individuals appear to have remained higher than would be expected based on rates seen in the general population. A low CD4 count, whether due to late HIV diagnosis, late initiation of cART, or incomplete adherence to cART, remains the dominant predictor of LE, and thus the individual's disease stage at initiation of cART (or thereafter) certainly contributes to these higher mortality rates. However, individuals with HIV also tend to exhibit lifestyles and behaviors that place them at increased risk of mortality, particularly from non-AIDS causes. Thus, although mortality rates among the HIV population may indeed remain slightly higher than those seen in the general population, they may be no higher than those seen in a more appropriately matched control group. Thus, further improvements in LE may now only be possible if some of the other underlying issues (for example, modification of lifestyle or behavioral factors) are tackled.

Abstract  Full-text [free] access

Editor’s notes: The uptake of antiretroviral therapy (ART) has increased dramatically in recent years, and current ART regimens are more efficacious and more forgiving of minor lapses in adherence. As a result the life expectancy of people living with HIV is approaching that of the general population in both resource-rich and resource-poor settings. However, despite the dramatic improvements, life expectancy for people living with HIV is still lower than the general population. This review shows that late HIV diagnosis and ART initiation, and imperfect retention in care are repeatedly identified as barriers to the normalization of life expectancy in HIV positive individuals. In addition, the review highlights non-HIV related factors that put people living with HIV at a higher mortality risk than the general population. This includes behavioural and lifestyle factors such as smoking, alcohol and recreational drug use, and other sexually transmitted co-infections. This review underscores the importance of early diagnosis and linkage to care for improving programme effectiveness. It also has implications for the design of future studies aiming to quantify the life expectancy deficit in HIV positive individuals such as identifying appropriately matched HIV-negative control populations for comparative mortality estimates. 

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Intrauterine infections, but not obstetric complications, more common among pregnant women with HIV

HIV and the Risk of Direct Obstetric Complications: A Systematic Review and Meta-Analysis. 

Calvert C, Ronsmans C. PLoS One. 2013 Oct 4;8(10):e74848. doi:10.1371/journal.pone.0074848.

Background: Women of reproductive age in parts of sub-Saharan Africa are faced both with high levels of HIV and the threat of dying from the direct complications of pregnancy. Clinicians practicing in such settings have reported a high incidence of direct obstetric complications among HIV-infected women, but the evidence supporting this is unclear. The aim of this systematic review is to establish whether HIV-infected women are at increased risk of direct obstetric complications.

Methods and findings: Studies comparing the frequency of obstetric haemorrhage, hypertensive disorders of pregnancy, dystocia and intrauterine infections in HIV-infected and uninfected women were identified. Summary estimates of the odds ratio (OR) for the association between HIV and each obstetric complication were calculated through meta-analyses. In total, 44 studies were included providing 66 data sets; 17 on haemorrhage, 19 on hypertensive disorders, five on dystocia and 25 on intrauterine infections. Meta-analysis of the OR from studies including vaginal deliveries indicated that HIV-infected women had over three times the risk of a puerperal sepsis compared with HIV-uninfected women [pooled OR: 3.43, 95% confidence interval (CI): 2.00-5.85]; this figure increased to nearly six amongst studies only including women who delivered by caesarean (pooled OR: 5.81, 95% CI: 2.42-13.97). For other obstetric complications the evidence was weak and inconsistent.

Conclusions: The higher risk of intrauterine infections in HIV-infected pregnant and postpartum women may require targeted strategies involving the prophylactic use of antibiotics during labour. However, as the huge excess of pregnancy-related mortality in HIV-infected women is unlikely to be due to a higher risk of direct obstetric complications, reducing this mortality will require non obstetric interventions involving access to ART in both pregnant and non-pregnant women.

Abstract  Full-text [free] access

Editor’s notes: Women with HIV are thought to have a higher risk of adverse outcomes during pregnancy. This review is valuable in summarizing available data on this topic. Many of the included studies predated the wide availability of antiretroviral therapy. There was a clear association between HIV infection and intrauterine infections, but not with the other obstetric complications, e.g., obstetric haemorrhage, hypertensive disorders of pregnancy, dystocia, examined in the review. Considering individual conditions analysed, HIV infection was associated with antepartum haemorrhage, (but not postpartum haemorrhage). It was also found to be associated with pregnancy-induced hypertension (but not pre-eclampsia or eclampsia), and uterine rupture or prolonged labour (but not other complications of dystocia). The authors note that the studies were generally of low quality, and there were too few studies to examine the effect of antiretroviral therapy on these complications.  

Given the excess of intrauterine infections in women with HIV, the authors suggest that these might be preventable with prophylactic antibiotics. Overall, where causes of maternal mortality are documented, pregnant women with HIV are more likely to die of non-pregnancy related infections, than of obstetric complications. Specifically, non-pregnancy related infections are tuberculosis, pneumonia or meningitis. Pregnant women living with HIV need access to antenatal services and a skilled attendant at delivery. But, the top priority with respect to reducing maternal mortality is effective antiretroviral therapy.

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Missed opportunities for vaginal delivery among women with HIV in Europe

Missed opportunities among HIV-positive women to control viral replication during pregnancy and to have a vaginal delivery.

 Aebi-Popp K, Mulcahy F, Glass TR, Rudin C, Martinez de Tejada B, Bertisch B, Fehr J, Grawe C, Scheibner K, Rickenbach M, Hoesli I, Thorne C; for the European Collaborative Study in EuroCoord and the Swiss Mother & Child HIV Cohort Study., J Acquir Immune Defic Syndr. 2013 Jul 9. [Epub ahead of print]

Introduction:  Most national guidelines for the prevention of mother-to-child transmission of HIV in Europe updated between 2001 and 2010 recommend vaginal deliveries for women with undetectable or very low viral load (VL). Our aim was to explore the impact of these new guidelines on the rates of vaginal deliveries among HIV-positive women in Europe.

Methods: In a pooled analysis of data on HIV-positive pregnant women enrolled in the Swiss Mother & Child HIV Cohort Study and the European Collaborative Study 2000 to 2010, deliveries were classified as occurring pre-or post-publication of national guidelines recommending vaginal delivery.

Results: Overall, 2 663 women with 3 013 deliveries were included from 10 countries; 28% women were diagnosed with HIV during pregnancy. Combination antiretroviral therapy was used in most pregnancies (2 020, 73%), starting during the first or second trimester in 78% and during the third trimester in 22%; in 25% pregnancies, the woman conceived on combination antiretroviral therapy. Overall, in 86% pregnancies, a VL < 400 copies per milliliter was achieved before delivery. The proportion of vaginal deliveries increased from 17% (414/2 377) before the change in guidelines to 52% (313/600) after; elective Caesarean section rates decreased from 65% to 27%. The proportion of women with undetectable VL having a Caesarean section was 55% after implementation of new guidelines. We observed a decrease of late preterm deliveries from 16% (377/2 354) before to 7% (42/599) after the change in guidelines (P < 0.001).

Conclusion: There are still missed opportunities for women with HIV to fully suppress their VL and to deliver vaginally in Europe.

Abstract access

Editor’s notes: In 1999, following a randomised controlled trial showing a lower risk of vertical HIV transmission among babies delivered by elective Caesarean section, pregnant women with HIV were advised to deliver by elective Caesarean section where this option was available to them. In the last decade, accumulating observational data suggested that women taking combination ART with suppressed viral load who delivered vaginally were at very low risk of vertical transmission. This led to revised guidelines allowing vaginal delivery for women with suppressed viral load on combination ART.

This analysis of European data (with largest numbers contributed by Italy, Belgium and Switzerland) shows the increasing number of women having vaginal deliveries over the last decade. However, a substantial proportion of women had unsuppressed viral load at the time of delivery, and some received no ART prior to delivery, suggesting the need to engage pregnant women with HIV in care earlier.  In addition, the data suggest that more women who have suppressed viral load could safely undergo vaginal delivery.  The proportion of infants acquiring HIV infection in the period after introduction of guidelines allowing vaginal delivery was 0.6%, which is lower than 1.6% prior to the guideline change but suggests that further efforts are required to ensure that all children in Europe are born HIV-free.

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Better virological outcomes with efavirenz compared to nevirapine

Outcomes for efavirenz versus nevirapine-containing regimens for treatment of HIV-1 infection: a systematic review and meta-analysis.

Pillay P, Ford N, Shubber Z, Ferrand RA., PLoS One. 2013 Jul 22;8(7):e68995. doi: 10.1371/journal.pone.0068995. Print 2013

Introduction: There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART).

Methods: We systematically reviewed virological outcomes in HIV-1 infected, treatment-naive patients on regimens containing EFV versus NVP from randomised trials and observational cohort studies. Data sources include PubMed, Embase, the Cochrane Central Register of Controlled Trials and conference proceedings of the International AIDS Society, Conference on Retroviruses and Opportunistic Infections, between 1996 to May 2013. Relative risks (RR) and 95% confidence intervals were synthesized using random-effects meta-analysis. Heterogeneity was assessed using the I(2) statistic, and subgroup analyses performed to assess the potential influence of study design, duration of follow up, location, and tuberculosis treatment. Sensitivity analyses explored the potential influence of different dosages of NVP and different viral load thresholds.

Results: Of 5011 citations retrieved, 38 reports of studies comprising 114 391 patients were included for review. EFV was significantly less likely than NVP to lead to virologic failure in both trials (RR 0.85 [0.73-0.99] I(2) = 0%) and observational studies (RR 0.65 [0.59-0.71] I(2) = 54%). EFV was more likely to achieve virologic success than NVP, though marginally significant, in both randomised controlled trials (RR 1.04 [1.00-1.08] I(2) = 0%) and observational studies (RR 1.06 [1.00-1.12] I(2) = 68%).

Conclusion: EFV-based first line ART is significantly less likely to lead to virologic failure compared to NVP-based ART. This finding supports the use of EFV as the preferred NNRTI in first-line treatment regimen for HIV treatment, particularly in resource limited settings.

Abstract  Full-text [free] access

Editor’s notes: Efavirenz and nevirapine are key antiretroviral agents, particularly in resource-limited settings. Nevirapine has been widely used, for reasons including safety during pregnancy and lower cost, despite lower potency and a higher risk of hepatotoxicity and severe allergic reactions, than with efavirenz. This article summarizes data on virological outcomes from clinical trials and observational cohort studies comparing efavirenz and nevirapine. The finding that efavirenz is associated with slightly better virological outcomes is not surprising but it is valuable to have the available data summarised. The result, along with recent recommendations allowing efavirenz to be taken throughout pregnancy, and price reductions, supports the move towards efavirenz-based fixed drug combinations as first-line antiretroviral treatment in resource-limited settings.

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Systematic review of supervised and unsupervised self-testing for HIV

Supervised and Unsupervised Self-Testing for HIV in High- and Low-Risk Populations: A Systematic Review.

Pant Pai N, Sharma J, Shivkumar S, Pillay S, Vadnais C, Joseph L, Dheda K, Peeling RW. PLoS Med. 2013 Apr;10(4):e1001414.doi: 10.1371/journal.pmed.1001414. Epub 2013 Apr 2.

Background: Stigma, discrimination, lack of privacy, and long waiting times partly explain why six out of ten individuals living with HIV do not access facility-based testing. By circumventing these barriers, self-testing offers potential for more people to know their sero-status. Recent approval of an in-home HIV self test in the US has sparked self-testing initiatives, yet data on acceptability, feasibility, and linkages to care are limited. We systematically reviewed evidence on supervised (self-testing and counselling aided by a health care professional) and unsupervised (performed by self-tester with access to phone/internet counselling) self-testing strategies.

Methods and Findings: Seven databases (Medline [via PubMed], Biosis, PsycINFO, Cinahl, African Medicus, LILACS, and EMBASE) and conference abstracts of six major HIV/sexually transmitted infections conferences were searched from 1st January 2000-30th October 2012. 1,221 citations were identified and 21 studies included for review. Seven studies evaluated an unsupervised strategy and 14 evaluated a supervised strategy. For both strategies, data on acceptability (range: 74%-96%), preference (range: 61%-91%), and partner self-testing (range: 80%-97%) were high. A high specificity (range: 99.8%-100%) was observed for both strategies, while a lower sensitivity was reported in the unsupervised (range: 92.9%-100%; one study) versus supervised (range: 97.4%-97.9%; three studies) strategy. Regarding feasibility of linkage to counselling and care, 96% (n = 102/106) of individuals testing positive for HIV stated they would seek post-test counselling (unsupervised strategy, one study). No extreme adverse events were noted. The majority of data (n = 11,019/12,402 individuals, 89%) were from high-income settings and 71% (n = 15/21) of studies were cross-sectional in design, thus limiting our analysis.

Conclusions: Both supervised and unsupervised testing strategies were highly acceptable, preferred, and more likely to result in partner self-testing. However, no studies evaluated post-test linkage with counselling and treatment outcomes and reporting quality was poor. Thus, controlled trials of high quality from diverse settings are warranted to confirm and extend these findings.

Abstract  Full text [free] access

Editor’s notes: The HIV self-testing agenda is gaining prominence due to a number of changing issues: the US FDA approved an oral point-of-care HIV self-test (OraQuick) for over-the-counter sale last year; international policy no longer emphasises individualised, in-depth pre-test counselling; ART is increasingly available worldwide; and the goal of universal access to treatment (Millennium Development Goal 6). These issues have reduced many of the posited barriers to self-testing, but some remain, for example, the possible psychological trauma of a positive result without immediate post-test counselling and greater difficulties in ensuring linkage to appropriate care and treatment. In general, self-testing had high acceptability and accuracy. Only one study looked at intentions to link to care, with no studies reporting actual data on linkage to care. The preferred mode and medium of counselling varied between and within study populations, suggesting a need to tailor strategies. The current lack of high quality studies on self-testing suggests an urgent need for more research on this additional route for maximising HIV testing coverage.

Africa, Asia, Europe, Northern America
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Declining prevalence of HIV-1 drug resistance in ART-exposed individuals in Western Europe

Declining prevalence of HIV-1 drug resistance in antiretroviral treatment-exposed individuals in Western Europe.

De Luca A, Dunn D, Zazzi M, Camacho R, Torti C, Fanti I et al. J Infect Dis. 2013 Apr 15;207(8):1216-20. doi: 10.1093/infdis/jit017. Epub 2013 Jan 11.

HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis.

Abstract access

Editor’s notes: Acquired drug resistance to antiretroviral therapy emerges in the context of incomplete viral suppression and drug-pressure. This retrospective cohort comprised clinical data and genotypes, taken as part of routine clinical practice, on ART-experienced patients managed in treatment programmes in seven countries in Europe (1997-2008). The prevalence of drug resistance mutations declined over this time period (all drug classes). Based on cumulative genotypes, the prevalence of extensive resistance to three drug classes (NRTI, NNRTI and major PI) was rare (3.2% in 2008) and only 1% of patients in 2008 had exhausted all available drug options. As the authors comment in the discussion, resistance tests were not part of routine clinical practice in the early part of this cohort. Selection bias could therefore partly explain the decline in prevalence. However, this study demonstrates that given access to all available ART regimens, regular viral load monitoring and an early switch strategy for patients with virological failure, even in cohorts with extensive ART experience (>50% had prior exposure to mono- or dual-NRTI therapy) the risk of triple class resistance is low. 

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