Articles tagged as "15 million accessing treatment"

High levels of nonnucleoside reverse transcriptase inhibitor resistance in newly diagnosed children

Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis.

Kuhn L, Hunt G, Technau KG, Coovadia A, Ledwaba J, Pickerill S, Penazzato M, Bertagnolio S, Mellins CA, Black V, Morris L, Abrams EJ. AIDS. 2014 Apr 30. [Epub ahead of print]

Background: In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children.

Methods: HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy for pregnant women, were being implemented.

Results: Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had nonnucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures, but resistance to NNRTI was detected in 24.0%, NRTI in 10.7%, and protease inhibitor in 1.3%.

Conclusion: The new PMTCT strategies dramatically reduce the number of children who acquire infection, but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pretreatment drug resistance. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.

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Editor’s notes: This study describes HIV drug resistance mutations among newly-diagnosed, treatment-naive children younger than two years of age. HIV was diagnosed in 2011 through routine clinical services at five centres in Johannesburg, South Africa. Out of the 385 children identified with a median age of 19 weeks, some 230 went on to be successfully genotyped. Of these, two-thirds had a history of exposure to antiretroviral drugs (ART). Some 89% to maternal ART (combination ART n=28, mono/dual prophylaxis n=110) and some 97% to infant ART (mono/dual prophylaxis n=151). High levels of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) were found in both those ‘exposed’ and ‘non-exposed’ to ART, 57% and 24% respectively. The authors hypothesise that poor maternal recall and poor record keeping could explain why nearly one quarter of ‘non-exposed’ infants had NNRTI resistance. Given these findings the authors conclude that boosted protease inhibitor-based regimens should be used as first-line ART in all infants, regardless of history of exposure to ART. 

Africa
South Africa
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Resistance at first-line treatment failure in children

High-level cross-resistance to didanosine observed in South African children failing an abacavir- or stavudine-based 1st-line regimen.

Steegen K, Levin L, Ketseoglou I, Bronze M, Papathanasopoulos MA, Carmona S, Stevens W. AIDS. 2014 Apr 30. [Epub ahead of print]

Background: The knowledge-base of emerging drug resistance profiles in children exposed to abacavir-based antiretroviral regimens in South Africa is very limited. This study investigated the suitability of didanosine-based 2nd-line regimens for children in the context of antiretroviral drug resistance patterns emerging after 1st-line virologic failure.

Methods: A retrospective dataset of 354 antiretroviral drug resistant genotypes from children failing either abacavir (n = 81) or stavudine (n = 273) based 1st-line regimens, was analysed. Samples were sent to the HIV genotyping laboratory at Charlotte Maxeke Johannesburg Academic Hospital, for routine testing. Pol sequences were submitted to the Stanford HIV drug resistance database for genotypic predictions.

Results: Children were exposed to abacavir or stavudine-based 1st-line regimens for an average of 21 and 36 months, respectively. The frequency of reduced susceptibility to didanosine was substantial in the abacavir-exposed group (69.1%).This reduced susceptibility was commonly attributed to L74V/I (n = 44) and to a lesser extent K65R (n = 10) mutations. Didanosine resistance was observed in 43.2% of patients exposed to stavudine-based regimens. In contrast, most children remained susceptible to stavudine regardless of exposure to abacavir (77.8%) or stavudine (74.7%). At least 80% of children remained susceptible to zidovudine irrespective of stavudine or abacavir-exposure. The presence of the K65R mutation was more common after abacavir pressure (12.3% vs 1.8%).

Conclusion: Analysis revealed that didanosine-based 2nd-line regimens have limitations for South African children, given the high frequency of mutations that confer cross-resistance to didanosine; especially after abacavir-exposure. This data has influenced South African paediatric treatment guidelines, which now recommend zidovudine-based 2nd-line regimens.

Abstract access 

Editor’s notes: This study describes resistance profiles in children who had been referred by their clinician for resistance testing at the time of first-line treatment failure. There were no guidelines for resistance testing in South Africa at this time, therefore referrals were made at the clinicians’ discretion. Sequences on children younger than 15 years old who were on stavudine + lamivudine or abacavir + lamivudine at the time of failure were eligible for inclusion in this study. At the time of genotyping, 34/91(37%) of children failing an abacavir-based regimen and 71/279 (25%) on a stavudine-based regimen were taking a boosted protease inhibitor. Some 16 people with wild-type virus (n=16) were excluded from subsequent analyses. Out of 273 people failing a stavudine-based regimen and 81 failing an abacavir-based regimen, 43% and 69% respectively had evidence of didanosine resistance. The majority remained susceptible to stavudine and zidovudine. K65R, which confers resistance to tenofovir, was more prevalent in those failing an abacavir-based regimen as compared to a stavudine-based regimen (12% versus 2%). High levels of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) were found. In contrast, more than 60% of children with prior exposure to protease inhibitors (PI) had no evidence of PI resistance. These findings support the use of zidovudine- and PI-based second-line regimens in children following first-line treatment failure on abacavir- or stavudine-based regimens.

HIV Treatment
Africa
South Africa
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Fewer clinical events with early antiretroviral therapy in a trial among serodiscordant couples

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

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

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

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

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

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

Abstract access 

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

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

Comorbidity, HIV Treatment
Africa, Asia, Latin America
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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.

Europe
Spain
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Improving antiretroviral therapy adherence among people who inject drugs

Methadone maintenance therapy decreases the rate of antiretroviral therapy discontinuation among HIV-positive illicit drug users.

Reddon H, Milloy MJ, Simo A, Montaner J, Wood E, Kerr T. AIDS Behav. 2014 Apr;18(4):740-6. doi: 10.1007/s10461-013-0584-z.

We sought to examine whether methadone maintenance therapy (MMT) decreased rates of antiretroviral therapy (ART) discontinuation and was associated with plasma HIV RNA responses among a cohort of illicit drug users. Cumulative ART discontinuation rates were estimated using Kaplan-Meier methods and factors independently associated with ART discontinuation were identified using Cox proportional hazards regression. Engagement in MMT was negatively and independently associated with ART discontinuation [Adjusted Relative Hazard = 0.67 (95 % CI 0.54-0.83); p < 0.001]. Among participants receiving ART and MMT, 81.6 % of plasma HIV-1 RNA assessments were <500 copies/mL, while 65.81 % of HIV-1 RNA assessments among those prescribed ART without MMT were <500 copies/mL (p < 0.001). These results demonstrate that engagement in MMT conferred a protective benefit against ART discontinuation and was associated with a significant increase in plasma HIV RNA suppression among HIV-infected opioid-dependent drug users.

Abstract access 

Editor’s notes: This study examined the effect of methadone maintenance therapy (MMT) on rates of discontinuation of antiretroviral therapy (ART) among people who inject drugs (PWID) in Vancouver, Canada. Data are taken from an established cohort of PWID followed up between 1996 and 2008. Cox regression models are used to account for multiple observations among individuals to allow for discontinuation and restarting MMT across the study period increasing the sample size. Key confounders associated with both use of MMT and adherence to ART are adjusted for, including sex, age, homelessness, frequency of injection, cocaine use and sex work. One limitation of this study is the fairly simplified definition of MMT used, which was defined as any self-report of MMT treatment in the last six months which ranged from a single dose to 100% adherence. MMT is taken orally and is supervised. However, there was no information on the range of uptake of MMT is given, what proportion were 100% adherent and what proportion had a single dose. The findings demonstrate that any contact with the MMT programme has a positive association with the continuation of ART and increased HIV RNA suppression. This is an important finding since previous research has demonstrated that reducing community levels of viral load among populations of PWID is associated with decreased incidence of HIV irrespective of injecting and sexual risk behaviours. This paper usefully contributes to the discussions on the best way to deliver ART to PWID. It supports previous research that has demonstrated the role of MMT and combination approaches in preventing and treating HIV. Given the lack of MMT in some countries where HIV is high among PWID, this is important. A systematic review to assess the effect of methadone on ARV adherence is needed to examine this question further. 

Northern America
Canada
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Men at greater risk of not accessing antiretroviral treatment than women

Sex differentials in the uptake of antiretroviral treatment in Zambia.

Gari S, Martin-Hilber A, Malungo JR, Musheke M, Merten S. AIDS Care. 2014 Mar 25. [Epub ahead of print]

This study explores socio-structural factors that influence uptake of antiretroviral treatment (ART) in Zambia and assess differences between men and women. We conducted a case-control study nested in a community- and health facility-based survey, between September 2010 and February 2011. Cases were defined as HIV-positive individuals who, while eligible, never started ART and controls were HIV-positive individuals who were on ART. Cases and controls were matched by place of residence. We performed a conditional logistic regression analysis using a discrete logistic model stratified by sex. Overall, a significantly larger proportion of men (32.7%) than women (25.6%) did not uptake ART (Pearson chi2 = 5.9135; p = 0.015). In the crude analysis, poor health status and low self-efficacy were common factors associated with non-uptake in both sexes. After adjusting for covariates, men were more likely than women to refuse ART even though men's self-rated health was lower than women's. In general, the adjusted analysis suggests that HIV status disclosure affects uptake in both sexes but women's uptake of ART is largely hampered by poverty-related factors while for men, side effects and social pressure, probably associated with masculinity, are more important barriers. Alarmingly men's health seems to deteriorate until they start treatment, in contrast to women. Understanding gender differences in uptake and attitudes to ART is a crucial component to providing effective and appropriate health care to both men and women living with HIV/AIDS in Zambia.

Abstract access 

Editor’s notes: There have been observed differences in the uptake of antiretroviral therapy (ART) among men and women living with HIV, with men often at greater risk of not using ART than women. Previous research on this topic has suggested that this is due to the fact that women often have stronger links to community networks. Therefore, women have more information about the availability and accessibility of ART services. This study suggests that social and structural factors have different effects on men’s and women’s decisions to enrol in ART. The authors found that non-disclosure of HIV status was strongly associated with non-uptake of ART among both sexes.

Reasons for men not being on ART seemed to be related to ideas about masculinity while women were more likely to not enrol owing to financial factors. Women who participated in community activities and who were part of a cohesive network within their neighbourhoods, were at lower risk of not enrolling in ART than their counterparts. Conversely, men from discohesive neighbourhoods were at higher risk for non-uptake of ART. Anticipation of side effects and poor health status were associated with poor uptake among men. The authors suggest that this may be due to the fact that ill-health and spending time worrying about one’s health can be seen as signs of weakness among men. These findings are consistent with patterns of HIV treatment seeking behaviour as men usually tend to seek care when the disease is at a late stage, and when CD4 counts are particularly low.

The authors suggest that ART clinics and health centres are often seen as female spaces and so men might not feel comfortable accessing them. Strong social ties, especially in situations where poverty is persistent, appear to have a positive effect on uptake among women. On the other hand, this seems to have the opposite effect in men. This could be because of social pressures associated with masculinity. The authors conclude that HIV programming needs to reach out to men in order to avoid turning HIV into a ‘feminised epidemic’ and that programmes focusing on men need to be expanded. 

Africa
Zambia
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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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Adherence programmes for HIV pre-exposure prophylaxis

Helping our patients take HIV pre-exposure prophylaxis (PrEP): a systematic review of adherence interventions.

Marcus J, Buisker T, Horvath T, Amico K, Fuchs J, Buchbinder S, Grant R, Liu A. HIV Med. 2014 Feb 24. doi: 10.1111/hiv.12132. [Epub ahead of print]

Objectives: Adherence is critical for maximizing the effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV infection. Strategies for promoting adherence to HIV treatment, and their potential application to PrEP adherence, have received considerable attention. However, adherence promotion strategies for prevention medications have not been well characterized and may be more applicable to PrEP. We aimed to identify adherence support interventions that have been effective in other prevention fields and could be applied in the HIV prevention context to support pill taking among PrEP users.

Methods: To identify adherence support interventions that could be evaluated and applied in the PrEP context, we conducted a systematic review across the following prevention fields: hypertension, latent tuberculosis infection, hyperlipidaemia, oral contraceptives, osteoporosis, malaria prophylaxis, and post-exposure prophylaxis for HIV infection. We included randomized controlled trials that evaluated the efficacy of interventions to improve adherence to daily oral medications prescribed for primary prevention in healthy individuals or for secondary prevention in asymptomatic individuals.

Results: Our searches identified 585 studies, of which 48 studies met the eligibility criteria and were included in the review; nine evaluated multiple strategies, yielding 64 separately tested interventions. Interventions with the strongest evidence for improving adherence included complex, resource-intensive interventions, which combined multiple adherence support approaches, and low-cost, low-intensity interventions that provided education or telephone calls for adherence support.

Conclusions: Our review identified adherence interventions with strong evidence of efficacy across prevention fields and provides recommendations for evaluating these interventions in upcoming PrEP studies.

Abstract access 

Editor’s notes: Several trials have demonstrated the efficacy of pre-exposure prophylaxis (PrEP) with antiretroviral drugs in preventing HIV infection. These trials have also shown that adherence to drugs is a pre-requisite for PrEP to be effective. Research studies testing PrEP have used similar approaches to support adherence, as those used among individuals living with HIV. However, adherence support strategies in healthy and asymptomatic individuals may differ from those that are effective in symptomatic populations.  Therefore, this descriptive review evaluates activities to specifically support adherence to oral medications used for preventing, rather than treating, a wide variety of health conditions.

The authors evaluated sixty-four different types of adherence strategies delivered separately or combined. Overall, two-thirds of activities evaluated showed a statistically significant improvement in one or more adherence measure, sustained across the study follow-up period. Interestingly, home-based strategies to support adherence were more effective than strategies delivered in a clinic setting.  Activities that combined multiple approaches were the most effective. However, these are complex and may be challenging to implement outside an experimental context. Telephone call reminders and provision of education also improved adherence and are relatively low-cost. The duration of follow-up for the studies that evaluated these adherence approaches was approximately six months and the long-term effectiveness is not known. 

Individuals taking medication for primary or secondary prevention of clinical conditions may have similar perceptions of risk and comparable barriers and facilitators of adherence, as people taking PrEP. However, the review includes a diverse study population and may differ in other ways from the populations that will be using PrEP. Nevertheless, the review does highlight some promising approaches that could be used to support adherence to PrEP. Studies to evaluate these strategies are urgently needed as PrEP is scaled up. These strategies need to be low cost and translatable to the context in which they are used.   

Northern America
United States of America
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Retention on antiretroviral therapy with “Option B+”: the Malawi experience

Retention in care under universal antiretroviral therapy for HIV-infected pregnant and breastfeeding women ('Option B+') in Malawi.

Tenthani L, Haas AD, Tweya H, Jahn A, van Oosterhout JJ, Chimbwandira F, Chirwa Z, Ng'ambi W, Bakali A, Phiri S, Myer L, Valeri F, Zwahlen M, Wandeler G, Keiser O; Ministry of Health in Malawi and IeDEA Southern Africa. AIDS. 2014 Feb 20;28(4):589-98. doi: 10.1097/QAD.0000000000000143

Objective: To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') in Malawi.

Design, setting, and participants: We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21 939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11 534).

Results: Of the women who started ART under Option B+ (n = 21 939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/µl or less, to never return after their initial clinic visit [odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2-6.1]. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%.

Conclusion: Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.

 Abstract access 

 Editor’s notes: “Option B+” refers to the strategy of starting combination antiretroviral therapy (ART) for pregnant women who are HIV positive, and then continuing ART lifelong. This strategy has many advantages from a programmatic perspective, including maintaining the mother’s health and reducing the risk of transmission in future pregnancies and to HIV-negative partners. Implementation of option B+ has increased ART coverage among pregnant women in Malawi, an important positive outcome. However, the full benefits of this strategy will only be realised if women remain in care and sustain virologic suppression. These data on retention are therefore important for programme managers.

Some 17% of women who started antiretroviral therapy during pregnancy were lost to follow-up by six months. Women starting ART during pregnancy were almost five times more likely never to return after the first visit, compared to women starting ART for their own health (based on a CD4 count below 350 or WHO stage three or four). These women are of particular concern because their loss from programme likely reflects a missed opportunity to prevent HIV transmission to their children. Effective strategies to maximise retention in care need to be identified and implemented.

On a methodological note, in this analysis, loss to follow-up was defined as missing a visit by more than 60 days, whereas WHO recommends a cut-off of 90 days. This illustrates the need for ART programmes to report standardised outcomes in order to facilitate comparisons.  

Africa
Malawi
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Pervasive geographic and transportation-related barriers to HIV services use in sub-Saharan Africa

Impact of geographic and transportation-related barriers on HIV outcomes in sub-Saharan Africa: a systematic review.

Lankowski AJ, Siedner MJ, Bangsberg DR, Tsai AC. AIDS Behav. 2014 Feb 23. [Epub ahead of print]

Difficulty obtaining reliable transportation to clinic is frequently cited as a barrier to HIV care in sub-Saharan Africa (SSA). Numerous studies have sought to characterize the impact of geographic and transportation-related barriers on HIV outcomes in SSA, but to date there has been no systematic attempt to summarize these findings. In this systematic review, we summarized this body of literature. We searched for studies conducted in SSA examining the following outcomes in the HIV care continuum: (1) voluntary counseling and testing, (2) pre-antiretroviral therapy (ART) linkage to care, (3) loss to follow-up and mortality, and (4) ART adherence and/or viral suppression. We identified 34 studies containing 52 unique estimates of association between a geographic or transportation-related barrier and an HIV outcome. There was an inverse effect in 23 estimates (44 %), a null association in 26 (50 %), and a paradoxical beneficial impact in 3 (6 %). We conclude that geographic and transportation-related barriers are associated with poor outcomes across the continuum of HIV care.

Abstract

Editor’s notes: This systematic review focuses on the importance of structural barriers to uptake of HIV treatment and care. Specifically, these are the association between geographic and transportation-related barriers and poor outcomes among HIV positive persons. Most of the quantitative and qualitative evidence reviewed in this paper (from 66 studies in sub-Saharan Africa) support the authors’ hypothesis that geographic and transportation-related barriers contribute to poor outcomes in HIV-positive individuals at all points along the continuum of HIV care. These were indexed in terms of voluntary counselling and testing, pre- antiretroviral therapy linkage to care, loss to follow-up, and adherence and/or viral suppression. A lack of association between these barriers and HIV services use was more common in studies where the study had clear limitations. For example, the use of self-reported as opposed to objective measures of exposures, small sample sizes, and the lack of control for confounding variables. The study has important policy implications related to the decentralisation of HIV treatment and care services, point-of-care services delivery, the provision of transportation stipends, the simplification of management protocols, and the reduction in the frequency of follow up visits.

Africa
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