Articles tagged as "HIV testing and treatment"

What works to link people living with HIV to care - a review

Facilitators and barriers in HIV linkage to care interventions: a qualitative evidence review.

Tso LS, Best J, Beanland R, Doherty M, Lackey M, Ma Q, Hall BJ, Yang B, Tucker JD. AIDS. 2016 Apr 6. [Epub ahead of print]

Objective: To synthesize qualitative evidence on linkage to care interventions for people living with HIV.

Design: Systematic literature review.

Methods: We searched nineteen databases for studies reporting qualitative evidence on linkage interventions. Data extraction and thematic analysis were used to synthesize findings. Quality was assessed using the CASP tool and certainty of evidence was evaluated using the CERQual approach.

Results: Twenty-five studies from eleven countries focused on adults (24 studies), adolescents (8 studies), and pregnant women (4 Facilitators included community-level factors (i.e. task-shifting, mobile outreach, integrated HIV and primary services, supportive cessation programs for substance users, active referrals, and dedicated case management teams) and individual-level factors (encouragement of peers/family and positive interactions with healthcare providers in transitioning into care). One key barrier for people living with HIV was perceived inability of providers to ensure confidentiality as part of linkage to care interventions. Providers reported difficulties navigating procedures across disparate facilities and having limited resources for linkage to care interventions.

Conclusions: Our findings extend the literature by highlighting the importance of task-shifting, mobile outreach, and integrated HIV and primary services. Both community and individual level factors may increase the feasibility and acceptability of HIV linkage to care interventions. These findings may inform policies to increase the reach of HIV services available in communities.

Abstract access  

Editor’s notes: As the authors of this paper observe, most evaluations of linkage to care programmes have focused on quantitative assessment. This useful paper provides a thorough overview of the findings from 25 studies which used qualitative methods for assessment. Linkage-to- care programmes feasible in different country settings were identified in this review.  The authors also highlight gaps, most notably a lack of information on linkage-to-care programmes for men. They also note the need for longitudinal assessments that look at changes over time.

This paper is a useful synthesis of findings. But it is also an excellent example of how to carry out a systematic review of qualitative research. The description of the qualitative meta-synthesis the authors performed adds additional value to this paper. 

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What works to link people living with HIV to care - a review

Facilitators and barriers in HIV linkage to care interventions: a qualitative evidence review.

Tso LS, Best J, Beanland R, Doherty M, Lackey M, Ma Q, Hall BJ, Yang B, Tucker JD. AIDS. 2016 Apr 6. [Epub ahead of print]

Objective: To synthesize qualitative evidence on linkage to care interventions for people living with HIV.

Design: Systematic literature review.

Methods: We searched nineteen databases for studies reporting qualitative evidence on linkage interventions. Data extraction and thematic analysis were used to synthesize findings. Quality was assessed using the CASP tool and certainty of evidence was evaluated using the CERQual approach.

Results: Twenty-five studies from eleven countries focused on adults (24 studies), adolescents (8 studies), and pregnant women (4 Facilitators included community-level factors (i.e. task-shifting, mobile outreach, integrated HIV and primary services, supportive cessation programs for substance users, active referrals, and dedicated case management teams) and individual-level factors (encouragement of peers/family and positive interactions with healthcare providers in transitioning into care). One key barrier for people living with HIV was perceived inability of providers to ensure confidentiality as part of linkage to care interventions. Providers reported difficulties navigating procedures across disparate facilities and having limited resources for linkage to care interventions.

Conclusions: Our findings extend the literature by highlighting the importance of task-shifting, mobile outreach, and integrated HIV and primary services. Both community and individual level factors may increase the feasibility and acceptability of HIV linkage to care interventions. These findings may inform policies to increase the reach of HIV services available in communities.

Abstract access  

Editor’s notes: As the authors of this paper observe, most evaluations of linkage to care programmes have focused on quantitative assessment. This useful paper provides a thorough overview of the findings from 25 studies which used qualitative methods for assessment. Linkage-to- care programmes feasible in different country settings were identified in this review.  The authors also highlight gaps, most notably a lack of information on linkage-to-care programmes for men. They also note the need for longitudinal assessments that look at changes over time.

This paper is a useful synthesis of findings. But it is also an excellent example of how to carry out a systematic review of qualitative research. The description of the qualitative meta-synthesis the authors performed adds additional value to this paper. 

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Comparing the performance of different community-based measures of viral load as correlates for HIV incidence

Community viral load, antiretroviral therapy coverage, and HIV incidence in India: a cross-sectional, comparative study.

Solomon SS, Mehta SH, McFall AM, Srikrishnan AK, Saravanan S, Laeyendecker O, Balakrishnan P, Celentano DD, Solomon S, Lucas GM. Lancet HIV. 2016 Apr;3(4):e183-90. doi: 10.1016/S2352-3018(16)00019-9. Epub 2016 Mar 11.

Background: HIV incidence is the best measure of treatment-programme effectiveness, but its measurement is difficult and expensive. The concept of community viral load as a modifiable driver of new HIV infections has attracted substantial attention. We set out to compare several measures of community viral load and antiretroviral therapy (ART) coverage as correlates of HIV incidence in high-risk populations.

Methods: We analysed data from a sample of people who inject drugs and men who have sex with men, who were participants of the baseline assessment of a cluster-randomised trial in progress across 22 cities in India (ClinicalTrials.gov number NCT01686750). We recruited the study population by use of respondent-driven sampling and did the baseline assessment at 27 community-based sites (12 for men who have sex with men and 15 for people who inject drugs). We estimated HIV incidence with a multiassay algorithm and calculated five community-based measures of HIV control: mean log10 HIV RNA in participants with HIV in a community either engaged in care (in-care viral load), aware of their status but not necessarily in care (aware viral load), or all HIV-positive individuals whether they were aware, in care, or not (population viral load); participants with HIV in a community with HIV RNA more than 150 copies per mL (prevalence of viraemia); and the proportion of participants with HIV who self-reported ART use in the previous 30 days (population ART coverage). All participants were tested for HIV, with additional testing in HIV-positive individuals. We assessed correlations between the measures and HIV incidence with Spearman correlation coefficients and linear regression analysis.

Findings: Between Oct 1, 2012, and Dec 19, 2013, we recruited 26 503 participants, 12 022 men who have sex with men and 14 481 people who inject drugs. Median incidence of HIV was 0.87% (IQR 0.40-1.17) in men who have sex with men and 1.43% (0.60-4.00) in people who inject drugs. Prevalence of viraemia was more strongly correlated with HIV incidence (correlation 0.81, 95% CI 0.62-0.91; p<0.0001) than all other measures, although correlation was significant with aware viral load (0.59, 0.27-0.79; p=0.001), population viral load (0.51, 0.16-0.74; p=0.007), and population ART coverage (-0.54, -0.76 to -0.20; p=0.004). In-care viral load was not correlated with HIV incidence (0.29, -0.10 to 0.60; p=0.14). With regression analysis, we estimated that to reduce HIV incidence by 1 percentage point in a community, prevalence of viraemia would need to be reduced by 4.34%, and ART use in HIV-positive individuals would need to increase by 19.5%.

Interpretation: Prevalence of viraemia had the strongest correlation with HIV incidence in this sample and might be a useful measure of the effectiveness of a treatment programme.

Abstract access    

Editor’s notes: The ideal metric of impact for a programme looking at the prevention benefits of treatment would be the reduction in HIV incidence in the target population. Incidence is however very difficult to measure. ‘Community viral load’ has been proposed as an alternative. However its estimation using data collected either in a routine clinical setting or from a cohort study can suffer from bias, due to the population included not being representative of the wider population of people living with HIV.

This paper describes a study among gay men and other men who have sex with men and people who inject drugs carried out at 27 sites in India. Participants were recruited using respondent-driven sampling (in which respondents recruit their peers to produce a generally representative sample of hard-to-reach populations). At each site incidence was estimated using a multi-assay algorithm designed to identify seroconversion occurring approximately within the last six months. Five community-based measures of viral load were measured at each site. Of these, the prevalence of HIV viraemia (i.e. the proportion of the population with a viral load greater than 150 copies per mL), was most strongly associated with HIV incidence, while mean viral load among people in-care was not associated. This latter finding is important if a case-based surveillance approach using only data collected at clinics is to be used to estimate incidence. Population ART coverage, a measure of the proportion of the site participants on ART was also strongly correlated with incidence. As this can be measured through a simple questionnaire, rather than lab-based assays, it could be an easily and cheaply obtainable correlate for incidence, albeit one potentially prone to response bias.

Asia
India
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HIV genotyping to focus prevention efforts

Near real-time monitoring of HIV transmission hotspots from routine HIV genotyping: an implementation case study.

Poon AF, Gustafson R, Daly P, Zerr L, Demlow SE, Wong J, Woods CK, Hogg RS, Krajden M, Moore D, Kendall P, Montaner JS, Harrigan PR. Lancet HIV. 2016 May;3(5):e231-8. doi: 10.1016/S2352-3018(16)00046-1. Epub 2016 Apr 7.

Background: HIV evolves rapidly and therefore infections with similar genetic sequences are likely linked by recent transmission events. Clusters of related infections can represent subpopulations with high rates of transmission. We describe the implementation of an automated near real-time system to monitor and characterise HIV transmission hotspots in British Columbia, Canada.

Methods: In this implementation case study, we applied a monitoring system to the British Columbia drug treatment database, which holds more than 32 000 anonymised HIV genotypes for nearly 9000 residents of British Columbia living with HIV. On average, five to six new HIV genotypes are deposited in the database every day, which triggers an automated reanalysis of the entire database. We extracted clusters of five or more individuals with short phylogenetic distances between their respective HIV sequences. The system generated monthly reports of the growth and characteristics of clusters that were distributed to public health officers.

Findings: In June, 2014, the monitoring system detected the expansion of a cluster by 11 new cases during 3 months, including eight cases with transmitted drug resistance. This cluster generally comprised young men who have sex with men. The subsequent report precipitated an enhanced public health follow-up to ensure linkage to care and treatment initiation in the affected subpopulation. Of the nine cases associated with this follow-up, all had already been linked to care and five cases had started treatment. Subsequent to the follow-up, three additional cases started treatment and most cases achieved suppressed viral loads. During the next 12 months, we detected 12 new cases in this cluster with reduction in the onward transmission of drug resistance.

Interpretation: Our findings show the first application of an automated phylogenetic system monitoring a clinical database to detect a recent HIV outbreak and support the ensuing public health response. By making secondary use of routinely collected HIV genotypes, this approach is cost-effective, attains near real-time monitoring of new cases, and can be implemented in all settings in which HIV genotyping is the standard of care.

Abstract access

Editor’s notes: HIV genetic sequence data have been used retrospectively to characterise transmission patterns and association with risk factors. This is the first report of the use of such data in real-time to monitor transmission and inform a public health response.  Under current treatment guidelines in British Columbia, an HIV genotype test is routinely done on all individuals at the time of diagnosis.  The results are fed in to an automated monitoring system that can be used detect transmission ‘clusters’ and track their development. The case study demonstrates the value of this system in detecting an outbreak of transmitted drug resistance which was prioritised for public health programmes.  The authors acknowledge the ethical dilemmas associated with using HIV sequence data to inform public health actions. Accordingly, all individuals in the cluster were offered counselling, testing and treatment so as not to focus on any one person. One limitation of the monitoring system is that it relies on information from people who have presented for HIV testing, so people who are undiagnosed or not engaged with care are not represented. Although monitoring based on HIV sequence data is only possible in certain settings, it may provide a cost-effective tool for focused HIV prevention in situations where the data are already being collected as part of the standard care.

Northern America
Canada
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Profound effect of ART on mortality through reduction of opportunistic infections

Incidence of opportunistic infections and the impact of antiretroviral therapy among HIV-infected adults in low and middle income countries: a systematic review and meta-analysis. 

Low A, Gavriilidis G, Larke N, Lajoie MR, Drouin O, Stover J, Muhe L, Easterbrook P. Clin Infect Dis. 2016 Mar 6. pii: ciw125. [Epub ahead of print]

Background: To understand regional burdens and inform delivery of health services, we conducted a systematic review and meta-analysis to evaluate the effect of antiretroviral therapy (ART) on incidence of key opportunistic infections (OIs) in HIV-infected adults in low and middle-income countries (LMIC).

Methods: Eligible studies describing the cumulative incidence of OIs and proportion on ART from 1990 to November 2013 were identified using multiple databases. Summary incident risks for the ART-naive period, and during and after the first year of ART, were calculated using random effects meta-analyses. Summary estimates from ART subgroups were compared using meta-regression. The number of OI cases and associated costs averted if ART was initiated at CD4 ≥200 cells/µl was estimated using UNAIDS country estimates and global average OI treatment cost per case.

Results: We identified 7965 citations, and included 126 studies describing 491 608 HIV-infected persons. In ART-naive patients, summary risk was highest (>5%) for oral candidiasis, tuberculosis, herpes zoster, and bacterial pneumonia. The reduction in incidence was greatest for all OIs during the first 12 months of ART (range 57-91%) except for tuberculosis, and was largest for oral candidiasis, PCP and toxoplasmosis. Earlier ART was estimated to have averted 857 828 cases in 2013 (95% confidence interval [CI], 828 032-874 853), with cost savings of $46.7 million (95% CI, 43.8-49.4).

Conclusions: There was a major reduction in risk for most OIs with ART use in LMICs, with the greatest effect seen in the first year of treatment. ART has resulted in substantial cost savings from OIs averted.

Abstract  Full-text [free] access

Editor’s notes: Opportunistic infections (OIs) remain the major cause of HIV-associated mortality. OIs account for substantially higher mortality in low and middle income countries (LMICs) compared to high income countries (HICs).

This paper describes the results of a systematic review and meta-analysis including about 500 000 people on ART in LMICs across three regions (sub-Saharan Africa, Asia, and Latin America). These large numbers enabled the investigators to look at the effect of ART on the incidence of key OIs during and after the first year of treatment.

Not surprisingly they found that the effect of ART reduced the risk of all OIs during the first year after ART initiation, although the reduction was less for tuberculosis. The authors attribute this to the occurrence of tuberculosis across a wide range of CD4 cell counts, a smaller effect of early immune restoration and the contribution of TB as a manifestation of immune reconstitution syndrome during the first months after ART initiation. Beyond one year after ART initiation, the reduction in tuberculosis was greater.

They conclude that the effect of ART on the incidence of most HIV-associated OIs is the key reason for the global decline in HIV-associated mortality. However, a significant proportion of HIV-positive persons still continue to present with advanced disease. Besides timely ART initiation, additional measures such as CTX prophylaxis, screening for TB and cryptococcal disease, and the use of isoniazid and fluconazole prophylaxis should be considered for late presenters. 

Africa, Asia, Latin America
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A new drug for cryptococcal meningitis?

Efficacy of adjunctive sertraline for the treatment of HIV-associated cryptococcal meningitis: an open-label dose-ranging study.


Rhein J, Morawski BM, Hullsiek KH, Nabeta HW, Kiggundu R, Tugume L, Musubire A, Akampurira A, Smith KD, Alhadab A, Williams DA, Abassi M, Bahr NC, Velamakanni SS, Fisher J, Nielsen K, Meya DB, Boulware DR, Team A-CS. Lancet Infect Dis. 2016 Mar 9. pii: S1473-3099(16)00074-8. doi: 10.1016/S1473-3099(16)00074-8. [Epub ahead of print]

Background: Cryptococcus is the most common cause of adult meningitis in Africa. We assessed the safety and microbiological efficacy of adjunctive sertraline, previously shown to have in-vitro and in-vivo activity against cryptococcus.

Methods: In this open-label dose-finding study, we recruited HIV-infected individuals with cryptococcal meningitis who presented to Mulago Hospital in Kampala, Uganda between Aug 14, 2013, and Aug 30, 2014. To assess safety and tolerability, the first 60 participants were given sertraline at escalating doses of 100 mg/day, 200 mg/day, 300 mg/day, or 400 mg/day as induction therapy for 2 weeks, followed by consolidation therapy with 200 mg/day for an additional 8 weeks. From Nov 29, 2013, participants were randomly assigned (1:1) to receive open-label sertraline at predetermined doses of 200 mg/day, 300 mg/day, or 400 mg/day as induction therapy for 2 weeks, followed by consolidation therapy with 200 mg/day for 8 weeks. Dose assignment was made via computer-generated, permuted block randomisation stratified by antiretroviral therapy (ART) status for people with a first episode of meningitis. The primary outcome was 2-week cerebrospinal fluid (CSF) clearance rate of cryptococcus, termed early fungicidal activity, measured in patients with a first episode of culture-positive meningitis and two or more CSF cultures. This study is registered with ClinicalTrials.gov, number NCT01802385. 

Findings: Of the 330 individuals assessed, 172 HIV-infected adults with cryptococcal meningitis were enrolled. We gave 100 mg/day sertraline to 17 patients, 200 mg/day to 12 patients, 300 mg/day to 14 patients, and 400 mg/day to 17 patients. 112 participants were randomly assigned to receive sertraline at 200 mg (n=48), 300 mg (n=36), or 400 mg (n=28) daily for the first 2 weeks, and 200 mg/day thereafter. The final population consisted of 17 participants in the 100 mg group, 60 in the 200 mg group, 50 in the 300 mg group, and 45 in the 400 mg in group. Participants receiving any sertraline dose averaged a CSF clearance rate of -0.37 colony forming units per mL per day (95% CI -0.41 to -0.33). Incidence of paradoxical immune reconstitution inflammatory syndrome was 5% (two of 43 newly starting ART) and no cases of relapse occurred over the 12-week study period. 38 (22%) of 172 participants had died at 2 weeks, and 69 (40%) had died at 12 weeks. Six grade 4 adverse events occurred in 17 participants receiving 100 mg, 14 events in 60 participants receiving 200 mg, 19 events in 50 participants receiving 300 mg, and eight events in 45 participants receiving 400 mg. Grade 4 or 5 adverse event risk did not differ between current US Food and Drug Administration-approved dosing of 100-200 mg/day and higher doses of 300-400 mg/day (hazard ratio 1.27, 95% CI 0.69-2.32; p=0.45).

Interpretation: Participants receiving sertraline had faster cryptococcal CSF clearance and a lower incidence of immune reconstitution inflammatory syndrome and relapse than that reported in the past. This inexpensive and off-patent oral medication is a promising adjunctive antifungal therapy.

Editor’s notes: Mortality from cryptococcal meningitis remains unacceptably high, especially in low-income settings. This is partly due to high cost and limited availability of effective antifungal agents.  Even when antifungal drugs are available, toxic side effects and suboptimal clearance of cryptococcus from the cerebrospinal fluid (CSF) result in continued morbidity and mortality.  There is an urgent need for new effective antifungal drugs in the treatment of cryptococcal meningitis which improve the rate of CSF sterilisation, have low toxicity, and are readily available.

Sertraline, a commonly used selective serotonin reuptake inhibitor antidepressant with excellent brain parenchymal penetration, has been shown to have potent in vitro and in vivo fungicidal activity against cryptococcus in mice. This is the first clinical study in humans to assess the efficacy of adjunctive sertraline for cryptococcal meningitis, when added to standard amphotericin B and high-dose fluconazole antifungal treatment. Faster cryptococcal CSF clearance and lower incidence of immune reconstitution inflammatory syndrome and relapse were seen in people receiving oral sertraline compared to a historical cohort. Repurposing of sertraline, a drug which is widely available, non-toxic and affordable, as an effective novel adjunctive fungicidal agent shows early promise. It is yet to be seen if improved cryptococcal CSF clearance will translate into better survival.  We will have to wait until 2018 to see the outcome of the Adjunctive Sertraline for the Treatment of Cryptococcal Meningitis (ASTRO-CM) randomised clinical trial.

Comorbidity, HIV Treatment
Africa
Uganda
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Substantial drop in opportunistic infections in children with ART

Incidence and prevalence of opportunistic and other infections and the impact of antiretroviral therapy among HIV-infected children in low and middle-income countries: a systematic review and meta-analysis. 

B-Lajoie MR, Drouin O, Bartlett G, Nguyen Q, Low A, Gavriilidis G, Easterbrook P, Muhe L. Clin Infect Dis. 2016 Mar 21. pii: ciw139. [Epub ahead of print]

Background: We conducted a systematic review and meta-analysis to evaluate the incidence and prevalence of 14 opportunistic infections (OIs) and other infections as well as the impact of antiretroviral therapy (ART) among HIV-infected children (<18 years) in low and middle-income countries (LMIC), to understand regional burden of disease, and inform delivery of HIV services.

Methods: Eligible studies described the incidence of OIs and other infections in ART-naive and exposed children from January 1990 to November 2013, using Medline, Global Health, Embase, Cinahl, Web of Knowledge and Lilacs databases. Summary incident risk and prevalent risk for each OI in ART-naive and ART-exposed children were calculated, and unadjusted odds ratios calculated for impact of ART. The number of OI cases and associated costs averted were estimated using the AIM model.

Results: We identified 4542 citations, and 88 studies were included, comprising 55 679 HIV-infected children. Bacterial pneumonia and tuberculosis were the most common incident and prevalent infections in both ART-naive and ART-exposed children. There was a significant reduction in incident risk with ART for the majority of OIs. There was a smaller impact on bacterial sepsis and pneumonia, and an increase observed for varicella zoster. ART initiation based on 2010 WHO guidelines criteria for ART initiation in children was estimated to potentially avert more than 161 000 OIs (2013 UNAIDS data) with estimated cost savings of at least USD $17 million per year.

Conclusion: There is a substantial decrease in the risk of most OIs with ART use in HIV-infected children in LMIC, and estimated large potential cost savings in OIs averted with ART use, although there are greater limitations in paediatric data compared to adults.

Abstract  Full-text [free] access

Editor’s notes: The scale-up of programmes to prevent mother-to-child HIV transmission has resulted in a 60% decline in paediatric HIV infections. The scale-up of antiretroviral therapy (ART), however, has been less successful in children, with only a third of eligible children aged under 15 years receiving ART as of 2014. In high-income countries, there has been a substantial decrease in the incidence of most opportunistic infections (OIs) following the introduction of ART. The impact of ART on burden of OIs in low and middle income countries (LMICs) is much less well-understood.

This meta-analysis estimated the incidence and prevalence of 14 key OIs and other infections in children (aged 0-18 years) before and after the introduction of ART across three geographical regions, namely sub-Saharan Africa, Latin America and the Caribbean, and Asia.

The use of ART has resulted in a decline in incidence of all but three infections, namely tuberculosis, pneumonia and candidiasis. These remain the most common incident and prevalent infections in ART-naïve and ART-exposed children. It is important to note that there is a high incidence of lower respiratory infections in children in LMIC regardless of HIV status.

There is a paucity of well-described or large studies in children compared to in adults. There was significant heterogeneity in the studies included in the review, and few studies reported important confounding factors such as use of co-trimoxazole prophylaxis, age at ART initiation and CD4 count. Also, regional differences could not be examined due to a limited number of studies in Latin America and Asia.

Notwithstanding these limitations, ART has resulted in a substantial cost-saving due to the numbers of OIs averted by use of ART. The 2015 WHO guidelines now recommend ART initiation in all children and this is likely to have an even larger impact on the incidence of OIs and mortality. Along with this, strategies to reduce the burden of TB and pneumonia in children are urgently needed.

Comorbidity, HIV Treatment
Africa, Asia, Latin America
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Combining community-based HIV testing methods to achieve high testing coverage

A hybrid mobile approach for population-wide HIV testing in rural east Africa: an observational study. 

Chamie G, Clark TD, Kabami J, Kadede K, Ssemmondo E, Steinfeld R, Lavoy G, Kwarisiima D, Sang N, Jain V, Thirumurthy H, Liegler T, Balzer LB, Petersen ML, Cohen CR, Bukusi EA, Kamya MR, Havlir DV, Charlebois ED. Lancet HIV. 2016 Mar;3(3):e111-9. doi: 10.1016/S2352-3018(15)00251-9. Epub 2016 Jan 26.

Background: Despite large investments in HIV testing, only an estimated 45% of HIV-infected people in sub-Saharan Africa know their HIV status. Optimum methods for maximising population-level testing remain unknown. We sought to show the effectiveness of a hybrid mobile HIV testing approach at achieving population-wide testing coverage.

Methods: We enumerated adult (≥15 years) residents of 32 communities in Uganda (n=20) and Kenya (n=12) using a door-to-door census. Stable residence was defined as living in the community for at least 6 months in the past year. In each community, we did 2 week multiple-disease community health campaigns (CHCs) that included HIV testing, counselling, and referral to care if HIV infected; people who did not participate in the CHCs were approached for home-based testing (HBT) for 1-2 months within the 1-6 months after the CHC. We measured population HIV testing coverage and predictors of testing via HBT rather than CHC and non-testing.

Findings: From April 2, 2013, to June 8, 2014, 168 772 adult residents were enumerated in the door-to-door census. HIV testing was achieved in 131 307 (89%) of 146 906 adults with stable residence. 13 043 of 136 033 (9.6%, 95% CI 9.4-9.8) adults with and without stable residence had HIV; median CD4 count was 514 cells per µL (IQR 355-703). Among 131 307 adults with stable residence tested, 56 106 (43%) reported no previous testing. Among 13 043 HIV-infected adults, 4932 (38%) were unaware of their status. Among 105 170 CHC attendees with stable residence 104 635 (99%) accepted HIV testing. Of 131 307 adults with stable residence tested, 104 635 (80%; range 60-93% across communities) tested via CHCs. In multivariable analyses of adults with stable residence, predictors of non-testing included being male (risk ratio [RR] 1.52, 95% CI 1.48-1.56), single marital status (1.70, 1.66-1.75), age 30-39 years (1.58, 1.52-1.65 vs 15-19 years), residence in Kenya (1.46, 1.41-1.50), and migration out of the community for at least 1 month in the past year (1.60, 1.53-1.68). Compared with unemployed people, testing for HIV was more common among farmers (RR 0.73, 95% CI 0.67-0.79) and students (0.73, 0.69-0.77); and compared with people with no education, testing was more common in those with primary education (0.84, 0.80-0.89).

Interpretation: A hybrid, mobile approach of multiple-disease CHCs followed by HBT allowed for flexibility at the community and individual level to help reach testing coverage goals. Men and mobile populations remain challenges for universal testing.

Abstract access

Editor’s notes: Achieving high levels of HIV testing coverage remains a challenge in many parts of sub-Saharan Africa. Conventional facility-based HIV testing models are insufficient to achieve the UNAIDS 90-90-90 targets and maximise the prevention benefits of treatment. This study was able to achieve extremely high levels of HIV testing coverage in a short period of time by strategically combining two community-based testing approaches. By offering testing through multiple-disease community health campaigns (CHC), followed by focused home-based testing (HBT) for individuals who did not attend the CHCs, nearly 90% of adult stable residents accepted HIV testing. This near-universal coverage was achieved in all 32 communities (range 84%‒95%) across two countries, in a variety of settings with different rates of HIV prevalence and of previous testing. Testing uptake in the CHCs varied considerably across the communities (52%‒82%), demonstrating the value of this hybrid approach to expand coverage. Non-stable residents, who were 13% of the population, had low rates of testing uptake (22%). High rates of mobility remain a particular challenge for universal HIV testing coverage, and additional strategies are necessary to engage this group. A potential limitation of a focused approach to HBT is the need for community enumeration.  Still the results illustrate that achieving high HIV testing coverage is feasible with a combination of community-based approaches.

Africa
Kenya, Uganda
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Kenya will have to scale, scale, scale to meet 90-90-90 targets

Progress in reversing the HIV epidemic through intensified access to antiretroviral therapy: results from a nationally representative population-based survey in Kenya, 2012.

Kim AA, Mukui I, N'Gan'ga L, Katana A, Koros D, Wamicwe J, De Cock KM, KAIS Study Group. PLoS One. 2016 Mar 1;11(3):e0148068. doi: 10.1371/journal.pone.0148068. eCollection 2016.

Background: In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) called for 90% of people living with HIV (PLHIV) to know their status, 90% of these to be on antiretroviral therapy (ART), and 90% of these to be virally suppressed by 2020 (90-90-90). It is not clear whether planned ART scale-up in countries whose eligibility criteria for ART initiation are based on recommendations from the 2013 World Health Organization treatment guidelines will be sufficient to meet UNAIDS' new global targets.

Materials and methods: Using data from a nationally representative population-based household survey of persons in Kenya we compared coverage and unmet need associated with HIV diagnosis, ART, and viral suppression among PLHIV aged 15-64 years in 2012 based on criteria outlined in the 2014 national ART guidelines and UNAIDS' 90-90-90 goals. Estimates were weighted to account for sampling probability and nonresponse.

Results: Eight in ten PLHIV aged 15-64 years needed ART based on treatment eligibility. Need for treatment based on the national treatment policy was 97.4% of treatment need based on UNAIDS' 90-90-90 goals, requiring an excess of 24 000 PLHIV to access treatment beyond those eligible for ART to achieve UNAIDS' 90-90-90 treatment target. The gap in treatment coverage was high, ranging from 43.1% nationally to 52.3% in Nyanza among treatment-eligible PLHIV and 44.6% nationally to 52.4% in Nyanza among all PLHIV.

Conclusion: Maintaining the current pace of ART scale-up in Kenya will result in thousands of PLHIV unreached, many with high viral load and at-risk of transmitting infection to others. Careful strategies for reaching 90-90-90 will be instrumental in determining whether intensified access to treatment can be achieved to reach all who require ART.

Abstract  Full-text [free] access 

Editor’s notes: The HIV field is pushing for aggressive scale-up of programmes to stem the HIV epidemic. In this regard, UNAIDS launched the 90-90-90 targets to motivate countries to increase awareness, testing and treatment of people living with HIV. This paper presents an analysis of data collected through the last national Kenya AIDS Indicator Survey (KAIS) which examines the number of people reached with testing and treatment in 2012 as compared with the 90-90-90 targets which the country adopted in 2014. The analysis illustrates that the scale up of testing and treatment will need to dramatically increase to meet the targets. The paper notes the importance of strategizing how best to reach the populations most affected. In Kenya’s case, a geographic approach to scaling up in higher incidence areas is now being implemented. Within the geographical approach, strategies include testing family members of people living with HIV, and community-based testing strategies (such as home-based testing and counselling and self-testing), delivered in settings with high HIV prevalence. Analyses such as the one presented in this paper can help other countries in similar situations to review how best to apply limited resources in order to meet targets. 

Africa
Kenya
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Tenofovir resistance – need for caution but not panic

Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study.

TenoRes Study Group. Lancet Infect Dis. 2016 Jan 28. pii: S1473-3099(15)00536-8. doi: 10.1016/S1473-3099(15)00536-8. [Epub ahead of print]

Background: Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART.

Methods: The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene.

Findings: We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per µL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]).

Interpretation: We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial.

Abstract  Full-text [free] access 

Editor’s notes: Global surveillance for tenofovir (TDF) resistance is important at a time of expanding use of TDF-containing regimens for treatment and prevention. This collaborative analysis used data collated from several small studies in different settings. Overall, around one in three people who had failed on TDF-containing treatment had evidence of TDF resistance, although this frequency varied between 20% in Europe to almost 60% in Africa. Mutations associated with NNRTIs and lamivudine/emtricitabine resistance were more common overall and were present in most people with TDF resistance.

The regional variation probably reflects differences in clinical practice and study inclusion criteria. All European studies involved cohorts with frequent viral load monitoring, whereas half of the African cohorts had no routine viral load monitoring. All European studies included people with virologic failure but with low-level viraemia (viral load <1000 copies/ml) whereas almost all African studies included only people with viral load >1000 copies/ml.

While these data provide useful estimates of the frequency of drug resistance mutations in people with virologic failure on first-line ART, there should be caution about extrapolating beyond this. Reports from cohort studies with an accurate denominator of all people starting TDF-containing first-line ART would be useful to give more reliable estimates of overall incidence of acquired TDF resistance. Moreover, there remains a need for representative population-based surveillance for acquired and transmitted drug resistance. So far, global surveillance has detected limited evidence of transmitted TDF-associated mutations, but this needs to be monitored closely, especially in high incidence settings.

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