Articles tagged as "treatment"

Understanding different levels and different models of integration

Editor’s notes: Integration between HIV services and programmes and other services and programmes sounds like common sense.  As people with HIV live longer they are more likely to develop other chronic conditions.  Some of these conditions may also be exacerbated by some anti-retroviral medicines, although modern treatment regimens have much less effect on lipid and insulin metabolism.  Low grade chronic inflammation may continue even in people whose HIV is suppressed and people whose CD4 count sunk to a low level before starting seem to be at greater risk of subsequent cardiovascular disease.  Then there are diseases that are more common among people living with HIV, such as tuberculosis and invasive cervical cancer.  And HIV programmes around the world have established some of the best clinical services for chronic care, with regular appointments, decentralized follow-up, algorithmic approaches to clinical changes and so on.  So it seems sensible to look for the synergies and build on them.

However, research on integration makes it clear that there are many different interpretations of what integration should or could mean.  In different epidemiological settings, the priorities will inevitably be very different.  Two useful systematic reviews this month by the same team, review this territory for cardiovascular diseases, diabetes and cervical cancer. 

Haldane et al. distinguish between the levels of integration.  Micro level integration involves direct patient care and adjusting diagnosis, treatment and support appropriately.  Meso level integration refers to changes made at the clinic or delivery system level, while macro level integration is about programme management, supply chains and systems organisation.  Despite a large literature (over 7600 papers) on the overlaps between HIV and cardiovascular diseases and diabetes, the authors found only 14 studies that allowed aspects of the integration to be assessed, and only one of these evaluated outcomes.  The others were descriptive studies which highlighted many innovative models, almost all at the meso-level.

Similarly for invasive cervical cancer, which is at least four times as common among women living with HIV as seronegative women, Sigfrid et al. found many papers but only 21 that met their inclusion criteria.  Their models of integration could all be said to be at the meso-level, with one stop shops; co-located services or more complex integrated pathways described.  Again, there were no good evaluations of the outcomes of these systematic changes to the way that services are delivered.  In most countries, all women with cervical cancer should at least be offered an HIV test and appropriate linkage to care expedited for those found to be seropositive.  Women living with HIV need regular screening for early cervical cancer and (as discussed last month) screening for human papillomavirus, the underlying cause of cervical cancer.  However, many ART clinics are now busy and crowded so that even if staff are trained, they do not have time or space or privacy to do cervical examinations.  HPV vaccination campaigns need to be carried out in schools before girls become sexually active.  This could be a good time to engage with sexuality education. However, many campaigns have tended to avoid the challenges of discussing sex with girls who are not yet sexually active, preferring to focus on the vaccine as a cancer prevention tool.  So, the lesson from both these papers is that we need to define more rigorously what we want to achieve with integration and then ensure that we evaluate whether or not our interventions achieve it.

Tuberculosis and HIV have been dancing together since the first descriptions of HIV in the 1980s.  The large majority of tuberculosis patients in many countries are now screened for HIV, with appropriate referral and increasing numbers of people living with HIV are screened regularly for the four classic symptoms of tuberculosis (weight loss, cough, night sweats and fever) and referred onwards for diagnosis.  Yet we still find that collaboration between programmes is not always easy. The number of people living with HIV who are also on tuberculosis treatment reported by the HIV programme may not be the same as the number of people on tuberculosis treatment who are also living with HIV reported by the tuberculosis programme.  Osei et al. report from the Volta Region of Ghana that more than 90% of tuberculosis patients had an HIV test recorded in the tuberculosis register, with an HIV prevalence of 18%.  As has been reported frequently elsewhere, the authors found that HIV was commoner in those with smear negative tuberculosis, and the outcome of treatment was less good.  Their recommendation for strengthening the collaboration between tuberculosis and HIV makes sense, although it has been WHO policy for many years.

The WHO guidance on collaborative TB/HIV activities has always included isoniazid preventive therapy.  However, this remains poorly implemented for reasons that are never very clear.  Despite no good evidence, many tuberculosis programme staff and clinicians worry about the risk of generating isoniazid resistant tuberculosis.  Many HIV programme staff feel that isoniazid remains in the realm of the tuberculosis programme, so that although they are happy to promote cotrimoxazole, they are much slower to prescribe isoniazid.  Many also feel that ART alone should be sufficient to prevent tuberculosis, despite randomized trials in high prevalence settings that demonstrate the additional benefits of isoniazid.  Shayo et al. make a strong economic argument for promoting isoniazid in their study in Tanzania.  They base their model on the rates of tuberculosis and mortality seen during the expansion of pilot programmes for isoniazid in Dar es Salaam.  Both tuberculosis and mortality were significantly lower in the clinics which were part of the pilot programme.  In fact, mortality was approximately tenfold lower, which seems unlikely to be simply due to isoniazid.  Some studies such as TEMPRANO have shown a mortality benefit from isoniazid, while many trials have failed to do so.  Given the non-randomized nature of the comparison, the authors do point out that their conclusions must be tentative.  Nonetheless, it is a convincing demonstration that isoniazid preventive therapy can be incorporated into a busy HIV care clinic and there is abundant evidence that this is the right thing to do.

One more tuberculosis study this month was carried out in Germany.  Karo et al. reviewed the immunology of the 139 people who developed tuberculosis among more than 10 000 people living with HIV in the German ClinSurv cohort.  The authors excluded people who already had tuberculosis at the time that HIV was diagnosed, and found that new diagnoses of tuberculosis were most common in the first couple of years after starting ART.  The authors also show that immune restoration was slower in people who developed tuberculosis.  There was still some deficit up to seven years after ART was started.  Again, their conclusion is that we should be using isoniazid to prevent tuberculosis in people living with HIV, especially people who have spent much of their lives in areas of the world, such as sub-Saharan Africa where tuberculosis is much more prevalent than in Europe.  It is often said that Mycobacterium tuberculosis is a very slow growing organism.  We must work harder to ensure that our response to it is not very slow too.  Tuberculosis remains the biggest killer of people with HIV in most of the world, yet for years we have known that a simple, cheap, non-toxic treatment can prevent it. 

 

Integrating cardiovascular diseases, hypertension, and diabetes with HIV services: a systematic review.

Haldane V, Legido-Quigley H, Chuah FLH, Sigfrid L, Murphy G, Ong SE, Cervero-Liceras F, Watt N, Balabanova D, Hogarth S, Maimaris W, Buse K, McKee M, Piot P, Perel P. AIDS Care. 2017 Jul 5:1-13. doi:10.1080/09540121.2017.1344350. [Epub ahead of print]

Non-communicable diseases (NCDs), including cardiovascular diseases (CVD), hypertension and diabetes together with HIV infection are among the major public health concerns worldwide. Health services for HIV and NCDs require health systems that provide for people's chronic care needs, which present an opportunity to coordinate efforts and create synergies between programs to benefit people living with HIV and/or AIDS and NCDs. This review included studies that reported service integration for HIV and/or AIDS with coronary heart diseases, chronic CVD, cerebrovascular diseases (stroke), hypertension or diabetes. We searched multiple databases from inception until October 2015. Articles were screened independently by two reviewers and assessed for risk of bias. 11 057 records were identified with 7 616 after duplicate removal. After screening titles and abstracts, 14 papers addressing 17 distinct interventions met the inclusion criteria. We categorized integration models by diseases (HIV with diabetes, HIV with hypertension and diabetes, HIV with CVD and finally HIV with hypertension and CVD and diabetes). Models also looked at integration from micro (patient focused integration) to macro (system level integrations). Most reported integration of hypertension and diabetes with HIV and AIDS services and described multidisciplinary collaboration, shared protocols, and incorporating screening activities into community campaigns. Integration took place exclusively at the meso-level, with no micro- or macro-level integrations described. Most were descriptive studies, with one cohort study reporting evaluative outcomes. Several innovative initiatives were identified and studies showed that CVD and HIV service integration is feasible. Integration should build on existing protocols and use the community as a locus for advocacy and health services, while promoting multidisciplinary teams, including greater involvement of pharmacists. There is a need for robust and well-designed studies at all levels - particularly macro-level studies, research looking at long-term outcomes of integration, and research in a more diverse range of countries.

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Integrating cervical cancer with HIV healthcare services: A systematic review.

Sigfrid L, Murphy G, Haldane V, Chuah FLH, Ong SE, Cervero-Liceras F, Watt N, Alvaro A, Otero-Garcia L, Balabanova D, Hogarth S, Maimaris W, Buse K, Mckee M, Piot P, Perel P, Legido-Quigley H. PLoS One. 2017 Jul 21;12(7):e0181156. doi: 10.1371/journal.pone.0181156. eCollection 2017.

Background: Cervical cancer is a major public health problem. Even though readily preventable, it is the fourth leading cause of death in women globally. Women living with HIV are at increased risk of invasive cervical cancer, highlighting the need for access to screening and treatment for this population. Integration of services has been proposed as an effective way of improving access to cervical cancer screening especially in areas of high HIV prevalence as well as lower resourced settings. This paper presents the results of a systematic review of programs integrating cervical cancer and HIV services globally, including feasibility, acceptability, clinical outcomes and facilitators for service delivery.

Methods: This is part of a larger systematic review on integration of services for HIV and non-communicable diseases. To be considered for inclusion studies had to report on programs to integrate cervical cancer and HIV services at the level of service delivery. We searched multiple databases including Global Health, Medline and Embase from inception until December 2015. Articles were screened independently by two reviewers for inclusion and data were extracted and assessed for risk of bias.

Main results: 11 057 records were identified initially. 7616 articles were screened by title and abstract for inclusion. A total of 21 papers reporting interventions integrating cervical cancer care and HIV services met the criteria for inclusion. All but one study described integration of cervical cancer screening services into existing HIV services. Most programs also offered treatment of minor lesions, a 'screen-and-treat' approach, with some also offering treatment of larger lesions within the same visit. Three distinct models of integration were identified. One model described integration within the same clinic through training of existing staff. Another model described integration through co-location of services, with the third model describing programs of integration through complex coordination across the care pathway. The studies suggested that integration of cervical cancer services with HIV services using all models was feasible and acceptable to patients. However, several barriers were reported, including high loss to follow up for further treatment, limited human-resources, and logistical and chain management support. Using visual screening methods can facilitate screening and treatment of minor to larger lesions in a single 'screen-and-treat' visit. Complex integration in a single-visit was shown to reduce loss to follow up. The use of existing health infrastructure and funding together with comprehensive staff training and supervision, community engagement and digital technology were some of the many other facilitators for integration reported across models.

Conclusions: This review shows that integration of cervical cancer screening and treatment with HIV services using different models of service delivery is feasible as well as acceptable to women living with HIV. However, the descriptive nature of most papers and lack of data on the effect on long-term outcomes for HIV or cervical cancer limits the inference on the effectiveness of the integrated programs. There is a need for strengthening of health systems across the care continuum and for high quality studies evaluating the effect of integration on HIV as well as on cervical cancer outcomes.

Abstract  Full-text [free] access 

 

The burden of HIV on tuberculosis patients in the Volta region of Ghana from 2012 to 2015: implication for tuberculosis control.

Osei E, Der J, Owusu R, Kofie P, Axame WK. BMC Infect Dis. 2017 Jul 19;17(1):504. doi: 10.1186/s12879-017-2598-z.

Background: The impact of HIV on TB, and the implications for TB control, has been acknowledged as a public health challenge. It is imperative therefore to assess the burden of HIV on TB patients as an indicator for monitoring the control efforts of the two diseases in this part of the world. This study aimed at determining the burden of HIV infection in TB patients.

Methods: We conducted a retrospective review of TB registers in five districts of the Volta Region of Ghana. Prevalence of TB/HIV co-infection was determined. Bivariate and multivariate logistic regression were used to identify the predictors of HIV infection among TB patients and statistical significance was set at p-value <0.05.

Results: Of the 1772 TB patients, 1633 (92.2%) were tested for HIV. The overall prevalence of TB/HIV co-infection was (18.2%; 95% CI: 16.4-20.1). The prevalence was significantly higher among females (24.1%; 95%CI: 20.8-27.7), compared to males (15.1%; 95% CI: 13.1-17.4) (p < 0.001) and among children <15 years of age (27.0%; 95% CI: 18.2-38.1), compared to the elderly ≥70 years (3.5%; 95% CI: 1.6-7.4) (p < 0.001). Treatment success rate was higher among patients with only TB (90%; 95% CI: 88.1-91.5) than among TB/HIV co-infected patients (77.0%; 95% CI: 71.7-81.7) (p < 0.001). Independent predictors of HIV infection were found to be: being female (AOR: 1.79; 95% CI: 1.38-2.13; p < 0.001); smear negative pulmonary TB (AOR: 1.84; 95% CI: 1.37-2.47; p < 0.001); and patients registered in Hohoe, Kadjebi, and Kpando districts with adjusted odds ratios of 1.69 (95% CI: 1.13-2.54; p = 0.011), 2.29 (95% CI: 1.46-3.57; p < 0.001), and 2.15 (95% CI: 1.44-3.21; p < 0.001) respectively. Patients ≥70 years of age and those registered in Keta Municipal were less likely to be HIV positive with odds ratios of 0.09 (95% CI: 0.04-0.26; p < 0.001) and 0.62 (95% CI: 0.38-0.99; p = 0.047) respectively.

Conclusion: TB/HIV co-infection rate in five study districts of the Volta region is quite high, occurs more frequently in female patients than males; among smear negative pulmonary TB patients, and children <15 years of age. Findings also demonstrate that HIV co-infection affects TB treatment outcomes adversely. Strengthening the TB/HIV collaborative efforts is required in order to reduce the burden of co-infection in patients.

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Cost-effectiveness of isoniazid preventive therapy among HIV-infected patients clinically screened for latent tuberculosis infection in Dar es Salaam, Tanzania: a prospective cohort study.

Shayo GA, Chitama D, Moshiro C, Aboud S, Bakari M, Mugusi F. BMC Public Health. 2017 Jul 19;18(1):35. doi: 10.1186/s12889-017-4597-9.

Background: One of the reasons why Isoniazid preventive therapy (IPT) for Tuberculosis (TB) is not widely used in low income countries is concerns on cost of excluding active TB. We analyzed the cost-effectiveness of IPT provision in Tanzania having ruled out active TB by a symptom-based screening tool.

Methods: Data on IPT cost-effectiveness was prospectively collected from an observational cohort study of 1283 HIV-infected patients on IPT and 1281 controls; followed up for 24 months. The time horizon for the analysis was 2 years. Number of TB cases prevented and deaths averted were used for effectiveness. A micro costing approach was used from a provider perspective. Cost was estimated on the basis of clinical records, market price or interviews with medical staff. We annualized the cost at a discount of 3%. A univariate sensitivity analysis was done. Results are presented in US$ at an average annual exchange rate for the year 2012 which was Tanzania shillings 1562.4 for 1 US $.

Results: The number of TB cases prevented was 420/100 000 persons receiving IPT. The number of deaths averted was 979/100 000 persons receiving IPT. Incremental cost due to IPT provision was US$ 170 490. The incremental cost-effective ratio was US $ 405.93 per TB case prevented and US $ 174.15 per death averted. These costs were less than 3 times the 768 US $ Gross Domestic Product (GDP) per capita for Tanzania in the year 2014, making IPT provision after ruling out active TB by the symptom-based screening tool cost-effective. The results were robust to changes in laboratory and radiological tests but not to changes in recurrent, personnel, medication and utility costs.

Conclusion: IPT should be given to HIV-infected patients who screen negative to symptom-based TB screening questionnaire. Its cost-effectiveness supports government policy to integrate IPT to HIV/AIDS care and treatment in the country, given the availability of budget and the capacity of health facilities.

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Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral therapy: implication for tuberculosis preventive therapy.

Karo B, Krause G, Castell S, Kollan C, Hamouda O, Haas W; ClinSurv HIV Study Group. BMC Infect Dis. 2017 Jul 25;17(1):517. doi: 10.1186/s12879-017-2627-y.

Background: Understanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-treated HIV-infected patients developing TB compared to those who remained free of TB.

Methods: We extracted data of HIV-infected patients from a multicenter cohort for the HIV clinical surveillance in Germany. No patients included in our study had TB at the beginning of the observation. Using a longitudinal mixed model, we assessed the differences in the mean change of biomarkers (CD4+ cell count, CD8+ cell count, CD4:CD8 ratio and viral load) since cART initiation in patients who remained free of TB vs. those developing TB. To detect the best-fit trajectories of the immunological biomarkers, we applied a multivariable fractional polynomials model.

Results: We analyzed a total of 10 671 HIV-infected patients including 139 patients who developed TB during follow-up. The highest TB incidences were observed during the first two years since cART initiation (0.32 and 0.50 per 100 person-years). In an adjusted multivariable mixed model, we found that the average change in CD4+ cell count recovery was significantly greater by 33 cells/μl in patients who remained free of TB compared with those developing TB. After the initial three months of cART, 65.6% of patients who remaining free of TB achieved CD4+ count of ≥400 cells/μl, while only 11.3% of patients developing TB reached this immunological status after the three months of cART. We found no differences in the average change of CD8+ cell count, CD4:CD8 ratio or viral load between the two-patient groups.

Conclusion: All HIV-infected patients responded to cART. However, patients developing TB showed reduced recovery in CD4+ cell count and this might partly explain the incident TB in HIV-infected patients receiving cART. These findings reinforce the importance of adjunctive TB preventive therapy for patients with reduced recovery in CD4+ cell count.

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Moving from facility to community-based models of HIV care - will it work?

Community-based interventions to improve and sustain antiretroviral therapy adherence, retention in HIV care and clinical outcomes in low- and middle-income countries for achieving the UNAIDS 90-90-90 targets.

Nachega JB, Adetokunboh O, Uthman OA, Knowlton AW, Altice FL, Schechter M, Galarraga O, Geng E, Peltzer K, Chang LW, Van Cutsem G, Jaffar SS, Ford N, Mellins CA, Remien RH, Mills EJ. Curr HIV/AIDS Rep. 2016 Oct;13(5):241-55. doi: 10.1007/s11904-016-0325-9.

Little is known about the effect of community versus health facility-based interventions to improve and sustain antiretroviral therapy (ART) adherence, virologic suppression, and retention in care among HIV-infected individuals in low- and middle-income countries (LMICs). We systematically searched four electronic databases for all available randomized controlled trials (RCTs) and comparative cohort studies in LMICs comparing community versus health facility-based interventions. Relative risks (RRs) for pre-defined adherence, treatment engagement (linkage and retention in care), and relevant clinical outcomes were pooled using random effect models. Eleven cohort studies and eleven RCTs (N = 97 657) were included. Meta-analysis of the included RCTs comparing community- versus health facility-based interventions found comparable outcomes in terms of ART adherence (RR = 1.02, 95 % CI 0.99 to 1.04), virologic suppression (RR = 1.00, 95 % CI 0.98 to 1.03), and all-cause mortality (RR = 0.93, 95 % CI 0.73 to 1.18). The result of pooled analysis from the RCTs (RR = 1.03, 95 % CI 1.01 to 1.06) and cohort studies (RR = 1.09, 95 % CI 1.03 to 1.15) found that participants assigned to community-based interventions had statistically significantly higher rates of treatment engagement. Two studies found community-based ART delivery model either cost-saving or cost-effective. Community- versus facility-based models of ART delivery resulted in at least comparable outcomes for clinically stable HIV-infected patients on treatment in LMICs and are likely to be cost-effective.

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Editor’s notes: The remarkable global scale-up of antiretroviral therapy (ART) programmes, while much-needed and impressive, has had inevitable consequences. These include overcrowding of health facilities, longer waiting times, reduced time for counselling and care of newly-enrolled people and restricted capacity to provide support for people who do not remain engaged with care. Furthermore, the UNAIDS 90-90-90 treatment target for 2020 to have 90% of people living with HIV know their HIV status, 90% of all diagnosed individuals receiving ART and 90% of people living with HIV on ART to be virally suppressed, will now require an additional 20 million people living with HIV to start treatment.

Community-based programmes to complement facility-based model of HIV care delivery are increasingly being recognised as an important and sustainable approach to address the growing numbers of people accessing care in high-HIV prevalence settings. This review compared outcomes of community-based versus facility-based models of ART delivery and treatment support. There was no statistical difference in optimal ART adherence, virologic suppression or all-cause mortality between participants assigned to community-based ART and facility-based ART in randomised controlled trials (RCTs). When data from RCTs and cohort studies were pooled, participants assigned to community-based ART appeared to have higher rates of retention in care at the end of the follow-up period. Notably, the few studies that did examine cost-effectiveness found community-based programmes to be cost-saving.

The findings demonstrate that community-level programmes are certainly not inferior to facility-based programmes. However, it is important to note some key limitations. Firstly, many of the studies are subject to selection bias, i.e. people at risk of poorer outcomes e.g. sicker people or people with a history of poor adherence may be excluded from receiving community-based programmes. The authors also highlight a high risk of “other forms of bias” in the cohort studies, but these are not specified. Secondly, adherence measures based on self-report may not be reliable. Thirdly, the review compared a heterogeneous set of programmes. Fourthly, as with other systematic reviews, publication bias is highly likely.   

Notwithstanding these limitations, this study suggests that community-based programmes have promise in supporting fragile and overcrowded facility-based healthcare systems in providing HIV care to a growing number of people. There may even be potential for integrating HIV care with care for other chronic conditions.

Well-designed studies are necessary, given the ambitious targets we have set ourselves, to explore the effectiveness and cost-effectiveness of community-based programmes. This is particularly important in under-represented groups with disproportionately poor outcomes such as children, adolescents and pregnant women. Further, for community-based programmes to be effective, it will be critical to ensure that adequate training and mentorship and ongoing monitoring for quality assurance is in place.      

Africa, Asia, Latin America
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Longitudinal HIV viral load measures give insights into disease burden and transmission risk in the USA

Durable viral suppression and transmission risk potential among persons with diagnosed HIV infection: United States, 2012-2013.

Crepaz N, Tang T, Marks G, Mugavero MJ, Espinoza L, Hall HI. Clin Infect Dis. 2016 Oct 1;63(7):976-83. doi: 10.1093/cid/ciw418. Epub 2016 Jun 29.

Background: We examined durable viral suppression, cumulative viral load (VL) burden, and transmission risk potential among human immunodeficiency virus (HIV)-diagnosed persons in care.

Methods: Using data from the National HIV Surveillance System from 17 jurisdictions with complete reporting of VL test results, we determined the percentage of persons in HIV care who achieved durable viral suppression (all VL results <200 copies/mL) and examined viremia copy-years and time spent above VL levels that increase the risk of HIV transmission during 2012-2013.

Results: Of 265 264 persons in HIV care in 2011, 238 641 had at least 2 VLs in 2012-2013. The median number of VLs per individual during the 2-year period was 5. Approximately 62% had durable viral suppression. The remaining 38% had high VL burden (geometric mean of viremia copy-years, 7261) and spent an average of 438 days, 316 days, and 215 days (60%, 43.2%, and 29.5% of the 2-year period) above 200, 1500, and 10 000 copies/mL. Women, blacks/African Americans, Hispanics/Latinos, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, and persons with gaps in care had higher viral burden and transmission risk potential.

Conclusions: Two-thirds of persons in HIV care had durable viral suppression during a 2-year period. One-third had high VL burden and spent substantial time above VL levels with increased risk of onward transmission. More intervention efforts are needed to improve retention in care and medication adherence so that more persons in HIV care achieve durable viral suppression.

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Editor’s notes: Virologic suppression is the ultimate goal of HIV care. It determines health outcomes and transmission risk. Most analyses assess viral suppression by considering a single viral load measure. However, adherence to antiretroviral therapy and engagement in HIV care are often not straightforward, but rather complex and dynamic. People living with HIV may transition in and out of treatment and care throughout their lifetime. Therefore, a single undetectable viral load may not equate to true virologic suppression in an individual, but rather only a snapshot. This has the potential for an inaccurate picture of HIV burden and transmission risk in a population.

Within this study, researchers used the longitudinal measures of durable viral suppression, viraemia copy years and time without viral load suppression to assess disease burden and HIV transmission risk in the United States of America. The analysis involved people ages 13 years or older diagnosed with HIV before 2011 and in care in one of 17 jurisdictions that reported complete CD4 and viral load data to the Centers for Disease Control and Prevention’s National HIV Surveillance System. Everyone had at least one viral load test in 2011 and at least two between 2012-2013, and all were alive at the end of 2013.

Of the 251 649 persons included, two thirds had durable viral suppression with all viral load values being <200 copies/mL over the two-year period. Of note, during the same time period an additional 20% (total 83%) of the cohort had a suppressed viral load on their latest test. This would have potentially underestimated disease burden if analysed in isolation. The remaining one-third, without durable viral suppression, had high plasma burden and spent substantial time without virologic suppression, increasing the risk of HIV transmission.  As would be expected, the percentages of persons with durable viral suppression were lower among people with gaps in care. Disparities in disease burden and transmission risk potential were seen in several other subgroups.

The use of longitudinal measures broadens insight into disease burden and transmission risk in this population. Of further interest would have been people that had no evidence of being in care in 2011 but had an unsuppressed viral load between 2012-13, thus contributing to the population disease burden. These people were unfortunately not included in the analyses but may increase overall population transmission risk over the two years.

The findings underscore the recognised need for focused care and treatment efforts to address these disparities in virologic suppression and improve retention in care in the United States of America. The study also encourages the use of longitudinal markers in informing public health planning and resource allocation.

Northern America
United States of America
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Community ART support groups: a partial solution for improving retention in care?

A decade of antiretroviral therapy scale-up in Mozambique: evaluation of outcome trends and new models of service delivery among more than 300 000 patients enrolled during 2004-2013.

Auld AF, Shiraishi RW, Couto A, Mbofana F, Colborn K, Alfredo C, Ellerbrock TV, Xavier C, Jobarteh K. J Acquir Immune Defic Syndr. 2016 Oct 1;73(2):e11-22. doi: 10.1097/QAI.0000000000001137.

Background: During 2004-2013 in Mozambique, 455 600 HIV-positive adults (≥15 years old) initiated antiretroviral therapy (ART). We evaluated trends in patient characteristics and outcomes during 2004-2013, outcomes of universal treatment for pregnant women (Option B+) implemented since 2013, and effect on outcomes of distributing ART to stable patients through Community ART Support Groups (CASG) since 2010.

Methods: Data for 306 335 adults starting ART during 2004-2013 at 170 ART facilities were analyzed. Mortality and loss to follow-up (LTFU) were estimated using competing risks models. Outcome determinants were estimated using proportional hazards models, including CASG participation as a time-varying covariate.

Results: Compared with ART enrollees in 2004, enrollees in 2013 were more commonly female (55% vs. 73%), more commonly pregnant if female (<1% vs. 30%), and had a higher median baseline CD4 count (139 vs. 235/µL). During 2004-2013, observed 6-month mortality declined from 7% to 2% but LTFU increased from 24% to 30%. Pregnant women starting ART with CD4 count >350/µL and WHO stage I/II under Option B+ guidelines in 2013 had low 6-month mortality (0.1%) but high 6-month LTFU (38%). During 2010-2013, 6766 patients joined CASGs. In multivariable analysis, compared with nonparticipation in CASG, CASG participation was associated with 35% lower LTFU but similar mortality.

Conclusions: Initiation of ART at earlier disease stages in later calendar years might explain observed declines in mortality. Retention interventions are needed to address trends of increasing LTFU overall and the high LTFU among Option B+ pregnant women specifically. Further expansion of CASG could help reduce LTFU.

Abstract access  

Editor’s notes: The UNAIDS 90–90–90 treatment target for 2020 calls for 90% of all people with HIV to be diagnosed, 90% of people with HIV diagnosed to receive ART and 90% of people on ART to have a suppressed viral load. To maximise the impact of ART, people living with HIV should be diagnosed early, initiated on ART and retained in ART care.  Engagement along the complete treatment cascade will determine the long-term success of the global response to HIV. 

This manuscript describes the trends in patient characteristics and outcomes over the first decade of scale-up of ART in Mozambique (2004-2013). During this period close to half a million people living with HIV were initiated on ART; six-month mortality declined from 7% to 2% but six-month loss to follow-up (LTFU) increased from 24% to 30%. The authors found that later calendar year of ART was associated with higher risk of LTFU; an increase in “silent” transfers (undocumented transfer between health facilities) might have contributed to this. There was an increasing female-to-male ratio over calendar period during the study, most likely due to scale-up of HIV testing during antenatal care and (since 2013) implementation of Option B+ (initiation of lifelong ART for all pregnant women). The authors conclude that increased enrolment among men is necessary to reduce the disproportionally high HIV-associated morbidity and mortality among men.  

Interestingly, this is the first study to report on nationwide outcomes of community ART support groups (CASG), and to quantify the effect of CASG on LTFU. Consistent with the recent systematic review by Nachega and colleagues (included in this issue of HIV This Month), the authors found no difference in mortality between patients who received their ART through CASG and patients who received their ART from facilities. Also consistent with this systematic review, CASG participation was associated with 35% lower LTFU rates. The authors therefore suggest ART distribution through CASG as a potential partial solution. Possible reasons for lower LTFU rates among CASG participants include reduced patient transport cost, reduced patient time at the clinic, increased patient accountability, and improved social support. However, the authors acknowledged that people agreeing to join a CASG might be people who would in any event be retained in care. CASG participants were more commonly unemployed and uneducated than non-participants, which might indicate that CASG participation is more attractive for patients with fewer financial resources.  

Men were less likely to participate in CASGs, emphasizing again the need for male-specific programmes. The authors advocate for further research, and suggest offering male-only CASG as a possible way to improve male participation in CASG.

Africa
Mozambique
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Social constraints on women’s access to HIV treatment cannot be ignored

'Lost to follow up': rethinking delayed and interrupted HIV treatment among married Swazi women.

Dlamini-Simelane TT, Moyer E. Health Policy Plan. 2016 Oct 13. pii: czw117. [Epub ahead of print]

Through various campaigns and strategies, more women are being tested for HIV in countries with a high prevalence of the virus. Despite the ready availability of treatment at government clinics in sub-Saharan African countries like Swaziland, women consistently report difficulty in maintaining access to treatment. Drawing on two individual case studies selected from a larger study of the so-called leaky cascade in Swaziland, we illustrate the protracted journeys married women undertake to initiate treatment. We demonstrate how women manoeuvre tactically after diagnosis, highlight factors that influence their decisions related to initiating treatment, and detail the actors involved in the decision-making process. Our research shows the persistence of structural factors that inhibit access, including economic constraints, gender inequality and patriarchal social norms. Patients referred as 'lost to follow up' are in many cases actively pursuing treatment within a context that includes the biomedical health system, but also extends well beyond it. We argue that the phrase 'lost to follow up' conceals the complex social navigation required by women to initiate and maintain access to treatment. Further, we suggest that many of the logistical challenges of monitoring and tracking people with HIV can be better addressed by taking into account the structural and social aspects of delayed treatment initiative.

Abstract access 

Editor’s notes: With new global guidelines for the treatment of HIV, in Swaziland, as elsewhere, there has been a focus on increasing access to point-of-care diagnostics. This paper uses case studies to examine the complex social and logistical factors that contribute to HIV-positive women ‘falling out’ of HIV treatment healthcare in Swaziland.  These losses are despite an enhanced logistical system. In particular, the authors argue that terms such as ‘treatment defaulters’ or ‘lost to follow up’ only define patients from the perspective of the healthcare system. Such terms, they suggest, hide the social and economic challenges that women living with HIV face in trying to start treatment. These challenges include family power structures, lack of autonomy, gender norms, and constraints on married women to access treatment.

The authors reveal that women’s decision making around initiating treatment in Swaziland involves navigating multiple social terrains. They demonstrate that when a married woman has been diagnosed with HIV in Swaziland, she is often not free to initiate treatment. Nor can she decide on her own to visit the clinic, especially if doing so requires money. Further to this they demonstrate that women’s ability to seek treatment is impacted by gender and generational power relations. Treatment access may also be affected by preserving the family honour. The husband, mother in-law and wider kinship network can constitute a ‘therapy management group’ and either accompany women to treatment or influence the routes taken. Where concerns arise for how a woman might be perceived or rejected by this group, women are at times compelled to conceal their HIV status. This might be deemed necessary to avoid dishonour for her birth family, thus ‘the therapy management group’ goes beyond providing advice and information. The group also prescribes the route a woman should follow as a good wife or daughter-in-law. The authors suggest that that labelling women who are actively seeking ways to access care as ‘lost to follow up’ ‘or ‘treatment defaulters’ obscures these challenges.

The authors conclude that married women’s decision making around HIV treatment in Swaziland is contingent upon social and economic circumstances.  Being diagnosed with HIV is not sufficient motivation to take up treatment. They argue that, in the light of this, programme implementers should focus on building women’s capacity to navigate the social constraints. This could include providing expert counsellors in each clinic to support such issues.

HIV Treatment, treatment
Africa
Swaziland
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Evaluating strategies to improve HIV care outcomes

Evaluating strategies to improve HIV care outcomes in Kenya: a modelling study.

Olney JJ, Braitstein P, Eaton JW, Sang E, Nyambura M, Kimaiyo S, McRobie E, Hogan JW, Hallett TB. Lancet HIV. 2016 Dec;3(12):e592-e600. pii: S2352-3018(16)30120-5. doi: 10.1016/S2352-3018(16)30120-5. Epub 2016 Oct 19.

Background: With expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health.

Methods: We created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya. We calibrated the model to a longitudinal dataset from the Academic Model Providing Access To Healthcare (known as AMPATH) programme describing the routes into care, losses from care, and clinical outcomes. We simulated the cost and effect of interventions at different stages of HIV care, including improvements to diagnosis, linkage to care, retention and adherence of ART, immediate ART eligibility, and a universal test-and-treat strategy.

Findings: We estimate that, of people dying from AIDS between 2010 and 2030, most will have initiated treatment (61%), but many will never have been diagnosed (25%) or will have been diagnosed but never started ART (14%). Many interventions targeting a single stage of the health-care cascade were likely to be cost-effective, but any individual intervention averted only a small percentage of deaths because the effect is attenuated by other weaknesses in care. However, a combination of five interventions (including improved linkage, point-of-care CD4 testing, voluntary counselling and testing with point-of-care CD4, and outreach to improve retention in pre-ART care and on-ART) would have a much larger impact, averting 1.10 million disability-adjusted life-years (DALYs) and 25% of expected new infections and would probably be cost-effective (US$571 per DALY averted). This strategy would improve health more efficiently than a universal test-and-treat intervention if there were no accompanying improvements to care ($1760 per DALY averted).

Interpretation: When resources are limited, combinations of interventions to improve care should be prioritised over high-cost strategies such as universal test-and-treat strategy, especially if this is not accompanied by improvements to the care cascade. International guidance on ART should reflect alternative routes to programme strengthening and encourage country programmes to evaluate the costs and population-health impact in addition to the clinical benefits of immediate initiation.

Abstract  Full-text (free) access

Editor’s notes: Antiretroviral therapy has substantially reduced HIV-associated morbidity and mortality. However, maintaining a strong care cascade is challenging. A mathematical model for HIV transmission and care cascade was used to quantify the previous experience of people dying from HIV in a setting with an established antiretroviral therapy programme. The model was also used to simulate the cost and effect of HIV care programmes. The model was parameterised with data from HIV care programme in western Kenya supported by the Academic Model Providing Access To Healthcare. The model was analysed to assess: the impact of individual HIV programmes on the care cascade and the effect on outcomes of people living with HIV. These were compared with the baseline scenario without any programme. Disability-adjusted life-years (DALYs) averted, cost of care and HIV-associated deaths were used to quantify the effects of the programmes. The authors found that, strengthening each part of the care cascade through a combination of programmes could cost-effectively improve ART programmes. This is a very interesting study which suggest the need to prioritise HIV programmes to improve care in ART programmes over high-cost strategies.

Africa
Kenya
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Health care navigators do not improve early outcomes on ART in South Africa

Sizanani: a randomized trial of health system navigators to improve linkage to HIV and TB care in South Africa.

Bassett IV, Coleman SM, Giddy J, Bogart LM, Chaisson CE, Ross D, Jacobsen MM, Robine M, Govender T, Freedberg KA, Katz JN, Walensky RP, Losina E. J Acquir Immune Defic Syndr. 2016 Oct 1;73(2):154-60. doi: 10.1097/QAI.0000000000001025.

Background: A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy (ART). We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis (TB) care among newly diagnosed HIV-infected outpatients in Durban, South Africa.

Methods: We conducted a randomized controlled trial (Sizanani Trial, NCT01188941) among adults (≥18 years) at 4 sites. Participants underwent TB screening and randomization into a health system navigator intervention or usual care. Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months. We assessed 9-month outcomes via medical records and the National Population Registry. Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants.

Results: Four thousand nine hundred three participants were enrolled and randomized; 1899 (39%) were HIV-infected, with 1146 (60%) ART-eligible and 523 (28%) TB coinfected at baseline. In the intervention, 212 (39% of outcome-eligible) reached primary outcome compared to 197 (42%) in usual care (RR 0.93, 95% CI: 0.80 to 1.08). One hundred thirty-one (14%) HIV-infected intervention participants died compared to 119 (13%) in usual care; death rates did not differ between arms (RR 1.06, 95% CI: 0.84 to 1.34). In the as-treated analysis, participants reached for ≥5 navigator calls were more likely to achieve study outcome.

Conclusions: approximately 40% of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis. Low rates of engagement in care, high death rates, and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes.

Abstract access  

Editor’s notes: Early mortality remains high among people starting antiretroviral therapy (ART) in low- and middle-income countries, and tuberculosis is consistently identified as a leading cause. In KwaZulu-Natal province, South Africa, where this study was conducted, tuberculosis incidence is very high, and around two-thirds of people starting tuberculosis treatment are HIV-positive. Previous studies have illustrated gaps between positive test results and linkage to HIV and tuberculosis care. For HIV-positive people with tuberculosis, accessing treatment for both HIV and tuberculosis is made more difficult by a lack of integrated care in many settings. Health care navigators have helped people with HIV link to care in the United States.

This study tested a programme whereby health care navigators helped newly-diagnosed HIV-positive people to link to HIV care, and if necessary also to tuberculosis treatment. The navigators had a counselling role, and also contacted patients by phone or text message reminders. Disappointingly, the programme did not improve outcomes at nine months after enrolment. All-cause mortality was high at around 14% by nine months, and was not reduced by the programme. This is an important result, contrasting with findings from other studies. The SEARCH trial in Uganda illustrated more rapid ART initiation resulting from a complex programme, primarily targeting health system rather than individual barriers. However, the primary outcome of the SEARCH analysis was ART initiation; there was no detectable effect on mortality, which was very low, suggesting a lower-risk study population. In the REMSTART study, a programme including point-of-care testing for cryptococcal antigen plus adherence support from community counsellors (along with routine tuberculosis investigation in both arms) was associated with a reduction in early mortality; the “active ingredient” of this programme was not clearly defined. Ideally, people with HIV need to start ART before they reach the stage of advanced disease. However, given the reality that many people do present with advanced disease, more work is necessary to define which programme could reduce their risk of mortality.

Africa
South Africa
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Poor linkage to care may undermine benefits of universal test and treat

Uptake of home-based HIV testing, linkage to care, and community attitudes about ART in rural KwaZulu-Natal, South Africa: descriptive results from the first phase of the ANRS 12249 TasP cluster-randomised trial.

Iwuji CC, Orne-Gliemann J, Larmarange J, Okesola N, Tanser F, Thiebaut R, Rekacewicz C, Newell ML, Dabis F. PLoS Med. 2016 Aug 9;13(8):e1002107. doi: 10.1371/journal.pmed.1002107. eCollection 2016.

Background: The 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.

Methods and findings: Between 9 March 2012 and 22 May 2014, five clusters in the intervention arm (immediate ART offered to all HIV-positive adults) and five clusters in the control arm (ART offered according to national guidelines, i.e., CD4 count ≤ 350 cells/µl) contributed to the first phase of the trial. Households were visited every 6 mo. Following informed consent and administration of a study questionnaire, each resident adult (≥16 y) was asked for a finger-prick blood sample, which was used to estimate HIV prevalence, and offered a rapid HIV test using a serial HIV testing algorithm. All HIV-positive adults were referred to the trial clinic in their cluster. Those not linked to care 3 mo after identification were contacted by a linkage-to-care team. Study procedures were not blinded. In all, 12 894 adults were registered as eligible for participation (5790 in intervention arm; 7104 in control arm), of whom 9927 (77.0%) were contacted at least once during household visits. HIV status was ever ascertained for a total of 8233/9927 (82.9%), including 2569 ascertained as HIV-positive (942 tested HIV-positive and 1627 reported a known HIV-positive status). Of the 1177 HIV-positive individuals not previously in care and followed for at least 6 mo in the trial, 559 (47.5%) visited their cluster trial clinic within 6 mo. In the intervention arm, 89% (194/218) initiated ART within 3 mo of their first clinic visit. In the control arm, 42.3% (83/196) had a CD4 count ≤350 cells/µl at first visit, of whom 92.8% initiated ART within 3 mo. Regarding attitudes about ART, 93% (8802/9460) of participants agreed with the statement that they would want to start ART as soon as possible if HIV-positive. Estimated baseline HIV prevalence was 30.5% (2028/6656) (95% CI 25.0%, 37.0%). HIV prevalence, uptake of home-based HIV testing, linkage to care within 6 mo, and initiation of ART within 3 mo in those with CD4 count ≤350 cells/µl did not differ significantly between the intervention and control clusters. Selection bias related to noncontact could not be entirely excluded.

Conclusions: Home-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

Trial registration: ClinicalTrials.gov NCT01509508.

Abstract  Full-text [free] access 

Editor’s notes: The UNAIDS treatment target set for 2020 aim for at least 90 percent of all people living with HIV to be diagnosed, at least 90 percent of people diagnosed to receive antiretroviral therapy, and for treatment to be effective and consistent enough in at least 90 percent of people on treatment to suppress the virus. This would result in about 73% of all HIV-positive people being virally suppressed. 

This paper describes the key process indicators (such as uptake of initial and repeat home-based HIV testing, linkage to care, uptake of ART, and viral suppression) along the treatment cascade during the two-year initial phase of a trial evaluating a treatment as prevention package in a rural South African setting. Although the investigators were unable to contact one-quarter of the potential key population - especially men - they found good acceptance of home-based HIV testing.

However, they found disappointingly low rates of linkage to care. Only about half of HIV-positive participants not yet in care attended a clinic within six months of diagnosis. This increased to two-thirds after 12 months, partly due the efforts of a linkage-to-care team. They contacted those not linked to care three months after an HIV-positive test. Among people who did present to the clinics, the rates of ART uptake, retention in care and viral suppression were high.

The main study (reported at the AIDS 2016 conference in Durban) did not demonstrate an effect of offering immediate ART on HIV incidence at population level, mainly due the low rates of linkage to care following HIV diagnosis. 

These results suggest that systems to improve linkage to care will be necessary if the individual and public health benefits of universal testing and treatment are to be maximised.

Africa
South Africa
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HIV treatment during acute infection can lead to false negative HIV antibody tests

Initiation of antiretroviral therapy during acute HIV-1 infection leads to a high rate of nonreactive HIV serology.

de Souza MS, Pinyakorn S, Akapirat S, Pattanachaiwit S, Fletcher JL, Chomchey N, Kroon ED, Ubolyam S, Michael NL, Robb ML, Phanuphak P, Kim JH, Phanuphak N, Ananworanich J. Clin Infect Dis. 2016 Aug 15;63(4):555-61. doi: 10.1093/cid/ciw365. Epub 2016 Jun 17.

Background: Third- and fourth-generation immunoassays (IAs) are widely used in the diagnosis of human immunodeficiency virus (HIV) infection. Antiretroviral therapy (ART) during acute HIV infection (AHI) may impact HIV-specific antibodies, with failure to develop antibody or seroreversion. We report on the ability of diagnostic tests to detect HIV-specific antibodies in Thai participants initiating ART during AHI.

Methods: Participants with detectable plasma HIV RNA but nonreactive HIV-specific immunoglobulin G, enrolled in an AHI study, were offered immediate initiation of ART. Participants were tested at initiation and at 12 and 24 weeks following treatment using standard second-, third-, and fourth-generation IAs and Western blot (WB).

Results: Participants (N = 234) initiating ART at a median of 19 days (range, 1-62 days) from HIV exposure demonstrated different frequencies of reactivity prior to and following 24 weeks of ART depending on the IA. Third-generation IA nonreactivity prior to ART was 48%, which decreased to 4% following ART (P < .001). Fourth-generation IA nonreactivity was 18% prior to ART and 17% following ART (P = .720). Negative WB results were observed in 89% and 12% of participants prior to and following 24 weeks of ART, respectively (P < .001). Seroreversion to nonreactivity during ART was observed to at least one of the tests in 20% of participants, with fourth-generation IA demonstrating the highest frequency (11%) of seroreversion.

Conclusions: HIV-specific antibodies may fail to develop and, when detected, may decline when ART is initiated during AHI. Although fourth-generation IA was the most sensitive at detecting AHI prior to ART, third-generation IA was the most sensitive during treatment.

Clinical trials registration: NCT00796146 and NCT00796263.

Abstract access  

Editor’s notes: Antibodies to HIV become detectable around three weeks after HIV infection. Fourth generation HIV tests detect both HIV antibodies and the p24 HIV antigen, and can therefore detect HIV infection earlier than second and third-generation tests, which are based on detection of antibodies. Fourth generation tests therefore allow for earlier initiation of antiretroviral therapy (ART) relative to second- and third-generation HIV tests.

There have been sporadic reports of seroreversion from being HIV antibody positive to negative, or failure to seroconvert to being HIV antibody positive, following initiation of ART, particularly from paediatric populations. This study examined the impact of ART initiation during acute HIV infection on HIV diagnostic test results. Although the fourth-generation HIV test was the most sensitive at detecting acute HIV infection, it also had the highest frequency of seroreversion. Conversely, third generation HIV tests were positive prior to the start of ART in just over half of participants, compared to nearly all by 12 weeks after ART initiation. Notably, the Western blot, which was historically used as a confirmatory test for HIV, had high rates of non-reactivity in acute infection and 12% of tests were negative at 24 weeks after treatment, demonstrating that this test is not informative as a confirmatory assay in the context of acutely-treated HIV infection.   

The recent WHO guidelines recommend ART for all HIV-positive people regardless of age and disease stage.  Initiating ART as early as possible following HIV infection has also been recommended as a means to limit the size of the viral reservoir and improve prognosis. It is therefore likely that increasing numbers of individuals will start ART during early infection. There may be instances where individuals on ART may retest either due to doubts about results, or when they relocate to other HIV services. Clinicians need to be aware of the possibility of false-negative HIV antibody tests among people taking ART, particularly among individuals who initiated treatment during acute infection.    

Asia
Thailand
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Near elimination of HIV transmission with combined ART and PrEP

Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1-serodiscordant couples: a prospective implementation study in Kenya and Uganda.

Baeten JM, Heffron R, Kidoguchi L, Mugo NR, Katabira E, Bukusi EA, Asiimwe S, Haberer JE, Morton J, Ngure K, Bulya N, Odoyo J, Tindimwebwa E, Hendrix C, Marzinke MA, Ware NC, Wyatt MA, Morrison S, Haugen H, Mujugira A, Donnell D, Celum C. PLoS Med. 2016 Aug 23;13(8):e1002099. doi: 10.1371/journal.pmed.1002099. eCollection 2016.

Background: Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.

Methods and findings: Between November 5, 2012, and January 5, 2015, we enrolled and followed 1013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.

Conclusions: Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.

Abstract  Full-text [free] access 

Editor’s notes: Long-term follow-up of the landmark HPTN-052 trial of ART for prevention of HIV transmission between HIV serodiscordant couples was covered in a recent issue of HIV This Month. In that trial, of the few transmission events that did occur, half were during the first few months of ART use in the HIV-positive partner, before viral load suppression. This study from Kenya and Uganda now suggests that offering pre-exposure prophylaxis (PrEP) to the HIV-negative partner to bridge the gap until virologic suppression may be an effective way to almost eliminate the risk of transmission.

In this study there were significant delays in ART initiation in the HIV-positive partner. At the start of the study the recommendation for ART initiation was a CD4+ cell count <350, and only half of the HIV-positive partners had initiated ART by six months. PrEP uptake by the HIV-negative partner was high during this time period and high levels of adherence were sustained, suggesting that this was a feasible and acceptable strategy for discordant couples.

The activities were delivered using specific clinical research facilities and staff, so the logical next step would be to demonstrate scalability with delivery through routine health systems and through more innovative community-based systems.  

Africa
Kenya, Uganda
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