Articles tagged as "HIV Treatment"

Improved survival with lymphoma in the antiretroviral therapy era

Evolution of HIV-associated lymphoma over 3 decades.

Ramaswami R, Chia G, Dalla Pria A, Pinato DJ, Parker K, Nelson M, Bower M. J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):177-83. doi: 10.1097/QAI.0000000000000946.

Introduction: The emergence of combined antiretroviral therapy (cART) and improvements in the management of opportunistic infections have altered the HIV epidemic over the last 30 years. We aimed to assess changes to the biology and outcomes of HIV-associated lymphomas over this period at the national center for HIV oncology in the United Kingdom.

Methods: Clinical characteristics at lymphoma diagnosis have been prospectively collected since 1986, along with details of lymphoma treatment and outcomes. The clinical features and outcomes were compared between 3 decades: pre-cART decade (1986-1995), early-cART decade (1996-2005), and late-cART decade (2006-2015).

Results: A total of 615 patients with HIV-associated lymphoma were included in the study: 158 patients in the pre-cART era, 200 patients in the early-cART era, and 257 patients in the late-cART era. In more recent decades, patients were older (P < 0.0001) and had higher CD4 cell counts (P < 0.0001) at lymphoma diagnosis. Over time, there has also been a shift in lymphoma histological subtypes, with an increase in lymphoma subtypes associated with moderate immunosuppression. The overall survival for patients with HIV-associated lymphoma has dramatically improved over the 3 decades (P < 0.0001).

Conclusion: Over the last 30 years, the clinical demographic of HIV-associated lymphomas has evolved, and the outcomes have improved.

Abstract access

Editor’s notes: Lymphomas are the second most common malignancy after Kaposi’s sarcoma among people living with HIV in Europe, Australia and northern America. This study examined how the biology and rates of survival have changed since combination antiretroviral therapy (cART) became available.

People living with HIV and diagnosed with lymphoma over the past thirty years in a specialist oncology centre in the United Kingdom were included in the study. The mean age at diagnosis of lymphoma increased over time, most likely reflecting improvement in life expectancy with cART. As would be expected, the mean CD4 count and the proportion of people with a suppressed viral load at lymphoma diagnosis increased, while proportion with an AIDS-defining illness before lymphoma diagnosis declined significantly.  

This study demonstrated a shift of the histological subtypes of lymphoma that are associated with less severe immunosuppression, for example the proportion of primary CNS lymphoma (PCNSL) and diffuse large B-cell lymphoma (DLBCL), which are associated with severe immunosuppression, declined, while the proportion of Burkitt’s lymphoma and Hodgkin’s lymphoma (associated with less profound immunosuppression) increased.

A key finding of this study was the significantly improved overall survival of people with lymphoma. The improved survival is not explained by changes in histological subtypes of lymphoma over time, as improvement in prognosis was observed for each histological subtype. The substantial improvement in overall survival is attributable to a number of factors. They include the availability of cART, attention to opportunistic infection prophylaxis, improved supportive care for people undergoing lymphoma treatment as well as improved modalities of lymphoma treatment. Such modalities include efficacious drugs that can be safely co-administered with cART, e.g., rituximab, novel agents and use of autologous stem cell transplants.  

Europe
United Kingdom
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Minimal evidence for serious adverse events resulting from in utero ARV exposure

The PHACS SMARTT Study: assessment of the safety of in utero exposure to antiretroviral drugs.

Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR, 3rd. Front Immunol. 2016 May 23;7:199. doi: 10.3389/fimmu.2016.00199. eCollection 2016.

The Surveillance Monitoring for ART Toxicities (SMARTT) cohort of the Pediatric HIV/AIDS Cohort Study includes over 3500 HIV-exposed but uninfected infants and children at 22 sites in the US, including Puerto Rico. The goal of the study is to determine the safety of in utero exposure to antiretrovirals (ARVs) and to estimate the incidence of adverse events. Domains being assessed include metabolic, growth and development, cardiac, neurological, neurodevelopmental (ND), behavior, language, and hearing. SMARTT employs an innovative trigger-based design as an efficient means to identify and evaluate adverse events. Participants who met a predefined clinical or laboratory threshold (trigger) undergo additional evaluations to define their case status. After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain) with exposure to combination ARVs (cARVs), any ARV class, or any specific ARV. However, several individual ARVs were significantly associated with case status in individual domains, including zidovudine for a metabolic case, first trimester stavudine for a language case, and didanosine plus stavudine for a ND case. We found an increased rate of preterm birth with first trimester exposure to protease inhibitor-based cARV. Although there was no overall increase in congenital anomalies with first trimester cARV, a significant increase was seen with exposure to atazanavir, ritonavir, and didanosine plus stavudine. Tenofovir exposure was associated with significantly lower mean whole-body bone mineral content in the newborn period and a lower length and head circumference at 1 year of age. With ND testing at 1 year of age, specific ARVs (atazanavir, ritonavir-boosted lopinavir, nelfinavir, and tenofovir) were associated with lower performance, although all groups were within the normal range. No ARVs or classes were associated with lower performance between 5 and 13 years of age. Atazanavir and saquinavir exposure were associated with late language emergence at 1 year, but not at 2 years of age. The results of the SMARTT study are generally reassuring, with little evidence for serious adverse events resulting from in utero ARV exposure. However, several findings of concern warrant further evaluation, and new ARVs used in pregnancy need to be evaluated.

Abstract  Full-text [free] access 

Editor’s notes: The SMARTT study set out to determine the safety of in utero exposure to antiretroviral (ARV) therapy using a trigger-based surveillance design to identify adverse events in a cohort of HIV-positive mothers and their HIV-exposed but HIV-negative children in the United States of America and Puerto Rico. A ‘trigger’ was set off if participants met a predefined clinical or laboratory threshold, with additional specified evaluations to determine if they met a predefined adverse event “case” definition.  After adjusting for birth cohort and other factors, there was no significant increase in the likelihood of meeting overall case status (case in any domain, such as growth and development or language etc.) with exposure to combination ARVs or any ARV class. No single ARV prophylaxis was associated with an increased risk of overall case status on adjusted analysis. However, several ARVs had significant associations in unadjusted analysis, namely between (1) maternal PI-based ARV prophylaxis during pregnancy and premature delivery and low birth weight; and (2) exposure to atazanavir and a twofold-higher risk of congenital anomalies. Overall the results from this study are reassuring, but some of the findings warrant further evaluation.

Latin America, Northern America
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One-stop clinic-based ART initiation strengthens HIV treatment cascade

Initiating antiretroviral therapy for HIV at a patient's first clinic visit: the RapIT randomized controlled trial.

Rosen S, Maskew M, Fox MP, Nyoni C, Mongwenyana C, Malete G, Sanne I, Bokaba D, Sauls C, Rohr J, Long L. PLoS Med. 2016 May 10;13(5):e1002015. doi: 10.1371/journal.pmed.1002015. eCollection 2016.

Background: High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.

Methods and findings: RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm") received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study ("standard arm") followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition from care after ART initiation between the groups among those who initiated within 90 d. Three hundred and seventy-seven patients were enrolled in the study between May 8, 2013 and August 29, 2014 (median CD4 count 210 cells/mm3). In the rapid arm, 119/187 patients (64%) initiated treatment and were virally suppressed at 10 mo, compared to 96/190 (51%) in the standard arm (relative risk [RR] 1.26 [1.05-1.50]). In the rapid arm 182/187 (97%) initiated ART ≤90 d, compared to 136/190 (72%) in the standard arm (RR 1.36, 95% confidence interval [CI], 1.24-1.49). Among 318 patients who did initiate ART within 90 d, the hazard of attrition within the first 10 mo did not differ between the treatment arms (hazard ratio [HR] 1.06; 95% CI 0.61-1.84). The study was limited by the small number of sites and small sample size, and the generalizability of the results to other settings and to non-research conditions is uncertain.

Conclusions: Offering single-visit ART initiation to adult patients in South Africa increased uptake of ART by 36% and viral suppression by 26%. This intervention should be considered for adoption in the public sector in Africa.

Abstract  Full-text [free] access 

Editor’s notes: This randomised controlled trial provides evidence that initiating ART at a single clinic visit limits pre-ART losses and increases the proportion in care with viral suppression within the first year of ART. Almost all people in the rapid arm initiated ART within 90 days. Attrition post-ART initiation remained quite high. One in three participants initiating ART in the rapid arm did not achieve the primary outcome of retention in care with viral suppression. However, this was not enough to offset the clear benefit of reduced pre-ART loss to follow-up.

There are a few things to note about the study. Firstly, the study design allowed for people who were enrolled at various stages in the pre-ART period, from HIV testing to receipt of CD4+ cell count. Fewer than half were enrolled on the day of HIV diagnosis. Secondly, the trial procedures relating to ART initiation were performed by research staff embedded in the health facilities. The one-stop ART initiation strategy was quite intensive, involving point-of-care testing for CD4+ cell count, TB, and routine pre-ART blood tests. This took over two hours for a single person, and more than four hours if TB testing was required. Lastly, the virologic suppression outcome was based on viral load measurement at any point between three and 12 months. It will therefore be particularly interesting to see longer-term data on virologic suppression and retention to see whether the effects were sustained.

The effectiveness and cost-effectiveness of this strategy should now be evaluated. The removal of CD4+ cell count eligibility criteria for ART might help to streamline the pre-initiation procedures, but additional effort might be required to make this process more efficient and suitable for implementation in routine care settings.  

Africa
South Africa
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Antiretroviral choice may affect malaria outcomes in children

Antiretroviral choice for HIV impacts antimalarial exposure and treatment outcomes in Ugandan children.

Parikh S, Kajubi R, Huang L, Ssebuliba J, Kiconco S, Gao Q, Li F, Were M, Kakuru A, Achan J, Mwebaza N, Aweeka FT. Clin Infect Dis. 2016 May 3. pii: ciw291. [Epub ahead of print]

Background: The optimal treatment of malaria in HIV-infected children requires consideration of critical drug-drug interactions in co-infected children, as these may significantly impact drug exposure and clinical outcomes.

Methods: We conducted an intensive and sparse pharmacokinetic and pharmacodynamic study in Uganda of the most widely adopted artemisinin-based combination therapy, artemether-lumefantrine. HIV-infected children on three different first-line antiretroviral therapies (ART) were compared to HIV-uninfected children not on ART, all of whom required treatment for Plasmodium falciparum malaria. Pharmacokinetic sampling for artemether, dihydroartemisinin (DHA) and lumefantrine exposure was conducted through day 21, and associations between drug exposure and outcomes through day 42 were investigated.

Results: 145 and 225 children were included in the intensive and sparse pharmacokinetic analyses, respectively. Compared to no ART, efavirenz reduced exposure to all antimalarial components by 2.1 to 3.4-fold; lopinavir/ritonavir increased lumefantrine exposure by 2.1-fold; and nevirapine reduced artemether exposure only. Day 7 concentrations of lumefantrine were 10-fold lower in children on efavirenz versus lopinavir/ritonavir-based ART, changes that were associated with an approximately 4-fold higher odds of recurrent malaria by day 28 in those on efavirenz versus lopinavir/ritonavir-based ART.

Conclusions: The choice of ART in children living in a malaria-endemic region has highly significant impacts on the pharmacokinetics and pharmacodynamics of artemether-lumefantrine treatment. Efavirenz-based ART reduces all antimalarial components and is associated with the highest risk of recurrent malaria following treatment. For those on efavirenz, close clinical follow-up for recurrent malaria following artemether-lumefantrine treatment, along with the study of modified dosing regimens that provide higher exposure is warranted.

Abstract access

Editor’s notes: This study looks at the pharmacokinetic (PK) and clinical outcomes for artemether/lumefantrine therapy of falciparum malaria in Ugandan children aged 1-8 years living without HIV and with HIV on antiretroviral therapy (ART) regimes containing efavirenz, nevirapine or lopinavir. The stand-out result is that malaria outcomes were better in children who were taking lopinavir-based ART, without any significant drug adverse effects. 

The most commonly-used ART combinations have extensive interactions with other classes of drugs.  The effects of these interactions on clinical outcomes cannot always be accurately predicted from PK studies in healthy adults. This is especially so for sick children whose drug handling may be different. Large PK studies of unwell children are difficult to do, so this study is a rare gem. In fact the PK results are largely as expected. Exposure to artemether and its active metabolite are reduced by efavirenz and nevirapine; and exposure to lumefantrine is reduced by efavirenz and increased by lopinavir with ritonavir. Lumefantrine is the component of the combination malaria therapy with a longer effect and is intended to provide protection from recurrence.

The big question is, what is the impact of these PK differences on clinical outcomes? This is where it gets complicated. In total some 370 malaria episodes were studied. The authors illustrate that the efavirenz group had substantially higher malaria recurrence than the lopinavir group. The lopinavir group had the highest levels of lumefantrine. The efavirenz group had similar outcomes to the HIV-negative group, despite having lower levels of lumefantrine.

The recurrence rate in this study, in an area of intense malaria transmission, is dominated by early reinfection rather than recrudesence. The great majority of children taking ART were also taking co-trimoxazole, which provides protection against malaria infection, giving all children taking ART additional protection versus malaria compared to HIV-negative children. The difference between the efavirenz and lopinavir groups is likely to be due to lumefantrine levels. Higher levels of lumefantrine persist in combination with lopinavir / ritonavir – an effect that might also apply to other protease inhibitors. WHO guidelines recommend lopinavir/ritonavir as part of first-line ART for children under three years old. Whether this effect is large enough to influence ART choices in older children will depend on local circumstances, particularly the malaria transmission rate 

Africa
Uganda
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Silent transfers result in underestimation of retention on ART

Retention in care and patient-reported reasons for undocumented transfer or stopping care among HIV-infected patients on antiretroviral therapy in eastern Africa: application of a sampling-based approach.

Geng EH, Odeny TA, Lyamuya R, Nakiwogga-Muwanga A, Diero L, Bwana M, Braitstein P, Somi G, Kambugu A, Bukusi E, Wenger M, Neilands TB, Glidden DV, Wools-Kaloustian K, Yiannoutsos C, Martin J, East Africa International Epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium. Clin Infect Dis. 2016 Apr 1;62(7):935-44. doi: 10.1093/cid/civ1004. Epub 2015 Dec 17.

Background: Improving the implementation of the global response to human immunodeficiency virus requires understanding retention after starting antiretroviral therapy (ART), but loss to follow-up undermines assessment of the magnitude of and reasons for stopping care.

Methods: We evaluated adults starting ART over 2.5 years in 14 clinics in Uganda, Tanzania, and Kenya. We traced a random sample of patients lost to follow-up and incorporated updated information in weighted competing risks estimates of retention. Reasons for nonreturn were surveyed.

Results: Among 18 081 patients, 3150 (18%) were lost to follow-up and 579 (18%) were traced. Of 497 (86%) with ascertained vital status, 340 (69%) were alive and, in 278 (82%) cases, updated care status was obtained. Among all patients initiating ART, weighted estimates incorporating tracing outcomes found that 2 years after ART, 69% were in care at their original clinic, 14% transferred (4% official and 10% unofficial), 6% were alive but out of care, 6% died in care (<60 days after last visit), and 6% died out of care (≥60 days after last visit). Among lost patients found in care elsewhere, structural barriers (eg, transportation) were most prevalent (65%), followed by clinic-based (eg, waiting times) (33%) and psychosocial (eg, stigma) (27%). Among patients not in care elsewhere, psychosocial barriers were most prevalent (76%), followed by structural (51%) and clinic based (15%).

Conclusions: Accounting for outcomes among those lost to follow-up yields a more informative assessment of retention. Structural barriers contribute most to silent transfers, whereas psychological and social barriers tend to result in longer-term care discontinuation.

Abstract access 

Editor’s notes: The authors explore outcomes by tracing a sample of people who were lost to follow-up from antiretroviral therapy (ART) clinics. They collected data on reasons provided by patients for undocumented transfer out, or stopping ART. The findings are important, both to be able to critically evaluate the success of ART programmes (and individual clinics) in retaining people in care, and to identify barriers to retention which may be amenable to change. Consistent with findings elsewhere, the most common outcome among “lost” ART clinic attendees was “silent” (unofficial) transfer to another clinic, which, in this three-country study, accounted for a 10% underestimation of retention in care over two years. This highlights the pressing need for improved electronic medical record systems with centralised identification, in order to be able to track individuals between facilities so that accurate retention data can be collated.

As ART programmes move towards universal immediate initiation, the rate of stopping care (or transferring) will likely increase. In this study, 22% of people who had stopped care gave “I felt well” as a reason. The need for programmes to respond to the structural, psychological and social barriers identified will become even more important. 

Africa
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Botswana within reach of UNAIDS 90-90-90 treatment target

Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey.

Gaolathe T, Wirth KE, Holme MP, Makhema J, Moyo S, Chakalisa U, Yankinda EK, Lei Q, Mmalane M, Novitsky V, Okui L, van Widenfelt E, Powis KM, Khan N, Bennett K, Bussmann H, Dryden-Peterson S, Lebelonyane R, El-Halabi S, Mills LA, Marukutira T, Wang R, Tchetgen EJ, DeGruttola V, Essex M, Lockman S, Botswana Combination Prevention Project study team. Lancet HIV. 2016 May;3(5):e221-30. doi: 10.1016/S2352-3018(16)00037-0. Epub 2016 Mar 24.

Background: HIV programmes face challenges achieving high rates of HIV testing and treatment needed to optimise health and to reduce transmission. We used data from the Botswana Combination Prevention Project study survey to assess Botswana's progress toward achieving UNAIDS targets for 2020: 90% of all people living with HIV knowing their status, 90% of these receiving sustained antiretroviral therapy (ART), and 90% of those having virological suppression (90-90-90).

Methods: A population-based sample of individuals was recruited and interviewed in 30 rural and periurban communities from Oct 30, 2013, to Nov 24, 2015, as part of a large, ongoing community-randomised trial designed to assess the effect of a combination prevention package on HIV incidence. A random sample of about 20% of households in each community was selected. Consenting household residents aged 16-64 years who were Botswana citizens or spouses of citizens responded to a questionnaire and had blood drawn for HIV testing in the absence of documentation of positive HIV status. Viral load testing was done in all HIV-infected participants, irrespective of treatment status. We used modified Poisson generalised estimating equations to obtain prevalence ratios, corresponding Huber robust SEs, and 95% Wald CIs to examine associations between individual sociodemographic factors and a binary outcome indicating achievement of the three individual and combined overall 90-90-90 targets. The study is registered at ClinicalTrials.gov, number NCT01965470.

Findings: 81% of enumerated eligible household members took part in the survey (10% refused and 9% were absent). Among 12 610 participants surveyed, 3596 (29%) were infected with HIV, and 2995 (83.3%, 95% CI 81.4-85.2) of these individuals already knew their HIV status. Among those who knew their HIV status, 2617 (87.4%, 95% CI 85.8-89.0) were receiving ART (95% of those eligible by national guidelines, and 73% of all infected people). Of the 2609 individuals receiving ART with a viral load measurement, 2517 (96.5%, 95% CI 96.0-97.0) had viral load of 400 copies per mL or less. Overall, 70.2% (95% CI 67.5-73.0) of HIV-infected people had virological suppression, close to the UNAIDS target of 73%.

Interpretation: UNAIDS 90-90-90 targets are achievable even in resource-constrained settings with high HIV burden.

Abstract 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 those people on treatment to suppress the virus. This would result in about 73% of all HIV-positive people being virally suppressed. 

This study estimated coverage of HIV diagnosis, antiretroviral therapy and viral suppression among 30 communities in Botswana, a country with a high HIV prevalence (~ 25%), to assess the country’s progress towards the UNAIDS treatment target. They found that overall, about 70% of people living with HIV had viral suppression (defined in this analysis as having a viral load of less than HIV RNA 400 copies per mL), close to the UNAIDS target of 73%. However, there is still substantial ongoing transmission (demonstrated by an HIV incidence of 1.4% per year in 2013). The authors attribute this mainly to the 30% of people living with HIV that remain unsuppressed (undiagnosed, or not on treatment, or not virally suppressed because of poor adherence or drug resistance). They also acknowledge that other factors such as the complexities of sexual networks, risk behaviour patterns, and biological factors may play a role.

Interestingly the authors found very high proportions of viral suppression. Nearly 97% of people on ART were virally suppressed. The authors also found that younger age was the strongest predictor of not reaching the ultimate target (diagnosed, on treatment and being virally suppressed). People living with HIV aged 20-29 years old were about 50% less likely to be virally suppressed compared with people 60 years and older. Young people living with HIV aged between 16-19 years old were 60% less likely to be virally suppressed. This emphasizes again the need for focussed programmes for adolescents and young people.

Botswana has reached this level of coverage even when the criterion for initiating antiretroviral therapy was a CD4 cell count below 350 cells per μL, even before moving to providing treatment for everyone diagnosed with HIV. The authors conclude that the high proportions of HIV testing, antiretroviral therapy and viral suppression provide good evidence that the UNAIDS treatment target is achievable.

Africa
Botswana
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SMS technology can decrease time to ART initiation in infants, Rwanda

TRACnet Internet and SMS technology improves time to antiretroviral therapy initiation among HIV-infected infants in Rwanda.

Kayumba K, Nsanzimana S, Binagwaho A, Mugwaneza P, Rusine J, Remera E, Koama JB, Ndahindwa V, Johnson P, Riedel DJ, Condo J. Pediatr Infect Dis J. 2016 Mar 30. [Epub ahead of print]

Background: Delays in testing HIV-exposed infants and obtaining results in resource-limited settings contribute to delays for initiating antiretroviral therapy (ART) in infants. To overcome this challenge, Rwanda expanded its national mobile and internet-based HIV/AIDS informatics system, called TRACnet, to include HIV PCR results in 2010. This study was performed to evaluate the impact of TRACnet technology on the time to delivery of test results and the subsequent initiation of ART in HIV-infected infants.

Methods: A retrospective cohort study was conducted on 380 infants who initiated ART in 190 health facilities in Rwanda from March 2010 to June 2013. Program data collected by the TRACnet system was extracted and analyzed.

Results: Since the introduction of TRACnet for processing PCR results, the time to receive results has significantly decreased from a median of 144 days [IQR 121-197] to 23 days [IQR 17-43]. The number of days between PCR sampling and health facility receipt of results decreased substantially from a median of 90 days [IQR 83-158] to 5 days [IQR 2-8]. After receiving PCR results at a health facility, it takes a median of 44 days [IQR 32-77] before ART initiation. Result turnaround time was significantly associated with time to initiating ART (P<0.001). An increased number of staff trained for HIV care and treatment was also significantly associated with decreased time to ART initiation (P=0.004).

Conclusions: The use of mobile technology for communication of HIV PCR results, coupled with well-trained and skilled personnel, can reduce delays in communicating results to providers. Such reductions may improve timely ART initiation in resource-limited settings.

Abstract access

Editor’s notes: Early identification and prompt treatment of infants who have perinatally acquired HIV is critical to decrease HIV-associated mortality in children. Testing of HIV-exposed infants is an integral part of prevention of mother-to-child HIV transmission programmes, and is termed early infant diagnosis (EID). Despite the scale-up of prevention of mother-to-child HIV transmission programmes, delays in obtaining HIV test results and in initiating infants on ART remains a serious programmatic challenge. Delays occur at several stages, including transport of specimens to centralised laboratories, processing of specimens by laboratories, receipt of results by health facilities and delay in initiation of antiretroviral therapy (ART) once positive results are received by health providers. Delays of up to several months between HIV testing and receipt of results have been observed in many high-burden countries.

In this study conducted in Rwanda, a short message service (SMS) was incorporated into the existing national TRACnet system to speed delivery of HIV test results from the central laboratory to health facilities. This interactive system is used for reporting by health facilities, either through a mobile phone or via the internet, depending on availability. Notably, this was complemented by strengthening all the processes between HIV testing and initiation of ART. This included training of nurses at health facilities, and improving the sample transportation process and the laboratory procedures at the central laboratory. The time from sample collection to receipt of results decreased from a median of 144 days to 23 days. Importantly this was also associated with a reducing in time to ART initiation.   

This study illustrates how a relatively simple SMS technology can be used to address structural barriers. Mobile phones are widely used in resource-constrained settings, and can be used to enhance efficiency of delivery of both HIV and other health services, as illustrated by this innovative study. However, success will require investment in improvement of transportation and laboratory systems, and training of health care providers, not only to utilise such systems, but also to respond to results in a timely manner. Further, there are further challenges in getting people to return to clinics to get their results and starting treatment. Strategies for engaging people will also be required if the ultimate outcome of prompt treatment of infants is to be realised. 

Africa
Rwanda
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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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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.

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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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