Articles tagged as "15 million accessing treatment"

Increasing transmitted resistance to antiretroviral therapy in low/middle-income countries - highest prevalence in MSM

Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis.

Pham QD, Wilson DP, Law MG, Kelleher AD, Zhang L. AIDS. 2014 Nov 28;28(18):2751-62. doi: 10.1097/QAD.0000000000000494.

Objectives: Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries.

Design/methods: We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups.

Results: A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM.

Conclusion: TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.

Abstract access 

Editor’s notes: HIV mutates very rapidly, and many early antiretroviral agents had a low genetic barrier to the development of resistance. Thus the emergence of virus resistant to antiretroviral agents, particularly to early drug classes, was inevitable. Surveillance for drug-resistant virus among people with no prior history of taking antiretroviral drugs (transmitted drug resistance) is essential to monitor the spread of drug resistance at population level.

This systematic review aimed to compare transmitted drug resistance in different geographical regions and between subpopulations of HIV-positive people by likely route of transmission. Transmitted resistance was most prevalent in high income settings. This is not surprising given wide use of suboptimal drug regimens before effective triple therapy was available. Reassuringly, the prevalence of transmitted resistance seems to have stabilised in high-income settings. The increase in transmitted resistance in low and middle income countries is of more concern. It is not surprising, given that first-line regimens comprising two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor are vulnerable to the development of resistance if the drug supply is interrupted or adherence is suboptimal. In addition, if viral load monitoring is not available, people remain on failing drug regimens for longer, and thus have more risk of transmitting resistant virus.

Within the subpopulations examined in this review, transmitted resistance was consistently higher in men who have sex with men, suggesting that resistance testing prior to treatment is particularly valuable for this population.

Limitations of the review include exclusion of studies that did not compare transmitted resistance between the specified subpopulations, and small sample size in many subgroups.

Continued surveillance for transmitted drug resistance is critical. This is most important in settings where individualised resistance testing is not available. This will ensure that people starting antiretroviral therapy receive treatment that will suppress their viral load effectively. Wider use of viral load monitoring, combined with access to effective second and third line regimens, will also help limit spread of drug resistance.

HIV Treatment
Angola, Argentina, Australia, Austria, Belgium, Benin, Botswana, Brazil, Burkina Faso, Cambodia, Cameroon, Canada, Central African Republic, Chad, China, Côte d'Ivoire, Croatia, Cuba, Cyprus, Denmark, Dominican Republic, El Salvador, Estonia, Ethiopia, France, Gabon, Georgia, Germany, Greece, Guatemala, Honduras, Hong Kong Special Administrative Region of China, Hungary, India, Indonesia, Ireland, Israel, Italy, Japan, Kazakhstan, Kenya, Latvia, Malawi, Malaysia, Moldova, Mozambique, Netherlands, Peru, Philippines, Poland, Portugal, Republic of Korea, Romania, Russia, Rwanda, Slovenia, South Africa, Spain, Swaziland, Sweden, Switzerland, Taiwan, Thailand, Uganda, United Kingdom of Great Britain and Northern Ireland, United Republic of Tanzania, United States of America, Viet Nam, Zambia, Zimbabwe
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Household food insecurity is associated with poor adherence to antiretroviral therapy

Household food insecurity associated with antiretroviral therapy adherence among HIV-infected patients in Windhoek, Namibia.

Hong SY, Fanelli TJ, Jonas A, Gweshe J, Tjituka F, Sheehan HM, Wanke C, Terrin N, Jordan MR, Tang AM. J Acquir Immune Defic Syndr. 2014 Dec 1;67(4):e115-22. doi: 10.1097/QAI.0000000000000308.

Objective: Food insecurity is emerging as an important barrier to antiretroviral therapy (ART) adherence. The objective of this study was to determine if food insecurity is associated with poor ART adherence among HIV-positive adults in a resource-limited setting that uses the public health model of delivery.

Design: A cross-sectional study using a 1-time questionnaire and routinely collected pharmacy data.

Methods: Participants were HIV-infected adults on ART at the public ART clinics in Windhoek, Namibia: Katutura State Hospital, Katutura Health Centre, and Windhoek Central Hospital. Food insecurity was measured by the Household Food Insecurity Access Scale (HFIAS). Adherence was assessed by the pharmacy adherence measure medication possession ratio (MPR). Multivariate regression was used to assess whether food insecurity was associated with ART adherence.

Results: Among 390 participants, 7% were food secure, 25% were mildly or moderately food insecure and 67% were severely food insecure. In adjusted analyses, severe household food insecurity was associated with MPR <80% [odds ratio (OR), 3.84; 95% confidence interval (CI): 1.65 to 8.95]. Higher household health care spending (OR, 1.92; 95% CI, 1.02 to 3.57) and longer duration of ART (OR, 0.82; 95% CI: 0.70 to 0.97) were also associated with <80% MPR.

Conclusions: Severe household food insecurity is present in more than half of the HIV-positive adults attending a public ART clinic in Windhoek, Namibia and is associated with poor ART adherence as measured by MPR. Ensuring reliable access to food should be an important component of ART delivery in resource-limited settings using the public health model of care.

Abstract access

Editor’s notes:  United Nations Subcommittee on Nutrition defines food insecurity as “the limited or uncertain availability of nutritionally adequate, safe foods, or the inability to acquire personally acceptable foods in socially acceptable ways.” Qualitative studies in resource-limited settings have identified food insecurity as a potential risk for antiretroviral (ART) non-adherence. This is one of the first quantitative studies to analyse this issue. The findings from this cross-sectional survey of people living with HIV on ART in Namibia, are striking.  Four of the ten top reasons given for missing a medication dose, were related to food insecurity, e.g. “Did not take ARVs because they make me hungry and I did not have enough food” or, “Did not take ARVs because I cannot afford good food while taking medicine”. After adjusting for potential confounders, severe household food insecurity was significantly and positively associated with poor ART adherence. Depression and travel to the clinic via walking, biking or hitchhiking were also significantly associated with poor adherence. Research into the potential causal pathway between food insecurity and ART adherence is required, including evaluation of programmes to assess the relative effectiveness of nutritional versus livelihood programmes. 

Africa
Namibia
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Co-enrolling family members improves retention of women on antiretroviral therapy

Family matters: co-enrollment of family members into care is associated with improved outcomes for HIV-infected women initiating antiretroviral therapy.

Myer L, Abrams EJ, Zhang Y, Duong J, El-Sadr WM, Carter RJ. J Acquir Immune Defic Syndr. 2014 Dec 1;67 Suppl 4:S243-9. doi: 10.1097/QAI.0000000000000379.

Background: Although there is widespread interest in understanding how models of care for delivering antiretroviral therapy (ART) may influence patient outcomes, family-focused approaches have received little attention. In particular, there have been few investigations of whether the co-enrollment of HIV-infected family members may improve adult ART outcomes over time.

Methods: We examined the association between co-enrollment of HIV-infected family members into care and outcomes of women initiating ART in 12 HIV care and treatment programs across sub-Saharan Africa. Using data from the mother-to-child transmission (MTCT) Plus Initiative, women starting ART were categorized according to the co-enrollment of an HIV-infected partner and/or HIV-infected child within the same program. Mortality and loss to follow-up were assessed for up to 5 years after women's ART initiation.

Results: Of the 2877 women initiating ART included in the analysis, 31% (n = 880) had at least 1 HIV-infected family member enrolled into care at the same program, including 24% (n = 689) who had an HIV-infected male partner, and 10% (n = 295) who had an HIV-infected child co-enrolled. There was no significant difference in the risk of death of women by family co-enrollment status (P = 0.286). However, the risk of loss to follow-up was greatest among women who did not have an HIV-infected family member co-enrolled (19% after 36 months on ART) compared with women who had an HIV-infected family member co-enrolled (3%-8% after 36 months on ART) (P < 0.001). These associations persisted after adjustment for demographic and clinical covariates and were consistent across countries and care programs.

Discussion: These data provide novel evidence for the association between adult outcomes on ART and co-enrollment of HIV-infected family members into care at the same program. Interventions that build on women's family contexts warrant further consideration in both research and policies to promote retention in ART services across sub-Saharan Africa.

Abstract  Full-text [free] access

Editor’s notes: With the dramatic increase in the number of people on antiretroviral therapy (ART) over the last decade, further understanding of the impact of different service delivery models on treatment outcomes (including death and retention-in-care) is needed. Previous studies have compared health systems approaches such as primary care versus hospital delivery, task-shifting to nurses and community-based approaches. This study is one of the first to focus on the impact of family-focused approaches on adult outcomes. In this large multi-country study of women enrolled in prevention of mother-to-child transmission programmes, co-enrolment of a family member living with HIV was not associated with mortality among women, but co-enrollment was associated with an approximate halving of the risk of being lost to follow up. This association was consistent across different sub-groups of age, parity, partner status and location. The strength and consistency of the finding highlights the central role that family and social support can play in shaping health-seeking behaviours among people living with HIV. Further research would include the effect of co-enrolment on treatment outcomes among men, and exploration of specific aspects of co-enrolment, such as disclosure. 

Africa
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Which activities promote adherence to antiretroviral therapy?

Interventions to promote adherence to antiretroviral therapy in Africa: a network meta-analysis.

Mills EJ, Lester R, Thorlund K, Lorenzi M, Muldoon K, Kanters S, Linnemayr S, Gross R, Calderon Y, Amico KR, Thirumurthy H, Pearson C, Remien RH, Mbuagbaw L, Thabane L, Chung MH, Wilson IB, Liu A, Uthman OA, Simoni J, Bangsberg D, Yaya S, Bärnighausen T, Ford N, Nachega JB, Lancet HIV 2014; 1: e104–11 doi:10.1016/S2352-3018(14)00003-4.

Background: Adherence to antiretroviral therapy (ART) is necessary for the improvement of the health of patients and for public health. We sought to determine the comparative effectiveness of different interventions for improving ART adherence in HIV-infected people living in Africa.

Methods: We searched for randomised trials of interventions to promote antiretroviral adherence within adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and ClinicalTrials.gov from inception to Oct 31, 2014, with the terms “HIV”, “ART”, “adherence”, and “Africa”. We created a network of the interventions by pooling the published and individual patients' data for comparable treatments and comparing them across the individual interventions with Bayesian network meta-analyses. The primary outcome was adherence defined as the proportion of patients meeting trial defined criteria; the secondary endpoint was viral suppression.

Findings: We obtained data for 14 randomised controlled trials, with 7110 patients. Interventions included daily and weekly short message service (SMS; text message) messaging, calendars, peer supporters, alarms, counselling, and basic and enhanced standard of care (SOC). Compared with SOC, we found distinguishable improvement in self-reported adherence with enhanced SOC (odds ratio [OR] 1·46, 95% credibility interval [CrI] 1·06–1·98), weekly SMS messages (1·65, 1·25–2·18), counselling and SMS combined (2·07, 1·22–3·53), and treatment supporters (1·83, 1·36–2·45). We found no compelling evidence for the remaining interventions.

Results: were similar when using viral suppression as an outcome, although the network contained less evidence than that for adherence. Treatment supporters with enhanced SOC (1·46, 1·09–1·97) and weekly SMS messages (1·55, 1·01–2·38) were significantly better than basic SOC.

Interpretation: Several recommendations for improving adherence are unsupported by the available evidence. These findings can inform future intervention choices for improving ART adherence in low-income settings.

Abstract access 

Editor’s notes: To maximise the impact of antiretroviral therapy (ART), people living with HIV should be diagnosed early, enrolled and retained in pre-ART care, initiated on ART and retained in ART care. Long-term adherence to achieve and maintain viral load suppression is the last step in the continuum of HIV care. Engagement along the complete treatment cascade will determine the long-term success of the global response to HIV.

A large number of potential programmes aimed at the improvement of engagement with care are available. While there is an urgent need for research on these programmes and on the effect of combined programmes, there is also the reality of a resource constrained environment. Network meta-analysis is a method to synthesise the evidence of programmes. The meta-analysis uses common comparators when these activities have not been compared head-to-head (resulting in indirect evidence), combined with evidence from head-to-head comparisons (direct evidence).

Using a network meta-analysis of randomized trials of programmes to improve ART adherence in Africa, the authors simultaneously compared eight groups of activities against standard care and against each other. The authors found that standard care augmented with intensified adherence counselling, or enhanced standard care, improved adherence to ART. Also weekly SMS messages, enhanced standard care combined with SMS, and enhanced standard care combined with having a treatment supporter were superior to standard care, with regards to self-reported adherence and viral suppression. The authors speculate that combinations of cognitive and behavioural programmes maximise the activity efficacy. Interestingly, their study found a large benefit for weekly but not for daily SMS messages. However the heterogeneity in the published treatment effects could be attributed to heterogeneity of the implemented programmes, especially of behavioural interventions. For example, the authors point out that there is a wide variability in the definition of standard care, and in the definition of treatment supporters.

The authors also note that several recommendations for improving adherence are unsupported by the evidence they examined using network meta-analysis.

Health care delivery
Africa
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Providing more than pills – health care workers and access to essential medicine in South Africa

Frontline health workers as brokers: provider perceptions, experiences and mitigating strategies to improve access to essential medicines in South Africa.

Magadzire B, Budden A, Ward K, Jeffery R, Sanders D. BMC Health Serv Res. 2014 Nov 5;14(1):520. [Epub ahead of print]

Background: Front-line health providers have a unique role as brokers (patient advocates) between the health system and patients in ensuring access to medicines (ATM). ATM is a fundamental component of health systems. This paper examines in a South African context supply- and demand- ATM barriers from the provider perspective using a five dimensional framework: availability (fit between existing resources and clients’ needs); accessibility (fit between physical location of healthcare and location of clients); accommodation (fit between the organisation of services and clients’ practical circumstances); acceptability (fit between clients’ and providers’ mutual expectations and appropriateness of care) and affordability (fit between cost of care and ability to pay).

Methods: This cross-sectional, qualitative study uses semi-structured interviews with nurses, pharmacy personnel and doctors. Thirty-six providers were purposively recruited from six public sector Community Health Centres in two districts in the Eastern Cape Province representing both rural and urban settings. Content analysis combined structured coding and grounded theory approaches. Finally, the five dimensional framework was applied to illustrate the interconnected facets of the issue.

Results: Factors perceived to affect ATM were identified. Availability of medicines was hampered by logistical bottlenecks in the medicines supply chain; poor public transport networks affected accessibility. Organization of disease programmes meshed poorly with the needs of patients with comorbidities and circular migrants who move between provinces searching for economic opportunities, proximity to services such as social grants and shopping centres influenced where patients obtain medicines. Acceptability was affected by, for example, HIV related stigma leading patients to seek distant services. Travel costs exacerbated by the interplay of several ATM barriers influenced affordability. Providers play a brokerage role by adopting flexible prescribing and dispensing for 'stable' patients and aligning clinic and social grant appointments to minimise clients’ routine costs. Occasionally they reported assisting patients with transport money.

Conclusion: All five ATM barriers are important and they interact in complex ways. Context-sensitive responses which minimise treatment interruption are needed. While broad-based changes encompassing all disease programmes to improve ATM are needed, a beginning could be to assess the appropriateness, feasibility and sustainability of existing brokerage mechanisms.

Abstract Full-text [free] access

Editor’s notes: The literature on health care providers and interactions with people accessing their services often casts the providers in a negative light. This paper focuses only on the providers and their observations on access to essential medicines in South Africa for treating HIV, TB, Type-2 diabetes and depression. The health care providers including nurses, doctors and pharmacy staff, talk of the challenges they face in providing care. Stock outs, transport problems, the mobility of their patients, who as a consequence miss appointments, and the poverty and hardship people face which hamper access to care. The authors provide a nuanced picture of the frustrations that the medical staff face as they try to provide care in an over-stretched public health system. Stories of their efforts to bend the rules to help mobile patients who need extra drugs while they travel, or the money given to help a very poor person get home are set alongside details of supply problems in remote rural clinics. The strength of this paper is that not only do the authors set out the barriers providers face in giving care, but also describe individual efforts made to improve things for people accessing services. These are not silent workers in the health service. They face challenges, yes, but they also have many ideas for how to make things better.

Africa
South Africa
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Laboratory monitoring of paediatric antiretroviral therapy not found to be cost-effective; but cotrimoxazole prophylaxis is

Opportunities for improving the efficiency of paediatric HIV treatment programmes: lessons from the ARROW trial.

Revill PA, Walker S, Mabugu T, Nathoo KJ, Mugyenyi P, Kekitinwa A, Munderi P, Bwakura-Dangarembizi M, Musiime V, Bakeera-Kitaka S, Nahirya-Ntege P, Walker AS, Sculpher MJ, Gibb DP. AIDS. 2014 Nov 13. [Epub ahead of print]

Objectives: To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART.

Design and methods: The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4 tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings.

Results: Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4 monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio = $769/QALY).Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to $12.0 per patient-year to ensure continued provision of cotrimoxazole.

Conclusion: Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4 testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources.

Abstract access 

Editor’s notes: The authors set out to compare the cost-effectiveness of laboratory monitoring versus clinical monitoring of paediatric antiretroviral therapy (ART), and to determine the cost-effectiveness of continuing cotrimoxazole prophylaxis on children after being stabilised on ART. Using data from a trial in Uganda and Zimbabwe, they found that delivering ART with laboratory monitoring was generally more costly when compared with clinical monitoring. This was despite the two approaches having similar health outcomes. Laboratory monitoring was found not to be cost-effective, except potentially in cases of adolescents aged 12 and older (and without carrying out associated toxicity tests). The authors also found that discontinuing cotrimoxazole prophylaxis was both more costly and less effective than continuing provision. Reductions in cost of hospitalisations and prescriptions for malaria and other infections exceeded the costs of providing cotrimoxazole itself. Cost-reductions were similar in both malaria-endemic and non-malaria-endemic settings.

The questions addressed by this study are important because of the context of paediatric HIV in sub-Saharan Africa. As of 2013 only about 32% of children in need, in the region received ART. This background of poor health infrastructure and large gaps in paediatric treatment makes decision-making on limited resource allocation all the more important. The findings on the effectiveness of co-delivery of cotrimoxazole are further evidence of the need for governments and funders alike to think of effective and creative ways of integrating HIV care and treatment priorities within the wider health system.

This study should also be observed in light of changing national and international guidelines on detection of treatment failure. As of 2013, WHO has recommended viral load monitoring as the preferred method. When compared to CD4 testing, viral load monitoring tends to lead to better health outcomes but also requires sophisticated laboratory technology and highly trained technicians. Changing from CD4 to viral load monitoring may be unaffordable and logistically unfeasible in many settings.

Additionally, more countries in sub-Saharan Africa are rolling out point-of-care CD4 testing technologies. As more competitors in the field enter the point-of-care market, prices are likely to decrease. Although the authors have accounted for these future possibilities in their analysis, cost-effectiveness of monitoring of paediatric ART ought to be revisited at a later time once the costs related to point-of-care technologies have been more thoroughly understood.

Africa
Uganda, Zimbabwe
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Addressing the HIV care continuum through home-based HIV testing

Initiation of antiretroviral therapy and viral suppression after home HIV testing and counselling in KwaZulu-Natal, South Africa, and Mbarara district, Uganda: a prospective, observational intervention study.

Barnabas RV, van Rooyen H, Tumwesigye E, Murnane PM, Baeten JM, Humphries H, Turyamureeba B, Joseph P, Krows M, Hughes JP, Celum C. The Lancet HIV Volume 1, Issue 2, November 2014, Pages e68–e76

Antiretroviral therapy significantly decreases HIV-associated morbidity, mortality, and HIV transmission through HIV viral load suppression. In settings of high prevalence, outreach strategies are needed to find asymptomatic HIV-positive people, to link them to HIV care, to initiate antiretroviral therapy, and to achieve viral suppression. We aimed to assess the effect of a community-based strategy of HIV testing and counselling (HTC) and linkage to care in households. We did an uncontrolled prospective intervention study in 1600 households in two rural communities in KwaZulu-Natal, South Africa, and Mbabara district, Uganda, between Sept 27, 2011, and May 6, 2013. The intervention consisted of home HTC and, for HIV-positive people, point-of-care CD4 count testing, referral to care, and follow-up visits by lay counsellors, including the offer of couples HTC. Eligible participants were resident adults who were able to consent to HIV testing. The outcomes at 12 months were linkage to care, antiretroviral therapy initiation among HIV-positive people eligible for therapy (CD4 count ≤350 cells per µL), and viral suppression. We identified 3545 adults in 1549 households in the two communities. 3393 adults (96%) were enrolled and tested for HIV, of whom 635 (19%) were HIV positive. At baseline, 229 (36%) HIV-positive people were newly identified, 406 (64%) were previously known to be HIV positive, and 254 (40%) were taking antiretroviral therapy. By month 12, 619 (97%) HIV-positive people had visited an HIV clinic, and of 123 participants eligible for antiretroviral therapy, 94 (76%) had initiated antiretroviral therapy by 12 months. Of the 77 participants on antiretroviral therapy by month 9, 59 (77%) achieved viral suppression by month 12. Among all HIV-positive people, the number with viral suppression (<1000 copies per mL) increased from 287 (50%) to 370 (65%; p<0·0001) at 12 months. There were no reported cases of study-related social harm during the study. Community-based HTC in rural South Africa and Uganda achieved high coverage of testing and linkage to care. Among people eligible for antiretroviral therapy, a high proportion initiated antiretroviral therapy and achieved viral suppression, suggesting high adherence. Our results could be generalisable to other southern African countries with a high burden of HIV, but pilot studies would be useful in other settings before initiation of clinical trials to estimate the effectiveness and cost-effectiveness of the intervention.

Abstract access 

Editor’s notes: HIV testing is the gateway to accessing treatment and prevention services. But the proportion of people who know their status remains low in many high HIV prevalence settings. In addition, there are serious challenges in facilitating linkage to HIV care, antiretroviral therapy (ART) uptake and adherence. Only a quarter of people living with HIV in sub-Saharan Africa are estimated to be virally suppressed on ART. Routine facility-based HIV testing, termed provider-initiated HIV testing and counselling, is recommended by World Health Organization. However, this strategy identifies individuals at a later stage of HIV infection as it relies on presentation to health care facilities after symptoms have developed. Community-based approaches may therefore be more effective in enabling earlier identification of HIV infection.

This study investigates the effectiveness of home-based HIV testing and counselling (HTC), combined with point-of-care CD4 count testing, referral to care and follow-up visits by lay counsellors at one, three, six, nine and 12 months following an HIV diagnosis. The study not only measured uptake of testing but also investigated the effect of the activity on linkage to care, ART initiation and viral suppression after 12 months.

The results of the study are promising, with high rates of uptake of HIV testing, of linkage to HIV care (including of individuals who had tested previously but had not engaged with health care services) and of initiation of ART. In addition, some 77% of individuals who initiated ART achieved viral suppression at 12 months and the numbers of HIV-positive individuals with viral suppression also increased significantly. The main strengths of this study is that it moves beyond HTC and addresses the entire HIV care continuum. The programme used lay counsellors and community workers which would address the healthcare worker shortage as well as potentially enable ownership of the programme by communities.  However, the incremental contribution of each component of this programme (home HTC, point-of-care CD4 testing and follow-up visits) in achieving the various outcomes is not clear. This merits further study before such a programme can be implemented. Cost-effectiveness studies are also needed if this approach is to be scaled-up in resource-limited settings. 

Africa
South Africa, Uganda
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Increase in pregnancy rates in west Africa after initiation of antiretroviral therapy

Incidence of pregnancy after antiretroviral therapy initiation and associated factors in 8 West African countries.

Burgos-Soto J, Balestre E, Minga A, Ajayi S, Sawadogo A, Zannou MD, Leroy V, Ekouevi DK, Dabis F, Becquet R, IeDEA West Africa Collaboration. J Acquir Immune Defic Syndr. 2014 Oct 1;67(2):e45-54. doi: 10.1097/QAI.0000000000000279.

Introduction: This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in 8 West African countries over a 10-year period.

Methods: A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged <50 years and starting ART for their own health between 1998 and 2011 were eligible. Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, hemoglobin, age, first ART regimen, and calendar year.

Results: Overall, 29 425 HIV-infected women aged 33 years in median (interquartile range, 28-38) contributed for 84 870 woman-years of follow-up to this analysis. The crude incidence of first pregnancy (2304 events) was 2.9 per 100 woman-years [95% confidence interval (CI): 2.7 to 3.0], the highest rate being reported among women aged 25-29 years: 4.7 per 100 woman-years; 95% CI: 4.3 to 5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4 to 11.4) and as high as 28.4% (95% CI: 26.3 to 30.6) among women aged 20-29 years at ART initiation.

Conclusions: The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world.

Abstract access 

Editor’s notes: Women of reproductive age are the largest population affected by HIV infection in sub-Saharan Africa. The wide availability of antiretroviral therapy (ART) has considerably decreased morbidity and mortality among women living with HIV. In addition, the risk of mother-to-child transmission of HIV has also been reduced. The authors hypothesised that the improvement in life expectancy is positively associated with procreation desires and fertility rates observed after ART initiation in several other settings. To test this hypothesis, they conducted a retrospective analysis using data from the International epidemiological Database to Evaluate AIDS (IeDEA). They found that the incidence of pregnancy was high after ART initiation among women living with HIV, although it was lower than among women without HIV in the same countries (four to six livebirths per 100 woman-years). The incidence rate of pregnancy increased slightly but progressively throughout years on ART, suggesting a positive effect of ART on fertility among women of reproductive age, particularly among young women. The authors suggest some biological mechanisms for the effect of ART on fertility. Further research in this area would be useful. Further, there is a large unmet need for family planning among women in west Africa, resulting in high rates of unintended pregnancies. This study highlights the need to understand the dynamics of fertility among women on ART, which is key to informing strategies integrating family planning into HIV care.

 
Africa
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Does pregnancy accelerate HIV progression?

Pregnancy and HIV disease progression: a systematic review and meta-analysis.

Calvert C, Ronsmans C. Trop Med Int Health. 2014 Oct 31. doi: 10.1111/tmi.12412. [Epub ahead of print]

Objective: To assess whether pregnancy accelerates HIV disease progression.

Methods: Studies comparing progression to HIV-related illness, low CD4 count, AIDS-defining illness, HIV-related death, or any death in HIV-infected pregnant and non-pregnant women were included. Relative risks (RR) for each outcome were combined using random effects meta-analysis and were stratified by antiretroviral therapy (ART) availability.

Results: 15 studies met the inclusion criteria. Pregnancy was not associated with progression to HIV-related illness [summary RR: 1.32, 95% confidence interval (CI): 0.66-2.61], AIDS-defining illness (summary RR: 0.97, 95%CI: 0.74-1.25) or mortality (summary RR: 0.97, 95%CI: 0.62-1.53), but there was an association with low CD4 counts (summary RR: 1.41, 95%CI: 0.99-2.02) and HIV-related death (summary RR: 1.65, 95%CI: 1.06-2.57). In settings where ART was available, there was no evidence that pregnancy accelerated progress to HIV/AIDS-defining illnesses, death and drop in CD4 count. In settings without ART availability, effect estimates were consistent with pregnancy increasing the risk of progression to HIV/AIDS-defining illnesses and HIV-related or all-cause mortality, but there were too few studies to draw meaningful conclusions.

Conclusions: In the absence of ART, pregnancy is associated with small but appreciable increases in the risk of several negative HIV outcomes, but the evidence is too weak to draw firm conclusions. When ART is available, the effects of pregnancy on HIV disease progression are attenuated and there is little reason to discourage healthy HIV-infected women who desire to become pregnant from doing so.

Abstract access 

Editor’s notes: The suppression of cell-mediated immunity during pregnancy is associated with increased susceptibility to and/or severity of many infections. Therefore the question of whether pregnancy accelerates HIV disease progression in HIV-positive women is pertinent. A previous systematic review published in the late 1990s found weak evidence that the odds of acquiring an AIDS-defining illness or death were higher among HIV-positive pregnant women than HIV-positive non-pregnant women. The findings from this meta-analysis also suggest that in the absence of antiretroviral therapy (ART), pregnancy is associated with an increase in the risk of several negative HIV outcomes. Fortunately ART appears to diminish the effects of pregnancy on HIV progression.  The authors also draw attention to the methodological weaknesses of the studies included and highlight the need for better quality data, examining whether pregnancy aggravates HIV progression.

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Resistance testing: not cost-effective in determining switches to second-line therapy

Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings.

Phillips A, Cambiano V, Nakagawa F, Magubu T, Miners A, Ford D, Pillay D, De Luca A, Lundgren J, Revill P. PLoS One. 2014 Oct 7;9(10):e109148. doi: 10.1371/journal.pone.0109148. eCollection 2014.

Background: To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations being identified.

Methods: An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa. Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted outcomes were assessed over 2015-2025 in terms of viral suppression, first line failure, switching to second line regimen, death, HIV incidence, disability-adjusted-life-years averted and costs. Potential future low costs of resistance tests ($30) were used.

Results: The most effective strategy, in terms of DALYs averted, was one using viral load monitoring without confirmation. The incremental cost-effectiveness ratio for this strategy was $2113 (the same as that for viral load monitoring with confirmation). ART monitoring strategies which involved resistance testing did not emerge as being more effective or cost effective than strategies not using it. The slightly reduced ART costs resulting from use of resistance testing, due to less use of second line regimens, was of similar magnitude to the costs of resistance tests.

Conclusion: Use of resistance testing at the time of first line failure as part of the decision whether to switch to second line therapy was not cost-effective, even though the test was assumed to be very inexpensive.

Abstract  Full-text [free] access

Editor’s notes: The landscape around first-line treatment modification is changing. The price of second-line treatment has dropped substantially in recent years and several new point-of-care monitoring technologies (CD4 count tests and viral load tests) are (or will soon be) on the market. It is within this context that this article looks at whether drug resistance testing could play a key role in antiretroviral therapy (ART) monitoring in low- and middle-income settings. Simulating the progression of the HIV epidemic in adults in Zimbabwe, Phillips et al. examined different combinations of monitoring strategies. These included CD4 count monitoring, viral load monitoring and confirmation, and resistance testing. They found that the most cost effective option involved using viral load monitoring without confirmation. The reduced costs of ART due to a decrease in use of second-line regimes as a result of the implementation of resistance tests were offset by the costs of the resistance tests themselves. However, the authors do not rule out potential cost-effectiveness for resistance testing under certain circumstances. This could be in ART initiation clinics where large numbers of people have resistance to first-line treatment, or in selecting drug regimens for ART-naïve pregnant women (as it is important to maximise the chance of viral suppression at the time of birth). Future modelling exercises on this issue may benefit from including real-life implementation issues such as health worker deviation from guidelines and system delays in returning of results.

HIV Treatment
Africa
Zimbabwe
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