Articles tagged as "Malawi"

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. 

  • share
0 comments.

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. 

  • share
0 comments.

Pilot integration of HIV and nutrition services shows great potential for health impact

Outcomes and cost-effectiveness of integrating HIV and nutrition service delivery: pilots in Malawi and Mozambique.

Bergmann JN, Legins K, Sint TT, Snidal S, Group UR, Amor YB, McCord GC. AIDS Behav. 2016 Apr 19. [Epub ahead of print]

This paper provides the first estimates of impact and cost-effectiveness for integrated HIV and nutrition service delivery in sub-Saharan Africa. HIV and undernutrition are synergistic co-epidemics impacting millions of children throughout the region. To alleviate this co-epidemic, UNICEF supported small-scale pilot programs in Malawi and Mozambique that integrated HIV and nutrition service delivery. We use trends from integration sites and comparison sites to estimate the number of lives saved, infections averted and/or undernutrition cases cured due to programmatic activities, and to estimate cost-effectiveness. Results suggest that Malawi's program had a cost-effectiveness of $11-29/DALY, while Mozambique's was $16-59/DALY. Some components were more effective than others ($1-4/DALY for Malawi's Male motivators vs. $179/DALY for Mozambique's One stop shops). These results suggest that integrating HIV and nutrition programming leads to a positive impact on health outcomes and should motivate additional work to evaluate impact and determine cost-effectiveness using an appropriate research design.

Abstract access

Editor’s notes: This paper presents outcomes and cost-effectiveness of a variety of programmes intended to facilitate integration of HIV treatment and care services with community management of acute malnutrition (CMAM) services in Malawi and Mozambique. In Malawi, programmes included SMS reminders to encourage attendance and adherence, “male motivators” who encouraged men to be involved in children’s health, and child health passports. In Mozambique, programmes included one-stop shops where children could access HIV-associated and vaccination services. Flowcharts to facilitate referral between HIV and nutrition services were also tried. Difference in difference estimates indicate substantial improvements in child health outcomes, and cost-effectiveness estimates are in line with other services. The programmes were funded by UNICEF, and not designed for research purposes. The authors therefore acknowledge some limitations in the external validity of their findings.  This paper should be taken as proof of concept rather than a final word on the effectiveness or cost-effectiveness of these activities. However, these preliminary estimates illustrate that there is great potential in facilitating integration of these two services.  Further research into integration of nutritional support services with HIV services is necessary.

Africa
Malawi, Mozambique
  • share
0 comments.

Profound effect of ART on mortality through reduction of opportunistic infections

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

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

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

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

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

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

Abstract  Full-text [free] access

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

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

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

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

Africa, Asia, Latin America
  • share
0 comments.

Option B+: the way forward for Malawi

Comparative cost-effectiveness of Option B+ for prevention of mother-to-child transmission of HIV in Malawi.

Tweya H, Keiser O, Haas AD, Tenthani L, Phiri S, Egger M, Estill J. AIDS. 2016 Mar 27;30(6):953-62. doi: 10.1097/QAD.0000000000001009.

Objective: To estimate the cost-effectiveness of prevention of mother-to-child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared with ART during pregnancy or breastfeeding only unless clinically indicated ('Option B').

Design: Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme.

Methods: Individual-based simulation model. We simulated cohorts of 10 000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterized the model with data from the literature and by analysing programmatic data. We compared total costs of antenatal and postnatal care, and lifetime costs and disability-adjusted life-years of the infected infants between Option B+ and Option B.

Results: During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared with 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted.

Conclusion: Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

Abstract access

Editor’s notes: Nearly a quarter of a million children acquire HIV from their mothers every year. Antiretroviral therapy (ART) in pregnant women greatly reduces the risk of mother-to-child HIV transmission to less than two percent. Malawi was the first country to introduce ‘Option B+’, a programme eliminating new HIV infections among children and keeping their mothers alive, in which all pregnant and breastfeeding women living with HIV start lifelong ART regardless of CD4 count or clinical staging. This study compares the cost-effectiveness of Option B+ in Malawi, with Option B, in which ART is recommended only for the duration of pregnancy or breastfeeding, unless the woman qualifies for ART for her own health. Both options have been recommended by World Health Organisation prevention of mother-to-child HIV transmission strategies.

The model simulated a cohort of 10 000 women pregnant for the first time, from conception to the time when the infants were two years old. The authors found that although the total costs of implementing Option B+ were higher than those of Option B, the former can reduce the costs of HIV care and treatment in the future by preventing new infections. The incremental cost-effectiveness ratio of Option B+ compared to Option B, ranged from USD 500 to USD 1300 per disability-adjusted life-years averted, depending on key assumptions around survival and care. The results support the implementation of Option B+ as it is likely to be a cost-effective strategy in the long term and the authors suggest it should be considered as the preferred strategy in low-income, high-fertility settings.

Like all models, this model has some limitations. It only considers women’s first two pregnancies, but the fertility rate in Malawi is high (5.5 births per woman). The model limits itself to mother-to-child HIV transmission, and does not take into account sexual transmission, which is likely to be lower in Option B+. Further research in these two areas would be worthwhile. The landscape is quickly changing, as World Health Organization guidelines now suggest testing and treatment strategies. However, until that policy is fully implemented and absorbed across the world, Option B+ will remain a key element in the HIV response.

Africa
Malawi
  • share
0 comments.

The conundrum of future funding for HIV – who pays and how?

Long-term financing needs for HIV control in sub-Saharan Africa in 2015-2050: a modelling study. 

Atun R, Chang AY, Ogbuoji O, Silva S, Resch S, Hontelez J, Barnighausen T. BMJ Open. 2016 Mar 6;6(3):e009656. doi: 10.1136/bmjopen-2015-009656.

Objectives: To estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in Africa under different scenarios of intervention scale-up. To analyse the gaps between current expenditures and funding obligation, and discuss the policy implications of future financing needs.

Design: We used the Goals module from Spectrum, and applied the most up-to-date cost and coverage data to provide a range of estimates for future financing obligations. The four different scale-up scenarios vary by treatment initiation threshold and service coverage level. We compared the model projections to current domestic and international financial sources available in selected SSA countries.

Results: In the 9 SSA countries, the estimated resources required for HIV prevention and treatment in 2015-2050 range from US$98 billion to maintain current coverage levels for treatment and prevention with eligibility for treatment initiation at CD4 count of <500/mm3 to US$261 billion if treatment were to be extended to all HIV-positive individuals and prevention scaled up. With the addition of new funding obligations for HIV–which arise implicitly through commitment to achieve higher than current treatment coverage levels–overall financial obligations (sum of debt levels and the present value of the stock of future HIV funding obligations) would rise substantially.

Conclusions: Investing upfront in scale-up of HIV services to achieve high coverage levels will reduce HIV incidence, prevention and future treatment expenditures by realising long-term preventive effects of ART to reduce HIV transmission. Future obligations are too substantial for most SSA countries to be met from domestic sources alone. New sources of funding, in addition to domestic sources, include innovative financing. Debt sustainability for sustained HIV response is an urgent imperative for affected countries and donors

Abstract  Full-text [free] access 

Editor’s notes: The authors of this interesting paper use the most up-to-date cost and coverage data to provide a range of estimates for future treatment financing obligations. Epidemiological parameters are included to fit the Goals model and key prevention services such as ‘prevention of mother-to-child HIV transmission’ and ‘voluntary medical male circumcision’ are also included.

Financing needs for the nine countries are estimated by varying treatment initiation threshold (everyone initiated on treatment versus initiation at CD4 of <500cells/mm3) and/or coverage level for prevention and treatment (‘current’ levels and a ‘scale up’ scenario). The authors also attempt to assess both the ethics and the cost of different approaches.

For all scenarios, there is a steady decline in proportion of treatment costs and an increase in the proportion of prevention costs. This apparent contradiction is largely because there will be fewer individuals on treatment over time but prevention costs rise because they are mostly invested in non-infected populations, which increases with population growth.

In the nine countries, estimated resources required for HIV prevention and treatment from 2015-2050 will be large. This is increased further when human resources and supplies increase at the rate of GDP per capita.

However, there is undoubtedly an ethical responsibility to not only continue financing people receiving ART, but, that the responsibility extends to people in equal need who are not on treatment. The ethics is underpinned by the evidence. This illustrates how ‘front-loading’ investments in HIV scale-up now to ensure high levels of coverage, will significantly reduce future HIV incidence and prevalence. 

Africa
  • share
0 comments.

Empirical TB treatment no better than isoniazid among people with low CD4 counts and negative TB tests

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial. 

Hosseinipour MC, Bisson GP, Miyahara S, Sun X, Moses A, Riviere C, Kirui FK, Badal-Faesen S, Lagat D, Nyirenda M, Naidoo K, Hakim J, Mugyenyi P, Henostroza G, Leger PD, Lama JR, Mohapi L, Alave J, Mave V, Veloso VG, Pillay S, Kumarasamy N, Bao J, Hogg E, Jones L, Zolopa A, Kumwenda J, Gupta A, Adult ACTGAST. Lancet. 2016 Mar 19;387(10024):1198-209. doi: 10.1016/S0140-6736(16)00546-8.

Background: Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings.

Methods: We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per µL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert® MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2.5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080.

Findings: Between Oct 31, 2011, and June 9, 2014, we enrolled 850 participants. Of these, we randomly assigned 424 to receive empirical tuberculosis therapy and 426 to the isoniazid preventive therapy group. The median CD4 cell count at baseline was 18 cells per µL (IQR 9-32). At week 24, 22 (5%) participants from each group died or were of unknown status (95% CI 3.5-7.8) for empirical group and for isoniazid preventive therapy (95% CI 3.4-7.8); absolute risk difference of -0.06% (95% CI -3.05 to 2.94). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%) participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the empirical group and 97 (23%) participants in the isoniazid preventive therapy group.

Interpretation: Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating antiretroviral therapy. The low mortality rate of the trial supports implementation of systematic tuberculosis screening and isoniazid preventive therapy in outpatients with advanced HIV disease.

Abstract access

Editor’s notes: Tuberculosis (TB) remains the leading cause of death among HIV-positive people worldwide. Existing diagnostic tests for TB lack sensitivity, particularly among HIV-positive people, and autopsy studies consistently illustrate that TB is common at death, but often not identified prior to death. This has led to questions about whether empirical TB treatment, meaning treatment for TB in the absence of bacteriological confirmation, should be more widely used among HIV-positive people.

This trial compared empirical TB treatment to isoniazid preventive therapy among adult outpatients with very low CD4 counts starting antiretroviral therapy (ART). People could be enrolled in the study if they did not have confirmed or suspected TB based on symptoms, locally-accessible diagnostic tests (including chest radiography and sputum smear) and, when available, testing with Xpert® MTB/RIF. There was no difference in mortality at six months between participants given empirical TB treatment compared to isoniazid preventive therapy. Mortality was remarkably low overall, particularly considering that participants had very low CD4 counts. It seems likely that the enrolment criteria excluded people at highest risk of death from participating in the study.

Screening for TB at the time of starting ART could reduce mortality if the tests are sufficiently sensitive, and if people identified to have TB receive effective treatment. However, this study was not designed to address how best to do this in resource-limited settings, where chest radiography and Xpert® MTB/RIF are often not accessible. This study does suggest that isoniazid preventive therapy can be given at the time of ART initiation among people who have been effectively screened for TB. The results of other studies of empirical TB treatment, with different designs in different populations, are awaited. Data from all these studies together may provide evidence to guide the optimal package of care for people presenting with advanced HIV disease. 

Comorbidity, HIV Treatment
Africa, Asia, Latin America
  • share
0 comments.

Tenofovir resistance – need for caution but not panic

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

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

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

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

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

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

Abstract  Full-text [free] access 

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

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

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

  • share
0 comments.

Understanding barriers and facilitators to uptake and adherence of ART under Option B+ in Lilongwe, Malawi

Why did I stop? Barriers and facilitators to uptake and adherence to ART in option B+ HIV care in Lilongwe, Malawi.

Kim MH, Zhou A, Mazenga A, Ahmed S, Markham C, Zomba G, Simon K, Kazembe PN, Abrams EJ. PLoS One. 2016 Feb 22;11(2):e0149527. doi: 10.1371/journal.pone.0149527. eCollection 2016.

Causes for loss-to-follow-up, including early refusals of and stopping antiretroviral therapy (ART), in Malawi's Option B+ program are poorly understood. This study examines the main barriers and facilitators to uptake and adherence to ART under Option B+. In depth interviews were conducted with HIV-infected women who were pregnant or postpartum in Lilongwe, Malawi (N = 65). Study participants included women who refused ART initiation (N = 10), initiated ART and then stopped (N = 26), and those who initiated ART and remained on treatment (N = 29). The barriers to ART initiation were varied and included concerns about partner support, feeling healthy, and needing time to think. The main reasons for stopping ART included side effects and lack of partner support. A substantial number of women started ART after initially refusing or stopping ART. There were several facilitators for re-starting ART, including encouragement from community health workers, side effects subsiding, decline in health, change in partner, and fear of future sickness. Amongst those who remained on ART, desire to prevent transmission and improve health were the most influential facilitators. Reasons for refusing and stopping ART were varied. ART-related side effects and feeling healthy were common barriers to ART initiation and adherence. Providing consistent pre-ART counseling, early support for patients experiencing side effects, and targeted efforts to bring women who stop treatment back into care may improve long term health outcomes.

Abstract  Full-text [free] access 

Editor’s notes: Option B+ is a policy recommendation of World Health Organisation (WHO) that offers all pregnant and breast-feeding women living with HIV, life-long antiretroviral therapy (ART), regardless of CD4 count or clinical stage. Few studies have examined the challenges faced by pregnant and breast-feeding women, as they navigate the prevention of mother-to-child transmission cascade. The objective of this study was to identify the main barriers and facilitators to uptake and adherence to ART under Option B+ in Lilongwe, Malawi. This was done by conducting qualitative interviews (n=65) with women living with HIV who were pregnant or post-partum and had initiated ART, and women who refused or had stopped treatment.

The most important facilitator for initially starting and remaining on ART was the need to prevent transmission to their infants and to maintain health (prevent illness). Furthermore, ART was viewed as a solution to women’s health issues. This was especially the case when women believed that their health problems were associated with their HIV infection. There were a number of reasons that emerged for refusing ART. For most women the urgency of having to initiate ART under Option B+ was a major challenge. Women felt that they needed time, either to discuss their status with their partner or to accept their own status. In particular, the desire to speak to their partners emerged quite prominently reflecting a fear of disclosure and concern about their partner’s reaction. Another reason was generally feeling healthy before initiating treatment. Women wanted to wait until their health declined before initiating treatment. Religious beliefs did not play a significant role for most women. Only one woman refused because she believed that God, not healthcare providers, would tell her when she needed to start treatment. Side effects were the most commonly reported reason for stopping ART. Half of the 26 (N = 13) respondents who stopped ART did so because they experienced side effects, which included dizziness, nausea or vomiting, nightmares and hallucinations (9%). Women who had side effects also expressed challenges with food security. Side effects made some women question the efficacy of ART. The lack of partner support was another important barrier to ART adherence as women reported fear of disclosing their status to their husbands. Interestingly, although partner support was factored into women’s decision making, in most cases it was not the main consideration. The majority of partners (n=44) accepted their wives’ status, often sending reminders to take ART every night. However, many women did not return to the clinic even though their partners accepted their status (N = 17). One woman, for instance, took the money her husband gave her for transport to the clinic and spent it on other things. Forgetting to take pills or losing pills were other reasons given for lack of adherence. Stigma within the community was acknowledged as an issue, but there were few reports of overt discrimination. Further, even though some women refused or stopped ART, many of them re-started for reasons such as, feeling encouraged by a community health worker (CHW) or someone like a CHW. This was through their monthly home visits to check on women’s use of ART and to provide treatment support such as explaining the side-effects, counselling husbands and encouraging women to re-start. Decline in health, fear of future sickness, as well as reduction in side-effects were mentioned as reasons for re-starting on ART.

Overall, study authors mention that in the context of Option B+, inadequate time in preparing to initiate ART, as well as side effects emerged as more significant barriers as compared to previous studies on barriers and facilitators in non-Option B+ contexts. Economic barriers to care did not emerge as very significant in this study when comparted to other studies; however, a lack of food affects the severity of side effects. This suggests that economic barriers may manifest as an indirect mechanism that affects ART use. A strength of this study is the use of in-depth interviews with a range of women; not just women who stayed on ART, but also women who refused, stopped and re-started in the context of Option B+. Even though there might be overlap between the findings here and other qualitative research, particular barriers become more salient for women initiating ART in the context of Option B+. In prior assessments, women were only initiated on ART after being immunologically compromised, an assessment which often took longer than a month. This gave women time to reflect and accept their condition and communicate with their partner. In the case of Option B+ women felt they needed this time to prepare. The study demonstrates that challenges with uptake and adherence to ART remain. More time and support for women in decision-making, consistent pre-ART counselling, and support with side-effects may contribute to improvements in the long-run. As ART becomes increasingly normalised, some of these barriers may disappear.

Africa
Malawi
  • share
0 comments.

The dapivirine ring confers moderate efficacy, but hope for a new prevention option

Use of a vaginal ring containing dapivirine for HIV-1 prevention in women.

Baeten JM, Palanee-Phillips T, Brown ER, Schwartz K, Soto-Torres LE, Govender V, Mgodi NM, Matovu Kiweewa F, Nair G, Mhlanga F, Siva S, Bekker LG, Jeenarain N, Gaffoor Z, Martinson F, Makanani B, Pather A, Naidoo L, Husnik M, Richardson BA, Parikh UM, Mellors JW, Marzinke MA, Hendrix CW, van der Straten A, Ramjee G, Chirenje ZM, Nakabiito C, Taha TE, Jones J, Mayo A, Scheckter R, Berthiaume J, Livant E, Jacobson C, Ndase P, White R, Patterson K, Germuga D, Galaska B, Bunge K, Singh D, Szydlo DW, Montgomery ET, Mensch BS, Torjesen K, Grossman CI, Chakhtoura N, Nel A, Rosenberg Z, McGowan I, Hillier S, Team M-AS N Engl J Med. 2016 Feb 22. [Epub ahead of print]

Background: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection.

Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe.

Results: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.05) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups.

Conclusions: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence.

 Abstract  Full-text [free] access 

Editor’s notes: Women bear a larger proportion of the HIV burden worldwide due to biological and behavioural factors. As a result, the HIV prevention field has focused research over the past couple of decades to identify new prevention options especially for women, to reduce this burden. The study presented in this paper is the first to publish phase III efficacy trial results for a vaginal ring containing the antiretroviral drug dapivirine for HIV prevention. The ring is designed to prevent HIV acquisition locally within the vagina in HIV negative women and kept in the body for a period of four weeks. This strategy is meant to address two components of adherence and side effects. A longer-acting product and local application is contrasted with the daily and systemic use of oral pre-exposure prophylaxis, a regimen which can be difficult to maintain. This study found that the dapivirine ring did not protect women with a high rate of efficacy, 27% overall. Interestingly, the sub-analyses of the data illustrated that there was better protection in women with better adherence, and in women who were over the age of 21. Further explorations of the data along with the qualitative findings from the study will surely provide more valuable insights into the low overall rate of efficacy, and perhaps most importantly into why age made such a difference in rates of protection. As mentioned in the paper, a second study on the ring, which was presented at CROI 2016, publishing similar results, and those results combined with the data from this study will further our knowledge regarding the viability of this HIV prevention option.  

Africa
Malawi, South Africa, Uganda, Zimbabwe
  • share
0 comments.