Articles tagged as "Botswana"

Antiretroviral therapy dramatically reduces transmission of HIV to sexual partners

Antiretroviral therapy for the prevention of HIV-1 transmission.

Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Cottle L, Zhang XC, Makhema J, Mills LA, Panchia R, Faesen S, Eron J, Gallant J, Havlir D, Swindells S, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano DD, Essex M, Hudelson SE, Redd AD, Fleming TR. N Engl J Med. 2016 Jul 18. [Epub ahead of print]

Background: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission.

Methods: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis.

Results: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant.

Conclusions: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

Abstract access

Editor’s notes: The HPTN 052 trial has been a landmark study in establishing antiretroviral therapy as a strategy for preventing onward transmission of HIV. It was a study of more than 800 couples. More than half of the couples were in African countries. In each couple, one sexual partner was HIV positive and the other HIV negative.  The participants living with HIV were randomised either to receive immediate antiretroviral therapy or to delay until their CD4 count fell to 350, an approved approach at that time. The HIV negative partners were then monitored for acquisition of HIV.  When new HIV infections occurred, the virus was studied for genetic similarity to the virus of the known positive partner. The interim analysis was published in 2011.  It illustrated the programme to be so effective that the randomisation was ended and all the participants living with HIV were offered antiretroviral therapy. 

This article presents data after five years of follow-up, and if anything the results are even more remarkable. In more than 10 000 person-years of follow up, there were only eight transmissions of genetically linked virus from participants receiving antiretroviral therapy. Of these transmissions, four occurred early in treatment when the viral load would not be expected to be suppressed.  The other four occurred after treatment failure. In this enormous study, there were therefore no linked transmissions from participants who were stable on treatment without detectable viraemia. The study provides powerful support for the UNAIDS 90-90-90 treatment target.  The widest possible effective use of antiretroviral therapy will not only improve the health of people treated but could have a dramatic effect on new HIV infections.

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HIV-exposed uninfected children – why the increased mortality risk?

HIV-exposed children account for more than half of 24-month mortality in Botswana.

Zash R, Souda S, Leidner J, Ribaudo H, Binda K, Moyo S, Powis KM, Petlo C, Mmalane M, Makhema J, Essex M, Lockman S, Shapiro R. BMC Pediatr. 2016 Jul 21;16:103. doi: 10.1186/s12887-016-0635-5.

Background: The contribution of HIV-exposure to childhood mortality in a setting with widespread antiretroviral treatment (ART) availability has not been determined.

Methods: From January 2012 to March 2013, mothers were enrolled within 48 h of delivery at 5 government postpartum wards in Botswana. Participants were followed by phone 1-3 monthly for 24 months. Risk factors for 24-month survival were assessed by Cox proportional hazards modeling.

Results: Three thousand mothers (1499 HIV-infected) and their 3033 children (1515 HIV-exposed) were enrolled. During pregnancy 58% received three-drug ART, 23% received zidovudine alone, 11% received no antiretrovirals (8% unknown); 2.1% of children were HIV-infected by 24 months. Vital status at 24 months was known for 3018 (99.5%) children; 106 (3.5%) died including 12 (38%) HIV-infected, 70 (4.7%) HIV-exposed uninfected, and 24 (1.6%) HIV-unexposed. Risk factors for mortality were child HIV-infection (aHR 22.6, 95% CI 10.7, 47.5), child HIV-exposure (aHR 2.7, 95% CI 1.7, 4.5) and maternal death (aHR 8.9, 95% CI 2.1, 37.1). Replacement feeding predicted mortality when modeled separately from HIV-exposure (aHR 2.3, 95% CI 1.5, 3.6), but colinearity with HIV-exposure status precluded investigation of its independent effect. Applied at the population level (26% maternal HIV prevalence), an estimated 52% of child mortality occurs among HIV-exposed or HIV-infected children.

Conclusions: In a programmatic setting with high maternal HIV prevalence and widespread maternal and child ART availability, HIV-exposed and HIV-infected children still account for most deaths at 24 months. Lack of breastfeeding was a likely contributor to excess mortality among HIV-exposed children.

Abstract  Full-text [free] access 

Editor’s notes: It has been known for some time that HIV-exposed but uninfected children have a higher risk of death than HIV-unexposed children. There is now a need for prospective studies to explore the mechanisms underlying this observation. In this study from Botswana, one of every 20 HIV-exposed but uninfected children had died by 24 months. Four in every five deaths in the HIV-exposed but uninfected children were attributed to infectious diseases, most commonly diarrhoeal illness and respiratory infections.

The analysis was unfortunately not able to unpick the effect of infant feeding on mortality in the HIV-exposed uninfected children. Only 16% of HIV-exposed children were breastfed. This is consistent with national guidelines at the time, where formula feeding was recommended for mothers living with HIV. It is reassuring that in recently updated national guidelines, exclusive breastfeeding for six months is now recommended for mothers living with HIV on ART with virologic suppression.

Mother-to-child HIV transmission at 24 months was still around 2%, and further infections may have been undiagnosed in children who died before being tested. More than one in three children living with HIV died within 24 months. This reminds us that while there is increasing interest in HIV-exposed uninfected children, our priority for now should still be achieving elimination of mother-to-child HIV transmission.

Africa
Botswana
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Changing norms: lessons from HIV advocacy for NCDs prevention

Ability of HIV advocacy to modify behavioral norms and treatment impact: a systematic review.

Sunguya BF, Munisamy M, Pongpanich S, Yasuoka J, Jimba M. Am J Public Health. 2016 Aug;106(8):e1-e8. Epub 2016 Jun 16.

Background: HIV advocacy programs are partly responsible for the global community's success in reducing the burden of HIV. The rising wave of the global burden of noncommunicable diseases (NCDs) has prompted the World Health Organization to espouse NCD advocacy efforts as a possible preventive strategy. HIV and NCDs share some similarities in their chronicity and risky behaviors, which are their associated etiology. Therefore, pooled evidence on the effectiveness of HIV advocacy programs and ideas shared could be replicated and applied during the conceptualization of NCD advocacy programs. Such evidence, however, has not been systematically reviewed to address the effectiveness of HIV advocacy programs, particularly programs that aimed at changing public behaviors deemed as risk factors.

Objectives: To determine the effectiveness of HIV advocacy programs and draw lessons from those that are effective to strengthen future noncommunicable disease advocacy programs.

Search methods: We searched for evidence regarding the effectiveness of HIV advocacy programs in medical databases: PubMed, The Cumulative Index to Nursing and Allied Health Literature Plus, Educational Resources and Information Center, and Web of Science, with articles dated from 1994 to 2014.

Search criteria. The review protocol was registered before this review. The inclusion criteria were studies on advocacy programs or interventions. We selected studies with the following designs: randomized controlled design studies, pre-post intervention studies, cohorts and other longitudinal studies, quasi-experimental design studies, and cross-sectional studies that reported changes in outcome variables of interest following advocacy programs. We constructed Boolean search terms and used them in PubMed as well as other databases, in line with a population, intervention, comparator, and outcome question. The flow of evidence search and reporting followed the standard Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

Data collection and analysis: We selected 2 outcome variables (i.e., changing social norms and a change in impact) out of 6 key outcomes of advocacy interventions. We assessed the risk of bias for all selected studies by using the Cochrane risk-of-bias tool for randomized studies and using the Risk of Bias for Nonrandomized Observational Studies for observational studies. We did not grade the collective quality of evidence because of differences between the studies, with regard to methods, study designs, and context. Moreover, we could not carry out meta-analyses because of heterogeneity and the diverse study designs; thus, we used a narrative synthesis to report the findings.

Main results: A total of 25 studies were eligible, of the 1463 studies retrieved from selected databases. Twenty-two of the studies indicated a shift in social norms as a result of HIV advocacy programs, and 3 indicated a change in impact. We drew 6 lessons from these programs that may be useful for noncommunicable disease advocacy: (1) involving at-risk populations in advocacy programs, (2) working with laypersons and community members, (3) working with peer advocates and activists, (4) targeting specific age groups and asking support from celebrities, (5) targeting several, but specific, risk factors, and (6) using an evidence-based approach through formative research.

Author conclusions: HIV advocacy programs have been effective in shifting social norms and facilitating a change in impact.

Public health implications: The lessons learned from these effective programs could be used to improve the design and implementation of future noncommunicable disease advocacy programs.

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Editor’s notes: This article presents the results of a systematic review to answer a question about the effectiveness of HIV advocacy in changing social norms and changing impact among key populations. The review was conducted to learn from effective HIV advocacy and apply similar strategies for the prevention and reduction of the global burden of non-communicable diseases. The review included quantitative research only. After searching 3320 articles, 25 articles met the inclusion criteria. The HIV advocacy activities reviewed ranged from local and mass campaigns using a variety of media, to social marketing, celebrities, drama, promotional activities and counselling. Changes in social norms were assessed using six specific variables, for example testing behaviour change or HIV-associated stigma. Changes in impact were analysed in two aspects, changes in HIV transmission and in adherence to antiretroviral therapy. The review has found significant evidence of the effect of HIV advocacy on the outcomes of interest. The authors highlight lessons from HIV advocacy that might be useful for future non-communicable diseases advocacy. These included the vital role of peer-educator and of lay members of the community and the involvement of key populations in programmes that focus on them.  In addition, there is a need to tailor programmes to specific (rather than multiple) risks using local and salient evidence. 

Africa, Northern America, Oceania
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Oral PrEP reduces risk of HIV and does not result in riskier sex

Effectiveness and safety of oral HIV pre-exposure prophylaxis (PrEP) for all populations: A systematic review and meta-analysis.

Fonner VA, Dalglish SL, Kennedy CE, Baggaley R, O'Reilly K R, Koechlin FM, Rodolph M, Hodges-Mameletzis I, Grant RM. AIDS. 2016 May 5. [Epub ahead of print]

Objective: Pre-exposure prophylaxis (PrEP) offers a promising new approach to HIV prevention. This systematic review and meta-analysis evaluated the evidence for use of oral PrEP containing tenofovir disoproxil fumarate (TDF) as an additional HIV prevention strategy in populations at substantial risk for HIV based on HIV acquisition, adverse events, drug resistance, sexual behavior, and reproductive health outcomes.

Design: Rigorous systematic review and meta-analysis.

Methods: A comprehensive search strategy reviewed three electronic databases and conference abstracts through April 2015. Pooled effect estimates were calculated using random-effects meta-analysis.

Results: Eighteen studies were included, comprising data from 39 articles and six conference abstracts. Across populations and PrEP regimens, PrEP significantly reduced the risk of HIV acquisition compared to placebo. Trials with PrEP use >70% demonstrated the highest PrEP effectiveness (RR = 0.30, 95% CI: 0.21-0.45, p < 0.001) compared to placebo. Trials with low PrEP use did not show a significantly protective effect. Adverse events were similar between PrEP and placebo groups. More cases of drug-resistant HIV infection were found among PrEP users who initiated PrEP while acutely HIV-infected, but incidence of acquiring drug-resistant HIV during PrEP use was low. Studies consistently found no association between PrEP use and changes in sexual risk behavior. PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness.

Conclusion: PrEP is protective against HIV infection across populations, presents few significant safety risks, and no evidence of behavioral risk compensation. The effective and cost-effective use of PrEP will require development of best practices for fostering uptake and adherence among people at substantial HIV-risk.

Abstract access

Editor’s notes: This systematic review is the first to aggregate data from across oral pre-exposure prophylaxis (PrEP) studies, including randomized control trials and observational studies, to present clear evidence on the effectiveness of oral PrEP use. The findings confirm that oral PrEP significantly reduces the risk of acquiring HIV if taken consistently and correctly across populations, countries, and most age groups. Differences in efficacy directly correlate with adherence, which accounts for the lower efficacy seen in some subgroups. Perhaps two of the most compelling analyses presented in this paper relate to resistance and behavioural disinhibition. The risk of resistance was shown to be quite low, and study participants exhibiting resistant HIV either enrolled in the studies during an acute infection stage or acquired resistant strains during the course of the research. Regarding behavioural disinhibition, indicators measured such as rates of sexually transmitted infections revealed that PrEP use in the efficacy trials was not associated with behavioural disinhibition and in some studies, resulted in even safer sexual behaviour than what was reported at baseline. Recently completed demonstration projects have reported increased rates of STIs among gay men and other men who have sex with men. However, in the open-label extensions included in this review, where counselling was more intensive, safer sex practices were maintained, thus suggesting that counselling can be effective in preventing behavioural disinhibition. 

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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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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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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
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Tenofovir resistance – need for caution but not panic

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

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

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

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

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

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

Abstract  Full-text [free] access 

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

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

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

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The effects of trauma follow people on the move

A systematic review of HIV risk behaviors and trauma among forced and unforced migrant populations from low and middle-income countries: state of the literature and future directions.

Michalopoulos LM, Aifah A, El-Bassel N. AIDS Behav. 2016 Feb;20(2):243-61. doi: 10.1007/s10461-015-1014-1.

The aim of the current systematic review is to examine the relationship between trauma and HIV risk behaviors among both forced and unforced migrant populations from low and middle income countries (LMIC). We conducted a review of studies published from 1995 to 2014. Data were extracted related to (1) the relationship between trauma and HIV risk behaviors, (2) methodological approach, (3) assessment methods, and (4) differences noted between forced and unforced migrants. A total of 340 records were retrieved with 24 studies meeting inclusion criteria. Our review demonstrated an overall relationship between trauma and HIV risk behaviors among migrant populations in LMIC, specifically with sexual violence and sexual risk behavior. However, findings from 10 studies were not in full support of the relationship. Findings from the review suggest that additional research using more rigorous methods is critically needed to understand the nature of the relationship experienced by this key-affected population.

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Editor’s notes: The number of forced and unforced migrants is growing globally. Refugees, asylum seekers, and internally displaced persons (IDP) are forced migrants who often migrate due to political violence or conflict. Labour migrants are seen as unforced migrants who choose to emigrate for economic reasons. About half of labour migrants worldwide are women who are increasingly migrating on their own being the sole income provider for their families. With respect to trauma exposure and HIV risk in settings of long-term political violence and conflict, the distinction between war migrant, non-war migrant, and long-term resident is blurred. This in-depth review of 24 studies related to low-and middle-income countries (LMIC), mostly from sub-Saharan Africa, found findings similar to those from non-migrant populations in high-income countries. These linked traumatic experiences among migrant populations with HIV risk behaviours. Sexual violence was consistently associated with HIV sexual risk behaviours and HIV infection across the studies. But there are big gaps in the scientific literature. For example, the relationship between trauma and HIV risks has been explored for female labour migrants who are sex workers but not among women who have other occupations. Most studies addressed sexual risk and alcohol dependence, but injecting drug risk behaviours and use of any illicit drugs were virtually ignored by most studies. Few studies examined a possible link for trauma that occurred pre-migration and post-migration. Three qualitative studies examined male migrants who have sex with men, finding that violent experiences and discrimination and stigma associated with homophobia, combined with other migrant-associated traumas, can compound their mental health outcomes and subsequent HIV risk behaviours – but all were only conducted in the last four years. No studies were found that focused on HIV prevention programmes to address trauma and HIV risks among migrant workers in LMIC. However, the studies do reveal important factors that prevention programmes would have to consider. For example, concerns among labour migrants about dangerous working conditions may take precedence over HIV risk perceptions and the need for safer sex. This systematic review presents a wealth of information while highlighting the need to improve the quality of scientific research examining the link between HIV and trauma among both forced and unforced migrants in LMIC. 

Africa, Asia, Europe, Latin America
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