Articles tagged as "United Republic of Tanzania"

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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Sex on the move

Exploring the relationship between population mobility and HIV risk: evidence from Tanzania.

Deane KD, Samwell Ngalya P, Boniface L, Bulugu G, Urassa M. Glob Public Health. 2016 May 27:1-16. [Epub ahead of print]

Migration and population mobility has long been regarded as an important structural driver of HIV. Following initial concerns regarding the spatial spread of the disease, mobile populations are viewed to engage in higher levels of risky sexual behaviours than non-mobile groups. However, beyond the case studies of mineworkers and truck drivers, the statistical evidence is inconclusive, suggesting that the relationship between mobility and risk is not well understood. This study investigated how engaging in specific livelihoods that involve mobility influences sexual behaviour and HIV risk. A qualitative research project, including focus groups and in-depth interviews with key mobile groups, was conducted in Northern Tanzania. The findings show that the patterns and conditions of moving related to the requirements of each different economic activity influence the nature of relationships that mobile groups have whilst away, how and where local sexual networks are accessed, and the practicalities of having sex. This has further implications for condom use. Risk behaviours are also shaped by local sexual norms related to transactional sex, emphasising that the roles of mobility and gender are interrelated, overlapping and difficult to disentangle.

Abstract access  

Editor’s notes: Case studies with truck drivers and mineworkers have clearly shown a relationship between migration, mobility and HIV risk in sub-Saharan Africa. It remains unclear to what extent findings from these case studies can be extrapolated across all mobile populations. Evidence from studies in other populations is inconclusive, inconsistent and in some cases contradictory. This, in part is due to the limitations of the statistical frameworks used which tend to reduce migration to an abstract individual variable and fail to recognise migration as a dynamic socio-economic phenomenon. These frameworks may also inadequately reflect the variability of migratory behaviour offering limited policy conclusions for addressing HIV risk arising from migration or population mobility.

This qualitative study was conducted in North-western Tanzania in a population in which 60% of men and 43% of women were classified as mobile. Data were collected through focus group discussions and individual interviews with both female and male farmers and maize traders.

The findings of this study suggest that patterns and conditions of moving can influence the nature of sexual relationships that mobile individuals have while away. The findings offer important insights for future, more nuanced statistical work. This would include considering why people move, where they go, patterns of movement, the specific economic activities in which they engage, and where they stay while they are away. The findings also highlight the importance of situating the risk behaviours of mobile individuals within the sexual norms and practices around sex and exchange, and particularly transactional sex. The authors note that being mobile may exacerbate gendered and economic inequalities making the relative influences of mobility and sexual norms difficult to disentangle. This further highlights the value of HIV prevention programmes being specifically tailored to the specific needs of mobile populations.

Africa
United Republic of Tanzania
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Role for LAM test in TB diagnosis among the sickest people living with HIV

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults.

Shah M, Hanrahan C, Wang ZY, Dendukuri N, Lawn SD, Denkinger CM, Steingart KR. Cochrane Database Syst Rev. 2016 May 10;5:CD011420. doi: 10.1002/14651858.CD011420.pub2.

Background: Rapid detection of tuberculosis (TB) among people living with human immunodeficiency virus (HIV) is a global health priority. HIV-associated TB may have different clinical presentations and is challenging to diagnose. Conventional sputum tests have reduced sensitivity in HIV-positive individuals, who have higher rates of extrapulmonary TB compared with HIV-negative individuals. The lateral flow urine lipoarabinomannan assay (LF-LAM) is a new, commercially available point-of-care test that detects lipoarabinomannan (LAM), a lipopolysaccharide present in mycobacterial cell walls, in people with active TB disease.

Objectives: To assess the accuracy of LF-LAM for the diagnosis of active TB disease in HIV-positive adults who have signs and symptoms suggestive of TB (TB diagnosis). To assess the accuracy of LF-LAM as a screening test for active TB disease in HIV-positive adults irrespective of signs and symptoms suggestive of TB (TB screening).

Search methods: We searched the following databases without language restriction on 5 February 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE (PubMed,1966); EMBASE (OVID, from 1980); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926) (all three using the Web of Science platform; MEDION; LILACS (BIREME, from 1982); SCOPUS (from 1995); the metaRegister of Controlled Trials (mRCT); the search portal of the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); and ProQuest Dissertations & Theses A&l (from 1861).

Selection criteria: Eligible study types included randomized controlled trials, cross-sectional studies, and cohort studies that determined LF-LAM accuracy for TB against a microbiological reference standard (culture or nucleic acid amplification test from any body site). A higher quality reference standard was one in which two or more specimen types were evaluated for TB, and a lower quality reference standard was one in which only one specimen type was evaluated for TB. Participants were HIV-positive people aged 15 years and older.

Data collection and analysis: Two review authors independently extracted data from each included study using a standardized form. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We evaluated the test at two different cut-offs: (grade 1 or 2, based on the reference card scale of five intensity bands). Most analyses used grade 2, the manufacturer's currently recommended cut-off for positivity. We carried out meta-analyses to estimate pooled sensitivity and specificity using a bivariate random-effects model and estimated the models using a Bayesian approach. We determined accuracy of LF-LAM combined with sputum microscopy or Xpert(R) MTB/RIF. In addition, we explored the influence of CD4 count on the accuracy estimates. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results: We included 12 studies: six studies evaluated LF-LAM for TB diagnosis and six studies evaluated the test for TB screening. All studies were cross-sectional or cohort studies. Studies for TB diagnosis were largely conducted among inpatients (median CD4 range 71 to 210 cells per µL) and studies for TB screening were largely conducted among outpatients (median CD4 range 127 to 437 cells per µL). All studies were conducted in low- or middle-income countries. Only two studies for TB diagnosis (33%) and one study for TB screening (17%) used a higher quality reference standard LF-LAM for TB diagnosis (grade 2 cut-off): meta-analyses showed median pooled sensitivity and specificity (95% credible interval (CrI)) of 45% (29% to 63%) and 92% (80% to 97%), (five studies, 2313 participants, 35% with TB, low quality evidence). The pooled sensitivity of a combination of LF-LAM and sputum microscopy (either test positive) was 59% (47% to 70%), which represented a 19% (4% to 36%) increase over sputum microscopy alone, while the pooled specificity was 92% (73% to 97%), which represented a 6% (1% to 24%) decrease from sputum microscopy alone (four studies, 1876 participants, 38% with TB). The pooled sensitivity of a combination of LF-LAM and sputum Xpert(R) MTB/RIF (either test positive) was 75% (61% to 87%) and represented a 13% (1% to 37%) increase over Xpert(R) MTB/RIF alone. The pooled specificity was 93% (81% to 97%) and represented a 4% (1% to 16%) decrease from Xpert(R) MTB/RIF alone (three studies, 909 participants, 36% with TB). Pooled sensitivity and specificity of LF-LAM were 56% (41% to 70%) and 90% (81% to 95%) in participants with a CD4 count of less than or equal to 100 cells per µL (five studies, 859 participants, 47% with TB) versus 26% (16% to 46%) and 92% (78% to 97%) in participants with a CD4 count greater than 100 cells per µL (five studies, 1410 participants, 30% with TB). LF-LAM for TB screening (grade 2 cut-off): for individual studies, sensitivity estimates (95% CrI) were 44% (30% to 58%), 28% (16% to 42%), and 0% (0% to 71%) and corresponding specificity estimates were 95% (92% to 97%), 94% (90% to 97%), and 95% (92% to 97%) (three studies, 1055 participants, 11% with TB, very low quality evidence). There were limited data for additional analyses. The main limitations of the review were the use of a lower quality reference standard in most included studies, and the small number of studies and participants included in the analyses. The results should, therefore, be interpreted with caution.

Authors' conclusions: We found that LF-LAM has low sensitivity to detect TB in adults living with HIV whether the test is used for diagnosis or screening. For TB diagnosis, the combination of LF-LAM with sputum microscopy suggests an increase in sensitivity for TB compared to either test alone, but with a decrease in specificity. In HIV-positive individuals with low CD4 counts who are seriously ill, LF-LAM may help with the diagnosis of TB.

Abstract  Full-text [free] access

Editor’s notes: Tuberculosis (TB) remains a leading cause of death among people living with HIV. Diagnostic tests for TB are suboptimal, and a test for TB with adequate performance which could be used by nurses in primary care clinics would be a great advance. Lipoarabinomannam (LAM) is a component of mycobacterial cell wall which can be found in urine. A lateral flow assay to detect LAM in urine is commercially available at low cost, and can be used in primary care settings without the need for laboratory equipment. However the test is insensitive, such that it has no useful role among HIV-negative people, but has better sensitivity among people living with HIV, leading to questions concerning its role in TB diagnostic pathways.

This systematic review puts together data concerning the performance of the LAM lateral flow assay when used either as a screening test or for diagnosis of TB among people living with HIV. Assessment is made more complicated because the recommended reference cut-off for the test has been changed, with relatively few studies performed after the recommended cut off became what is referred to here as the “higher quality” reference standard (grade two test band intensity, rather than grade one as was previously recommended). Based on the grade two cut–off, the pooled estimate of sensitivity of the test was 45%. As expected, sensitivity was better for individuals with low CD4 counts.

This review informed WHO recommendations on the use of the LAM assay, suggesting that its use should be restricted to assisting with TB diagnosis in people living with HIV with low CD4 counts who are seriously ill. This is consistent with the results of the recent trial (PMID: 26970721) comparing management of hospitalised HIV-positive people reporting one or more TB symptoms with routine testing of urine for LAM compared to standard diagnostic tests, which found that the addition of LAM testing resulted in a small reduction in eight-week mortality.

Overall, LAM is inadequate as a single test for TB, and an accurate diagnostic test that could be used in-session for TB diagnosis in primary care clinics remains a pressing priority.

Comorbidity, HIV testing
Africa
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Silent transfers result in underestimation of retention on ART

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

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

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

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

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

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

Abstract access 

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

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

Africa
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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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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
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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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Near-patient TB test reduces hospital deaths in HIV-positive adults

Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial. 

Peter JG, Zijenah LS, Chanda D, Clowes P, Lesosky M, Gina P, Mehta N, Calligaro G, Lombard CJ, Kadzirange G, Bandason T, Chansa A, Liusha N, Mangu C, Mtafya B, Msila H, Rachow A, Hoelscher M, Mwaba P, Theron G, Dheda K. Lancet. 2016 Mar 19;387(10024):1187-97. doi: 10.1016/S0140-6736(15)01092-2. Epub 2016 Mar 10.

Background: HIV-associated tuberculosis is difficult to diagnose and results in high mortality. Frequent extra-pulmonary presentation, inability to obtain sputum, and paucibacillary samples limits the usefulness of nucleic-acid amplification tests and smear microscopy. We therefore assessed a urine-based, lateral flow, point-of-care, lipoarabinomannan assay (LAM) and the effect of a LAM-guided anti-tuberculosis treatment initiation strategy on mortality.

Methods: We did a pragmatic, randomised, parallel-group, multicentre trial in ten hospitals in Africa--four in South Africa, two in Tanzania, two in Zambia, and two in Zimbabwe. Eligible patients were HIV-positive adults aged at least 18 years with at least one of the following symptoms of tuberculosis (fever, cough, night sweats, or self-reported weight loss) and illness severity necessitating admission to hospital. Exclusion criteria included receipt of any anti-tuberculosis medicine in the 60 days before enrolment. We randomly assigned patients (1:1) to either LAM plus routine diagnostic tests for tuberculosis (smear microscopy, Xpert-MTB/RIF, and culture; LAM group) or routine diagnostic tests alone (no LAM group) using computer-generated allocation lists in blocks of ten. All patients were asked to provide a urine sample of at least 30 mL at enrolment, and trained research nurses did the LAM test in patients allocated to this group using the Alere Determine tuberculosis LAM Ag lateral flow strip test (Alere, USA) at the bedside on enrolment. On the basis of a positive test result, the nurses made a recommendation for initiating anti-tuberculosis treatment. The attending physician made an independent decision about whether to start treatment or not. Neither patients nor health-care workers were masked to group allocation and test results. The primary endpoint was 8-week all-cause mortality assessed in the modified intention-to-treat population (those who received their allocated intervention). This trial is registered with ClinicalTrials.gov, number NCT01770730.

Findings: Between Jan 1, 2013, and Oct 2, 2014, we screened 8728 patients and randomly assigned 2659 to treatment (1336 to LAM, 1323 to no LAM). 108 patients did not receive their allocated treatment, mainly because they did not meet the inclusion criteria, and 23 were excluded from analysis, leaving 2528 in the final modified intention-to-treat analysis (1257 in the LAM group, 1271 in the no LAM group). Overall all-cause 8-week mortality occurred in 578 (23%) patients, 261 (21%) in LAM and 317 (25%) in no LAM, an absolute reduction of 4% (95% CI 1-7). The risk ratio adjusted for country was 0.83 (95% CI 0.73-0.96), p=0.012, with a relative risk reduction of 17% (95% CI 4-28). With the time-to-event analysis, there were 159 deaths per 100 person-years in LAM and 196 per 100 person-years in no LAM (hazard ratio adjusted for country 0.82 [95% CI 0.70-0.96], p=0.015). No adverse events were associated with LAM testing.

Interpretation: Bedside LAM-guided initiation of anti-tuberculosis treatment in HIV-positive hospital in-patients with suspected tuberculosis was associated with reduced 8-week mortality. The implementation of LAM testing is likely to offer the greatest benefit in hospitals where diagnostic resources are most scarce and where patients present with severe illness, advanced immunosuppression, and an inability to self-expectorate sputum.

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Editor’s notes: TB is a leading cause of hospitalization and in-hospital death among people living with HIV worldwide. This randomised controlled trial in southern Africa provides strong evidence of the impact of a simple, urine-based test in HIV-positive adults admitted to hospital with symptoms of TB. Use of the lateral flow lipoarabinomannan (LAM) test, in addition to a package of routine TB diagnostic tests, led to a modest reduction in all-cause mortality. This reduction in mortality occurred despite only a small increase in the proportion starting TB treatment, suggesting that LAM testing might have enabled more precision in the identification of people with TB.

Half of all deaths occurred in people with CD4 cell count ≤50 cells/µL and the impact of the urinary LAM test was greatest in this group, as suggested by previous studies. This may lead to strengthening of WHO policy recommendations to use the lateral flow LAM test to assist with TB diagnosis in people admitted to hospital with advanced HIV and with symptoms and signs of TB. There is still no strong evidence to suggest a role for LAM testing at more peripheral levels of the health system or in people who are not seriously ill.

The heterogeneity in effect between countries is notable, although the trial was not powered to detect mortality differences at each site. The availability and use of other diagnostics (which could include sputum smear microscopy, Xpert®, chest X-ray, ultrasound and computed tomography), and the level of physician input in clinical management, differed substantially across sites and could have modified the effect of LAM testing. Additional exploration of data from this trial and from other ongoing studies should help to further define the role of urine LAM in the TB diagnostic bundle in different health care settings.

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ART reduces fertility differences by HIV status among women living in sub-Saharan Africa

Measuring the impact of antiretroviral therapy roll-out on population level fertility in three African countries. 

Marston M, Nakiyingi-Miiro J, Hosegood V, Lutalo T, Mtenga B, Zaba B, and on behalf of the ALPHA network. PLoS One. 2016 Mar 25;11(3):e0151877. doi: 10.1371/journal.pone.0151877. eCollection 2016.

Background: UNAIDS official estimates of national HIV prevalence are based on trends observed in antenatal clinic surveillance, after adjustment for the reduced fertility of HIV positive women. Uptake of ART may impact on the fertility of HIV positive women, implying a need to re-estimate the adjustment factors used in these calculations. We analyse the effect of antiretroviral therapy (ART) provision on population-level fertility in Southern and East Africa, comparing trends in HIV infected women against the secular trends observed in uninfected women.

Methods: We used fertility data from four community-based demographic and HIV surveillance sites: Kisesa (Tanzania), Masaka and Rakai (Uganda) and uMkhanyakude (South Africa). All births to women aged 15-44 years old were included in the analysis, classified by mother's age and HIV status at time of birth, and ART availability in the community. Calendar time period of data availability relative to ART introduction varied across the sites, from 5 years prior to ART roll-out, to 9 years after. Calendar time was classified according to ART availability, grouped into pre ART, ART introduction (available in at least one health facility serving study site) and ART available (available in all designated health facilities serving study site). We used Poisson regression to calculate age adjusted fertility rate ratios over time by HIV status, and investigated the interaction between ART period and HIV status to ascertain whether trends over time were different for HIV positive and negative women.

Results: Age-adjusted fertility rates declined significantly over time for HIV negative women in all four studies. However HIV positives either had no change in fertility (Masaka, Rakai) or experienced a significant increase over the same period (Kisesa, uMkhanyakude). HIV positive fertility was significantly lower than negative in both the pre ART period (age adjusted fertility rate ratio (FRR) range 0.51 95%CI 0.42-0.61 to 0.73 95%CI 0.64-0.83) and when ART was widely available (FRR range 0.57 95%CI 0.52-0.62 to 0.83 95%CI 0.78-0.87), but the difference has narrowed. The interaction terms describing the difference in trends between HIV positives and negatives are generally significant.

Conclusions: Differences in fertility between HIV positive and HIV negative women are narrowing over time as ART becomes more widely available in these communities. Routine adjustment of ANC data for estimating national HIV prevalence will need to allow for the impact of treatment.

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Editor’s notes: Antenatal care (ANC) clinics records on demographic characteristics and HIV status of attenders are a major component of primary data used to estimate HIV prevalence in sub-Saharan Africa. Prior to scale-up of antiretroviral therapy (ART), the fertility of women living with HIV was lower than that for people without HIV. This means that prevalence estimates from ANC data were adjusted to avoid underestimating the true population fertility rates.

This paper analyses the changing fertility patterns in four longitudinal community-based cohorts in eastern and southern Africa. The study finds that differences in fertility rates between women living with HIV and women without HIV are narrowing as ART is scaled-up, although substantial differences still exist. There was considerable variation in the patterns between the sites reflecting the differing local epidemic profiles. The authors explain this variation as being due to various factors including biological (increased fertility associated with viral suppression), or behavioural (increased fertility among women experiencing widowhood and then forming new partnerships). The impact of treatment on fertility needs to be incorporated into models of HIV prevalence estimated from ANC data, to inform national policy makers measuring their progress towards HIV elimination targets.

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