Articles tagged as "Biomedical interventions and prevention tools"

Police violence and female sex work in south India

Change over time in police interactions and HIV risk behavior among female sex workers in Andhra Pradesh, India.

Erausquin JT, Reed E, Blankenship KM. AIDS Behav. 2015 Jun;19(6):1108-15. doi: 10.1007/s10461-014-0926-5.

Little is known about the effectiveness of intervening to change interactions between female sex workers (FSWs) and police in order to reduce HIV risk. Using data collected in the context of a HIV prevention intervention that included components to change policing practices (n = 1680), we examine the association of FSWs' reports of negative police interactions and HIV risk behaviors and whether these associations varied over time. Results show negative police interactions declined significantly over time. FSWs who had more than one negative police interaction were more likely to experience STI symptoms (AOR 2.97 [95 % CI 2.27-3.89]), inconsistently use condoms with their clients (AOR 1.36 [95 % CI 1.03-1.79]), and accept more money for condomless sex (AOR 2.37 [95 % CI 1.76-3.21]). Over time, these associations were stable or increased. Even where interventions have reduced the number of police incidents experienced by FSWs, stakeholders in HIV prevention must remain vigilant in challenging these incidents.

Abstract access 

Editor’s notes: Laws relating to sex work are frequently ambiguous. This allows considerable police discretion about who to arrest and under what charges. Bribes and arrest both have real monetary costs for female sex workers, who are already usually economically vulnerable. Financial pressure and or poverty can push women into agreeing to riskier sex with riskier clients in riskier places. This paper examined if negative police experience is associated with increased HIV risk behaviours; and if negative police experience changed over time following comprehensive HIV prevention programming.

The study found negative police interactions in the previous six months were frequent. Police raided workplace (36.1%), police arrested respondent (14.5%), police accepted bribe or gift so respondent could avoid trouble (14.8%), police had sex with respondent so she could avoid trouble (11.1%) and police took condoms away (7.6%). Negative police interactions were linked with an increased HIV risk including STI symptoms in the past 12 months; inconsistent condom use with clients in the past seven days and accepting more money for sex without a condom. However, there was a reduction over time in the proportion of women experiencing one or more negative police interactions in the past six months (21.2% versus 16.2%).  Risk behaviours also reduced over time.

This study adds to emerging literature that it is possible to intervene against violence exposure and negative police interaction as part of HIV prevention programming. It also underscores the importance of structural drivers in enhancing HIV risk among female sex worker populations.

Asia
India
  • share
0 comments.

The need to improve follow-up among voluntary medical male circumcision clients

Implementation and operational research: evaluation of loss-to-follow-up and postoperative adverse events in a voluntary medical male circumcision program in Nyanza Province, Kenya.

Reed JB, Grund J, Liu Y, Mwandi Z, Howard AA, McNairy ML, Chesang K, Cherutich P, Bock N. J Acquir Immune Defic Syndr. 2015 May 1;69(1):e13-23. doi: 10.1097/QAI.0000000000000535.

Background: More than 4.7 million voluntary medical male circumcisions (VMMCs) had been provided by HIV prevention programs in sub-Saharan Africa through 2013. All VMMC clients are recommended to return to the clinic for postoperative follow-up, although adherence is variable. The clinical status of clients who do not return is largely unknown.

Methods: VMMC clients from Nyanza Province, Kenya, aged older than or equal to 13 years, were recruited immediately after surgery from April to October 2012 from high-volume sites. Medical record reviews at 13-14 days after surgery indicated which clients had been adherent with recommended follow-up (ADFU) and which were lost-to-follow-up (LTFU). Clients in the LTFU group received clinical evaluations at home approximately 2 weeks postsurgery. Adverse events (AEs) and AE rates were compared between the ADFU and LTFU groups.

Results: Of 4504 males approached in 50 VMMC sites, 1699 (37.7%) were eligible and enrolled and 1600 of 1699 (94.2%) contributed to follow-up and AE data. Medical record review indicated 897 of 1600 (56.1%) were LTFU, and 762 (84.9%) of these received home-based clinical evaluations. The rate of moderate or severe AE diagnosis was 6.8% in the LTFU group vs. 3.3% in the ADFU group (relative risk = 2.1, 95% confidence interval: 1.3 to 3.4).

Conclusions: The moderate or severe AE diagnosis rate was approximately 2 times higher in the LTFU group. National programs should consider instituting surveillance systems to detect AEs that might otherwise go unnoticed. Providers should emphasize the importance of follow-up and actively contact LTFU clients to ensure care is provided throughout the entire postoperative course for all.

Abstract access 

Editor’s notes: Latest estimates suggest that over nine million men have undergone voluntary medical male circumcision (VMMC) to reduce their risk of HIV infection. In Kenya, VMMC clients are instructed to return to the clinic site within seven days of surgery for follow-up including assessment of adverse events (AEs). In this large study, over half of circumcised men from 50 sites did not return to the clinic for follow-up. These men were more likely to be 18 to 24 years (versus younger or older than this), with little formal education, without access to a car, and using multiple transportation methods. Follow-up of these men at home indicated that they had over twice the risk of a moderate or severe AE compared with individuals who did adhere to recommended follow-up (ADFU).  The difference in risk between the ADFU and LTFU groups was mainly for infection, wound disruption and pain. The study confirms that VMMC clients who do not return to the clinic should not be assumed to be healing without complications, and VMMC programmes should try novel approaches to improve follow-up rates and continue to reinforce the importance of follow-up.

Africa
Kenya
  • share
0 comments.

Self-report and pill count: unreliable measures of adherence in HIV prevention trials

Accuracy of self-report and pill-count measures of adherence in the FEM-PrEP clinical trial: implications for future HIV-prevention trials.

Agot K, Taylor D, Corneli AL, Wang M, Ambia J, Kashuba AD, Parker C, Lemons A, Malahleha M, Lombaard J, Van Damme L. AIDS Behav. 2015 May;19(5):743-51. doi: 10.1007/s10461-014-0859-z.

Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7 days had the highest PPV, while pill-count data consistent with missing ≤1 day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p = 0.014) and weeks of time in the study (OR 1.02; p < 0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed.

Abstract  Full-text [free] access

Editor’s notes: A number of studies have demonstrated that pre-exposure prophylaxis (PrEP) is effective in reducing HIV transmission when adherence is high. Understanding factors affecting adherence, and evaluating methods to best measure adherence are therefore of crucial importance. Despite excellent self-reported adherence, the FEM-PrEP and VOICE trials did not illustrate a benefit of PrEP. In this study, drug concentrations were assessed in 1200 visits from 150 FEM-PrEP trial participants to determine adherence. These results were used to assess the accuracy of three measures of self-reported adherence and also pill counting. All four measures had poor positive predictive value, ranging from 26.2% to 42.4%. There was an increase in misreporting of adherence over time which may be associated with lower adherence levels over time. In semi-structured interviews, most participants said that they did not misreport adherence. The authors call for improvements in methods to reduce socially desirable responses through participant self-report, and examination of the reasons why people join HIV prevention trials. Future trials may also need to consider using drug concentrations in addition to currently used methods to better estimate adherence.

Africa
Kenya, South Africa
  • share
0 comments.

High early mortality after ART initiation despite screening for TB and cryptococcal disease

Implementation and operational research: Integrated pre-antiretroviral therapy screening and treatment for tuberculosis and cryptococcal antigenemia.

Pac L, Horwitz MM, Namutebi AM, Auerbach BJ, Semeere A, Namulema T, Schwarz M, Bbosa R, Muruta A, Meya DB, Manabe YC. J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):e69-76. doi: 10.1097/QAI.0000000000000527.

Objective: To demonstrate the feasibility of integrated screening for cryptococcal antigenemia and tuberculosis (TB) before antiretroviral therapy (ART) initiation and to assess disease specific and all-cause mortality in the first 6 months of follow-up.

Methods: We enrolled a cohort of HIV-infected, ART-naive adults with CD4 counts ≤250 cells per microliter in rural Uganda who were followed for 6 months after ART initiation. All subjects underwent screening for TB; those with CD4 ≤100 cells per microliter also had cryptococcal antigen (CrAg) screening. For those who screened positive, standard treatment for TB or preemptive treatment for cryptococcal infection was initiated, followed by ART 2 weeks later.

Results: Of 540 participants enrolled, pre-ART screening detected 10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count ≤100 cells/muL) with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed with TB and 1 patient developed cryptococcal meningitis. Overall 7.2% of participants died (incidence rate 15.6 per 100 person-years at risk). Death rates were significantly higher among subjects with TB and cryptococcal antigenemia compared with subjects without these diagnoses. In multivariate analysis, significant risk factors for mortality were male sex, baseline anemia of hemoglobin ≤10 mg/dL, wasting defined as body mass index ≤15.5 kg/m, and opportunistic infections (TB, positive serum CrAg).

Conclusions: Pre-ART screening for opportunistic infections detects many prevalent cases of TB and cryptococcal infection. However, severely immunosuppressed and symptomatic HIV patients continue to experience high mortality after ART initiation.

Abstract access 

Editor’s notes: Early mortality remains high among people starting antiretroviral therapy (ART) in resource-constrained settings. The risk of death is strongly associated with low baseline CD4 count. Leading causes of death in this population include tuberculosis (TB) and cryptococcal disease.

ART-naïve people with CD4 counts of 250 cells/µl or less were included in this study at a district hospital in Uganda. All were offered screening for TB, and people with CD4 counts below 100 cells/µl also had screening for cryptococcal antigen with follow-on management for people screening positive. The TB screening protocol comprised symptom screening plus an initial sputum for smear microscopy and culture, and a second sputum for smear was taken if the first was negative. Further investigations appear to have been according to clinical presentation rather than standardised. Overall, 13.3% of participants were diagnosed with TB. Some 6.8% of people with CD4 below 100 cells/µl had a positive serum cryptococcal antigen test. One was diagnosed with and treated for cryptococcal meningitis and the other 11 were treated with high dose fluconazole.

Despite the high prevalence of TB and cryptococcal disease detected and treated, the overall mortality was 7.2% (39/540) by six months. This is a minimum estimate, since it assumes that the 33 additional people who were lost to follow-up, transferred or withdrawn were all alive at six months. The mortality rate was higher among people diagnosed with TB, and was very high among people who were cryptococcal antigen positive, despite fluconazole treatment. The article does not describe the care pathways in detail, so it is not clear whether there were delays in treatment initiation which could be reduced, for example if point-of-care diagnostic testing with immediate results had been available at enrolment. In addition there is no comparison group and so the effect of this package of care on mortality is not clear. However the results suggest that early mortality may remain substantial among people presenting with advanced HIV disease in the absence of even more intensive management.

Several trials are in progress to evaluate programmes aiming to reduce early mortality among people starting ART, including trials of empirical TB treatment (i.e. without bacteriological confirmation). In last month’s HIV This Month we featured a trial of a cryptococcal screen and treat programme plus community support which reduced 12-month mortality from 18% to 13%. The results of these trials will inform the optimal package of care for people presenting with low CD4 counts. Ultimately, earlier HIV testing and linkage to care would be the ideal way to reduce the high mortality among people starting ART with very low CD4 counts.

Avoid TB deaths
Africa
Uganda
  • share
0 comments.

Hepatitis B virus co-infection: a challenge to successful ART in sub-Saharan Africa?

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

Stabinski L, OʼConnor S, Barnhart M, Kahn RJ, Hamm TE. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S274-85. doi: 10.1097/QAI.0000000000000496.

Background: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS).

Methods: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed.

Results: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively.

Conclusions: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.

Abstract access 

Editor’s notes: The routes of transmission for hepatitis B virus (HBV) and HIV are the same, and they frequently co-infect individuals in high HIV prevalence settings. HIV has also been shown to accelerate the progression of HBV. This has important implications for ART programmes, given also the potential for hepatotoxicity of ART. The response of both infections to certain antivirals gives an opportunity to treat both infections simultaneously, but also the potential to engender resistant strains of virus if treatment is optimised for one and not the other.

This paper reviews the evidence that might support inclusion of HBV screening as part of HIV care programmes. No clinical trials have been done in this area, so the review is based on observational studies. The data are incomplete and geographically patchy, largely from Nigeria and South Africa. However, this does not prevent the authors from concluding that the co-infection risk is sufficiently high and the consequences of lack of treatment sufficiently severe to consider allocation of scarce resources to identify and manage HBV co-infection in HIV programmes. Appropriate validated screening tools - rapid tests for hepatitis B surface antigen - are available. The potential benefit warrants consideration of this issue in sub-Saharan Africa, and inclusion of HBV surveillance alongside HIV to resolve the paucity of data in most countries. This should be rapidly followed by further consideration of the cost- and risk-benefit of introduction of an HBV screening and treatment programme.

Interested readers might also refer to a review by Matthews et al. (J Clin Virol 2014;6:20-33) which considers similar questions and also discusses hepatitis C co-infection.

Avoid TB deaths
Africa
  • share
0 comments.

Hepatitis B virus co-infection: a challenge to successful ART in sub-Saharan Africa?

Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings.

Stabinski L, OʼConnor S, Barnhart M, Kahn RJ, Hamm TE. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S274-85. doi: 10.1097/QAI.0000000000000496.

Background: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS).

Methods: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed.

Results: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively.

Conclusions: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS.

Abstract access 

Editor’s notes: The routes of transmission for hepatitis B virus (HBV) and HIV are the same, and they frequently co-infect individuals in high HIV prevalence settings. HIV has also been shown to accelerate the progression of HBV. This has important implications for ART programmes, given also the potential for hepatotoxicity of ART. The response of both infections to certain antivirals gives an opportunity to treat both infections simultaneously, but also the potential to engender resistant strains of virus if treatment is optimised for one and not the other.

This paper reviews the evidence that might support inclusion of HBV screening as part of HIV care programmes. No clinical trials have been done in this area, so the review is based on observational studies. The data are incomplete and geographically patchy, largely from Nigeria and South Africa. However, this does not prevent the authors to conclude that the co-infection risk is sufficiently high and the consequences of lack of treatment sufficiently severe to consider allocation of scarce resources to identify and manage HBV co-infection in HIV programmes. Appropriate validated screening tools such as rapid tests for hepatitis B surface antigen are available. The potential benefit warrants consideration of this issue in sub-Saharan Africa, and inclusion of HBV surveillance alongside HIV to resolve the paucity of data in most countries. This should be rapidly followed by further consideration of the cost- and risk-benefit of introduction of an HBV screening and treatment programme.

Interested readers might also refer to a review by Matthews et al. (J Clin Virol 2014;6:20-33) which considers similar questions and also discusses hepatitis C co-infection.

Avoid TB deaths
Africa
  • share
0 comments.

Re-focusing the response in Niger – a greater need for sex worker programmes?

Reorienting the HIV response in Niger toward sex work interventions: from better evidence to targeted and expanded practice. 

Fraser N, Kerr CC, Harouna Z, Alhousseini Z, Cheikh N, Gray R, Shattock A, Wilson DP, Haacker M, Shubber Z, Masaki E, Karamoko D, Görgens M. J Acquir Immune Defic Syndr. 2015 Mar 1;68 Suppl 2:S213-20. doi: 10.1097/QAI.0000000000000456.

Background: Niger's low-burden, sex-work-driven HIV epidemic is situated in a context of high economic and demographic growth. Resource availability of HIV/AIDS has been decreasing recently. In 2007-2012, only 1% of HIV expenditure was for sex work interventions, but an estimated 37% of HIV incidence was directly linked to sex work in 2012. The Government of Niger requested assistance to determine an efficient allocation of its HIV resources and to strengthen HIV programming for sex workers. 

Methods: Optima, an integrated epidemiologic and optimization tool, was applied using local HIV epidemic, demographic, programmatic, expenditure, and cost data. A mathematical optimization algorithm was used to determine the best resource allocation for minimizing HIV incidence and disability-adjusted life years (DALYs) over 10 years. 

Results: Efficient allocation of the available HIV resources, to minimize incidence and DALYs, would increase expenditure for sex work interventions from 1% to 4%-5%, almost double expenditure for antiretroviral treatment and for the prevention of mother-to-child transmission, and reduce expenditure for HIV programs focusing on the general population. Such an investment could prevent an additional 12% of new infections despite a budget of less than half of the 2012 reference year. Most averted infections would arise from increased funding for sex work interventions. 

Conclusions: This allocative efficiency analysis makes the case for increased investment in sex work interventions to minimize future HIV incidence and DALYs. Optimal HIV resource allocation combined with improved program implementation could have even greater HIV impact. Technical assistance is being provided to make the money invested in sex work programs work better and help Niger to achieve a cost-effective and sustainable HIV response.

Abstract access  

Editor’s notes: Niger has a low-level HIV epidemic concentrated in key populations such as female sex workers, with prevalence levels of 17% in 2011. Only around 23% of female sex workers report using a condom at every sexual act, making them a highly vulnerable group. Additionally there are barriers to using the health centres such as service costs, and the geographic distance.

This article summarizes the HIV epidemic and response situation in Niger with a focus on female sex workers, including modelled trends using Optima. It then presents new evidence on different resource allocation scenarios and the projected impact on the HIV epidemic. Optima, a deterministic mathematical model for HIV optimization and prioritization, was applied to local epidemiologic, demographic, programmatic, expenditure, and cost data. 

The optimization function uses an algorithm to find the best allocation of resources to meet the objective of either minimizing HIV incidence or disability-adjusted life years (DALYs) until 2024. Contrary to the current approach of allocating 31% of spending to the general population and less than 1% to female sex workers, the Optima function advocates increased spending on antiretroviral therapy from 27% to 48%. Optima supports a focussed approach to reduce HIV incidence in female sex workers including mapping populations and a “programme intelligence” approach akin to that implemented in India and Nigeria.   

Africa, Asia
  • share
0 comments.

Can a simple risk score predict chronic kidney disease among people living with HIV?

Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study.

Mocroft A, Lundgren JD, Ross M, Law M, Reiss P, Kirk O, Smith C, Wentworth D, Neuhaus J, Fux CA, Moranne O, Morlat P, Johnson MA, Ryom L, D:A:D study group, the Royal Free Hospital Clinic Cohort, and the INSIGHT, SMART, and ESPRIT study groups. PLoS Med. 2015 Mar 31;12(3):e1001809. doi: 10.1371/journal.pmed.1001809. eCollection 2015.

Background: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.

Methods and findings: A total of 17 954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR >60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103 185 person-years of follow-up (PYFU; incidence 6.2/1000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score <0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1702 (95% CI 1166-3367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2548 individuals, of whom 94 individuals developed CKD (3.7%) during 18 376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria.

Conclusions: Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

Abstract  Full-text [free] access

Editor’s notes: The nephrotoxicity of antiretroviral drugs, particularly tenofovir, is of concern, particularly where there is limited access to laboratory monitoring of kidney function. The development of kidney impairment among people with HIV is associated with poor outcomes, and in low resource settings where dialysis is not available this can be catastrophic.

This study, like previous work, attempts to address this problem by developing a risk score for the development of chronic kidney disease (CKD). The strength of this study is the availability of data for over 17 000 men and women living with HIV enrolled in cohort studies for many years, and in over 40 countries globally. The resulting risk score uses nine simple clinical variables which predict CKD both overall, and after starting potentially nephrotoxic antiretrovirals. A short risk score, not including cardiovascular risk factors, which may be more suitable for low resource settings, shows almost as good a prediction of CKD.

So will this risk score become widely used in clinical decision making? For high income countries this tool may be useful to identify people where strategies to prevent cardiovascular and renal disease are best focussed. It may also be useful to identify people at high risk of developing CKD for whom use of tenofovir may be unacceptable, especially when monitoring of kidney function is limited. However, few of the enrolled people were from low and middle income countries, and there was limited information on the race of participants. Therefore, the risk score may need to be validated in low resource settings before it can be widely used. Whether the use of the tool would help to improve clinical outcomes where kidney function is frequently monitored is unclear.

Meanwhile, a new drug formulation, tenofovir alafenamide (TAF), is currently in clinical trials. This appears to be associated with less renal toxicity, and to be safe and well tolerated among adults with decreased kidney function. If future trial results support this evidence, and tenofovir alafenamide becomes widely available, concern about drug nephrotoxicity may become a less pressing clinical issue.

  • share
0 comments.

Oral and vaginal pre-exposure prophylaxis: no evidence of benefit among young African women

Tenofovir-based pre-exposure prophylaxis for HIV infection among African women.

Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, Palanee T, Nakabiito C, van der Straten A, Noguchi L, Hendrix CW, Dai JY, Ganesh S, Mkhize B, Taljaard M, Parikh UM, Piper J, Masse B, Grossman C, Rooney J, Schwartz JL, Watts H, Marzinke MA, Hillier SL, McGowan IM, Chirenje ZM, VOICE Study Team. N Engl J Med. 2015 Feb 5;372(6):509-18. doi: 10.1056/NEJMoa1402269.

Background: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.

Methods: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as pre-exposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly.

Results: Of 12 320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events.

Conclusions: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low.

Abstract   Full-text [free] access

Editor’s notes: Randomised controlled trials across a range of settings and populations have demonstrated a benefit of antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV acquisition, when adherence is high. This study compared two oral PreP regimens and a vaginal gel against placebo oral/gel among predominantly young, unmarried women in South Africa, Uganda and Zimbabwe. There was no evidence of a difference in HIV incidence between the groups. Although self-reported adherence was good, as estimated by the amount of product returned, or in interviews, tenofovir (TFV) was detected in only 25-30% of plasma samples analysed. TFV detection in plasma at the first quarterly visit was associated with both TFV detection at later visits and lower risk of HIV acquisition. But this may be partly confounded by differences in HIV exposure which were not measured. This trial has important implications for HIV prevention and implementation of programmes with proven efficacy. This includes the fact that HIV incidence continues to be high in some settings despite increasing coverage of ART. There is a need to assess products with sustained delivery of ART, e.g. vaginal rings or injections, and for real-time monitoring of biomarkers for adherence rather than reliance on self-report and returned-product count.

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

Is genotype resistance testing cost-effective for the ART naïve?

Cost-effectiveness of genotype testing for primary resistance in Brazil.

Luz PM, Morris BL, Grinsztejn B, Freedberg KA, Veloso VG, Walensky RP, Losina E, Nakamura YM, Girouard MP, Sax PE, Struchiner CJ, Paltiel AD. J Acquir Immune Defic Syndr. 2015 Feb 1;68(2):152-61. doi: 10.1097/QAI.0000000000000426.

Objective: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil.

Design: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype).

Methods: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US $13 400, genotype test cost of US $230, and primary resistance prevalence of 4.4%. Life expectancy and costs were discounted 3% per year. Genotype was defined as "cost-effective" compared with No Genotype if its incremental cost-effectiveness ratio was less than 3 times the 2012 Brazilian per capita GDP of US $12 300.

Results: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45 000 to $44 770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges.

Conclusions: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil.

Abstract  Full-text [free] access

Editor’s notes: This study aims to provide guidance on when HIV genotype-resistance testing should be used during the course of antiretroviral therapy (ART). Previous studies in high income countries suggest that use prior to ART initiation may be cost-effective. In more resource constrained settings, two previous studies suggest that genotype-resistance testing may be cost-effective following first-line treatment failure. But none have examined use of these tests on the ART-naïve.

This study compares genotype-resistance testing prior to ART initiation to the current policy of testing post treatment failure, for the population of Brazil. The study finds that genotype-resistance testing is likely to be cost saving in Brazil. The authors predict modest increases in life expectancy for individuals on ART. Cost savings are achieved from predicted reductions in complications and the duration of expensive ART regimens. Costs savings are primarily incurred for non-nucleoside reverse-transcriptase inhibitors (NNRTI) resistant people. These savings outweigh the cost of the genotype-resistance test. The study usefully highlights that the extent of cost savings (and cost-effectiveness) depends primarily on test cost, future ART costs and prevalence of NNRTI resistance in the study population. For most plausible ranges of NNRTI prevalence and costs observed in Brazil, genotype-resistance testing prior to ART initiation is likely to be cost-effective. However, both costs and NNRTI prevalence vary by setting; as does the threshold by which technologies are judged to be cost-effective. These factors therefore need to be considered before applying these results to policy change around the use of genotype-resistance testing more broadly.

Latin America
Brazil
  • share
0 comments.