Articles tagged as "United Republic of Tanzania"

Men who have sex with men in sub-Saharan Africa: a review of the evidence

Emerging themes for sensitivity training modules of African healthcare workers attending to men who have sex with men: a systematic review.

Dijkstra M, van der Elst EM, Micheni M, Gichuru E, Musyoki H, Duby Z, Lange JM, Graham SM, Sanders EJ. Int Health. 2015 May;7(3):151-162. Epub 2015 Jan 16.

Sensitivity training of front-line African health care workers (HCWs) attending to men who have sex with men (MSM) is actively promoted through national HIV prevention programming in Kenya. Over 970 Kenyan-based HCWs have completed an eight-modular online training free of charge (http://www.marps-africa.org) since its creation in 2011. Before updating these modules, we performed a systematic review of published literature of MSM studies conducted in sub-Saharan Africa (sSA) in the period 2011-2014, to investigate if recent studies provided: important new knowledge currently not addressed in existing online modules; contested information of existing module topics; or added depth to topics covered already. We used learning objectives of the eight existing modules to categorise data from the literature. If data could not be categorised, new modules were suggested. Our review identified 142 MSM studies with data from sSA, including 34 studies requiring module updates, one study contesting current content, and 107 studies reinforcing existing module content. ART adherence and community engagement were identified as new modules. Recent MSM studies conducted in sSA provided new knowledge, contested existing information, and identified new areas of MSM service needs currently unaddressed in the online training.

Abstract  Full-text [free] access

Editor’s notes: Same sex practices remain criminalised in sub-Saharan Africa. Gay men and other men who have sex with men face stigma, discrimination, harassment and arrest. Health care workers frequently have no training on issues affecting gay men and other men who have sex with men and are ill-prepared to work sensitively with them. Together these can deter these men from accessing health care and HIV/STI services, increasing their risk of HIV and other poor health outcomes.

This study conducted a systematic review of gay men and other men who have sex with men in sub-Saharan Africa. The findings were used to update an on-line training programme for health care workers in Kenya. This previously comprised modules on i) men who have sex with men and HIV in Africa ii) homophobia: stigma and its effects; iii) sexual identity, coming out and disclosure; iv) anal sex and common sexual practices; v) HIV and STIs; vi) condom and lubricant use; vii) mental health: anxiety, depression and substance use; and viii) risk-reduction counselling. The review updated the training programme with new evidence and two new modules were introduced: ix) ART adherence; and x) community engagement.

Health care workers play a crucial role in reducing stigma and discrimination facing gay men and other men who have sex with men. This systematic review provided a valuable step in updating an important, accessible training programme. Reducing homoprejudice and ensuring health care workers have accurate and up-to-date knowledge are key to improving service uptake by gay men and other men who have sex with men.

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People living with HIV at higher risk of developing disabilities in sub-Saharan Africa

The relationship between HIV and prevalence of disabilities in sub-Saharan Africa: systematic review.

Banks LM, Zuurmond M, Ferrand R, Kuper H. Trop Med Int Health. 2015 Apr;20(4):411-29. doi: 10.1111/tmi.12449. Epub 2015 Jan 14.

Objective: To systematically review evidence on the prevalence and risk of disabilities among children and adults living with HIV in sub-Saharan Africa.

Methods: Articles were identified from 1980 to June 2013 through searching seven electronic databases. Epidemiological studies conducted in sub-Saharan Africa that explored the association between HIV status and general disability or specific impairments, with or without an HIV-uninfected comparison group, were eligible for inclusion.

Results: Of 12 867 records initially identified, 61 papers were deemed eligible for inclusion. The prevalence of disability was high across age groups, impairment types and study locations. Furthermore, 73% of studies using an HIV- comparator found significantly lower levels of functioning in people living with HIV (PLHIV). By disability type, the results were as follows: (i) for studies measuring physical impairments (n = 14), median prevalence of limitations in mobility and motor function among PLHIV was 25.0% (95% CI: 21.8-28.2%). Five of eight comparator studies found significantly reduced functioning among PLHIV; for arthritis, two of three studies which used an HIV- comparison group found significantly increased prevalence among PLHIV; (ii) for sensory impairment studies (n = 17), median prevalence of visual impairment was 11.2% (95%CI: 9.5-13.1%) and hearing impairment was 24.1% (95%CI: 19.2-29.0%) in PLHIV. Significantly increased prevalence among PLHIV was found in one of four (vision) and three of three studies (hearing) with comparators; (iii) for cognitive impairment in adults (n = 30), median prevalence for dementia was 25.3% (95% CI: 22.0-28.6%) and 40.9% (95% CI: 37.7-44.1%) for general cognitive impairment. Across all types of cognitive impairment, twelve of fourteen studies found a significant detrimental effect of HIV infection; (iv) for developmental delay in children with HIV (n = 20), median prevalence of motor delay was 67.7% (95% CI: 62.2-73.2%). All nine studies that included a comparator found a significant difference between PLHIV and controls; for cognitive development and global delay, a significant detrimental effect of HIV was found in five of six and one of two studies, respectively. In the nine cohort studies comparing vertically infected and uninfected children, eight showed a significant gap in development over time in children with HIV. Finally, fifteen of thirty-one (48%) studies found a statistically significant dose-response relationship between indicators of disease progression (CD4 or WHO stage) and disability.

Conclusions: HIV is widespread in sub-Saharan Africa and the evidence suggests that it is linked to disabilities, affecting a range of body structures and functions. More research is needed to better understand the implications of HIV-related disability for individuals, their families as well as those working in the fields of disability and HIV so that appropriate interventions can be developed.

Abstract  Full-text [free] access

Editor’s notes: As ART is scaled-up, and people living with HIV live longer, an increasing number of people will face challenges of HIV-associated disability. Disability may be partly a direct effect of living with HIV, but may also be an indirect effect, for example due to side effects of treatment. There has been relatively little research on this topic, particularly in low and middle-income countries and this is the first systematic review of the prevalence of disability among people living with HIV in sub-Saharan Africa. The review found a high prevalence of all categories of disability. The majority of studies had an HIV-negative comparison group among whom levels of disability were lower than among people living with HIV. Developmental delay was the impairment most strongly linked to HIV, with prevalence as high as 78% in children living with HIV. To minimize the chance that the observed association was due to reverse causality, the review excluded studies which clearly focused on disability as a risk factor for HIV, although it is likely that some studies still included individuals in whom disability preceded HIV infection. There was also relatively little data on ART status and duration in many studies, which may impact on the association of HIV and disability.  Despite these limitations, this study highlights the need to focus on prevention and management of HIV-associated disability in sub-Saharan Africa and development of effective, low-cost evidence-informed activities.

Africa
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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
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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
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Need for further water, sanitation and hygiene programmes among people living with HIV

The impact of water, sanitation, and hygiene interventions on the health and well-being of people living with HIV: a systematic review.

Yates T, Lantagne D, Mintz E, Quick R. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S318-30. doi: 10.1097/QAI.0000000000000487.

Background: Access to improved water supply and sanitation is poor in low-income and middle-income countries. Persons living with HIV/AIDS (PLHIV) experience more severe diarrhea, hospitalizations, and deaths from diarrhea because of waterborne pathogens than immunocompetent populations, even when on antiretroviral therapy (ART).

Methods: We examined the existing literature on the impact of water, sanitation, and hygiene (WASH) interventions on PLHIV for these outcomes: (1) mortality, (2) morbidity, (3) retention in HIV care, (4) quality of life, and (5) prevention of ongoing HIV transmission. Cost-effectiveness was also assessed. Relevant abstracts and articles were gathered, reviewed, and prioritized by thematic outcomes of interest. Articles meeting inclusion criteria were summarized in a grid for comparison.

Results: We reviewed 3355 citations, evaluated 132 abstracts, and read 33 articles. The majority of the 16 included articles focused on morbidity, with less emphasis on mortality. Contaminated water, lack of sanitation, and poor hygienic practices in homes of PLHIV increase the risk of diarrhea, which can result in increased viral load, decreased CD4 counts, and reduced absorption of nutrients and antiretroviral medication. We found WASH programming, particularly water supply, household water treatment, and hygiene interventions, reduced morbidity. Data were inconclusive on mortality. Research gaps remain in retention in care, quality of life, and prevention of ongoing HIV transmission. Compared with the standard threshold of 3 times GDP per capita, WASH interventions were cost-effective, particularly when incorporated into complementary programs.

Conclusions: Although research is required to address behavioral aspects, evidence supports that WASH programming is beneficial for PLHIV.

Abstract access 

Editor’s notes: Researchers, implementers, and policy makers have been examining how to better integrate programmes with overlapping burdens of morbidity and mortality. This paper illustrates how access to clean water and good sanitation practices, or lack thereof, can impact the health of people living with HIV. Water, sanitation, and hygiene (WASH) programmes can improve the negative effects poor water quality and bad sanitation have on people living with HIV. They reduce or even eliminate diarrheal infections, which allow for better absorption of HIV treatment medication that leads to a reduction in viral load and increased CD4 counts. While this systematic review revealed evidence on the reduced burden of morbidity that WASH programmes can confer, little has been done in the way of research linking WASH programmes to mortality in people living with HIV, nor how they may affect adherence or retention in care. Side effects of HIV treatment is a common reason why people stop taking medications, and common side effects are nausea and diarrhoea. It is possible that intestinal issues caused by unsafe drinking water could exacerbate the impact of side effects on people already experiencing them, therefore reducing motivation to continue taking their ARVs. This paper also suggests that synergies in cost sharing and increasing cost effectiveness could be achieved by integrating programmes. However further research is necessary to fully understand the logistical and cost implications.

 

Africa, Asia
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Cryptococcal antigen screening plus home visits reduces early mortality

Cryptococcal meningitis screening and community-based early adherence support in people with advanced HIV infection starting antiretroviral therapy in Tanzania and Zambia: an open-label, randomised controlled trial.

Mfinanga S, Chanda D, Kivuyo SL, Guinness L, Bottomley C, Simms V, Chijoka C, Masasi A, Kimaro G, Ngowi B, Kahwa A, Mwaba P, Harrison TS, Egwaga S, Jaffar S, REMSTART trial team. Lancet. 2015 Mar 9. pii: S0140-6736(15)60164-7. doi: 10.1016/S0140-6736(15)60164-7. [Epub ahead of print]

Background: Mortality in people in Africa with HIV infection starting antiretroviral therapy (ART) is high, particularly in those with advanced disease. We assessed the effect of a short period of community support to supplement clinic-based services combined with serum cryptococcal antigen screening.

Methods: We did an open-label, randomised controlled trial in six urban clinics in Dar es Salaam, Tanzania, and Lusaka, Zambia. From February, 2012, we enrolled eligible individuals with HIV infection (age ≥18 years, CD4 count of <200 cells per uL, ART naive) and randomly assigned them to either the standard clinic-based care supplemented with community support or standard clinic-based care alone, stratified by country and clinic, in permuted block sizes of ten. Clinic plus community support consisted of screening for serum cryptococcal antigen combined with antifungal therapy for patients testing antigen positive, weekly home visits for the first 4 weeks on ART by lay workers to provide support, and in Tanzania alone, re-screening for tuberculosis at 6-8 weeks after ART initiation. The primary endpoint was all-cause mortality at 12 months, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number registry, number ISCRTN 20410413.

Findings: Between Feb 9, 2012, and Sept 30, 2013, 1001 patients were randomly assigned to clinic plus community support and 998 to standard care. 89 (9%) of 1001 participants in the clinic plus community support group did not receive their assigned intervention, and 11 (1%) of 998 participants in the standard care group received a home visit or a cryptococcal antigen screen rather than only standard care. At 12 months, 25 (2%) of 1001 participants in the clinic plus community support group and 24 (2%) of 998 participants in the standard care group had been lost to follow-up, and were censored at their last visit for the primary analysis. At 12 months, 134 (13%) of 1001 participants in the clinic plus community support group had died compared with 180 (18%) of 998 in the standard care group. Mortality was 28% (95% CI 10-43) lower in the clinic plus community support group than in standard care group (p=0.004).

Interpretation: Screening and pre-emptive treatment for cryptococcal infection combined with a short initial period of adherence support after initiation of ART could substantially reduce mortality in HIV programmes in Africa.

Abstract access 

Editor’s notes: Despite the huge success of antiretroviral programme roll-out, early mortality among people initiating antiretroviral therapy (ART) in low- and middle-income countries remains high, and reducing early mortality is a priority. The risk of early mortality is highest among people with low CD4 counts. Although there has been an increase over calendar time in the median CD4 count at ART start, many people still start ART with low CD4 counts, and continue to be at high risk of death.

Cryptococcal disease is consistently identified at autopsy among HIV-positive people, although less commonly than tuberculosis and other lung infections. Cryptococcal disease is typically seen among individuals with very low CD4 counts, and has high case-fatality, for reasons including late presentation and suboptimal treatment and care. Among people with low CD4 counts, cryptococcal antigen can be detected in blood several weeks before cryptococcal disease becomes symptomatic. In 2011, the World Health Organization (WHO) issued rapid advice concerning prevention and treatment of cryptococcal meningitis in resource-constrained settings. This included a conditional recommendation (based on low-quality evidence) to screen individuals with CD4 counts below 100 cells per µl for cryptococcal antigen, followed by treatment either for cryptococcal meningitis, or with fluconazole for asymptomatic cryptococcal antigenaemia, as appropriate.

This trial is the first to provide evidence that this strategy can save lives. This was a pragmatic, individually randomised trial enrolling HIV-positive, ART-naïve people initially with CD4 counts below 100 cells per µl. Because of slow enrolment, inclusion criteria were later expanded to include people with CD4 counts below 200 cells per µl. The programme had two components. The first involved screening for cryptococcal antigen with a point-of-care test using a finger prick blood sample, followed by management in line with WHO guidelines. The second was adherence support, with trained lay workers visiting participants at or near their homes weekly for the first four weeks. The lay workers delivered ART, provided adherence support and monitored for adverse events.

The reduction of mortality from 18% to 13% in the intervention arm is clearly important, but also intriguing in terms of identifying the “active ingredient”. This may be difficult in a pragmatic trial of a programme with more than one component. For example, there was no cryptococcal antigen testing in control arm participants. Thus we cannot assess precisely the reduction in mortality attributable to this component of the programme. The authors estimate that cryptococcal antigen screening and treatment contributed about half of the observed effect. This component is also interesting because in practice, implementation of the cryptococcal antigen “screen and treat” pathway in the trial was not exactly as per WHO guidelines. WHO guidelines recommend lumbar puncture for people who screen positive for cryptococcal antigen and have symptoms suggesting meningitis. However, in this trial 76% of people testing cryptococcal antigen positive refused lumbar puncture, similar to experience elsewhere. Despite the programme, 32% of people in the intervention arm who were cryptococcal antigen positive died. This suggests that the fluconazole that most people received may have been inadequate, and that alternatives to lumbar puncture are necessary to identify people at highest risk who would benefit from full treatment for cryptococcal meningitis with amphotericin B. Quantifying the cryptococcal antigen titre in blood might serve this purpose, and needs further investigation.

In a previous trial in Uganda, home-based ART care (monthly delivery of ART by lay workers) was as effective as clinic-based care, in terms of virologic failure. However, other programmes similarly aiming to provide support for individuals starting ART have been less successful. For example a recently-presented trial of health “navigators” who used mobile phones and text messages to help people living with HIV link to ART and, where relevant, TB treatment, did not reduce mortality at nine months. Supporting adherence and retention is clearly critical to the long-term success of ART programmes. The challenge is defining how to do this most effectively and sustainably.

As part of this trial, in both arms ART was intended to be started within four to seven days of the first visit where possible, substantially faster than was previously routine. All participants were asked to provide sputum for testing for tuberculosis with Xpert MTB/RIF, regardless of reported symptoms. Some 16% of participants were already on tuberculosis treatment at enrolment. A further 11% were newly-diagnosed with tuberculosis at enrolment, roughly half based on sputum smear or clinical features and half based on the Xpert MTB/RIF result. This emphasises the importance of routine investigation for tuberculosis among people presenting to start ART. In the United Republic of Tanzania, people not on tuberculosis treatment were rescreened with Xpert MTB/RIF six weeks after enrolment. A further 5% were found to have tuberculosis, highlighting the inadequate sensitivity of Xpert MTB/RIF on sputum in this group of people.

Overall this trial provides encouragement that early on-ART mortality among people with low CD4 counts can be reduced. This is achieved with targeted treatment of cryptococcal disease and home-based early adherence support, in the context of universal screening for tuberculosis and rapid ART initiation. Ongoing studies are investigating whether empirical treatment for tuberculosis will reduce early mortality among similar patient populations. These results together will help define the optimum package of care to minimise mortality among individuals presenting with low CD4 cell counts. At the same time, HIV testing needs to be promoted so that people living with HIV can start ART before reaching the stage of advanced disease where mortality is such a risk.

Avoid TB deaths
Africa
United Republic of Tanzania, Zambia
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Boosted protease inhibitor monotherapy as second-line ART: a strategy for resource-limited settings?

Lopinavir/ritonavir monotherapy as second-line antiretroviral treatment in resource-limited settings - week 104 analysis of ACTG A5230.

Kumarasamy N, Aga E, Ribaudo HJ, Wallis CL, Katzenstein DA, Stevens WS, Norton MR, Klingman KL, Hosseinipour MC, Crump JA, Supparatpinyo K, Badal-Faesen S, Bartlett JA. Clin Infect Dis. 2015 Feb 18. pii: civ109. [Epub ahead of print]

Objective: ACTG A5230 evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure on first-line regimens in Africa and Asia.

Methods: Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000copies/mL. All subjects received LPV/r 400/100mg twice daily. Virologic failure (VF) was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200mg/tenofovir 300mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r-monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models.

Results: 123 subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 /123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39/41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400copies/mL over 104 weeks on LPV/r-monotherapy was 60% [95% CI 50%, 68%]; 80-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level<400 copies/mL at weeks 24, 48 and 104 revealed that 61%, 62% and 65% were suppressed to <40 copies/mL, respectively.

Conclusion: LPV/r monotherapy after first-line virologic failure with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.

Abstract access 

Editor’s notes: First-line antiretroviral therapy failure is increasingly encountered in resource-limited settings. However limited access to viral load monitoring means that treatment failure is often not recognised until immunological or clinical failure occurs. Late switching can lead to the accumulation of resistance mutations. Resistance to nucleoside reverse transcriptase inhibitors (NRTI) is of particular concern as this class remains a component of second-line, boosted protease inhibitor (bPI)-based regimens. Several studies have now looked at boosted protease inhibitor monotherapy as an alternative strategy. A strategy which aims to limit the toxicity and additional cost associated with NRTIs. In general boosted protease inhibitor monotherapy has been found to have inferior virologic outcomes when compared to bPI plus two NRTIs or bPI plus raltegravir.

In this study, while short term virologic outcomes were favourable (87% probability of continued virologic suppression over 24 weeks); longer term outcomes with bPI monotherapy were less good. However, with frequent viral load monitoring, 4-12 weekly, early detection of virologic failure and intensification with two NRTIs, outcomes in the bPI monotherapy arm improved substantially. This strategy warrants further investigation. But without markedly increasing access to viral load monitoring and lowering the cost to allow frequent testing, it is difficult to see how this strategy could be implemented in practice in resource-constrained settings. 

HIV Treatment
Africa, Asia
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Stigma, alcohol dependence and consulting traditional doctors associated with non-adherence to ART

Incomplete adherence among treatment-experienced adults on antiretroviral therapy in Tanzania, Uganda and Zambia.

Denison JA, Koole O, Tsui S, Menten J, Torpey K, van Praag E, Mukadi YD, Colebunders R, Auld AF, Agolory S, Kaplan JE, Mulenga M, Kwesigabo GP, Wabwire-Mangen F, Bangsberg DR. AIDS. 2015 Jan 28;29(3):361-71. doi: 10.1097/QAD.0000000000000543.

Objectives: To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa.

Design: A cross-sectional study.

Methods: Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed. Client self-reports (3-day, 30-day, Case Index ≥48 consecutive hours of missed ART), healthcare provider estimates and the pharmacy medication possession ratio (MPR) were used to estimate ART adherence. Participants from two facilities per country underwent HIV RNA testing. Optimal adherence measures were selected on the basis of degree of association with concurrent HIV RNA dichotomized at less than or greater/equal to 1000 copies/ml. Multivariate regression analysis, adjusted for site-level clustering, assessed associations between incomplete adherence and individual and programme factors.

Results: A total of 4489 participants were included, of whom 1498 underwent HIV RNA testing. Nonadherence ranged from 3.2% missing at least 48 consecutive hours to 40.1% having an MPR of less than 90%. The percentage with HIV RNA at least 1000 copies/ml ranged from 7.2 to 17.2% across study sites (mean = 9.9%). Having at least 48 consecutive hours of missed ART was the adherence measure most strongly related to virologic failure. Factors significantly related to incomplete adherence included visiting a traditional healer, screening positive for alcohol abuse, experiencing more HIV symptoms, having an ART regimen without nevirapine and greater levels of internalized stigma.

Conclusion: Results support more in-depth investigations of the role of traditional healers, and the development of interventions to address alcohol abuse and internalized stigma among treatment-experienced adult ART patients.

Abstract access

Editor’s notes: Antiretroviral therapy (ART) non-adherence is a strong predictor of incomplete viral suppression, disease progression and mortality in people living with HIV. Declining adherence rates over long-term follow-up of people on ART have been illustrated in a number of observational studies in both low- and high-income settings. This multi-country study gives valuable insight into the challenges that treatment-experienced people living with HIV in low-income countries face on a daily basis. Incomplete adherence was found to be associated with a number of social and behavioural factors. These include internalised stigma, alcohol dependence, low levels of social support and consulting a traditional healer/herbalist. The factor most strongly associated with incomplete adherence was visiting a traditional healer because of HIV. The data contribute to the growing evidence on the role that traditional healers may have in care-seeking behaviours and influencing sustained ART adherence. Findings from this study corroborate research from other studies that alcohol abuse and HIV stigma are broad and consistent correlates of ART adherence. The study also highlights the variability of existing adherence measures and the need for accurate programme-level methods for assessing pill-taking behaviour in order to inform programme strategies and assess impact.

Improving adherence and thereby longer-term healthy outcomes for people living with HIV requires programmatic activities to address alcohol dependence and internalised stigma among treatment-experienced adults. Greater understanding of the role that traditional healers/herbalists play in how people living with HIV manage their infection is also needed to support life-long ART adherence in sub-Saharan Africa.

Africa
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The impact of homophobia and criminalisation on MSM HIV vulnerability worldwide

Sexual stigma, criminalization, investment, and access to HIV services among men who have sex with men worldwide.

Arreola S, Santos GM, Beck J, Sundararaj M, Wilson PA, Hebert P, Makofane K, Do TD, Ayala G. AIDS Behav. 2015 Feb;19(2):227-34. doi: 10.1007/s10461-014-0869-x.

Globally, HIV disproportionately affects men who have sex with men (MSM). This study explored associations between access to HIV services and (1) individual-level perceived sexual stigma; (2) country-level criminalization of homosexuality; and (3) country-level investment in HIV services for MSM. 3340 MSM completed an online survey assessing access to HIV services. MSM from over 115 countries were categorized according to criminalization of homosexuality policy and investment in HIV services targeting MSM. Lower access to condoms, lubricants, and HIV testing were each associated with greater perceived sexual stigma, existence of homosexuality criminalization policies, and less investment in HIV services. Lower access to HIV treatment was associated with greater perceived sexual stigma and criminalization. Criminalization of homosexuality and low investment in HIV services were both associated with greater perceived sexual stigma. Efforts to prevent and treat HIV among MSM should be coupled with structural interventions to reduce stigma, overturn homosexuality criminalization policies, and increase investment in MSM-specific HIV services.

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Editor’s notes: Homosexuality is still illegal in 39% of the 193 UN recognised countries. This criminalisation likely increases HIV vulnerability among gay men and other men who have sex with men. In this study, 3340 gay men and other men who have sex with men from more than 115 countries completed an online survey about their perceptions of homophobia and their ease of accessing basic HIV prevention services. The authors conducted an ecological analysis to examine the relationship between the uptake of HIV services among gay men and other men who have sex with men. The authors looked at structural factors at the individual level which included their perceptions of homophobia within the society in which they live and at the country level including criminalising policies. More than 50% of respondents reported difficulty in accessing HIV services including condoms, lubricants, HIV testing services and antiretroviral therapy (ART). Perceived homophobia, criminalization of homosexual behaviour, and low country investment in HIV services were each associated with reduced access to condoms, lubricants, HIV testing services and ART. Improving access to HIV services for gay men and other men who have sex with men is urgently required as they carry a disproportionate burden of HIV in low and middle income countries. This study adds to a body of evidence which suggests that addressing structural barriers such as the criminalisation of homosexuality and sexual stigma (homophobia) will be necessary to reduce HIV vulnerability among gay men and other men who have sex with men, globally.

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Further evidence of an association with the injectable contraceptive, depot-medroxyprogesterone acetate with risk of HIV

Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.

Morrison CS, Chen PL, Kwok C, Baeten JM, Brown J, Crook AM, Van Damme L, Delany-Moretlwe S, Francis SC, Friedland BA, Hayes RJ, Heffron R, Kapiga S, Karim QA, Karpoff S, Kaul R, McClelland RS, McCormack S, McGrath N, Myer L, Rees H, van der Straten A, Watson-Jones D, van de Wijgert JH, Stalter R, Low N. PLoS Med. 2015 Jan 22;12(1):e1001778. doi: 10.1371/journal.pmed.1001778. eCollection 2015.

Background: Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.

Methods and findings: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37 124 women (43 613 woman-years) and 1830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship.

Conclusions: This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.

Abstract  Full-text [free] access

Editor’s notes: As seen in the paper published this month by Ralph et al, observational studies have reported that hormonal contraception, in particular injectable progestins depot-medroxyprogesterone acetate (DMPA), may increase risk of HIV infection. This individual patient data meta-analysis adds further to the evidence. A major strength of the study is the large sample size. It provides sufficient power to examine associations between specific contraceptives and HIV risk and to investigate effect modification in pre-specified sub-group analyses. Furthermore, using individual-level data allowed a consistent approach to coding and adjustment for confounding. If the association is real, this has important implications for sexual and reproductive health in areas of sub-Saharan Africa where the incidence of HIV acquisition and unintended pregnancy is high.

 


 

Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies.

Ralph LJ, McCoy SI, Shiu K, Padian NS. Lancet Infect Dis. 2015 Jan 8. pii: S1473-3099(14)71052-7. doi: 10.1016/S1473-3099(14)71052-7. [Epub ahead of print]

Background: The evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies.

Methods: We updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features.

Findings: We identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1.40, 95% CI 1.16-1.69). This risk was lower in the eight studies done in women in the general population (pooled HR 1.31, 95% CI 1.10-1.57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I2 51.1%, 95% CI 0-79.3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I2 54%, 0-88.7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1.00, 0.86-1.16) or five studies of norethisterone enanthate (pooled HR 1.10, 0.88-1.37).

Interpretation: Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive.

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Editor’s notes: This meta-analysis has similar findings to the individual patient data (IPD) meta-analysis by Morrison et al, also published this month. The study finds that depot medroxyprogesterone (DMPA) is associated with a moderate increase in HIV risk, and little evidence of a risk associated with combined oral contraceptives or norethisterone enanthate (NET-EN). The policy implications of this finding are unclear. As with the IPD analysis, this meta-analysis is based on observational studies and does not provide conclusive evidence that DMPA causes the increased risk of HIV. However, it does provide refined estimates for modelling studies to assess the implications of possible withdrawal of DMPA on maternal and HIV-associated mortality, so that context-specific contraceptive policies can be considered.

Africa
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