Articles tagged as "HIV This Month 2016 #01 - January 2016"

Mechanism found for increased HIV risk in women using injectable progestin-only contraception

Association between injectable progestin-only contraceptives and HIV acquisition and HIV target cell frequency in the female genital tract in South African women: a prospective cohort study.

Byrne EH, Anahtar MN, Cohen KE, Moodley A, Padavattan N, Ismail N, Bowman BA, Olson GS, Mabhula A, Leslie A, Ndung'u T, Walker BD, Ghebremichael MS, Dong KL, Kwon DS. Lancet Infect Dis. 2015 Dec 23. pii: S1473-3099(15)00429-6. doi: 10.1016/S1473-3099(15)00429-6. [Epub ahead of print]

Background: The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies, but the biological mechanisms of this risk remain poorly understood. We aimed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract.

Methods: In this prospective cohort, we enrolled HIV-negative South African women aged 18-23 years who were not pregnant and were living in Umlazi, South Africa from the Females Rising through Education, Support, and Health (FRESH) study. We tested for HIV-1 twice per week to monitor incident infection. Every 3 months, we collected demographic and behavioural data in addition to blood and cervical samples. The study objective was to characterise host immune determinants of HIV acquisition risk, including those associated with injectable progestin-only contraceptive use. Hazard ratios (HRs) were estimated using Cox proportional hazards methods.

Findings: Between Nov 19, 2012, and May 31, 2015, we characterised 432 HIV-uninfected South African women from the FRESH study. In this cohort, 152 women used injectable progestin-only contraceptives, 43 used other forms of contraception, and 222 women used no method of long-term contraception. Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV (12.06 per 100 person-years, 95% CI 6.41-20.63) than women using no long-term contraception (3.71 per 100 person-years, 1.36-8.07; adjusted hazard ratio [aHR] 2.93, 95% CI 1.09-7.868, p=0.0326). HIV-negative injectable progestin-only contraceptive users had 3.92 times the frequency of cervical HIV target cells (CCR5+ CD4 T cells) compared with women using no long-term contraceptive (p=0.0241). Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3.25 times higher frequency of cervical target cells compared with those in the follicular phase (p=0.0488), suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives.

Interpretation: Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix, the site of initial HIV entry in most women, providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure.

Abstract access 

Editor’s notes: Several observational studies have reported increased risk of HIV acquisition in women using injectable progestin-only contraception. In this study, injectable progestin-only contraceptive use was associated with a higher frequency of activated CCR5+ CD4 T cells in the cervix. These cells are the target for HIV, and thus an increase in their number may increase the risk of HIV acquisition by accelerating viral dissemination after genital tract exposure to HIV. This study also found a significantly higher frequency of activated cervical target cells during the luteal phase of the menstrual cycle in women who were not using injectable progestin-only contraception. These findings suggest that the increased HIV acquisition risk may be mediated by both exogenous and endogenous progestin exposure. This study provides novel insights into the role of progestins, and provides a potential biological explanation for an increased risk of HIV acquisition among women using injectable progestin-only contraception. This work will hopefully inform the development of biological prophylactics to reduce HIV acquisition in women. Whether these findings will influence recommendations for contraceptive use in women living in high HIV incidence settings remains to be determined.  

South Africa
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HIV contributes to stroke among young people

HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: A case-control study.

Benjamin LA, Corbett EL, Connor MD, Mzinganjira H, Kampondeni S, Choko A, Hopkins M, Emsley HC, Bryer A, Faragher B, Heyderman RS, Allain TJ, Solomon T. Neurology. 2015 Dec 18. pii: 10.1212/WNL.0000000000002278. [Epub ahead of print]

Objective: To investigate HIV, its treatment, and hypertension as stroke risk factors in Malawian adults.

Methods: We performed a case-control study of 222 adults with acute stroke, confirmed by MRI in 86%, and 503 population controls, frequency-matched for age, sex, and place of residence, using Global Positioning System for random selection. Multivariate logistic regression models were used for case-control comparisons.

Results: HIV infection (population attributable fraction [PAF] 15%) and hypertension (PAF 46%) were strongly linked to stroke. HIV was the predominant risk factor for young stroke (≤45 years), with a prevalence of 67% and an adjusted odds ratio (aOR) (95% confidence interval) of 5.57 (2.43-12.8) (PAF 42%). There was an increased risk of a stroke in patients with untreated HIV infection (aOR 4.48 [2.44-8.24], p < 0.001), but the highest risk was in the first 6 months after starting antiretroviral therapy (ART) (aOR 15.6 [4.21-46.6], p < 0.001); this group had a lower median CD4+ T-lymphocyte count (92 vs 375 cells/mm3, p = 0.004). In older participants (HIV prevalence 17%), HIV was associated with stroke, but with a lower PAF than hypertension (5% vs 68%). There was no interaction between HIV and hypertension on stroke risk.

Conclusions: In a population with high HIV prevalence, where stroke incidence is increasing, we have shown that HIV is an important risk factor. Early ART use in immunosuppressed patients poses an additional and potentially treatable stroke risk. Immune reconstitution inflammatory syndrome may be contributing to the disease mechanisms.

Abstract Full-text [free] access

Editor’s notes: Stroke incidence is increasing across sub-Saharan Africa. Globally, hypertension accounts for most of the strokes. However, in sub-Saharan Africa, stroke is not uncommon among younger people, among whom the prevalence of hypertension is low. Therefore other factors may play a role.

This article reports on a case-control study with prospective recruitment of cases and community controls, examining the role of HIV, antiretroviral therapy, and the interaction between HIV and hypertension as risk factors for stroke in a setting with high HIV prevalence.

The investigators confirmed 86% of their cases with brain imaging, and found that the majority (78%) had findings consistent with ischemic stroke. Not surprisingly they found that overall, hypertension accounted for about half (46%) of the stroke cases. Interestingly only one-quarter of all people with hypertension in the study (cases and controls) were on hypertensive treatment.

However, among younger people (≤45 years) with stroke, HIV infection was the most important risk factor and accounted for 42% of the cases. HIV-positive people experienced the greatest risk of stroke during their first six months after ART initiation.

The HIV-positive stroke cases had a lower CD4 cell count compared to HIV-positive controls on the same duration of ART. Immunosuppression is a risk factor for immune constitution inflammatory syndrome (IRIS), and IRIS could thus be a plausible mechanism of stroke among people initiating ART.

The results of this study reinforce the need to start ART before people have advanced immunosuppression, which will reduce IRIS-associated morbidity. The latest WHO guidelines, ‘Treat all’, which recommend starting all HIV-positive people on antiretroviral therapy as soon after diagnosis as possible, have the potential to contribute to this.  

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Following TB diagnostic algorithms: could do better

What happens after a negative test for tuberculosis? Evaluating adherence to TB diagnostic algorithms in South African primary health clinics.

McCarthy K, Grant AD, Chihota V, Ginindza S, Mvusi L, Churchyard G, Fielding K. J Acquir Immune Defic Syndr. 2015 Nov 25. [Epub ahead of print]

Introduction and background: Diagnostic tests for tuberculosis (TB) using sputum have suboptimal sensitivity among HIV-positive persons. We assessed health care worker adherence to TB diagnostic algorithms after negative sputum test result/s.

Methods: The XTEND trial compared outcomes among people tested for TB in primary care clinics using Xpert® MTB/RIF vs. smear microscopy as the initial test. We analysed data from XTEND participants who were HIV-positive or HIV status unknown, whose initial sputum Xpert® MTB/RIF or microscopy result was negative. If chest radiography, sputum culture or hospital referral took place, the algorithm for TB diagnosis was considered followed. Analysis of intervention (Xpert® MTB/RIF) effect on algorithm adherence used methods for cluster-randomised trials with small number of clusters.

Results: Amongst 4037 XTEND participants with initial negative test results, 2155 (53%) reported being or testing HIV positive and 540 (14%) had unknown HIV status. Amongst 2155 HIV-positive participants (684 [32%] male, mean age 37 years [range 18-79 years]), there was evidence of algorithm adherence amongst 515 (24%). Adherence was less likely among persons tested initially with Xpert® MTB/RIF vs. smear (14% [142/1031] vs 32% [364/1122], adjusted risk ratio 0.34 [95% CI 0.17-0.65]) and for participants with unknown vs. positive HIV status (59/540 [11%] vs. 507/2155 [24%]).

Conclusions: We observed poorer adherence to TB diagnostic algorithms amongst HIV-positive persons tested initially with Xpert® MTB/RIF vs. microscopy. Poor adherence to TB diagnostic algorithms and incomplete coverage of HIV testing represents a missed opportunity to diagnose TB and HIV, and may contribute to TB mortality.

Abstract access

Editor’s notes: Despite advances in the TB diagnostic field in recent years, molecular tests such as Xpert® MTB/RIF will still miss a substantial proportion of HIV-positive people with active TB disease. For that reason, diagnostic algorithms have been developed to guide further evaluation of people with symptoms suggestive of TB who test negative with Xpert®. This paper presents findings from South Africa that, in the context of a cluster-randomised trial, few people received further investigation according to the algorithm.

Only one in seven of the HIV-positive people with a negative Xpert® MTB/RIF had any further investigations recorded. Sputum culture was the most common investigation in this group but was done for only around one in ten. It should be noted that the outcome of having further investigations was largely based on review of clinic and laboratory records. As a result, it is possible that additional investigations were performed but remained undocumented. Although considerable between-clinic variation in performance was noted, the reasons underlying this were not explored in this analysis. The algorithm for people living with HIV was not overly complex and was broadly similar to the algorithm in place previously for investigation of people with a negative sputum smear. The observation that algorithm adherence was lower than for people with a negative smear suggests that health care workers might have had false confidence in the negative Xpert® result. In the broader context, this study took place at a time when there was much hype around Xpert® as a tool that would revolutionise the diagnosis of TB. It would not be surprising if this resulted in health care workers being over-confident in their interpretation of negative test results.

There are other possible explanations for the low numbers having additional investigations:

  • People may not have returned for their initial test result so further investigation was not possible (this is not quantified here)
  • People did return but symptoms had fully resolved or they were unable to produce sputum for further investigation
  • Health care workers used clinical judgement to decide on the need for further investigation rather than adhering strictly to the algorithm. This is supported at least partly by the fact that people with more TB symptoms were more likely to receive additional investigations. The yield of culture is not reported here – that might have given a further clue as to whether the people selected to have further investigations were individuals with a high likelihood of TB.  

These issues and others may need to be explored in future analyses to determine whether modifications to the algorithm are required or whether strengthened training and support of health care workers would improve adherence to the algorithm.

Avoid TB deaths
South Africa
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HIV and gay men and other men who have sex with men: an expanding and underfunded epidemic

Financing the response to HIV among gay men and other men who have sex with men: case studies from eight diverse countries.

Grosso A, Ryan O, Tram KH, Baral S. Glob Public Health. 2015 Dec;10(10):1172-84. doi: 10.1080/17441692.2015.1043314. Epub 2015 Jul 3.

Despite reductions in the number of new HIV infections globally, the HIV epidemic among men who have sex with men (MSM) is expanding. This study characterises financing of HIV programmes for MSM and the impact of criminalisation on levels of funding, using data from five countries that criminalise same-sex sexual practices (Ethiopia, Mozambique, Guyana, India and Nigeria) and three that do not (China, Ukraine and Vietnam). For each country, all publicly available documents from the Global Fund to Fight AIDS, Tuberculosis and Malaria for approved HIV/AIDS grants in Rounds 5-9 and Country Operational Plans detailing investments made through the President's Emergency Plan for AIDS Relief (PEPFAR) from US fiscal year (FY) 2007-2009 were examined. Eleven of 20 HIV proposals to the Global Fund contained programmes for MSM totalling approximately $40 million or 6% of proposed budgets. In six countries providing activity-level data on MSM programming, PEPFAR funding that served this population and others ranged from $23.3 million in FY2007 to $35.4 million in FY2009, representing 0.5-25.9% of overall, non-treatment funding over this period. Countries that criminalise same-sex sexual practices spend fewer resources on HIV programmes serving MSM. However, they also show consistent underfunding of programmes serving MSM regardless of context or geography.

 Abstract access

Editor’s notes: Despite encouraging indicators on the reduction of new HIV infections worldwide, the epidemic among gay men and other men who have sex with men continues to grow. This is due to both biological and structural factors. With many governments failing to take responsibility for this at-risk population, funding for gay men and other men who have sex with men-specific programmes often comes from international donors. This study looks at Global Fund and PEPFAR financing of programmes for gay men and other men who have sex with men, comparing funding availability and services offered both in settings where homosexuality is criminalised and settings where it is not.

The study finds that most proposed funding focuses on behaviour change communication, and less frequently on improving sexual health services, community outreach and education. Nations that criminalise homosexuality allocated about 2% of funding towards gay men and other men who have sex with men services, while countries without punitive measures allocated close to 7%. Importantly, both were felt to be inadequately small sums of money in relation to the size of the epidemic. Key stakeholder interviews from criminalising countries suggest that legal restrictions make it more difficult to provide services focused on gay men and other men who have sex with men. Although, little is known about the degree to which gay men and other men who have sex with men access services focused on the general population. The authors also note that countries that criminalise homosexuality may request funds for gay men and other men who have sex with men believing that donors will look favourably on budgets that include these activities. After receiving funds, these countries may re-programme activities, reducing or removing these focussed programmes.

There is comparatively little research done on HIV and gay men and other men who have sex with men in low- and middle-income countries, in particular in African settings. This article contributes to an expanding literature on the subject and raises questions about the role that international donors should play in ensuring an equitable access to services, particularly in the context of reprogramming. This highlights how real impact on the incidence of HIV among gay men and other men who have sex with men requires both demand generation and accountability in equal measure.

Africa, Asia, Europe, Latin America
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Violence experience of women living with HIV: a global study

Violence. Enough already: findings from a global participatory survey among women living with HIV.

Orza L, Bewley S, Chung C, Crone ET, Nagadya H, Vazquez M, Welbourn A. J Int AIDS Soc. 2015 Dec 1;18(6 Suppl 5):20285. doi: 10.7448/IAS.18.6.20285. eCollection 2015.

Introduction: Women living with HIV are vulnerable to gender-based violence (GBV) before and after diagnosis, in multiple settings. This study's aim was to explore how GBV is experienced by women living with HIV, how this affects women's sexual and reproductive health (SRH) and human rights (HR), and the implications for policymakers.

Methods: A community-based, participatory, user-led, mixed-methods study was conducted, with women living with HIV from key affected populations. Simple descriptive frequencies were used for quantitative data. Thematic coding of open qualitative responses was performed and validated with key respondents.

Results: In total, 945 women living with HIV from 94 countries participated in the study. Eighty-nine percent of 480 respondents to an optional section on GBV reported having experienced or feared violence, either before, since and/or because of their HIV diagnosis. GBV reporting was higher after HIV diagnosis (intimate partner, family/neighbours, community and health settings). Women described a complex and iterative relationship between GBV and HIV occurring throughout their lives, including breaches of confidentiality and lack of SRH choice in healthcare settings, forced/coerced treatments, HR abuses, moralistic and judgemental attitudes (including towards women from key populations), and fear of losing child custody. Respondents recommended healthcare practitioners and policymakers address stigma and discrimination, training, awareness-raising, and HR abuses in healthcare settings.

Conclusions: Respondents reported increased GBV with partners and in families, communities and healthcare settings after their HIV diagnosis and across the life-cycle. Measures of GBV must be sought and monitored, particularly within healthcare settings that should be safe. Respondents offered policymakers a comprehensive range of recommendations to achieve their SRH and HR goals. Global guidance documents and policies are more likely to succeed for the end-users if lived experiences are used.

Abstract  Full-text [free] access

Editor’s notes: Violence against women who are living with HIV is common globally. This paper reports on a study of 832 women living with HIV from 94 countries who participated in an online survey, recruited through a non-random snowball sampling model. The survey comprised quantitative and qualitative (free text) components. Participants included women who had ever or were currently using injection drugs (14%), who had ever or were currently selling sex (14%), and who had ever or were currently homeless (14%). Lifetime experience of violence among respondents was high (86%). Perpetrators included: intimate partner (59%), family member / neighbour (45%), community member (53%), health care workers (53%) and police, military, prison or detention services (17%). Findings suggest that violence is not a one off occurrence and cannot easily be packaged as a cause or a consequence of HIV. Instead violence occurs throughout women’s lives, takes multiple forms, and has a complex and iterative relationship with HIV.

The study population did not represent all women living with HIV, and was biased towards women with internet access who have an activist interest. Nonetheless, the study provides further evidence of the breadth and frequency of gender based violence experienced by women living with HIV. Key recommendations for policy makers include training of health care workers working in sexual and reproductive services to offer non-discriminatory services to women living with HIV and to effectively respond to disclosures of gender based violence (such as intimate partner violence) as part of the package of care.

Algeria, Angola, Argentina, Armenia, Australia, Austria, Azerbaijan, Belarus, Belgium, Belize, Bolivarian Republic of Venezuela, Bolivia, Botswana, Burkina Faso, Burundi, Cambodia, Cameroon, Canada, Chile, China, Colombia, Costa Rica, Côte d'Ivoire, Czech Republic, Democratic Republic of the Congo, Denmark, Dominican Republic, Ecuador, El Salvador, Estonia, Ethiopia, France, Gabon, Germany, Ghana, Greece, Guatemala, Honduras, Hungary, India, Indonesia, Ireland, Italy, Jamaica, Kazakhstan, Kenya, Kyrgyzstan, Lesotho, Malawi, Mali, Mexico, Moldova, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, New Zealand, Nicaragua, Nigeria, Norway, Panama, Paraguay, Peru, Poland, Republic of the Congo, Romania, Russian Federation, Rwanda, Serbia, South Africa, Spain, Sri Lanka, Sudan, Swaziland, Switzerland, Tajikistan, Togo, Transdniestria, Turkey, Uganda, Ukraine, United Kingdom, United Republic of Tanzania, United States of America, Uruguay, Uzbekistan, Viet Nam, Zambia, Zimbabwe
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Violence and educational outcomes among young children in South Africa and Malawi

Exposure to violence predicts poor educational outcomes in young children in South Africa and Malawi.

Sherr L, Hensels IS, Skeen S, Tomlinson M, Roberts KJ, Macedo A. Int Health. 2015 Dec 17. pii: ihv070. [Epub ahead of print]

Background: Violence during childhood may affect short and long-term educational factors. There is scant literature on younger children from resource poor settings.

Methods: This study assessed child violence experiences (harsh punishment and exposure to domestic or community violence) and school enrolment, progress and attendance in children attending community-based organisations in South Africa and Malawi (n=989) at baseline and at 15 months' follow-up, examining differential experience of HIV positive, HIV affected and HIV unaffected children.

Results: Violence exposure was high: 45.4% experienced some form of psychological violence, 47.8% physical violence, 46.7% domestic violence and 41.8% community violence. Primary school enrolment was 96%. Violence was not associated with school enrolment at baseline but, controlling for baseline, children exposed to psychological violence for discipline were more than ten times less likely to be enrolled at follow-up (OR 0.09; 95% CI 0.01 to 0.57). Harsh discipline was associated with poor school progress. For children HIV positive a detrimental effect of harsh physical discipline was found on school performance (OR 0.10; 95% CI 0.02 to 0.61).

Conclusion: Violence experiences were associated with a number of educational outcomes, which may have long-term consequences. Community-based organisations may be well placed to address such violence, with a particular emphasis on the challenges faced by children who are HIV positive.

Abstract  Full-text [free] access

Editor’s notes: There is substantial evidence that demonstrates the negative effects of the experience of violence in childhood on child mental health. However, there is little evidence on the impact of violence on educational outcomes. This is due to measurement and study design, such as data being primarily cross-sectional and studies being confined to adolescents, where younger children are excluded. This study reports data from a longitudinal study of young children aged 4–13 years affected by HIV enrolled at community-based organisations (CBOs) in South Africa and Malawi. The study examined the relationship between exposure to violence at home or in the community on educational outcomes at baseline and follow-up (12–15 months later). In particular, attention was given to HIV positive and HIV affected children in order to explore the effects of HIV as a factor of either violence experience or educational risk in this age group. HIV affected children are children who may not be HIV positive themselves, but living in a household with a HIV positive member.

In this sample of young children (n=989), close to 14% were HIV positive. School enrolment and attendance was high, although HIV positive children had slightly lower attendance and enrolment in the correct grade for their age, compared to HIV affected children. At baseline, overall exposure to violence at home and in the community was very high. Over half of the sample had been exposed to two or more types of violence, whereas less than one in six reported no violence exposure at all. At both baseline and at follow-up, there was no association found between community violence and school enrolment and attendance or grade progression. In terms of violence experienced at home (domestic violence), at baseline there was an association with grade progression for children in households with no HIV. At follow-up, in particular for children living with HIV, use of physical violence to discipline the child had a detrimental effect on grade progression. Furthermore, at follow-up, the use of psychological violence to discipline children had an effect on school enrolment. Hence, children of caregivers using psychological violence for discipline were significantly less likely to be enrolled in school at follow-up, if they were not enrolled at baseline. Thus, findings from this study highlight that despite high rates of violence exposure in this population, children who are HIV positive, in particular, appear to be most at risk of poor educational outcomes. This is likely to be due to a range of inter-related risk factors that affect educational outcomes: parental death, shifting care arrangements, change in school, illness-induced poverty and increased care-giving responsibilities.  All these factors might affect a child’s ability to access schooling and perform well in the context of HIV. As shown, educational outcomes were specifically linked to harsh punishment, as opposed to community or domestic violence. Thus, CBOs that provide services for children affected by HIV might be key to intervening on this issue. Furthermore, younger children in HIV endemic countries are particularly vulnerable and educational achievement in the early years is an important pre-requisite for ongoing educational milestones.  

Malawi, South Africa
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