Articles tagged as "HIV This Month 2015 #12 - December 2015"

Weighing up the risks and benefits of trial participation: understanding non-adherence in a PrEP trial

Participants' explanations for non-adherence in the FEM-PrEP clinical trial.

Corneli A, Perry B, McKenna K, Agot K, Ahmed K, Taylor J, Malamatsho F, Odhiambo J, Skhosana J, Van Damme L. J Acquir Immune Defic Syndr. 2015 Nov 3. [Epub ahead of print]

Background: FEM-PrEP - a clinical trial of daily, oral emtricitabine/tenofovir disoproxil fumarate for HIV prevention among women in sub-Saharan Africa - did not show a reduction in HIV acquisition because of low adherence to the study pill. We conducted a follow-up study to identify reasons for non-adherence.

Methods: Qualitative, semi-structured interviews (n=88) and quantitative, audio computer-assisted self-interviews (n=224) were conducted with former FEM-PrEP participants in Bondo, Kenya, and Pretoria, South Africa. Thematic analysis was used to analyze the qualitative data, and descriptive statistics were used to describe ACASI responses. Data are presented within the five categories of Ickovics' and Meisler's conceptual framework on adherence: 1) the individual, 2) trial characteristics and study pill regimen, 3) patient-provider relationship, 4) clinical setting, and 5) the disease.

Results: Participants' explanations for non-adherence were primarily situated within three of the framework's five categories: 1) the individual, 2) trial characteristics and study pill regimen, and 3) the disease. Concerns about the investigational nature of the drug being tested and side effects were the prominent reasons reported for non-adherence. Participants also described being discouraged from taking the study pill by members of the community, their sexual partners, and other participants, primarily because of these same concerns. Limited acceptability of the pill's attributes influenced non-adherence for some participants as did concerns about HIV-related stigma. Additionally, many participants reported that others continued in FEM-PrEP while not taking the study pill because of the trial's ancillary benefits and visit reimbursement - factors related to the clinical setting. Negative patient-provider relationships were infrequently reported as a factor that influenced non-adherence.

Conclusion: Despite substantial study staff engagement with participants and communities, concerns about the study pill and discouragement from others appeared to have influenced non-adherence considerably. Alternative study designs or procedures and enhanced community engagement paradigms may be needed in future studies.

Abstract access 

Editor’s notes: The authors of this important paper on a PrEP trial, end with a note of caution. They note that when interpreting the findings we should remember that the women in this study were taking a ‘study product’. The women were not taking a product of proven efficacy. Therefore, as the authors state, it would be wrong to assume that ‘African women cannot and will not be adherent if provided with PrEP outside of a clinical trial setting’. If they had been told that the product was efficacious, they may have behaved differently. This is important because a key message of the paper is that trial participants managed their participation so they felt comfortable in the trial. Many wanted to ensure they received benefits from their participation, including good health care, but they also wanted to manage risk. Risk associated with fears about the trial drug and risk from the disapproval of sexual partners about their participation. It is also very clear in these findings that the participants could manage the expectations of the trial team, by telling them what they wanted to hear during the trial. This suggests the limited value of ‘adherence questionnaires’ in some settings. The authors provide a powerful illustration of the value of mixed methods in trials of this sort. Drug concentration data told the researchers that many women were not adhering to the drug. Qualitative semi-structured interviews using this drug concentration data with the individual women helped the team to understand why. The authors also discuss the influence of community and family members in undermining participant faith in the trial. They explain the lengths that the trial team went to, to inform community members about the trial. Considerable time was given to sharing information. Doubts remained; concerns that were enough to discourage participation. This too is an important finding underlining the value of investing in community engagement in research. But it also highlights the need to find ways to enhance not just engagement, but also understanding and trust. 

Africa
Kenya, South Africa
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Condoms are highly effective at preventing HSV-2 acquisition, especially for women

Effect of condom use on per-act HSV-2 transmission risk in HIV-1, HSV-2-discordant couples.

Magaret AS, Mujugira A, Hughes JP, Lingappa J, Bukusi EA, DeBruyn G, Delany-Moretlwe S, Fife KH, Gray GE, Kapiga S, Karita E, Mugo NR, Rees H, Ronald A, Vwalika B, Were E, Celum C, Wald A, Partners in Prevention HSVHIVTST. Clin Infect Dis. 2015 Nov 17. pii: civ908. [Epub ahead of print]

Background: The efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not been previously measured on a per-act basis.

Methods: We examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts.

Results: Transmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060).

Conclusions: Condoms are recommended as an effective preventive method for heterosexual transmission of HSV-2.

Abstract access

Editor’s notes: HSV-2 is extremely prevalent in sub-Saharan Africa, and an important co-factor in HIV transmission. Although condoms are recommended for preventing HSV-2 infection, there have been no previous studies of their effectiveness on a per-sex act basis. This study in HIV and HSV-2 discordant couples participating in an HIV prevention trial examined the risk of HSV-2 transmission for each sex act with and without male condoms. At enrolment, index partners were living with both HIV and HSV-2 infections; susceptible partners were negative for both infections.

The authors found that condoms provided greater protection against HSV-2 acquisition for women than for men, reducing the risk of transmission by 96% from men to women, and by 65% from women to men. However, the overall risk of HSV-2 infection was much higher for women – for each condomless sex act, women were nearly 20 times more likely than men to become infected. As a result, even when using condoms, susceptible women had only a slightly lower risk of infection than men did without condoms. Interestingly, HSV-2 suppressive therapy with acyclovir did not have any effect on HSV-2 transmission, for either sex. Although the authors were not able to confirm that the HSV-2 transmissions occurred within the partnership (e.g. by sequencing the HSV2 DNA), an analysis restricted to couples who never reported sex outside the partnership illustrated very similar results.

The difference in the protection provided by condoms between the sexes may be explained by the fact that, in men, HSV-2 viral shedding is primarily from the penile shaft whereas in women the virus is shed from the wider area of the perineum, and hence condoms are less effective for female-male transmission. These findings indicate that, in individuals who are both HIV and HSV-2 positive, male condoms are extremely effective in preventing male-to-female transmission of HSV-2, and also provide some protection against female-to-male transmission. Although condoms may not provide the same level of protection in populations who are HIV negative, their promotion remains an important public health activity for preventing HSV-2 infection.

Africa
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Benefits of targeting prevention at attendees of HIV testing services, Brazil

Efficient identification of HIV serodiscordant couples by existing HIV testing programs in south Brazil.

Pilcher CD, Bisol CA, Paganella MP, Vallabhaneni S, da Motta LR, Kato SK, Sperhacke RD, Kallas EG, Hecht FM, Diaz RS. PLoS One. 2015; 10(11): e0142638. Published online Nov 12.

Objective: To examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil.

Methods: We surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population.

Results: Among 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5).

Conclusion: It is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission.

Abstract Full-text [free] access

Editor’s notes: This study from Brazil highlights the fact that asking individuals attending HIV testing services whether they had a steady partner living with HIV can identify a large number of key populations who should be an important focus for HIV prevention services. In this study, a striking proportion (15%) of testers reported that they were in a serodiscordant relationship with an individual living with HIV. This provides an important opportunity to link these key populations to proven prevention services, including medical male circumcision and pre-exposure prophylaxis. There was also clear evidence that these individuals are at high risk of HIV, e.g. they were almost twice as likely to have an acute HIV infection compared with testers with “general population” partners. This suggests that individuals in serodiscordant relationships sought HIV testing services when they thought they had been exposed to a high risk sexual event. The paper does not report the treatment status of the partners living with HIV and it is not clear if participants were asked about this. The authors conclude that it is feasible to identify HIV susceptible individuals at testing sites. It is also important to remember that this is not only to focus on people with a partner living with HIV, but also all people testing HIV-positive. People in the latter group are a key population for prevention too, as they are at risk for transmitting HIV within their steady partnership which was previously concordant HIV-negative.

Latin America
Brazil
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You’re not a man until you’re a father. Young men’s desire for fatherhood and HIV-associated risk

Fatherhood, marriage and HIV risk among young men in rural Uganda.

Mathur, S, Higgins, J. A, Thummalachetty N, Rasmussen, M, Kelley, L, Nakyanjo, N, Nalugoda, F, Santelli, J. S, Cult Health Sex 2015 Nov 5:1-15 (Epub ahead of print)

Compared to a large body of work on how gender may affect young women’s vulnerability to HIV, we know little about how masculine ideals and practices relating to marriage and fertility desires shape young men’s HIV risk. Using life-history interview data with 30 HIV-positive and HIV-negative young men aged 15–24 years, this analysis offers an in-depth perspective on young men’s transition through adolescence, the desire for fatherhood and experience of sexual partnerships in rural Uganda. Young men consistently reported the desire for fatherhood as a cornerstone of masculinity and transition to adulthood. Ideally young men wanted children within socially sanctioned unions. Yet, most young men were unable to realise their marital intentions. Gendered expectations to be economic providers combined with structural constraints, such as limited access to educational and income-generating opportunities, led some young men to engage in a variety of HIV-risk behaviours. Multiple partnerships and limited condom use were at times an attempt by some young men to attain some part of their aspirations related to fatherhood and marriage. Our findings suggest that young men possess relationship and parenthood aspirations that – in an environment of economic scarcity – may influence HIV-related risk.

Abstract access

Editor’s notes: Gender-specific HIV risks are influenced by biological, social and structural factors. In comparison to factors that affect women’s HIV risk, relatively little is known about how constructions on masculinity affect men’s HIV risk, particularly with relation to young men’s desire for marriage and biological children. In the context meeting fertility ideals, men’s demonstration of masculinity within structural contexts of social change and economic instability, may be associated with certain risk behaviours, including multiple partnerships and inconsistent condom use.

This study utilised data from in-depth life history interviews with 30 HIV-positive and HIV-negative young men aged 15-24 years in southern Uganda. Young men who had acquired bio-medically confirmed HIV over the course of the year between June 2010 and June 2011 and their HIV-negative counterparts were pair-matched by gender, marital status, age and village of residence. The sample included married (n=10), never married (n=16) and previously married men (n=4). Respondents participated in two interviews, approximately two to three weeks apart. Interviews were audio recorded.

Three major themes emerged from the interviews. First, respondents mentioned fatherhood and formal marriage as milestones in the transition to adulthood for young men and a crucial part of the masculine ideal in rural Uganda. Second, truncated educational options and limited economic opportunities made it difficult for young men to acquire formal marriages and fulfil their desires for fatherhood. Third, young men who faced obstacles in trying to achieve these masculine ideals often engaged in alternative strategies, such as condomless sex or having multiple partners, to fulfil their desires for marriage and children; these strategies in turn increased young men’s vulnerability to HIV infection. Regardless of their HIV status young men consistently expressed their desire for marriage and children; described similar economic challenges, and pursued alternative strategies for achieving their masculine ideals. The findings of this study illustrate how the confluence of idealised male masculinities and structural inequalities may play a key role in young men’s vulnerability to HIV.

Africa
Uganda
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HIV tests at church-based baby showers raise odds of testing 11-fold for pregnant women

Effect of a congregation-based intervention on uptake of HIV testing and linkage to care in pregnant women in Nigeria (baby shower): a cluster randomised trial.

Ezeanolue EE, Obiefune MC, Ezeanolue CO, Ehiri JE, Osuji A, Ogidi AG, Hunt AT, Patel D, Yang W, Pharr J, Ogedegbe G. Lancet Glob Health. 2015 Nov;3(11):e692-700. doi: 10.1016/S2214-109X(15)00195-3.

Background: Few effective community-based interventions exist to increase HIV testing and uptake of antiretroviral therapy (ART) in pregnant women in hard-to-reach resource-limited settings. We assessed whether delivery of an intervention through churches, the Healthy Beginning Initiative, would increase uptake of HIV testing in pregnant women compared with standard health facility referral.

Methods: In this cluster randomised trial, we enrolled self-identified pregnant women aged 18 years and older who attended churches in southeast Nigeria. We randomised churches (clusters) to intervention or control groups, stratified by mean annual number of infant baptisms (<80 vs ≥80). The Healthy Beginning Initiative intervention included health education and on-site laboratory testing implemented during baby showers in intervention group churches, whereas participants in control group churches were referred to health facilities as standard. Participants and investigators were aware of church allocation. The primary outcome was confirmed HIV testing. This trial is registered with ClinicalTrials.gov, identifier number NCT 01795261.

Findings: Between Jan 20, 2013, and Aug 31, 2014, we enrolled 3002 participants at 40 churches (20 per group). 1309 (79%) of 1647 women attended antenatal care in the intervention group compared with 1080 (80%) of 1355 in the control group. 1514 women (92%) in the intervention group had an HIV test compared with 740 (55%) controls (adjusted odds ratio 11.2, 95% CI 8.77-14.25; p<0.0001).

Interpretation: Culturally adapted, community-based programmes such as the Healthy Beginning Initiative can be effective in increasing HIV screening in pregnant women in resource-limited settings.

Abstract Full-text [free] access

Editor’s notes: HIV testing is a key entry point for prevention of mother-to-child transmission. Community-based, decentralised HIV testing outside health facilities can increase uptake of testing among pregnant women, but this does not always follow through into good linkage to care.

In Nigeria faith-based organisations have a strong social network and a wider presence than health facilities. This trial co-ordinated churches in predominantly Christian southeast Nigeria to identify pregnant women early and organise a baby shower where on-site laboratory tests were provided. To avoid stigma the programme offered testing for five other conditions alongside HIV. Women who tested positive for HIV infection were linked to care and followed up at a post-delivery baby reception at the church. Women in the programme arm were more likely to have an HIV test and if positive they were more likely to access care before delivery and to start ART during pregnancy.

The results illustrate the benefits of engagement with faith-based organisations to reach communities that are poorly served by health facilities. The fact male partners played a role in the baby shower may have increased uptake, as pregnant women are more likely to accept HIV testing when male partners are also involved. The main costs were Mama Packs (a gift of essentials for a safe delivery, presented at the baby shower) and integrated lab tests. The activity was so popular that communities continued with it after the trial ended. The programme is now being adapted for mosques in northern Nigeria and Hindu temples in India. 

Africa
Nigeria
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Contraception for women on ART – a balancing act

Pregnancy rates in HIV-positive women using contraceptives and efavirenz-based or nevirapine-based antiretroviral therapy in Kenya: a retrospective cohort study.

Patel RC, Onono M, Gandhi M, Blat C, Hagey J, Shade SB, Vittinghoff E, Bukusi EA, Newmann SJ, Cohen CR. Lancet HIV. 2015 Nov;2(11):e474-82. doi: 10.1016/S2352-3018(15)00184-8. Epub 2015 Oct 22.

Background: Concerns have been raised about efavirenz reducing the effectiveness of contraceptive implants. We aimed to establish whether pregnancy rates differ between HIV-positive women who use various contraceptive methods and either efavirenz-based or nevirapine-based antiretroviral therapy (ART) regimens.

Methods: We did this retrospective cohort study of HIV-positive women aged 15-45 years enrolled in 19 HIV care facilities supported by Family AIDS Care and Education Services in western Kenya between Jan 1, 2011, and Dec 31, 2013. Our primary outcome was incident pregnancy diagnosed clinically. The primary exposure was a combination of contraceptive method and efavirenz-based or nevirapine-based ART regimen. We used Poisson models, adjusting for repeated measures, and demographic, behavioural, and clinical factors, to compare pregnancy rates among women receiving different contraceptive and ART combinations.

Findings: 24 560 women contributed 37 635 years of follow-up with 3337 incident pregnancies. In women using implants, adjusted pregnancy incidence was 1.1 per 100 person-years (95% CI 0.72-1.5) for nevirapine-based ART users and 3.3 per 100 person-years (1.8-4.8) for efavirenz-based ART users (adjusted incidence rate ratio [IRR] 3.0, 95% CI 1.3-4.6). In women using depot medroxyprogesterone acetate, adjusted pregnancy incidence was 4.5 per 100 person-years (95% CI 3.7-5.2) for nevirapine-based ART users and 5.4 per 100 person-years (4.0-6.8) for efavirenz-based ART users (adjusted IRR 1.2, 95% CI 0.91-1.5). Women using other contraceptive methods, except for intrauterine devices and permanent methods, had 3.1-4.1 higher rates of pregnancy than did those using implants, with 1.6-2.8 higher rates in women using efavirenz-based ART.

Interpretation: Although HIV-positive women using implants and efavirenz-based ART had a three-times higher risk of contraceptive failure than did those using nevirapine-based ART, these women still had lower contraceptive failure rates than did those receiving all other contraceptive methods except for intrauterine devices and permanent methods. Guidelines for contraceptive and ART combinations should balance the failure rates for each contraceptive method and ART regimen combination against the high effectiveness of implants.

Abstract access 

Editor’s notes: Contraceptive use by women living with HIV who wish to prevent pregnancy remains a key component of the strategy to eliminate new HIV infections among children. Progesterone-based implants are the most effective reversible contraceptive method, but there is some evidence to suggest that their efficacy may be reduced in women receiving efavirenz (EFV)-based antiretroviral therapy (ART).

Overall contraceptive use in these women of childbearing age was low – 70% of the time women were using no contraception or less effective methods only (condoms or natural methods). Overall pregnancy rates were low with the hormonal implant, broadly equivalent to women with intrauterine devices and much lower than with depot injectable and oral contraceptive methods. There was some evidence that the rate of pregnancy in women using the implant was higher for women on EFV-based ART compared to women on nevirapine-based ART. However, the rate of pregnancy remained lower than with injectable or oral contraceptives.

Although this may provide some support to the evidence of reduced implant efficacy with EFV-based ART, it is clear that this can still be an effective contraceptive method. This evidence seems unlikely to change existing WHO recommendations that all forms of contraception should be available to women living with HIV. The low rate of contraceptive use highlights the need to improve access for women living with HIV to quality integrated sexual and reproductive health services. The data from this study suggest that for women wishing to avoid pregnancy, the choice of contraceptive method may be more important than the choice of ART regimen.  

Africa
Kenya
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Can nevirapine-exposed children switch to efavirenz?

Efavirenz-based antiretroviral therapy among nevirapine-exposed HIV-infected children in South Africa: a randomized clinical trial.

Coovadia A, Abrams EJ, Strehlau R, Shiau S, Pinillos F, Martens L, Patel F, Hunt G, Tsai WY, Kuhn L. JAMA. 2015 Nov 3;314(17):1808-17. doi: 10.1001/jama.2015.13631.

Importance: Advantages of using efavirenz as part of treatment for children infected with human immunodeficiency virus (HIV) include once-daily dosing, simplification of co-treatment for tuberculosis, preservation of ritonavir-boosted lopinavir for second-line treatment, and harmonization of adult and pediatric treatment regimens. However, there have been concerns about possible reduced viral efficacy of efavirenz in children exposed to nevirapine for prevention of mother-to-child transmission.

Objective: To evaluate whether nevirapine-exposed children achieving initial viral suppression with ritonavir-boosted lopinavir-based therapy can transition to efavirenz-based therapy without risk of viral failure.

Design, setting, and participants: Randomized, open-label noninferiority trial conducted at Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa, from June 2010 to December 2013, enrolling 300 HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission who were aged 3 years or older and had plasma HIV RNA of less than 50 copies/mL during ritonavir-boosted lopinavir-based therapy; 298 were randomized and 292 (98%) were followed up to 48 weeks after randomization.

Interventions: Participants were randomly assigned to switch to efavirenz-based therapy (n = 150) or continue ritonavir-boosted lopinavir-based therapy (n = 148).

Main outcomes and measures: Risk difference between groups in (1) viral rebound (ie, ≥1 HIV RNA measurement of >50 copies/mL) and (2) viral failure (ie, confirmed HIV RNA >1000 copies/mL) with a noninferiority bound of -0.10. Immunologic and clinical responses were secondary end points.

Results: The Kaplan-Meier probability of viral rebound by 48 weeks was 0.176 (n = 26) in the efavirenz group and 0.284 (n = 42) in the ritonavir-boosted lopinavir group. Probabilities of viral failure were 0.027 (n = 4) in the efavirenz group and 0.020 (n = 3) in the ritonavir-boosted lopinavir group. The risk difference for viral rebound was 0.107 (1-sided 95% CI, 0.028 to infinity) and for viral failure was -0.007 (1-sided 95% CI, -0.036 to infinity). We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end points. By 48 weeks, CD4 cell percentage was 2.88% (95% CI, 1.26%-4.49%) higher in the efavirenz group than in the ritonavir-boosted lopinavir group.

Conclusions and relevance: Among HIV-infected children exposed to nevirapine for prevention of mother-to-child transmission and with initial viral suppression with ritonavir-boosted lopinavir-based therapy, switching to efavirenz-based therapy compared with continuing ritonavir-boosted lopinavir-based therapy did not result in significantly higher rates of viral rebound or viral failure. This therapeutic approach may offer advantages in children such as these.

Abstract Full-text [free] access

Editor’s notes: For infants and young children (aged under three years), World Health Organization recommends ritonavir-boosted lopinavir therapy as the first-line antiretroviral therapy regimen. This is because of concerns about the increased risk of virologic failure with non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimens among infants previously exposed to NNRTIs for prevention of mother-to-child HIV transmission, and better virologic efficacy of a lopinavir-based regimen even in unexposed HIV-positive infants and young children. However, there are several significant issues associated with use of boosted lopinavir therapy in children. Firstly, the syrup form of the drug has an unpleasant taste posing major adherence challenges. Secondly, there are pharmacokinetic constraints restricting its use in children who are also being treated for tuberculosis. Thirdly, there are metabolic toxicities associated with the use of boosted lopinavir therapy.

In this open-labelled non-inferiority trial, the investigators examined whether efavirenz can be used in children aged over three years, previously exposed to nevirapine as part of prevention of mother-to-child HIV transmission, who have achieved virologic suppression with lopinavir-based therapy. Efavirenz was found to be non-inferior for both the trial endpoints, namely risk of viral rebound and risk of virologic failure. There were no differences in CD4 counts or other clinical endpoints such as height- or weight-for age, anaemia or neutropenia, skin reactions or serious elevations in transaminases between the groups. In addition, children randomised to switch to efavirenz had a significantly better lipid profile than people who continued to take lopinavir-based therapy. Children randomised to receive efavirenz had significantly higher rates of neuropsychiatric disturbances, but these did not persist beyond eight weeks and notably there were no differences in proportions with behavioural problems between the two arms at the end of follow-up.

The findings of this study strongly support the switch to efavirenz in children who have achieved virologic suppression. Some caveats of this study are that the findings cannot be generalised to children who are aged under three years or to children failing boosted lopinavir therapy. In addition, it is not clear how long children can be maintained on lopinavir-based therapy before a switch to efavirenz can be made.

There is currently no guidance on managing children aged over three years taking lopinavir therapy. This study provides strong evidence to support the switch to efavirenz among virally-suppressed children aged over three years. This is important given the considerable advantages of efavirenz, including preservation of protease inhibitor-based regimens for second line treatment, harmonising paediatric with adult guidelines that recommend efavirenz as first-line therapy, once-daily dosing, better palatability and lower cost.

Africa
South Africa
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Benefits of available ART greater for women than men in South Africa, with many men not engaging with care

Mass HIV treatment and sex disparities in life expectancy: demographic surveillance in rural South Africa.

Bor J, Rosen S, Chimbindi N, Haber N, Herbst K, Mutevedzi T, Tanser F, Pillay D, Bärnighausen T. PLoS Med. 2015 Nov 24;12(11):e1001905. doi: 10.1371/journal.pmed.1001905. eCollection 2015.

Background: Women have better patient outcomes in HIV care and treatment than men in sub-Saharan Africa. We assessed - at the population level - whether and to what extent mass HIV treatment is associated with changes in sex disparities in adult life expectancy, a summary metric of survival capturing mortality across the full cascade of HIV care. We also determined sex-specific trends in HIV mortality and the distribution of HIV-related deaths in men and women prior to and at each stage of the clinical cascade.

Methods and findings: Data were collected on all deaths occurring from 2001 to 2011 in a large population-based surveillance cohort (52 964 women and 45 688 men, ages 15 y and older) in rural KwaZulu-Natal, South Africa. Cause of death was ascertained by verbal autopsy (93% response rate). Demographic data were linked at the individual level to clinical records from the public sector HIV treatment and care program that serves the region. Annual rates of HIV-related mortality were assessed for men and women separately, and female-to-male rate ratios were estimated in exponential hazard models. Sex-specific trends in adult life expectancy and HIV-cause-deleted adult life expectancy were calculated. The proportions of HIV deaths that accrued to men and women at different stages in the HIV cascade of care were estimated annually. Following the beginning of HIV treatment scale-up in 2004, HIV mortality declined among both men and women. Female adult life expectancy increased from 51.3 y (95% CI 49.7, 52.8) in 2003 to 64.5 y (95% CI 62.7, 66.4) in 2011, a gain of 13.2 y. Male adult life expectancy increased from 46.9 y (95% CI 45.6, 48.2) in 2003 to 55.9 y (95% CI 54.3, 57.5) in 2011, a gain of 9.0 y. The gap between female and male adult life expectancy doubled, from 4.4 y in 2003 to 8.6 y in 2011, a difference of 4.3 y (95% CI 0.9, 7.6). For women, HIV mortality declined from 1.60 deaths per 100 person-years (95% CI 1.46, 1.75) in 2003 to 0.56 per 100 person-years (95% CI 0.48, 0.65) in 2011. For men, HIV-related mortality declined from 1.71 per 100 person-years (95% CI 1.55, 1.88) to 0.76 per 100 person-years (95% CI 0.67, 0.87) in the same period. The female-to-male rate ratio for HIV mortality declined from 0.93 (95% CI 0.82-1.07) in 2003 to 0.73 (95% CI 0.60-0.89) in 2011, a statistically significant decline (p = 0.046). In 2011, 57% and 41% of HIV-related deaths occurred among men and women, respectively, who had never sought care for HIV in spite of the widespread availability of free HIV treatment. The results presented here come from a poor rural setting in southern Africa with high HIV prevalence and high HIV treatment coverage; broader generalizability is unknown. Additionally, factors other than HIV treatment scale-up may have influenced population mortality trends.

Conclusions: Mass HIV treatment has been accompanied by faster declines in HIV mortality among women than men and a growing female-male disparity in adult life expectancy at the population level. In 2011, over half of male HIV deaths occurred in men who had never sought clinical HIV care. Interventions to increase HIV testing and linkage to care among men are urgently needed.

Abstract Full-text [free] access

Editor’s notes: In South Africa and many other sub-Saharan African countries, mass treatment with anti-retroviral therapy (ART) has led to dramatic decreases in mortality and increases in life expectancy. South Africa has provided ART free-of-charge since 2004, but HIV-associated diseases remain the leading cause of death in adults. This paper uses clinical and demographic data from a longitudinal cohort in a rural area of KwaZulu-Natal in South Africa to assess how gender differences in adult life expectancy and HIV-associated mortality changed between 2001 and 2011.

Overall life expectancy increased for both genders since 2004 with the effect significantly greater for females than males. The gender differential in life expectancy over the period 2004-2011 increased from 4.4 to 8.6 years. The analysis illustrates that this decrease was due to decreases in HIV-associated mortality rates, as HIV-cause-deleted life expectancy (i.e. life expectancy that would have occurred in the absence of HIV) remained constant over this period.

This study emphasizes the HIV treatment gap for men, with approximately half of all HIV-associated deaths in this population occurred among men who had never sought care. Mortality for men was significantly higher than that for women at each stage of the treatment cascade.

Although this study draws on data from one rural setting, many of the underlying characteristics reflect those seen in many other rural areas of the country. Further work is necessary to understand the underlying social and cultural factors that underlie these findings which could then lead to the development of programmes designed to address them. Such cross-disciplinary research which engages with people designing and implementing HIV programmes will need to be significantly enhanced over the coming decade in order to meet the UNAIDS 90:90:90 targets.

Africa
South Africa
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Living with HIV on the move: migrant workers in north India

Complex routes into HIV care for migrant workers: a qualitative study from north India.

Rai T, Lambert HS, Ward H. AIDS Care. 2015 Nov 26:1-6. [Epub ahead of print]

Migrant workers are designated a bridge population in the spread of HIV and therefore if infected, should be diagnosed and treated early. This study examined pathways to HIV diagnosis and access to care for rural-to-urban circular migrant workers and partners of migrants in northern India, identifying structural, social and individual level factors that shaped their journeys into care. We conducted a qualitative study using in-depth interviews with HIV-positive men (n = 20) and women (n = 13) with a history of circular migration, recruited from an antiretroviral therapy centre in one district of Uttar Pradesh, north India. Migrants and partners of migrants faced a complex series of obstacles to accessing HIV testing and care. Employment insecurity, lack of entitlement to sick pay or subsidised healthcare at destination and the household's economic reliance on their migration-based livelihood led many men to continue working until they became incapacitated by HIV-related morbidity. During periods of deteriorating health they often exhausted their savings on private treatments focused on symptom management, and sought HIV testing and treatment at a public hospital only following a medical or financial emergency. Wives of migrants had generally been diagnosed following their husbands' diagnosis or death, with access to testing and treatment mediated via family members. For some, a delay in disclosure of husband's HIV status led to delays in their own testing. Diagnosing and treating HIV infection early is important in slowing down the spread of the epidemic and targeting those at greatest risk should be a priority. However, despite targeted campaigns, circumstances associated with migration may prevent migrant workers and their partners from accessing testing and treatment until they become sick. The insecurity of migrant work, the dominance of private healthcare and gender differences in health-seeking behaviour delay early diagnosis and treatment initiation.

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Editor’s notes: Migrant workers who move for work in their own country face challenges in accessing health care and social support. In a country as large and diverse as India internal migration can be particularly taxing. For people living with HIV, or who acquire HIV while migrating for work, the challenges can be immense. This paper sets out concisely the issues these migrants face, trying to access information, treatment and support both in the place they move to and at home. The authors explain how migrant men might delay treatment because of their need to work, and perhaps also to keep their HIV-status secret. For the wives of migrants, this delay can severely affect their own access to health care. Free antiretroviral therapy is available, but as the authors suggest, many migrant workers do not know that. This lack of knowledge highlights the importance of providing better support for migrant workers. Support for access to free, or at least affordable, health care is something many migrant workers require; for migrant workers living with HIV that support is essential.

Asia
India
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ART for people living with TB and HIV: practice still lags behind policy

The impact of HIV status and antiretroviral treatment on TB treatment outcomes of new tuberculosis patients attending co-located TB and ART services in South Africa: a retrospective cohort study.

Nglazi MD, Bekker LG, Wood R, Kaplan R. BMC Infect Dis. 2015 Nov 19;15(1):536. doi: 10.1186/s12879-015-1275-3.

Background: The implementation of collaborative TB-HIV services is challenging. We, therefore, assessed TB treatment outcomes in relation to HIV infection and antiretroviral therapy (ART) among TB patients attending a primary care service with co-located ART and TB clinics in Cape Town, South Africa.

Methods: In this retrospective cohort study, all new TB patients aged ≥ 15 years who registered and initiated TB treatment between 1 October 2009 and 30 June 2011 were identified from an electronic database. The effects of HIV-infection and ART on TB treatment outcomes were analysed using a multinomial logistic regression model, in which treatment success was the reference outcome.

Results: The 797 new TB patients included in the analysis were categorized as follows: HIV- negative, in 325 patients (40.8 %); HIV-positive on ART, in 339 patients (42.5 %) and HIV-positive not on ART, in 133 patients (16.7 %). Overall, bivariate analyses showed no significant difference in death and default rates between HIV-positive TB patients on ART and HIV-negative patients. Statistically significant higher mortality rates were found among HIV-positive patients not on ART compared to HIV-negative patients (unadjusted odds ratio (OR) 3.25; 95 % confidence interval (CI) 1.53-6.91). When multivariate analyses were conducted, the only significant difference between the patient categories on TB treatment outcomes was that HIV-positive TB patients not on ART had significantly higher mortality rates than HIV-negative patients (adjusted OR 4.12; 95 % CI 1.76-9.66). Among HIV-positive TB patients (n = 472), 28.2 % deemed eligible did not initiate ART in spite of the co-location of TB and ART services. When multivariate analyses were restricted to HIV-positive patients in the cohort, we found that being HIV-positive not on ART was associated with higher mortality (adjusted OR 7.12; 95 % CI 2.95-18.47) and higher default rates (adjusted OR 2.27; 95 % CI 1.15-4.47).

Conclusions: There was no significant difference in death and default rates between HIV-positive TB patients on ART and HIV negative TB patients. Despite the co-location of services 28.2% of 472 HIV-positive TB patients deemed eligible did not initiate ART. These patients had a significantly higher death and default rates.

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Editor’s notes: There is clear evidence that for people with TB and HIV, particularly individuals with low CD4+ cell counts (<350 cells/µL), being on antiretroviral therapy (ART) during TB treatment reduces the risk of mortality. However, practice still lags far behind policy in this area, as in 2013, globally, only around a third of known HIV-positive people with TB were treated with ART. This paper from a single health centre in South Africa highlights the impact of this treatment gap, and emphasizes the fact that co-location of TB and HIV services does not always translate to integrated patient-centred care.

The people included in this analysis were treated for TB between 2009 and 2011, which was before South Africa adopted guidelines recommending ART for all people with TB testing positive for HIV. Nevertheless, the majority of the people living with HIV had CD4+ cell counts that would have made them eligible for ART at the time of the study. Although overall outcomes were relatively good, one in six people starting TB treatment died or were lost to follow-up. Mortality among HIV-positive people not on ART was substantially higher than individuals on ART and people who were HIV-negative. One in four people who were ART-eligible did not start ART. It was not clear whether some did not start ART because they had already died or had been lost to follow-up. In this analysis, there was no differentiation between people already on ART at the time of starting TB treatment and people who started ART during TB treatment.

This study illustrates that co-location of HIV and TB services does not necessarily meet peoples’ needs if care remains fragmented. Care was provided by different people, and the HIV and TB programmes had separate organizational structures, as is still common. Workable models of integrated, patient-centred care for HIV and TB are necessary. Furthermore, to achieve targets of ending TB deaths, we still need a deeper understanding of why people die after starting TB treatment.  

Avoid TB deaths
Africa
South Africa
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