Articles tagged as "Malawi"

Almost a quarter of deaths in pregnant and post-partum women may be attributable to HIV

Effect of HIV infection on pregnancy-related mortality in sub-Saharan Africa: secondary analyses of pooled community-based data from the network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA).

Zaba B, Calvert C, Marston M, Isingo R, Nakiyingi-Miiro J, Lutalo T, Crampin A, Robertson L, Herbst K, Newell ML, Todd J, Byass P, Boerma T, Ronsmans C. Lancet. 2013 May 18;381(9879):1763-71.

Background: Model-based estimates of the global proportions of maternal deaths that are in HIV-infected women range from 7% to 21%, and the effects of HIV on the risk of maternal death is highly uncertain. We used longitudinal data from the Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA) network to estimate the excess mortality associated with HIV during pregnancy and the post-partum period in sub-Saharan Africa.

Methods: The ALPHA network pooled data gathered between June, 1989 and April, 2012 in six community-based studies in eastern and southern Africa with HIV serological surveillance and verbal-autopsy reporting. Deaths occurring during pregnancy and up to 42 days post partum were defined as pregnancy related. Pregnant or post-partum person-years were calculated for HIV-infected and HIV-uninfected women, and HIV-infected to HIV-uninfected mortality rate ratios and HIV-attributable rates were compared between pregnant or post-partum women and women who were not pregnant or post partum.

FINDINGS: 138,074 women aged 15-49 years contributed 636,213 person-years of observation. 49,568 women had 86,963 pregnancies. 6760 of these women died, 235 of them during pregnancy or the post-partum period. Mean prevalence of HIV infection across all person-years in the pooled data was 17.2% (95% CI 17.0-17.3), but 60 of 118 (50.8%) of the women of known HIV status who died during pregnancy or post partum were HIV infected. The mortality rate ratio of HIV-infected to HIV-uninfected women was 20.5 (18.9-22.4) in women who were not pregnant or post partum and 8.2 (5.7-11.8) in pregnant or post-partum women. Excess mortality attributable to HIV was 51.8 (47.8-53.8) per 1000 person-years in women who were not pregnant or post partum and 11.8 (8.4-15.3) per 1000 person-years in pregnant or post-partum women.

Interpretation: HIV-infected pregnant or post-partum women had around eight times higher mortality than did their HIV-uninfected counterparts. On the basis of this estimate, we predict that roughly 24% of deaths in pregnant or post-partum women are attributable to HIV in sub-Saharan Africa, suggesting that safe motherhood programmes should pay special attention to the needs of HIV-infected pregnant or post-partum women.

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Editor’s notes: This study is the first to estimate the contribution of HIV to mortality in pregnant and post-partum women using HIV sero-surveillance and verbal autopsy data from a network of studies in eastern and southern Africa. While there is variation by country, excess mortality due to HIV was considerably higher in non-pregnant women compared with pregnant/post-partum women. This is not entirely surprising as fertility falls with advancing HIV, so only healthier women with HIV conceive – the so-called ‘healthy pregnant woman effect’. They are therefore less likely to die while pregnant/post-partum. However, the study estimates that almost a quarter of deaths in pregnant/post-partum women are attributable to HIV. This highlights the importance of integrating HIV into safe motherhood programmes. It is noteworthy that the majority of women at the time of this study would not have had access to antiretroviral treatment to benefit their own health (as opposed to single dose treatment to reduce mother-to-child transmission alone). While pointing to the potential benefits of the WHO PMTCT B option, the study emphasizes the potential further advantage of PMTCT B+ to reduce HIV related morbidity and mortality, both for women’s own health and their unborn infants, with implications for current and future pregnancies.

Africa
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Systematic review of supervised and unsupervised self-testing for HIV

Supervised and Unsupervised Self-Testing for HIV in High- and Low-Risk Populations: A Systematic Review.

Pant Pai N, Sharma J, Shivkumar S, Pillay S, Vadnais C, Joseph L, Dheda K, Peeling RW. PLoS Med. 2013 Apr;10(4):e1001414.doi: 10.1371/journal.pmed.1001414. Epub 2013 Apr 2.

Background: Stigma, discrimination, lack of privacy, and long waiting times partly explain why six out of ten individuals living with HIV do not access facility-based testing. By circumventing these barriers, self-testing offers potential for more people to know their sero-status. Recent approval of an in-home HIV self test in the US has sparked self-testing initiatives, yet data on acceptability, feasibility, and linkages to care are limited. We systematically reviewed evidence on supervised (self-testing and counselling aided by a health care professional) and unsupervised (performed by self-tester with access to phone/internet counselling) self-testing strategies.

Methods and Findings: Seven databases (Medline [via PubMed], Biosis, PsycINFO, Cinahl, African Medicus, LILACS, and EMBASE) and conference abstracts of six major HIV/sexually transmitted infections conferences were searched from 1st January 2000-30th October 2012. 1,221 citations were identified and 21 studies included for review. Seven studies evaluated an unsupervised strategy and 14 evaluated a supervised strategy. For both strategies, data on acceptability (range: 74%-96%), preference (range: 61%-91%), and partner self-testing (range: 80%-97%) were high. A high specificity (range: 99.8%-100%) was observed for both strategies, while a lower sensitivity was reported in the unsupervised (range: 92.9%-100%; one study) versus supervised (range: 97.4%-97.9%; three studies) strategy. Regarding feasibility of linkage to counselling and care, 96% (n = 102/106) of individuals testing positive for HIV stated they would seek post-test counselling (unsupervised strategy, one study). No extreme adverse events were noted. The majority of data (n = 11,019/12,402 individuals, 89%) were from high-income settings and 71% (n = 15/21) of studies were cross-sectional in design, thus limiting our analysis.

Conclusions: Both supervised and unsupervised testing strategies were highly acceptable, preferred, and more likely to result in partner self-testing. However, no studies evaluated post-test linkage with counselling and treatment outcomes and reporting quality was poor. Thus, controlled trials of high quality from diverse settings are warranted to confirm and extend these findings.

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Editor’s notes: The HIV self-testing agenda is gaining prominence due to a number of changing issues: the US FDA approved an oral point-of-care HIV self-test (OraQuick) for over-the-counter sale last year; international policy no longer emphasises individualised, in-depth pre-test counselling; ART is increasingly available worldwide; and the goal of universal access to treatment (Millennium Development Goal 6). These issues have reduced many of the posited barriers to self-testing, but some remain, for example, the possible psychological trauma of a positive result without immediate post-test counselling and greater difficulties in ensuring linkage to appropriate care and treatment. In general, self-testing had high acceptability and accuracy. Only one study looked at intentions to link to care, with no studies reporting actual data on linkage to care. The preferred mode and medium of counselling varied between and within study populations, suggesting a need to tailor strategies. The current lack of high quality studies on self-testing suggests an urgent need for more research on this additional route for maximising HIV testing coverage.

Africa, Asia, Europe, Northern America
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Review of research and policy priorities for self-testing for HIV

A Review of Self-Testing for HIV: Research and Policy Priorities in a New Era of HIV Prevention.

Napierala Mavedzenge S, Baggaley R, Corbett EL. Clin Infect Dis. 2013 Apr 16. [Epub ahead of print]

Inadequate uptake of testing for human immunodeficiency virus (HIV) remains a primary bottleneck toward universal access to treatment and care, and is an obstacle to realizing the potential of new interventions for preventing HIV infection, including treatment for prevention and preexposure prophylaxis. HIV self-testing offers an approach to scaling up testing that could be high impact, low cost, confidential, and empowering for users. Although HIV self-testing was first considered >20 years ago, it has not been widely implemented. We conducted a review of policy and research on HIV self-testing, which indicates that policy is shifting toward a more flexible approach with less emphasis on pretest counseling and that HIV self-testing has been adopted in a number of settings. Empirical research on self-testing is limited, resulting in a lack of an evidence base upon which to base policy recommendations. Relevant research and investment in programs are urgently needed to enable consideration of developing formalized self-testing programs.

Abstract  Full text [free] access

Editor’s notes: This second review of HIV self-testing this month adds to the review by Pant Pai et al. in several ways, including by: highlighting other articles not included in the previous review; including a very helpful summary of current gaps in research on self-testing; and providing details of the Kenyan guidelines on self-testing (Kenya is the first African country to develop guidance on over-the-counter HIV self-testing kits for the general population). Some of the key research gaps highlighted include: the effect of self-testing provision on uptake of HIV testing including repeat testing; levels of harm caused e.g. due to lack of immediate post-test counselling, coercive testing, etc.; how to maximise linkage to care; how to best provide for couples testing; the most appropriate use of social marketing; and how to best utilise mHealth. These two reviews are worth reading in tandem.

Africa, Asia, Europe, Northern America
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Efavirenz dose adjustments are probably not required in patients taking concurrent rifampicin

Relationship between weight, efavirenz exposure and virologic suppression in HIV-infected patients on rifampin-based TB treatment in the ACTG A5221 STRIDE study

Luetkemeyer AF, Rosenkranz SL, Lu D, Marzan F, Ive P, Hogg E, et al. Adult AIDS Clinical Trials Group A5221 Study Team. Clinical Infectious Diseases Advance Access published April 19, 2013.

Background: Rifampin (RIF) upregulates CYP 450 isoenzymes potentially lowering efavirenz (EFV) exposure. The US EFV package insert recommends EFV dose increase for patients on RIF weighing ≥50 kg. We conducted a pharmacokinetic study to evaluate EFV trough concentrations (Cmin) and HIV virologic suppression in patients on EFV (600 mg) and RIFbased TB treatment as part of a multicenter randomized trial (ACTG A5221)

Methods: EFV Cmin was measured using HPLC 20‐28 hours post‐EFV dose at weeks 4,8,16,24 on‐RIF and weeks 4,8 off‐RIF. Results evaluated with two‐sided Wilcoxon rank‐sum, chi‐square and Fisher's Exact tests and logistic regression (5% Type I error rate).

Results: 780 patients from 11 countries received EFV, 543 provided ≥ 1 EFV Cmin. Median (IQR) weight was 52.8 kg (48.0,59.5), BMI 19.4 kg/m2 (17.5,21.6), age 34 (29,41), 63% male, race Black (74%), Hispanic (20%), non‐Hispanic White (5%), Asian (1%). Median Cmin was 1.96μg/mL onRIF vs. 1.80 offRIF (p=0.067). EFV concentrations were significantly higher onRIF vs. offRIF in Blacks (2.08 vs. 1.75, p=0.005). Weight ≥60 kg onRIF, compared to <60 kg, was associated with lower EFV Cmin (1.68 vs. 2.02, p=0.021). However, weight ≥60 kg was associated with more frequent HIV RNA<400 copies/mL at week 48, compared to weight <60 kg (81.9% vs. 73.8%, p=0.023).

Conclusions: Coadministration of EFV and RIFbased TB therapy was associated with a trend toward higher, not lower, EFV Cmin compared to EFV alone, which was statistically significant in Black patients. Patients weighing ≥60 kg had lower median EFV Cmin vs. those <60 kg, but there was no association of higher weight with reduced virologic suppression. These data do not support weightbased dosing of EFV with RIF co-administration.

Abstract access 

Editor’s notes: Effective treatment of HIV-TB co-infection is complicated by drug-drug interactions. Rifampicin, the key component of effective anti-TB therapy, is a potent inducer of the cytochrome P450 enzymes which metabolize many antiretrovirals including efavirenz. Appropriate dosing of efavirenz in patients taking concomitant TB treatment has been debated, with both US and British national treatment guidelines recommending efavirenz dose increases. The WHO does not recommend adjusting dosing. This study, an analysis of efavirenz levels from 543 participants in the STRIDE study of ART timing in TB co-infected patients, suggests that efavirenz dose adjustments are not required in patients taking concurrent rifampicin based TB treatment. Efavirenz levels were not reduced in patients who were taking TB treatment. In fact trough efavirenz levels were slightly increased in patients during TB treatment. This increase in efavirenz levels was most marked in black patients. Virological outcomes with efavirenz based ART in this cohort of patients on TB treatment were good, with 76% fully suppressed at 48 weeks.  Perhaps unsurprisingly, efavirenz levels were slightly lower in patients weighing over 60 kg compared to those below 60 kg, but this did not translate into worse virological outcomes. Given the racial differences seen in efavirenz metabolism in this study there is a question about the generalisability of the study to certain populations, notably Caucasians who only made up 5% of the study population. However the demographics were representative of the vast majority of HIV-TB co-infected patients worldwide. These results strongly suggest that efavirenz at standard doses can be safely used in patients receiving rifampicin based TB treatment, avoiding the need to complicate ART treatment regimens in the large number of individuals receiving TB treatment in resource-limited public health programmes.

Avoid TB deaths
Comorbidity, HIV Treatment
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Lifelong ART eligibility increases treatment rates for pregnant and breastfeeding women in Malawi

Impact of an innovative approach to prevent mother-to-child transmission of HIV - Malawi, July 2011 - September 2012.

Chimbwandira F, Mhango E, Makombe S, Midiani D, Mwansambo C, Njala J, et al. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2013 Mar 1;62(8):148-51.

Antiretroviral medications can reduce rates of mother-to-child transmission of human immunodeficiency virus (HIV) to less than 5%. However, in 2011, only 57% of HIV-infected pregnant women in low- and middle-income countries received a World Health Organization (WHO)-recommended regimen for prevention of mother-to-child transmission (PMTCT), and an estimated 300,000 infants acquired HIV infection from their mothers in sub-Saharan Africa; 15,700 (5.2%) of these infants were born in Malawi. An important barrier to PMTCT in Malawi is the limited laboratory capacity for CD4 cell count, which is recommended by WHO to determine which antiretroviral medications to start. In the third quarter of 2011, the Malawi Ministry of Health (MOH) implemented an innovative approach (called "Option B+"), in which all HIV-infected pregnant and breastfeeding women are eligible for lifelong antiretroviral therapy (ART) regardless of CD4 count. Since that time, several countries (including Rwanda, Uganda, and Haiti) have adopted the Option B+ policy, and WHO was prompted to release a technical update in April 2012 describing the advantages and challenges of this approach as well as the need to evaluate country experiences with Option B+. Using data collected through routine program supervision, this report is the first to summarize Malawi's experience implementing Option B+ under the direction of the MOH and supported by the Office of the Global AIDS Coordinator (OGAC) through the President's Emergency Plan for AIDS Relief (PEPFAR). In Malawi, the number of pregnant and breastfeeding women started on ART per quarter increased by 748%, from 1,257 in the second quarter of 2011 (before Option B+ implementation) to 10,663 in the third quarter of 2012 (1 year after implementation). Of the 2,949 women who started ART under Option B+ in the third quarter of 2011 and did not transfer care, 2,267 (77%) continue to receive ART at 12 months; this retention rate is similar to the rate for all adults in the national program. Option B+ is an important innovation that could accelerate progress in Malawi and other countries toward the goal of eliminating mother-to-child transmission of HIV worldwide.

Abstract access 

Editor’s notes: The efficacy of antiretroviral medications for the elimination of new infections among children is well demonstrated; however barriers including lack of trained personnel, lack of integrated ART and antenatal care services, and poor laboratory capacity mean that almost half of pregnant women living with HIV in low and middle income countries do not receive WHO-recommended regimens. This report from Malawi, where “option B+” was implemented, removing the need for CD4 cell count testing in HIV-infected pregnant and breastfeeding women, coupled with decentralization and integration of ART into antenatal clinics, task shifting policies, and extensive training and supervision, demonstrates that very rapid scale-ups in ART provision for the elimination of new infections among children  are possible in resource-limited settings. Encouragingly, these preliminary data suggest that retention in care at 12 months in women started on ART under “option B+” were comparable to rates in the Malawian adult ART programme (in marked contrast to data reviewed in last month’s issue from South Africa, where only 40% of women who initiated ART during pregnancy were retained in care at 6 months). Whilst longer term adherence and outcome data in the “option B+” cohort are required to ensure that lifelong ART adherence can be maintained, along with evaluation of its effectiveness in reducing vertical HIV transmission at a population level, these results provide important initial evidence for the feasibility of such an approach. Innovations such as this will be critical not just in meeting the goal of reducing new HIV infections in children by 90% by 2015, but also in serving as a model for how ART can be scaled up in other populations to prevent the ongoing high rates of mortality and onward HIV transmission seen in many African countries.

Africa
Malawi
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Generalized HIV epidemics require generalized prevention efforts

Extra-couple HIV transmission in sub-Saharan Africa: a mathematical modelling study of survey data.

Bellan SE, Fiorella KJ, Melesse DY, Getz WM, Williams BG, Dushoff J. Lancet. 2013 Feb 4. pii: S0140-6736(12)61960-6. doi: 10.1016/S0140-6736(12)61960-6. [Epub ahead of print]

The proportion of heterosexual HIV transmission in sub-Saharan Africa that occurs within cohabiting partnerships, compared with that in single people or extra-couple relationships, is widely debated. The proportional contribution of different routes of transmission to new HIV infections was estimated. As plans to use antiretroviral drugs as a strategy for population-level prevention progress, understanding the importance of different transmission routes is crucial to target intervention efforts. A mechanistic model of HIV transmission was built with data from Demographic and Health Surveys (DHS) for 2003-2011, of 27 201 cohabiting couples (men aged 15-59 years and women aged 15-49 years) from 18 sub-Saharan African countries with information about relationship duration, age at sexual debut, and HIV serostatus. This model was combined with estimates of HIV survival times and country-specific estimates of HIV prevalence and coverage of antiretroviral therapy (ART). The proportion of recorded infections in surveyed cohabiting couples that occurred before couple formation was estimated, between couple members, and because of extra-couple intercourse. In surveyed couples, we estimated that extra-couple transmission accounted for 27-61% of all HIV infections in men and 21-51% of all those in women, with ranges showing intercountry variation. It was estimated that in 2011, extra-couple transmission accounted for 32-65% of new incident HIV infections in men in cohabiting couples, and 10-47% of new infections in women in such couples. These findings suggest that transmission within couples occurs largely from men to women; however, the latter sex have a very high-risk period before couple formation. Because of the large contribution of extra-couple transmission to new HIV infections, interventions for HIV prevention should target the general sexually active population and not only serodiscordant couples.

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Editor’s notes: Understanding the individual and population level risks for HIV transmission and acquisition is essential for designing HIV transmission prevention programmes that can lead to an AIDS-free generation. The frequency of pre-marital or extra-marital sexual activity is not necessarily different in high prevalence countries than in lower prevalence settings, a number of theories have been suggested, including frequency of multiple concurrent partnerships. Newer data has indicated that a significant percentage of people living with HIV are in serodiscordant couples with HIV-negative partners – hence a focus on identification of such serodiscordancy and promotion of condom use within cohabitating serodiscordant couples. While these interventions remain important, this article highlights that quite significant proportions of HIV transmission in couples occurs outside of the framework of the cohabitating couple. HIV prevention campaigns, for persons in couples as well as single individuals must remain focused on the general sexually active population.  

Africa
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TAG: Integrated TB and HIV care leads to impressive TB treatment outcomes

Comparison of Treatment Outcomes of New Smear- Positive Pulmonary Tuberculosis Patients by HIV and Antiretroviral Status in a TB/HIV Clinic, Malawi.

Tweya H, Feldacker C, Phiri S, Ben-Smith A, Fenner L, Jahn A, Kalulu M, Weigel R, Kamba C, Banda R, Egger M, Keiser O. PLoS One. 2013;8(2):e56248. doi: 10.1371/journal.pone.0056248. Epub 2013 Feb 15.

Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues. All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi’s largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression. Results: Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14–1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio: 1.83; 95% CI: 1.29–2.60). HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients.

Abstract access 

Editor’s notes: TB remains the major cause of mortality in people living with HIV in high prevalence countries, but most specifically when ART coverage is low. The HIV prevalence in this review of a large number of patients with pulmonary TB – 56%, was higher than previously cited estimates of 40%, and historical evidence indicates that TB outcomes are better in those patients who are HIV-negative. This study was based at a program that integrates TB and HIV services at a large public facility in Malawi. A virtue of this service integration is that 96% of the TB patients knew their HIV status. It is notable that with this rather large sample, the treatment success rate was only slightly less in those patients living with HIV- 85% TB cure versus 88% in the patients who were HIV-negative. A closer review of the data indicates that those HIV-positive patients on ART had significantly better TB treatment outcome, reinforcing results from other studies.  Given newer recommendations that co-infected patients be started on ART, it is unfortunate that only 38% of the HIV-positive patients in this clinic with TB were started on ART.  As treatment guidelines and recommendations become further integrated into clinic practice we can be optimistic that the TB treatment success rate for patients living with HIV will come even closer to the TB treatment success rate of the patients who are HIV-negative.

Avoid TB deaths
Comorbidity, HIV Treatment
Africa
Malawi
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HIV infection increases mortality among HIV-positive pregnant women

The contribution of HIV to pregnancy-related mortality: a systematic review and meta-analysis.

Calvert C, Ronsmans PC. AIDS. 2013 Feb 25. [Epub ahead of print]

Whilst much is known about the contribution of HIV to adult mortality, remarkably little is known about the mortality attributable to HIV during pregnancy. In this paper the proportion of pregnancy-related deaths attributable to HIV based on empirical data was estimated from a systematic review of the strength of association between HIV and pregnancy-related mortality. Studies comparing mortality during pregnancy and the postpartum in HIV-infected and uninfected women were included. Summary estimates of the relative and attributable risks for the association between HIV and pregnancy-related mortality were calculated through meta-analyses. Varying estimates of HIV prevalence were used to predict the impact of the HIV epidemic on pregnancy-related mortality at the population level. 23 studies were included (17 from sub-Saharan Africa). Meta-analysis of the risk ratios (RR) indicated that HIV-infected women had eight times the risk of a pregnancy-related death compared with HIV-uninfected women (pooled RR: 7.74, 95% CI 5.37-11.16). The excess mortality attributable to HIV among HIV-infected pregnant and postpartum women was 994 per 100,000 pregnant women. We predict that 12% of all deaths during pregnancy and up to one year postpartum are attributable to HIV/AIDS in regions with a prevalence of HIV among pregnant women of 2%. This figure rises to 50% in regions with a prevalence of 15%.  The substantial excess of pregnancy-related mortality associated with HIV highlights the importance of integrating HIV and reproductive health services in areas of high HIV prevalence and pregnancy-related mortality.

Abstract access 

Editor’s notes: Millennium Development Goals include commitments to reduce maternal mortality. While HIV is a leading cause of death among women of reproductive age in sub-Saharan Africa, the contribution of HIV infection to overall maternal mortality is Africa has been less described. This analysis of this study indicates that a significant proportion of maternal deaths is due to HIV. While the contribution of HIV to maternal mortality is high in relatively low prevalence settings, it is remarkably and tragically high in high prevalence countries such as is seen in southern Africa: with an estimated 50% of maternal deaths due to HIV infection when prevalence is 15%. This modeling highlights the ongoing essential need to prevent new HIV infections if the MDGs will be met.

Epidemiology, Gender
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Comparing adverse effects of nevirapine and efavirenz

Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis.

Shubber Z, Calmy A, Andrieux-Meyer I, Vitoria M, Renaud-Thery F, Shaffer N, Hargreaves S, Mills EJ, Ford N. AIDS. 2013 Jan 22. [Epub ahead of print]

Since 2002, the World Health Organization has recommended either nevirapine (NVP) or efavirenz (EFV) as part of first-line antiretroviral therapy. These two drugs are known to have differing toxicity profiles, but the clinical importance of these toxicities overall is not well established. The authors systematically reviewed adverse events among treatment-naïve HIV-positive adults and children receiving either NVP or EFV as part of first-line antiretroviral therapy. The primary outcome was drug discontinuation as a result of any adverse event; specific toxicities were evaluated as secondary outcomes. Point estimates and 95% confidence intervals (95% CI) were calculated and proportions and odds ratios (OR) pooled using fixed-effects meta-analysis. Data was reviewed on 26446 adult and 3975 children from 8 randomized trials and 26 prospective cohorts. Overall, adults on NVP were more than two times more likely to discontinue treatment due to any adverse event compared to patients on EFV (OR 2.2, 95%CI 1.9-2.6). Severe hepatotoxicity (OR 3.3, 95%CI 2.5-4.2), severe skin toxicity (OR 3.9, 95%CI 2.5-5.4), and severe hypersensitivity reactions (OR 2.4, 95%CI 1.9-2.9) were more likely to occur among patients on NVP. Patients receiving EFV were more likely to experience severe CNS-events (OR 3.4, 95%CI 2.1-5.4). Similar associations were seen in children. Compared to NVP, EFV is associated with a lower frequency of severe adverse events, in particular treatment discontinuations. This finding supports a move towards efavirenz-based therapy as the preferred first-line treatment regimen for HIV treatment within a public health approach.

Abstract access 

Editor’s notes: As increased progress is being made towards universal access to treatment, increased attention is being addressed towards retention in care and on treatment. Simpler, less toxic regimens have been a cornerstone of the Treatment 2.0 initiative of UNAIDS and WHO. Nevirapine has been widely utilized as an essential component of three drug antiretroviral therapy, in part due to low cost and safety at a population level. While efavirenz does have a greater incidence of central nervous system side effects (many of them manageable with supportive treatment), the overall discontinuation rate is significantly lower than with nevirapine. This data in combination with the continued reduction in efavirenz price, and incorporation into combination pill form, supports the move towards increased use of efavirenz for first line antiretroviral therapy.

HIV Treatment
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Addressing barriers to universal access: focus on the pre-ART phase

Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub-Saharan Africa: a systematic review.

Kranzer K, Govindasamy D, Ford N, Johnston V, Lawn SD. J Int AIDS Soc. 2012 Nov 19;15(2):17383.

Introduction: Recent years have seen an increasing recognition of the need to improve access and retention in care for people living with HIV/AIDS. This review aims to quantify patients along the continuum of care in sub-Saharan Africa and review possible interventions.

Methods: We defined the different steps making up the care pathway and quantified losses at each step between acquisition of HIV infection and retention in care on antiretroviral therapy (ART). We conducted a systematic review of data from studies conducted in sub-Saharan Africa and published between 2000 and June 2011 for four of these steps and performed a meta-analysis when indicated; existing data syntheses were used for the remaining two steps.

Results: The World Health Organization estimates that only 39% of HIV-positive individuals are aware of their status. Among patients who know their HIV-positive status, just 57% (95% CI, 48 to 66%) completed assessment of ART eligibility. Of eight studies using an ART eligibility threshold of≤200 cells/µL, 41% of patients (95% CI, 27% to 55%) were eligible for treatment, while of six studies using an ART eligibility threshold of≤350 cells/µL, 57% of patients (95% CI, 50 to 63%) were eligible. Of those not yet eligible for ART, the median proportion remaining in pre-ART care was 45%. Of eligible individuals, just 66% (95% CI, 58 to 73%) started ART and the proportion remaining on therapy after three years has previously been estimated as 65%. However, recent studies highlight that this is not a simple linear pathway, as patients cycle in and out of care. Published studies of interventions have mainly focused on reducing losses at HIV testing and during ART care, whereas few have addressed linkage and retention during the pre-ART period.

Conclusions: Losses occur throughout the care pathway, especially prior to ART initiation, and for some patients this is a transient event, as they may re-engage in care at a later time. However, data regarding interventions to address this issue are scarce. Research is urgently needed to identify effective solutions so that a far greater proportion of infected individuals can benefit from long-term ART.

Abstract access


 

Who Starts? Factors Associated with Starting Antiretroviral Therapy among Eligible Patients in Two, Public HIV Clinics in Lilongwe, Malawi. 

Feldacker C, Johnson D, Hosseinipour M, Phiri S, Tweya H. PLoS One. 2012;7(11):e50871. Epub 2012 Nov 30.

Background: Lighthouse Trust operates two, public, integrated HIV clinics, Lighthouse (LH) and Martin Preuss Center (MPC), in Lilongwe, Malawi. Approximately 20% of patients eligible for antiretroviral therapy (ART) do not start ART. We explore individual and geographic factors that influence whether ART-eligible patients initiate ART.

Methods: Adult patients eligible for ART between 2008-2011 were included. Analysis was stratified by clinic. Using logistic regression, we evaluated factors associated with initiating ART including gender, age, body mass index (BMI), employment, tuberculosis (TB), eligible at initial registration, WHO stage, CD4, months in pre-ART care (from initial registration to eligibility date), and patient neighborhood distance to clinic.

Results: Of 14,216 study patients, 4841 were from LH; 9285 were from MPC. At LH and MPC, respectively, median age was 34.2 and 33.8 years; median BMI was 22.0 and 20.6; and median distance was 5.6 and 4.9 Km. In multivariate models, odds of starting ART was highest among those older than 35 years and those eligible for ART based on WHO stages 3-4 vs. those in WHO stages 1-2 with CD4<250. Patients with 1-12 months in pre-ART were at least 11 times more likely to start ART than peers with less pre-ART time. At LH, living 2.5-5 Km from the clinic increased the likelihood of starting ART over patients living closer.

Conclusions: Length of the pre-ART period is the most significant predictor of starting ART among eligible patients. Better understanding of motivation for retention in pre-ART care may reduce attrition along the treatment cascade.

Abstract access


 

Attrition from HIV Testing to Antiretroviral Therapy Initiation among Patients Newly Diagnosed with HIV in Haiti.

Noel E, Esperance M, McLaughlin M, Bertrand R, Devieux J, Severe P, Marcelin A, Nicotera J, Delcher C, Griswold M, Meredith G, Pape JW, Koenig SP. J Acquir Immune Defic Syndr. 2012 Dec 18. [Epub ahead of print]

Objective: We report rates and risk factors for attrition in the first cohort of patients followed through all stages from HIV testing to ART initiation.

Design: Cohort study of all patients diagnosed with HIV between January and June, 2009.

Methods: We calculated the proportion of patients who completed CD4 cell counts and initiated ART or remained in pre-ART care during two years of follow-up, and assessed predictors of attrition.

Results: Of 1,427 patients newly diagnosed with HIV, 680 (48%) either initiated ART or were retained in pre-ART care for the subsequent two years. One thousand eighty-three patients (76%) received a CD4 cell count and 973 (90%) returned for result; 297 (31%) had CD4 cell count <200 cells/µl and of these, 256 (86%) initiated ART. Among 429 patients with CD4 >350 cells/µl, 215 (50%) started ART or were retained in pre-ART care. Active TB was associated with lower odds of attrition prior to CD4 cell count (OR: 0.08; 95% CI: 0.03-0.25) but also higher odds of attrition prior to ART initiation (OR: 2.46; 95% CI: 1.29-4.71). Lower annual income (≤$US125) was associated with higher odds of attrition prior to CD4 cell count (OR 1.65; 95% CI: 1.25-2.19), and prior to ART initiation among those with CD4 cell count >350 cells/µl (OR: 1.74; 95% CI: 1.20-2.52).After tracking patients through a national database, the retention rate increased to only 57%.

Conclusion: Fewer than half of patients newly diagnosed with HIV initiate ART or remain in pre-ART care for two years in a clinic providing comprehensive services. Additional efforts to improve retention in pre-ART are critically needed.

Abstract access

Editor’s notes: The first of three papers presents a systematic review of the published data addressing the entire HIV care pathway, including HIV testing, pre-ART care comprising assessment of ART eligibility, retention in pre-ART care prior to ART eligibility, initiation of ART and retention in ART care. The second paper describes factors associated with ART initiation in a large cohort of patients in Malawi.The third paper presents the results of a prospective cohort study conducted at the GHESKIO clinic, the oldest and largest HIV testing facility in Haiti. GHESKIO tests nearly 30 000 patients per year for HIV, and follows patients from HIV testing through pre-ART care, ART initiation and follow-up. Their results show high rates of attrition at every step from HIV testing to ART initiation, losses occurring mainly prior to ART initiation with fewer than half of patients newly diagnosed with HIV initiating ART or remaining in pre-ART care. This is a vital study because it confirms the results of other relevant studies conducted in Africa, and highlights how the care pathway, especially prior to ART initiation is a global challenge. All research conducted in different parts of the world concur with the urgent need to address operational questions to improve the retention in pre-ART care (prior to ART eligibility and initiation).

All three papers raise a very sensitive issue, which has been poorly explored, the pre-ART care phase. Indeed, the current inclination towards earlier initiation of ART requires earlier diagnosis and regular monitoring until treatment eligibility. Poor pre-ART retention in care, or the failure to link patients from HIV testing to HIV care and retain them until they are eligible for ART, is a problem that has recently surfaced in the research literature. Without effective retention in pre-ART care – beginning with HIV testing and continuing until the first antiretrovirals are dispensed – even patients who have long been aware of their HIV status will access care only when seriously ill, which is often well after treatment eligibility. Unfortunately, only a handful of quantitative studies reporting on rates of pre-ART linkage and loss in sub-Saharan Africa have been published, and many of these are limited in the time periods and outcomes they consider. More operational research addressing the retention in care of individuals not yet eligible for ART is therefore essential. There appear to be several reasons for the poor showing of pre-ART care. Most patients during this stage are asymptomatic and may not perceive themselves to require medical care. Since little therapeutic care is offered during the pre-ART period, patients must take on faith that making the effort to come to the clinic for monitoring is worth the costs of doing so. Current approaches to providing care often require multiple clinic visits, e.g., to first provide a blood sample for a CD4 count and then return a week later to receive the results. Choosing to "wait and see what happens" may well be a preferred strategy for patients who lack resources for transport, risk losing employment by taking time off work, or fear being recognized as a client of an HIV clinic.  A number of interventions are being tried to improve retention in pre-ART care, though very few have been rigorously evaluated. Most interventions aim either to reduce the costs that patients perceive in seeking pre-ART care or increasing the perceived benefits of care. Interventions to reduce costs are more common and focus on structural changes in the delivery of care (fewer visits, more convenient locations, shorter waiting times, etc.). Interventions to increase benefits may offer more services at each visit (e.g., provision of cotrimoxazole or food parcels). There is little evidence so far as to whether these interventions will be effective. A possible way forward might also be the involvement of the local personnel such as community-based workers. Community may provide tangible support in increasing knowledge of HIV, obtain information about any changes or movements in patients’ lives, continue to follow patients in the social environment where they live, and support them to make periodic clinic visits.

HIV testing, HIV Treatment
Africa, Latin America
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