Articles tagged as "Asia"

China's national free paediatric ART programme is shown to be effective and should be expanded

Mortality and treatment outcomes of China's National Pediatric antiretroviral therapy program.

Zhao Y, Li C, Sun X, Mu W, McGoogan JM, He Y, Cheng Y, Tang Z, Li H, Ni M, Ma Y, Chen RY, Liu Z, Zhang F. Clin Infect Dis. 2013 Mar;56(5):735-44. doi: 10.1093/cid/cis941.

BACKGROUND: The aim of this study was to describe 3-year mortality rates, associated risk factors, and long-term clinical outcomes of children enrolled in China's national free pediatric antiretroviral therapy (ART) program.

METHODS: Records were abstracted from the national human immunodeficiency virus (HIV)/AIDS case reporting and national pediatric ART databases for all HIV-positive children ≤15 years old who initiated ART prior to December 2010. Mortality risk factors over 3 years of follow-up were examined using Cox proportional hazards regression models. Life tables were used to determine survival rate over time. Longitudinal plots of CD4(+) T-cell percentage (CD4%), hemoglobin level, weight-for-age z (WAZ) score, and height-for-age z (HAZ) score were created using generalized estimating equation models.

RESULTS: Among the 1818 children included in our cohort, 93 deaths were recorded in 4022 child-years (CY) of observed time for an overall mortality rate of 2.31 per 100 CY (95% confidence interval [CI], 1.75-2.78). The strongest factor associated with mortality was baseline WAZ score <-2 (adjusted hazard ratio [HR] = 9.1; 95% CI, 2.5-33.2), followed by World Health Organization stage III or IV disease (adjusted HR = 2.4; 95% CI, 1.1-5.2), and hemoglobin <90 g/L (adjusted HR = 2.2; 95% CI, 1.2-3.9). CD4%, hemoglobin level, WAZ score, and HAZ score increased over time.

CONCLUSIONS: Our finding that 94% of children engaged in this program are still alive and of improved health after 3 years of treatment demonstrates that China's national pediatric ART program is effective. This program needs to be expanded to better meet treatment demands, and efforts to identify HIV-positive children earlier must be prioritized.

Abstract access 

Editor’s notes: This retrospective study presents encouraging treatment outcomes, in terms of both retention in care and mortality, among children in China’s national paediatric antiretroviral treatment programme. The very low loss to follow up is attributed to China’s household registration system and systems for tracking and following up people on ART. As the authors note, with a median age at ART initiation of 6.2 years, this cohort is biased towards children with a better chance of survival, given that it does not include children who acquired HIV by vertical transmission but died before starting ART. In addition, a substantial number of children were reported to the national HIV/AIDS Case Reporting System but were lost to follow up before starting ART. The report emphasises the need for earlier diagnosis and treatment initiation among children in China. 

Asia
China
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Good treatment outcomes in a drug-user centered national HIV treatment program

Outcomes of antiretroviral therapy in Vietnam: results from a national evaluation.

Nguyen DB, Do NT, Shiraishi RW, Le YN, Tran QH, Huu Nguyen H, Medland N, Nguyen LT, Struminger BB. PLoS One. 2013;8(2):e55750. doi: 10.1371/journal.pone.0055750. Epub 2013 Feb 15.

Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam's national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations. Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART. Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data. Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4-76.5, median age 30, interquartile range [IQR]: 26-34, 62.0% reported a history of intravenous drug use, CI: 58.6-65.3). Median baseline CD4 cell count was 78 cells/mm (IQR: 30-162) and 30.4% (CI: 25.8-35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8-89.9), 84.0% (CI: 81.8-86.0), 78.8% (CI: 75.7-81.6), and 74.6% (CI: 69.6-79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45-153), 142 (IQR: 78-217), 213 (IQR: 120-329), and 254 (IQR: 135-391) cells/mm. Patients who were PWID showed significantly poorer retention. The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.

Abstract access 

Editor’s notes: The HIV epidemic is concentrated among key populations, primarily among people who inject drugs, and less so among men who have sex with men, and sex workers. As of December 2011 an estimated 53% of those clinically or immunologically eligible. While concerns remain regarding the human rights of key populations in Vietnam, of note needle and syringe programs and methadone maintenance programs, key HIV prevention interventions, are available in most provinces. This study reviewed chart information on almost 7000 patients. 62% of patients on ART had a history of intravenous drug use and most patients started on ART at fairly advanced immunosuppression. Retention at 6 and 12 months was quite high for patients with and without a history of IV drug use- those with such a history began to have significantly lower retention by 2 years after treatment initiation. This study was not able to tease out the reasons for this later divergence in retention results.

People who use drugs remain a key population – well designed and managed programs can overcome previously raised concerns about the ability to engage and maintain drug users in HIV care. In addition to directly sensitizing the care and treatment programs to the specific needs of drugs users, syringe and needle exchange programs and provision of opioid substitution therapy have been demonstrated to have a HIV prevention impact. Given the relatively recent expansion of such services in Vietnam, hopefully more recent data will demonstrate a further narrowing of the retention differences between drug users and other populations on HIV treatment.

Asia
Viet Nam
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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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Adverse events associated with nevirapine use in pregnancy

Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis.

Ford N, Calmy A, Andrieux-Meyer I, Hargreaves S, Mills EJ, Shubber Z. AIDS. 2013 Jan 5. [Epub ahead of print]

The risk of adverse drug events associated with nevirapine is suggested to be greater in pregnant women. The authors conducted a systematic review and meta-analysis of severe adverse events in HIV-positive women who initiated NVP while pregnant. Six databases were searched for studies reporting adverse events among HIV-positive pregnant women who had received nevirapine-based antiretroviral therapy for at least seven days. Data were pooled by the fixed-effects method. Twenty studies (3582 pregnant women) from 14 countries were included in the final review. The pooled proportion of patients experiencing a severe hepatotoxic event was 3.6% (95%CI 2.4-4.8%), severe rash was experienced by 3.3% of patients (95%CI 2.1-4.5%), and 6.2% (95%CI 4.0-8.4%) of patients discontinued nevirapine due to an adverse event. These results were comparable to frequencies observed in the general adult patient population, and to frequencies reported in non-pregnant women within the same cohort. For pregnant women with a CD4 cell count >250 cells/mm there was a non-significant tendency towards an increased likelihood of cutaneous events overall (OR 1.1, 95%CI 0.8-1.6) and severe cutaneous adverse events (OR 1.4, 95%CI 0.8-2.4) and consequently an increased risk of toxicity-driven regimen substitution (OR 1.7, 95%CI 1.1-2.6). These results suggest that the frequency of adverse events associated with nevirapine use in pregnant women, while high, is no higher than reported for nevirapine in the general adult population. Pregnant women with a high CD4 count may be at increased risk of adverse events, but evidence supporting this association is weak.

Abstract access 

Editor’s notes: The selection of antiretroviral drug regimens has been particularly challenging for HIV-positive pregnant women. Adverse events are less frequent for men and women with efavirenz use compared to nevirapine, and increasingly efavirenz is a preferred choice. However, due to concerns about the safety of efavirenz in pregnancy, nevirapine continues to be widely used as a component of antiretroviral treatment for pregnant women. However, there have been suggestions that HIV-positive pregnant women have higher rates of nevirapine-associated adverse events, especially for those women with high CD4, compared to non-pregnant women on nevirapine. This meta-analysis of 20 studies did demonstrate a relatively high frequency of adverse events in women who use nevirapine, but not at rates higher than among non-pregnant women on HIV treatment with nevirapine. The data about efavirenz safety for the fetus is being carefully reviewed to elucidate if widespread use of efavirenz is preferable to nevirapine during pregnancy.

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Increasing HIV testing among male partners in PMTCT settings

Increasing HIV testing among male partners. The Prenahtest ANRS 12127 multi-country randomised trial.

Orne-Gliemann J, Balestre E, Tchendjou P, Miric M, Darak S, Butsashvili M, Perez-Then E, Eboko F, Plazy M, Kulkarni S, Loû AD, Dabis F; for the Prenahtest ANRS 12127 Study Group. AIDS. 2013 Jan 22. [Epub ahead of print]

Couple-oriented post-test HIV counselling (COC) provides pregnant women with tools and strategies to invite her partner to HIV counselling and testing. A randomised trial of the efficacy of COC on partner HIV testing in low/medium HIV prevalence settings (Cameroon, Dominican Republic, Georgia, India) was conducted. Pregnant women were randomised to receive standard post-test HIV counselling (SC) or COC and followed until six months postpartum. Partner HIV testing events were notified by site laboratories, self-reported by women or both combined. Impact of COC on partner HIV testing was measured in intention-to-treat analysis. Socio-behavioural factors associated with partner HIV testing were evaluated using multivariable logistic regression. Among 1943 pregnant women enrolled, partner HIV testing rates (combined indicator) were 24.7% among women from COC group vs 14.3% in SC group in Cameroon (Odds Ratio [OR] = 2.0 95%CI [1.2-3.1]), 23.1% vs 20.3% in Dominican Republic (OR = 1.2 [0.8-1.8]), 26.8% vs 1.2% in Georgia (OR = 29.6 [9.1-95.6]) and 35.4% vs 26.6% in India (OR = 1.5 [1.0-2.2]). Women having received COC did not report more conjugal violence or union break-ups than in the SC group. The main factors associated with partner HIV testing were a history of HIV testing among men in Cameroon, Dominican Republic and Georgia and the existence of couple communication around HIV testing in Georgia and India. A simple prenatal intervention taking into account the couple relationship increases the uptake of HIV testing among men in different socio-cultural settings. COC could contribute to the efforts towards eliminating mother-to-child transmission of HIV.

Abstract access 

Editor’s notes: Programmes geared towards the elimination of new HIV infections in children and keeping their mothers alive worldwide have grappled with the challenge to increase partner testing. Partner HIV discordancy is common, and interventions can be tailored to the couple status categories. Antenatal care settings have not necessarily oriented their programming to be male-friendly. It is notable that generally couples-oriented counseling and testing (COC) did increase uptake of HIV testing by male partners, though there was wide variation between countries. In addition, male testing rates remained relatively low in the intervention couples.   It is clear that additional strategies to augment partner testing will need to be implemented and evaluated. This study did provide some reassuring information that conjugal violence and union break-ups were not more common in the COC group. The study sites were in low and medium HIV prevalence settings and these results need to be compared to similar interventions in high prevalence settings.

Africa, Asia, Latin America
Cameroon, Dominican Republic, Georgia, India
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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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Lost in translation: antiretroviral treatment for discordant couples in the real world

Antiretroviral therapy to prevent HIV transmission in serodiscordant couples in China (2003-11): a national observational cohort study.

Jia Z, Ruan Y, Li Q, Xie P, Li P, Wang X, Chen RY, Shao Y. Lancet. 2012 Nov 30. pii: S0140-6736(12)61898-4. [Epub ahead of print]

Background: On the basis of the results of the randomised clinical trial HPTN 052 and observational studies, WHO has recommended that antiretroviral therapy be offered to all HIV-infected individuals with uninfected partners of the opposite sex (serodiscordant couples) to reduce the risk of transmission. Whether or not such a public health approach is feasible and the outcomes are sustainable at a large scale and in a developing country setting has not previously been assessed.

Methods: In this retrospective observational cohort study, we included treated and treatment-naive HIV-positive individuals with HIV-negative partners of the opposite sex who had been added to the national HIV epidemiology and treatment databases between Jan 1, 2003 and Dec 31, 2011. We analysed the annual rate of HIV infection in HIV-negative partners during follow-up, stratified by treatment status of the index partner. Cox proportional hazards analyses were done to examine factors related to HIV transmission.

Findings: Based on data from 38 862 serodiscordant couples, with 101 295·1 person-years of follow-up for the seronegative partners, rates of HIV infection were 2·6 per 100 person-years (95% CI 2·4-2·8) among the 14 805 couples in the treatment-naive cohort (median baseline CD4 count for HIV-positive partners 441 cells per μl [IQR 314-590]) and 1·3 per 100 person-years (1·2-1·3) among the 24 057 couples in the treated cohort (median baseline CD4 count for HIV-positive partners 168 cells per μl [62-269]). We calculated a 26% relative reduction in HIV transmission (adjusted hazard ratio 0·74, 95% CI 0·65-0·84) in the treated cohort. The reduction in transmission was seen across almost all demographic subgroups and was significant in the first year (0·64, 0·54-0·76), and among couples in which the HIV-positive partner had been infected by blood or plasma transfusion (0·76, 0·59-0·99) or heterosexual intercourse (0·69, 0·56-0·84), but not among couples in which the HIV-positive partner was infected by injecting drugs (0·98, 0·71-1·36).

Interpretation: Antiretroviral therapy for HIV-positive individuals in serodiscordant couples reduced HIV transmission across China, which suggests that the treatment-as-prevention approach is a feasible public health prevention strategy on a national scale in a developing country context. The durability and generalisability of such protection, however, needs to be further studied.

Funding: Chinese Government's 12th Five-Year Plan, the National Natural Science Foundation of China, and the Canadian International Development Research Centre.

Abstract access

Editor’s notes: There are numerous ways to look at treatment as prevention. The first important issue is somehow semantic. This paper very appropriately uses the wording "antiretrovirals to prevent transmission", which is the right definition for this kind of intervention. Indeed, the wording "treatment as prevention" shall imply a "clinical indication", which is not always there for prevention purposes.

Regarding the use of antiretrovirals for transmission prevention in discordant couples, the amazing 96% reduction shown by the HPTN052 study was appropriately described as the "Science — breakthrough of the year" in 2011. However, this very important paper from China emphasises the operational challenges, by describing the realistic efficiency, of this "public health prevention strategy on a national scale in a developing country context". Indeed, protection effect was there, but not 96%, just 26%. Not bad, but still significantly lower than that observed in the trial. Very clearly, some of the potential benefits have been "lost in translation". Indeed, as we know, real world data are very often different from what we see in trials. Indirectly, this paper raises another question:  the potential need to introduce PrEP (or possibly PEP) in discordant couples: clearly, the infected partner needs ART. However, there might be conditions (e.g. a desire to become pregnant) in which the HIV negative partner should take PrEP. In other words, as we seek discordant couples, are we more likely to recommend treating both partners?  In stable relationships: are we going to treat the HIV negative partner for a lifetime, as absolutely required for the index case?  These questions should clearly be addressed in future trials.

Asia
China
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"Start then switch": an interesting option in phasing out d4T

A 72-week randomized study of the safety and efficacy of a stavudine to zidovudine switch at 24 weeks compared to zidovudine or tenofovir disoproxil fumarate when given with lamivudine and nevirapine.

Phanuphak N, Ananworanich J, Teeratakulpisarn N, Jadwattanakul T, Kerr SJ, Chomchey N, Hongchookiat P, Mathajittiphun P, Pinyakorn S, Rungrojrat P, Praihirunyakit P, Gerschenson M, Phanuphak P, Valcour V, Kim JH, Shikuma C; the SEARCH 003 Study Group. Antivir Ther. 2012 Dec 7. doi: 10.3851/IMP2497. [Epub ahead of print]

Background: Due to superior long-term toxicity profiles, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF) are preferred over stavudine (d4T) for first-line antiretroviral regimens. However, short-term d4T use could be beneficial in avoiding AZT-induced anaemia.

Methods: We randomized (1:1:1) 150 treatment-naive Thai HIV-infected adults with CD4(+) T-cell count <350 cells/mm(3) to arm 1 (24-week GPO-VIR S30® [d4T plus lamivudine (3TC) plus nevirapine (NVP)] followed by 48-week GPO-VIR Z250® [AZT plus 3TC plus NVP]), arm 2 (72-week GPO-VIR Z250®) or arm 3 (72-week TDF plus emtricitabine [FTC] plus NVP). Haemoglobin (Hb), dual energy x-ray absorptiometry, neuropathic signs, estimated glomerular filtration rate (eGFR), CD4(+) T-cell count, plasma HIV RNA and adherence were assessed.

Results: In an intention-to-treat analysis, mean Hb decreased from baseline to week 24 in arm 2 compared with arm 1 (-0.19 versus 0.68 g/dl; P=0.001) and arm 3 (0.48 g/dl; P=0.010). Neuropathic signs were more common in arm 2 compared with arm 3 (20.4 versus 4.2%; P=0.028) at week 24. There were no differences in changes in peripheral fat and eGFR from baseline to weeks 24 and 72 among arms. CD4(+) T-cell count increased more in arm 1 than arms 2 and 3 from baseline to week 24 (168 versus 117 and 118 cells/mm(3); P=0.01 and 0.02, respectively) but the increase from baseline to week 72 was similar among arms.

Conclusions: A 24-week d4T lead-in therapy caused less anaemia and greater initial CD4(+) T-cell count increase than initiating treatment with AZT. This strategy could be considered in patients with baseline anaemia or low CD4(+) T-cell count. If confirmed in a larger study, this may guide global recommendations on antiretroviral initiation where AZT is more commonly used than TDF.

Abstract access

Editor’s notes: The 2010 WHO ART guidelines recommend that initial ART in treatment naive HIV infected adults should contain a NNRTI (either NVP or EFV) plus two NRTIs, one of which should be 3TC (or FTC) and the other AZT or TDF. The next revision of the guidelines may put even higher value on avoiding d4T toxicity, on the need to select regimens that are suitable for use across most patient groups and on the clinical and patient compliance benefits of using fixed dose combinations. Over the last two years, progress on discontinuation of d4T use as the initial option has occurred. However, some countries have made rapid and substantial progress, while others have taken a phased approach (e.g. only new initiations). Indeed, the reasons to phase out d4T in countries with limited resources are numerous, and mainly include the long-term adverse effects of thymidine analogues (AZT and d4T) which became evident after years of widespread use, since the ‘90s, in countries without financial constraints, where these drugs have not been used for many years. Now that the goal is universal access and the target is putting 15 million persons in urgent need on antiretrovirals, avoiding double standards has become an imperative. However, d4T is not a bad drug in terms of virological efficacy, and this randomized study is of some interest, because it proves the relative "safety" of d4T when used for short periods of time. These results may help guide the progressive phasing out of d4T in countries where the newly recommended drugs and combinations may not become immediately available, where TDF cost is still an issue, and where d4T procurement has been substantial.

HIV Treatment
Asia
Thailand
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Persons left behind: transgender women

Worldwide burden of HIV in transgender women: a systematic review and meta-analysis.

Baral SD, Poteat T, Strömdahl S, Wirtz AL, Guadamuz TE, Beyrer C. Lancet Infect Dis. 2012 Dec 20. pii: S1473-3099(12)70315-8. [Epub ahead of print]

Background: Previous systematic reviews have identified a high prevalence of HIV infection in transgender women in the USA and in those who sell sex (compared with both female and male sex workers). However, little is known about the burden of HIV infection in transgender women worldwide. We aimed to better assess the relative HIV burden in all transgender women worldwide.

Methods: We did a systematic review and meta-analysis of studies that assessed HIV infection burdens in transgender women that were published between Jan 1, 2000, and Nov 30, 2011. Meta-analysis was completed with the Mantel-Haenszel method, and random-effects modelling was used to compare HIV burdens in transgender women with that in adults in the countries for which data were available.

Findings: Data were only available for countries with male-predominant HIV epidemics, which included the USA, six Asia-Pacific countries, five in Latin America, and three in Europe. The pooled HIV prevalence was 19·1% (95% CI 17·4-20·7) in 11 066 transgender women worldwide. In 7197 transgender women sampled in ten low-income and middle-income countries, HIV prevalence was 17·7% (95% CI 15·6-19·8). In 3869 transgender women sampled in five high-income countries, HIV prevalence was 21·6% (95% CI 18·8-24·3). The odds ratio for being infected with HIV in transgender women compared with all adults of reproductive age across the 15 countries was 48·8 (95% CI 21·2-76·3) and did not differ for those in low-income and middle-income countries compared with those in high-income countries.

Interpretation: Our findings suggest that transgender women are a very high burden population for HIV and are in urgent need of prevention, treatment, and care services. The meta-analysis showed remarkable consistency and severity of the HIV disease burden among transgender women.

Abstract access

Editor’s notes: This paper systematically reviews studies on the prevalence of HIV infection among transgender women in different countries from three continents. Results unfortunately show that there is a dramatic consistency in HIV prevalence data, which reach peaks often above 20%, irrespective of the financial context of the countries where transgenders live. In addition, there is a common theme: risk factors including stigma, discrimination and marginalisation are all factors which dramatically increase the risk of becoming infected by HIV. Not only are transgender women probably the group with the highest risk of acquiring the infection, but they are also in urgent need of prevention, possibly including pre- and post-exposure prophylaxis, and of tailored support and care. But these might not be enough, if marginalisation is supported in some countries with a legal environment contradicting international human rights frameworks.

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Integration of HIV and TB services: a model to shift from "vertical to horizontal"

Integrating tuberculosis and HIV services in low- and middle-income countries: a systematic review.

Legido-Quigley H, Montgomery CM, Khan P, Atun R, Fakoya A, Getahun H, Grant AD. Trop Med Int Health. 2012 Dec 10. [Epub ahead of print]

Objectives: Given the imperative to scale up integrated tuberculosis (TB) and HIV services in settings where both are of major public health importance, we aimed to synthesise knowledge concerning implementation of TB/HIV service integration.

Methods: Systematic review of studies describing a strategy to facilitate TB and HIV service integration, searching 15 bibliographic databases including Medline, Embase and the Cochrane library; and relevant conference abstracts.

Results: Sixty-three of 1936 peer-reviewed articles and 70 of 170 abstracts met our inclusion criteria. We identified five models: entry via TB service, with referral for HIV testing and care; entry via TB service, on-site HIV testing, and referral for HIV care; entry via HIV service with referral for TB screening and treatment; entry via HIV service, on-site TB screening, and referral for TB diagnosis and treatment; and TB and HIV services provided at a single facility. Referral-based models are most easily implemented, but referral failure is a key risk. Closer integration requires more staff training and additional infrastructure (e.g. private space for HIV counselling; integrated records). Infection control is a major concern. More integrated models hold potential efficiencies from both provider and user perspective. Most papers report 'outcomes' (e.g. proportion of TB patients tested for HIV); few report downstream 'impacts' such as outcomes of TB treatment or antiretroviral therapy. Very few studies address the perspectives of service users or staff, or costs or cost-effectiveness.

Conclusions: While scaling up integrated services, robust comparisons of the impacts of different models are needed using standardised outcome measures.

Abstract access

Editor’s notes:This study emphasizes the need to implement the most effective integrated services for the prevention and cure of HIV and TB.  TB remains one of the most deadly infectious diseases that dramatically impacts on people in sub-Saharan Africa and represent the major cause of death in those living with HIV in the region. In fact, the progressive weakening of the immune system in HIV-positive people increases the likelihood of contracting/reactivating tuberculosis. Already in 2004, the WHO published "A Interim Policy on TBV/HIV Collaborative Activities" with the purpose of providing a guide to establish integration of TB and HIV services, and to reduce the TB load in people living with HIV. An updated document "WHO policy on collaborative TB/HIV activities: guidelines for national programmes and other stakeholders" is now available. The document provides guidance for integrating care activities between TB and HIV health services. However, to put this paper into perspective, a consensus can be reached by saying that integration shall not just be about HIV and TB. Indeed, the old debate between "vertical approaches (e.g. disease focused)" and horizontal approaches (e.g. health systems focused) shall now be concluded and integration of services shall expand to care of other diseases, particularly when, at the horizon, an epidemic of chronic non-communicable diseases is slowly but surely rising in Africa. In summary, HIV is a chronic infection impacting the lifecycle; with periods of illness and wellness, with multiple clinical and psychosocial needs, requiring lifelong care and treatment with a secure supply of medicines and laboratory tests.

It is evident that HIV care may inform appropriate responses to other health threats which share the same demand for services, training of health care workers, support for adherence, infrastructure and equipment, programme management, drug and laboratory supplies, linkage to care and community involvement. In other words, there is a wide recognition of the spillover effect of HIV interventions towards health systems strengthening, not only to the benefit of other communicable diseases, but also of child and maternal health and of chronic non-communicable diseases (like diabetes, hypertension and cancer).

Africa, Asia, Europe, Latin America
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