HIV This Week Issue #95

Welcome to the 95th issue of HIV This Week!  In this issue, we cover the following topics:

1. Young people


2. Hormonal contraception


3. Sexual transmission


4. Male circumcision


5. HIV and older people


6. Financing


7. Drug resistance


8. Social determinants


9. Basic Science


10. Orphans and vulnerable children


11. Treatment


12. Maternal and child mortality


13. Injecting drug use


14. Early infant diagnosis


15. People living with HIV


16. Sex work


17. Prisons


To find out how you can access a majority of scientific journals free of charge, please see the last page of this issue or check the HIV This Week website clicking here. If you are reading this through the kindness of a friend and would like to subscribe to receive HIV This Week pdf issues by email, you can sign up by clicking here. To unsubscribe, please click the following link: unsubscribe. We want to be as helpful to you as we can, so please let us know what your interests are and what you think of HIV This Week by sending a comment to hivthisweek(at)unaids.org or by posting one on the HIV This Week blog. If you would like to recommend an article for inclusion, please contact HIV This Week here. Don’t forget that you can find a wealth of information on the HIV epidemic and responses to it at www.unaids.org.

Cate Hankins, Science Adviser to UNAIDS

Derek Christie, Research officer

Sylvia Béké-Wilson, Assistant

Creative Consulting & Development Works, Research Consultants

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Young people

A tale of two countries: rethinking sexual risk for HIV among young people in South Africa and the United States

Pettifor AE, Levandowski BA, Macphail C, Miller WC, Tabor J, Ford C, Stein CR, Rees H, Cohen M. J Adolesc Health. 2011 Sep;49(3):237-243.e1.

Pettifor and colleagues compared the sexual behaviours of young people in South Africa and the United States of America with the aim to better understand the potential role of sexual behaviour in HIV transmission in these two countries that have strikingly different HIV epidemics. Nationally representative, population-based surveys of young people aged 18-24 years from South Africa (n = 7548) and the USA (n = 13,451) were used for the present study. The prevalence of HIV was 10.2% in South Africa and <1% in the USA. Young women and men in the USA reported an earlier age of first sex than those in South Africa (mean age of coital debut for women: USA [16.5], South Africa [17.4]; for men: USA [16.4], SA [16.7]). The median number of lifetime partners is higher in the USA than in South Africa: women: USA (4), South Africa (2); men: USA (4), South Africa (3). The use of condom at last sex is reported to be lower in the USA than in South Africa: women: USA (36.1%), South Africa (45.4%); men: USA (48%), South Africa (58%). On average, young women in South Africa report greater age differences with their sex partners than young women in the USA. Young people in the USA report riskier sexual behaviours than young people in South Africa, despite the much higher prevalence of HIV infection in South Africa. Factors above and beyond sexual behaviour likely play a key role in the ongoing transmission of HIV in South African youth, and thus should be urgently uncovered to develop maximally effective prevention strategies.

For abstract access click here

Editor’s note: This comparison of two nationally representative surveys of young people starkly underscores that behaviour is not the sole determinant of HIV risk. South African young people had their first sex at a later age, have fewer sexual partners, and practise more safer sex than their American counterparts. How can the more than 10-fold difference in HIV prevalence be explained?  The first thought goes to larger age gaps between sexual partners. This means sexual mixing with older partners who can act as a bridge population to younger cohorts…. but there has to be more to it than that. In South Africa, male circumcision levels are far lower, herpes simplex 2 infection levels are higher, genital tract inflammation is higher, co-infections (tuberculosis, helminths) that can increase viral set points are more common, and the prevalence of the CCR5Δ32 coreceptor is lower. But social determinants, such as gender power imbalances, poverty, coerced sex and rape, lack of youth friendly services, and stigma are likely playing important roles. Although these surveys were conducted in 2003 (South Africa) and 2001-2 (USA) using somewhat different methodologies, the finding that ‘ordinary’ sexual behaviour can place young people, particularly young women, in South Africa at such high risk should galvanise leaders at all levels to call for urgent action. Advocates are calling out ‘where the hell is the gel’ and researchers are testing microfinance and conditional cash transfers, but it will take a paradigm shift at all levels to prioritise investment in protecting young people from what is a preventable, chronic, lifelong disease. 

National responses
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Hormonal contraception

Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study

Renee Heffron, Deborah Donnell, Prof Helen Rees, Connie Celum, Nelly Mugo, Edwin Were, Guy de Bruyn, Edith Nakku-Joloba, Kenneth Ngure, James Kiarie, Robert W Coombs, Jared M Baeten, The Lancet Infectious Diseases, Early Online Publication, 4 October 2011

Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. Heffron and colleagues aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. In this prospective study, they followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, they compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. Cox proportional hazards regression and marginal structural modelling were used to assess the effect of contraceptive use on HIV-1 risk. Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 [IQR 12·6–24·2] months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06–3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 [IQR 12·8–24·2] months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12–3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1.

For abstract access click here

Editor’s note: The issue of hormonal contraception and HIV risk continues to perplex. Observational studies have both suggested a link and not found one. This study of HIV serodiscordant couples was not specifically designed to examine this issue and had too few women on contraceptive pills to draw any conclusions. However, a doubling of the risk of HIV acquisition for HIV-negative women using injectable DMPA (depot-medroxyprogesterone acetate) and a doubling of the risk of HIV transmission from HIV-positive women using DMPA to their seronegative partners are cause for concern. Contraception improves the health of women and children worldwide and it plays a crucial role in helping women with, or at risk of, HIV infection to prevent the adverse social and health consequences of unintended pregnancies. WHO and partners are convening a technical consultation in early 2012 to re-examine the totality of evidence on the potential effects of hormonal contraception and of intrauterine devices on HIV acquisition, disease progression, and infectivity/transmission to sexual partners. The need to conduct randomized controlled trials to determine whether hormonal contraception increases the risk of HIV acquisition in women and/or of HIV transmission to men will be assessed, along with feasibility. In the meantime, we need to reinforce the importance of correct and consistent condom use, regardless of whether another method of contraception is being used. It is and has been for decades the ‘dual protection’ message.

Gender
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Sexual transmission

Risk for HIV and unprotected sexual behaviour in male primary partners of transgender women

Operario D, Nemoto T, Iwamoto M, Moore T. Arch Sex Behav. 2011 May 21.

Men who have sex with transgender women are a potentially high-risk population for HIV and other sexually transmitted infections. Operario and colleagues administered structured quantitative surveys to 174 men whose primary partner was a transgender woman. They assessed men's demographic characteristics, sexual behaviours, substance use, and social-psychological factors, including condom use self-efficacy and depression. Overall, 19% reported being HIV-positive (8% had been diagnosed with AIDS), 11% had at least one other sexually transmitted infection during the past year, and 16% reported being in a HIV serodiscordant relationship with their primary partner. In the past 3 months, 40% had unprotected anal or vaginal sex with any partner. In multivariate analysis, significant correlates of having unprotected sex included younger age, concurrent partnerships, alcohol intoxication, and low condom use self-efficacy; depression was marginally associated with having unprotected sex. Interventions are needed to reduce risk for HIV and other sexually transmitted infections among men who have sex with transgender women. Prevention programmes for these men should build condom use self-efficacy and address the contributions of alcohol intoxication, concurrent sex partnerships, and depression to sexual risk behaviour.

For abstract access click here

Editor’s note: A study of men in primary relationships with transgender women is very rare. Being in a ‘primary relationship’ was defined as two adults committed to each other above anyone else. The couples were identified through snowball referral techniques (Do you know couples like yours that could be interested in the study? Could you refer them to us?) and through direct approaches to couples in bars, nightclubs, book stores, community based organisations, health clinics, parks, and street locations where study advertisements were posted. The average relationship duration was 2.9 years and 47% of the couples in this convenience sample lived together. This paper describes the male partners¾they reported being bisexual (45%), homosexual (23%), heterosexual (23%), and other or not willing to categorise themselves (9%). Men whose primary partner was post-operative were more likely than those with a pre-operative transgender partner to identify as heterosexual (53% vs. 20%). Overall 58% of the men in this San Francisco Bay area study described the relationship as monogamous, however one in five of them, and 12% of their transgender partners, had sex with an outside partner during the current primary partnership. Whether or not these couples are serodiscordant (one in six are), couples-based interventions aimed at strengthening safer sex practices are warranted, without preconceived assumptions about the sexual orientation of the men. 

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Male circumcision

Adult male circumcision as an intervention against HIV: an operational study of uptake in a South African community (ANRS 12126)

Lissouba P, Taljaard D, Rech D, Dermaux-Msimang V, Legeai C, Lewis D, Singh B, Puren A, Auvert B. BMC Infect Dis. 2011 Sep 26;11(1):253.

The objective of this study was to evaluate the knowledge, attitudes, and beliefs about adult male circumcision, assess the association of adult male circumcision with HIV incidence and prevalence, and estimate adult male circumcision uptake in a Southern African community. A cross-sectional biomedical survey (ANRS-12126) was conducted in 2007-2008 among a random sample of 1198 men aged 15 to 49 from Orange Farm (South Africa). Face-to-face interviews were conducted by structured questionnaire. Recent HIV infections were evaluated using the BED incidence assay. Circumcision status was self-reported and clinically assessed. Adjusted HIV incidence rate ratios and prevalence ratios were calculated using Poisson regression. The response rate was 73.9%. Most respondents agreed that circumcised men could become HIV infected and needed to use condoms, although 19.3% (95%CI: 17.1% to 21.6%) asserted that adult male circumcision protected fully against HIV. Among self-reported circumcised men, 44.9% (95%CI: 39.6% to 50.3%) had intact foreskins. Men without foreskins had lower HIV incidence and prevalence than men with foreskins (aIRR=0.35; 95%CI: 0.14 to 0.88; aPR=0.45, 95%CI: 0.26 to 0.79). No significant difference was found between self-reported circumcised men with foreskins and other uncircumcised men. Intention to undergo adult male circumcision was associated with ethnic group and partner and family support of adult male circumcision. Uptake of adult male circumcision was 58.8% (95%CI: 55.4% to 62.0%). Adult male circumcision uptake in this community is high but communication and counselling should emphasize what clinical adult male circumcision is and its effect on HIV acquisition. These findings suggest that adult male circumcision roll-out is promising but requires careful implementation strategies to be successful against the African HIV epidemic.

For abstract access click here

Editor’s note: This first study to examine uptake of voluntary medical male circumcision (VMMC) among a random sample of the general population produced interesting findings. The most salient are the 55% lower HIV prevalence and 65% lower incidence in clinically circumcised men – the latter is more than the risk reduction of 60% seen in the randomised controlled trial conducted before 2005 in the same setting. More important from the point of view of programming is that 45% of men who reported that they were circumcised were found to have foreskins when they were examined. Men who have undergone initiation rituals may call themselves circumcised even if they have an intact foreskin. This suggests the importance of community education for both men and women, perhaps involving photos, about what a circumcised penis looks, along with information on the benefits of VMMC in high HIV prevalence settings. 81% of uncircumcised men in the study stated their intention to undergo VMMC and 72% of these were circumcised through the study (59% uptake). The most important factors influencing the decision to undergo VMMC were being from a traditionally circumcising ethnic group, believing that VMMC was safe, and having partner and family support. 

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Male circumcision

Acceptability of medical male circumcision in the traditionally circumcising communities in Northern Tanzania
Wambura M, Mwanga JR, Mosha JF, Mshana G, Mosha F, Changalucha J. BMC Public Health. 2011 May 23;11:373
Data from traditionally circumcising communities show that non-circumcised males and those circumcised in the medical settings are stigmatised. This is because traditional circumcision embodies local notions of bravery as anaesthetics are not used. This study was conducted to assess the acceptability of safe medical circumcision before the onset of sexual activity for HIV infection risk reduction in a traditionally circumcising community in Tanzania. A cross-sectional study was conducted among males and females aged 18-44 years in traditionally circumcising communities of Tarime District in Mara Region, North-eastern Tanzania. A face-to-face questionnaire was administered to females to collect information on the attitudes of women towards circumcision and the preferred age for circumcision. A similar questionnaire was administered to males to collect information on sociodemographic, preferred age for circumcision, factors influencing circumcision, client satisfaction, complications and beliefs surrounding the practice. Results were available for 170 males and 189 females. Of the males, 168 (98.8%) were circumcised and 61 (36.3%) of those circumcised had the procedure done in the medical setting. Of those interviewed, 165 (97.1%) males and 179 (94.7%) females supported medical male circumcision for their sons. Of these, 107 (64.8%) males and 130 (72.6%) females preferred prepubertal medical male circumcision (12 years or less). Preference for prepubertal circumcision was significantly associated with non-Kurya ethnic group, circumcision in the medical setting and residence in urban areas for males in the adjusted analysis. For females, preference for prepubertal circumcision was significantly associated with non-Kurya ethnic group and being born in urban areas in the adjusted analysis. There is a shift of preference from traditional male circumcision to medical male circumcision in this traditionally circumcising population. However, this preference has not changed the circumcision practices in the communities because of the community social pressure. The male circumcision national programme should take advantage of this preference for medical male circumcision by introducing safe and affordable circumcision services and mobilising communities in a culturally sensitive manner to take up circumcision services.

For abstract access click here

Editor’s note: Given the numbers of male circumcisions that the 13 priority countries in sub-Saharan Africa are aiming to complete by 2015, many people believe that less attention should be given to communities that have high male circumcision prevalence already through traditional circumcising practices. This study suggests that these communities should not be left behind. Parents are concerned about bleeding, delays in wound healing, and adverse events. They also would prefer that the procedure
be done before sexual activity starts. Although 97% of men and 95% of women in this study supported voluntary medical male circumcision (VMMC) for their sons, 64% of men had been circumcised traditionally and uptake of VMMC is low due to social pressure and increased cost. If safe, affordable, and culturally sensitive VMMC services were made available, as they have been elsewhere in parts of Africa that practice traditional circumcision, it would not be long before parents and young people align
their actions with their preferences. There will be more on male circumcision in the next issue of HIV This Week, but in the meantime, do check out the Joint Strategic Action Framework on Voluntary Medical Male Circumcision that was launched by UNAIDS and PEPFAR on behalf of WHO and other partners last week at the International Conference on AIDS and Sexually Transmitted Infections in Africa held in Addis Ababa, Ethiopia. You can find it at: http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspubl...

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HIV and older people

HIV attitudes, awareness and testing among older adults in Africa

Negin J, Nemser B, Cumming R, Lelerai E, Ben Amor Y, Pronyk P. AIDS Behav. 2011 Jul 8.

In Africa, older adults aged 50 and older are still sexually active and play a critical role as caregivers, yet little is known about their attitudes towards HIV and awareness of services. In this study, surveys were conducted in nine African sites. A multilevel model was fitted to evaluate the relationship between age and outcome variables. The study reveals that people aged 50 years and older have lower levels of HIV-related knowledge and awareness than those aged 25-49. Older adults were less likely to have been tested for HIV and women aged 50 and older showed particularly low levels of awareness.

For abstract access click here

Editor’s note: In 2010, a study estimated that 3 million people aged 50 and over were living with HIV in sub-Saharan Africa, representing fully 14% of those over age 15 with HIV infection. Some of these people have aged into this age category due to the life-prolonging benefits of antiretroviral therapy but others are becoming newly infected each day. Many do not know that they have HIV infection. Why do we never hear about older people with HIV? Our HIV prevention progress indicators for sexual transmission refer to people aged 15-49 years and prevalence data collected through Demographic and Health Surveys (DHS) and presented by UNAIDS do not include people aged 50 years and older. This measurement neglect is reflected in lack of programming to raise awareness and knowledge levels, develop communication and condom negotiation skills, and address stigma and discrimination in this age group commonly seen primarily as a caregiver source. Some countries are jumping ahead: South Africa has held caregiver workshops to improve attitudes and knowledge and has added males older than 50 to its list of most-at-risk populations (key populations). Across the nine clusters in eight countries in this Millennium Villages Project study, the lowest ‘ever tested for HIV’ levels were in Senegal (0% for both men and women) and the highest in Rwanda (23% for men and 17% for women). More attention to people aged 50 and older is needed now if they are to avoid HIV infection, access HIV testing, start timely antiretroviral treatment, and have a positive intergenerational influence on community attitudes and knowledge as sexually active and informed educators, as well as caretakers.

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Financing

Has HIV/AIDS displaced other health funding priorities? Evidence from a new dataset of development aid for health

Lordan G, Tang KK, Carmignani F. Soc Sci Med. 2011 Jul 9.

In recent times there has been a sense that HIV control has been attracting a significantly larger portion of donor health funding to the extent that it crowds out funding for other health concerns. Although there is no doubt that HIV has absorbed a large share of development assistance for health, whether HIV is actually diverting funding away from other health concerns has yet to be analyzed fully. To fill this vacuum, this study aims to test if a higher level of HIV funding is related to a displacement in funding for other health concerns, and if yes, to quantify the magnitude of the displacement effect. Specifically, Lordan and colleagues consider whether HIV development assistance for health has displaced i) TB, ii) malaria iii) health sector and 'other' development assistance for health in terms of the dollar amount received for aid. They consider this question within a regression framework controlling for time and recipient heterogeneity. The authors find displacement effects for malaria and health sector funding but not TB. In particular, the displacement effect for malaria is large and worrying.

For abstract access click here

Editor’s note: This study of 44 low- and middle-income countries that have a significant burden of HIV, tuberculosis (TB), and malaria, along with a health sector in need of strengthening, assessed the extent of dollar displacement, rather than share displacement, that donor HIV funding may be incurring. This means that it examined changes in the actual amount of aid provided for HIV, TB, malaria, and health sector strengthening, rather than changes in the share of aid devoted specifically to HIV. As we know, the amount of development assistance for health (DAH) devoted to HIV has increased over time. TB has not suffered, perhaps because donors see funding for the two diseases to be complementary. Malaria, killing one million people in 2008 and accounting for 20% of African childhood mortality, clearly ranks highly for donor attention by the criteria of burden of disease. As well, lower per-capita income in high malaria-burden countries suggests less capacity for domestic resource mobilisation for malaria. Yet, this study estimates that for every 1% increase in funds devoted to HIV in a year, there is an 11% decrease the following year in funds devoted to malaria. This rises to 19% when considering only the 29 countries with malaria prevalence above 1% of the population. Aside from the concern about likely ‘crowding out’ of malaria funding by HIV funding, this study suggests that donor commitments are barely medium-term, let along long-term, a factor that is undermining country-led processes for resource allocation planning for both diseases.

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Financing

Long-term costs and health impact of continued global fund support for antiretroviral therapy

Stover J, Korenromp EL, Blakley M, Komatsu R, Viisainen K, Bollinger L, Atun R. PLoS One. 2011;6(6):e21048.

By the end of 2011 Global Fund investments will be supporting 3.5 million people on antiretroviral therapy in 104 low- and middle-income countries. Stover and colleagues estimated the cost and health impact of continuing treatment for these patients through 2020. Survival on first-line and second-line antiretroviral therapy regimens is estimated based on annual retention rates reported by national AIDS programmes. Costs per patient-year were calculated from country-reported antiretroviral procurement prices, and expenditures on laboratory tests, health care utilisation, and end-of-life care from in-depth costing studies. Of the 3.5 million patients on antiretroviral therapy in 2011, 2.3 million will still need treatment in 2020. The annual cost of maintaining antiretroviral therapy falls from $1.9 billion in 2011 to $1.7 billion in 2020, as a result of a declining number of surviving patients partially offset by increasing costs as more patients migrate to second-line therapy. The Global Fund is expected to continue being a major contributor to meeting this financial need, alongside other international funders and domestic resources. Costs would be $150 million less in 2020 with an annual 5% decline in first-line ARV prices and $150-370 million less with a 5%-12% annual decline in second-line prices, but $200 million higher in 2020 with phase out of stavudine (d4T), or $200 million higher with increased migration to second-line regimens expected if all countries routinely adopted viral load monitoring. Deaths postponed by antiretroviral therapy correspond to 830,000 life-years saved in 2011, increasing to around 2.3 million life-years every year between 2015 and 2020. Annual patient-level direct costs of supporting a patient cohort remain fairly stable over 2011-2020, if current antiretroviral prices and delivery costs are maintained. Second-line antiretroviral prices are a major cost driver, underscoring the importance of investing in treatment quality to improve retention on first-line regimens.

For abstract access click here

Editor’s note: This analysis of the cost and impact of continuing treatment for the 3.5 million of people who are co-supported by the Global Fund, compared to stopping it, provides food for thought. For the 6.6 million people on antiretroviral therapy now, retention on treatment is excellent after the first year, based on data from 38 national AIDS programmes in 2008: 80% not dying or lost to follow-up at 1 year, 75% at 2 years, 74% at 3 years, and 73% at 4 years. If treatment were to be stopped now for those receiving it, 18% would die in the first year, 46% after two years, 64% after three years, 76% after 4 years, 84% after 5 years, and 97% after 6 years. Median survival after treatment cessation would be 2 to 3 years. If the Global Fund did not support any new people to start antiretroviral therapy, the costs to maintain those already on treatment through to 2020 would decline. Costs increase as more people are moved off d4T first-line regimens or start costly second-line regimens (24% will likely be on second-line by 2020), however deaths result in 10% reduced costs overall. Antiretroviral drugs constitute 42% of first-line regimen and 81% of second-line regimen costs, underscoring the importance of further price reductions. Routine viral load testing, CD4 cunts, and clinical monitoring for timely detection of and responses to adherence difficulties, will prevent unnecessary switching to second-line regimens. The most striking finding is the number of life-years saved each year¾it rises to 2.3 million by 2017 when virtually everyone treated today would have died in the absence of treatment. Setting aside moral, ethical, and treatment for prevention arguments, continued and increased investment in antiretroviral treatment makes economic sense, not only for those already on treatment but also for those eligible and waiting. 

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Drug resistance

HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study

Hamers RL, Wallis CL, Kityo C, Siwale M, Mandaliya K, Conradie F, Botes ME, Wellington M, Osibogun A, Sigaloff KC, Nankya I, Schuurman R, Wit FW, Stevens WS, van Vugt M, de Wit TF; for PharmAccess African Studies to Evaluate Resistance (PASER). Lancet Infect Dis. 2011 Oct;11(10):750-9.

There are few data on the epidemiology of primary HIV-1 drug resistance after the roll-out of antiretroviral treatment in sub-Saharan Africa. Hamers and colleagues aimed to assess the prevalence of primary resistance in six African countries after antiretroviral treatment roll-out and if wider use of antiretroviral treatment in sub-Saharan Africa is associated with rising prevalence of drug resistance. They did a cross-sectional study in antiretroviral-naive adults infected with HIV-1 who had not started first-line antiretroviral treatment, recruited between 2007 and 2009 from 11 regions in Kenya, Nigeria, South Africa, Uganda, Zambia, and Zimbabwe. They did population-based sequencing of the pol gene on plasma specimens with greater than 1000 copies per mL of HIV RNA. They identified drug-resistance mutations with the WHO list for transmitted resistance. The prevalence of sequences containing at least one drug-resistance mutation was calculated accounting for the sampling weights of the sites. They assessed the risk factors of resistance with multilevel logistic regression with random coefficients. 2436 (94.1%) of 2590 participants had a pretreatment genotypic resistance result. 1486 participants (57.4%) were women, 1575 (60.8%) had WHO clinical stage 3 or 4 disease, and the median CD4 count was 133 cells per μL (IQR 62-204). Overall sample-weighted drug-resistance prevalence was 5.6% (139 of 2436; 95% CI 4.6-6.7), ranging from 1.1% (two of 176; 0.0-2.7) in Pretoria, South Africa, to 12.3% (22 of 179; 7.5-17.1) in Kampala, Uganda. The pooled prevalence for all three Ugandan sites was 11.6% (66 of 570; 8.9-14.2), compared with 3.5% (73 of 1866; 2.5-4.5) for all other sites. Drug class-specific resistance prevalence was 2.5% (54 of 2436; 1.8-3.2) for nucleoside reverse-transcriptase inhibitors (NRTIs), 3.3% (83 of 2436; 2.5-4.2) for non-NRTIs (NNRTIs), 1.3% (31 of 2436; 0.8-1.8) for protease inhibitors, and 1.2% (25 of 2436; 0.7-1.7) for dual-class resistance to reverse-transcriptase inhibitors and non-reverse transcriptase inhibitors. The most common drug-resistance mutations were K103N (43 [1.8%] of 2436), thymidine analogue mutations (33 [1.6%] of 2436), M184V (25 [1.2%] of 2436), and Y181C/I (19 [0.7%] of 2436). The odds ratio for drug resistance associated with each additional year since the start of the antiretroviral treatment roll-out in a region was 1.38 (95% CI 1.13-1.68; p=0.001). The higher prevalence of primary drug resistance in Uganda than in other African countries is probably related to the earlier start of antiretroviral treatment roll-out in Uganda. Resistance surveillance and prevention should be prioritised in settings where antiretroviral treatment programmes are scaled up.

For abstract access click here

Editor’s note: PASER-M is a multicentre prospective cohort of people receiving first- or second-line antiretroviral therapy in 13 clinical sites in 6 African countries. Pre-treatment viral loads in 2436 people who were antiretroviral-naïve were sequenced for drug resistance giving a weighted prevalence result of 5.6%. The lowest prevalence was in Pretoria (1.1%) and the highest was in Kampala (12.3%). South Africa is the only country with routine viral load monitoring while Uganda is the country with the oldest history of antiretroviral treatment. These findings emphasise the importance of viral load monitoring. Without it, many people are unnecessarily switched to more expensive and toxic second-line therapies or remain on failing first-line regimens that can provoke drug resistance. Onward transmission of drug-resistant strains can compromise the effectiveness of the first-line regimens that are part of the public health approach (2 NRTIs and one NNRTI). Pre-treatment drug resistance testing is used in high-income countries where 9 to 15% of antiretroviral-naïve people have at least one drug-resistant variant in order to guide individual treatment choices. At a minimum, low- and middle-income countries need to move rapidly to routine viral load monitoring to reduce the risk of resistance undermining treatment programme successes.

Treatment
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