HIV This Week

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.

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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.