Global trends in antiretroviral resistance in treatment-naive individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative study and meta-regression analysis
ABSTRACT The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the effectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug resistance in treatment-naive individuals with HIV since initiation of rollout in resource-limited settings.
We did a systematic search for studies and conference abstracts published between January, 2001, and July, 2011, and included additional data from the WHO HIV drug resistance surveillance programme. We assessed the prevalence of drug-resistance mutations in untreated individuals with respect to time since rollout in a series of random-effects meta-regression models.
Study-level data were available for 26,102 patients from sub-Saharan Africa, Asia, and Latin America. We recorded no difference between chronic and recent infection on the prevalence of one or more drug-resistance mutations for any region. East Africa had the highest estimated rate of increase at 29% per year (95% CI 15 to 45; p=0·0001) since rollout, with an estimated prevalence of HIV-1 drug resistance at 8 years after rollout of 7·4% (4·3 to 12·7). We recorded an annual increase of 14% (0% to 29%; p=0·054) in southern Africa and a non-significant increase of 3% (-0·9 to 16; p=0·618) in west and central Africa. There was no change in resistance over time in Latin America, and because of much country-level heterogeneity the meta-regression analysis was not appropriate for Asia. With respect to class of antiretroviral, there were substantial increases in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year [21 to 52]; p<0·0001) and southern Africa (23% per year [7 to 42]; p=0·0049). No increase was noted for the other drug classes in any region.
Our findings suggest a significant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub-Saharan Africa; this rise is driven by NNRTI resistance in studies from east and southern Africa. The findings are of concern and draw attention to the need for enhanced surveillance and drug-resistance prevention efforts by national HIV treatment programmes. Nevertheless, estimated levels, although increasing, are not unexpected in view of the large expansion of antiretroviral treatment coverage seen in low-income and middle-income countries--no changes in antiretroviral treatment guidelines are warranted at the moment.
Bill & Melinda Gates Foundation and the European Community's Seventh Framework Programme.
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ABSTRACT: In 2010, 3.5 million people were living with HIV in the World Health Organization Southeast Asia Region (SEAR), giving this region the greatest burden of HIV after Africa. Scale-up of antiretroviral therapy has resulted in over 717,000 benefitting from it by the end of 2010. A systematic review of studies of HIV drug resistance in the SEAR published between 2000 and 2011 was performed. Of 10 studies of transmitted HIV drug resistance in recently infected patients, all but two reported low levels (< 5%) of transmitted resistance. Of 23 studies of HIV drug resistance in pretreatment populations initiating antiretroviral therapy, three reported moderate levels (5-15%) of HIV drug resistance and 20 reported low levels. Amongst 17 studies of acquired HIV drug resistance, levels of nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance ranged from 52 to 92% and 43 to 100%, respectively, amongst those with virological failure. Overall, data included in this review suggest that currently recommended first- and second-line regimens are appropriate for the cohorts studied. However, data were only available from two of 11 Southeast Asia Region countries and studies largely examined urban populations. Results are unlikely to be representative of the region. Studies lacked standardized methods, which greatly limits comparability of data and their use for public health and antiretroviral therapy program planning. Routine, standardized, and nationally representative HIV drug resistance surveillance should be strongly encouraged in the Southeast Asia Region countries to best characterize population-level HIV drug resistance. National-level HIV drug resistance surveillance data may be used to optimize delivery of HIV care and treatment and minimize emergence of population-level HIV drug resistance, thus promoting the long-term efficacy and durability of available first- and second-line antiretroviral therapy regimens.AIDS reviews 15(3):162-70. · 4.02 Impact Factor
- The Lancet 10/2012; 380(9849):1229-30. DOI:10.1016/S0140-6736(12)61715-2 · 45.22 Impact Factor
Article: Optimizing HIV treatment.[Show abstract] [Hide abstract]
ABSTRACT: PURPOSE OF REVIEW: There are at least eight million people eligible for antiretroviral treatment but not receiving it. An additional 19 million people will need to start treatment in the future, as their HIV disease progresses. Funding for Universal Access to HIV treatment has been restricted by the Global Financial Crisis. RECENT FINDINGS: There are three large randomized trials ongoing, designed to establish the efficacy of lower than approved doses of antiretrovirals. If successful, the results of these trials could lower costs of antiretrovirals and improve the safety profiles. Clinical trials evaluating efavirenz, atazanavir, ritonavir and stavudine are discussed. The costs of these and other antiretrovirals are presented. SUMMARY: The results of these trials could significantly lower the costs of Universal Access. Assuming 15 million people on antiretroviral treatment, the reduction in unit costs of tenofovir (TDF)/3TC/efavirenz from dose optimization of efavirenz to 400 mg once daily would save US$16 per person, leading to an overall saving of US$192 million per year. The switch from zidovudine (ZDV)/3TC/atazanavir (ATV)/r 300/100 once daily to dolutegravir along with ATV/r 200/50 once daily would save US$267 per person, leading to an overall saving of US$801 million. The combined saving in costs from first- and second-line treatment would therefore be US$993 million per year.Current opinion in HIV and AIDS 11/2012; DOI:10.1097/COH.0b013e32835b7f28 · 4.39 Impact Factor