{"id":15525,"date":"2011-08-01T11:12:06","date_gmt":"2011-08-01T11:12:06","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=15525"},"modified":"2011-08-01T11:12:06","modified_gmt":"2011-08-01T11:12:06","slug":"lopinavirr-monotherapy-used-as-second-line-therapy-in-resource-limited-settings","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/15525","title":{"rendered":"Lopinavir\/r monotherapy used as second-line therapy in resource-limited settings"},"content":{"rendered":"

Polly Clayden, HIV i-Base<\/strong><\/p>\n

WHO guidelines recommend the use of boosted protease inhibitors second line in resource limited settings. Findings from strategies looking at using lopinavir\/ritonavir (LPV\/r) have been uncertain to date, both in limited and richer resourced settings.<\/p>\n

Two posters at CROI 2011 presented data from studies evaluating LPV\/r monotherapy, with showed further conflicting results.<\/p>\n

ACTG 5230 evaluated lopinavir\/ritonavir (LPV\/r) monotherapy in a pilot study. It was a single arm multinational trial with sites in Malawi, Tanzania, South Africa, Thailand and India.<\/p>\n

Participants had previously received first line NNRTI-containing regimens for at least six months and had detectable viral load 1,000\u0096200,000 copies\/mL. All participants received LPV\/r monotherapy BID. The primary endpoint was remaining on monotherapy without virological failure at 24 weeks. This was defined as: failure to suppress viral load to <400 copies\/mL by week 24, or confirmed rebound to >400 copies\/mL at or after week 16 following confirmed suppression.<\/p>\n

People with virologic failure received intensification with emtricitabine (FTC) 200 mg\/tenofovir (TDF) 300 mg.<\/p>\n

There were 123 participants enrolled in this trial. About 60% were women and they were a median of 39 years of age, with a median CD4 of 164 cells\/mm3 and viral load of 4.34 log10<\/sub> copies\/mL (17% were >100,000 copies\/mL).<\/p>\n

Other baseline characteristics included: 93% with >1 year HAART, 98% with >1 NNRTI mutation and 95% with >1 NRTI mutation (87% M184V, 84% TAM, 11% K65R, 4% Q151M\/L).<\/p>\n

The majority, of participants completed 24 weeks of follow-up with the exception of one death at week 20 with a viral load of <400 copies\/mL.<\/p>\n

The investigators reported, at week 24, 107 (87%; 95% CI 80-92%) of participants remained on LPV\/r monotherapy without virologic failure.<\/p>\n

Of the remaining, 15 met the criteria for virologic failure and one added FTC\/TDF before failure. Of 13 participants with data after intensification, 11 (85%) suppressed viral load to <400 copies\/mL.<\/p>\n

At virologic failure, 2\/11 participants who were successfully sequenced had selected new resistance mutations (both had A71T and V82F). The overall mean CD4 count increase from baseline to week 24 was 107 cells\/mm3. Overall 31 (25%) of participants experienced grade 3 or 4 toxicities. The most commonly reported grade 3 or 4 toxicities (9% of participants) were metabolic (mostly elevated lipids). Self reported adherence was high; at week 24, 83% of participants reported no missed doses.<\/p>\n

The investigators concluded that LPV\/r monotherapy showed promising preliminary activity as second-line HAART following failure of first-line NNRTI-containing regimens at 24 weeks. The lower bound of the 90% CI (81-92%) of the observed success rate (87%) was above 65%.<\/p>\n

Torsak Bunupuradah and colleagues from the HIV STAR Study in Thailand looked at LPV\/r monotherapy as second line but they also evaluated viral suppression to <50 copies\/mL and included a comparison arm with triple therapy.<\/p>\n

The STAR investigators enrolled 200 participants with viral load >1000 copies\/mL on NNRTI-containing first line therapy. Participants were randomised to receive either LPV\/r monotherapy ot LPV\/r + TDF + 3TC.<\/p>\n

Treatment failure was defined as viral load >400 copies\/mL at >24 weeks. Participants meeting these criteria in the monotherapy arm received intensification with TDF + 3TC.<\/p>\n

Participants in this study were about 60% men with a median age of 37 years, CD4 of 188 cells\/mm3, and viral load of\u00a0 4.1 log10 copies\/mL.<\/p>\n

Prior to switching, 92% of participants were receiving 3TC, 63% d4T, 23% AZT and 5% TDF. Nevirapine and efavirenz were received by 86% and 14% participants, respectively. Without significant differences between arms, 15% of participants had =3 TAMS, 82% had M184V\/I, 6% had Q151M, and 7% had K65R.<\/p>\n

By intent-to-treat analyses at 48 weeks, the proportion of patients with viral load <400 copies\/mL the LPV\/r monotherapy arm was 75% vs 86% in the TDF\/3TC\/LPV\/r arm, p=0.53. But, only 61% of the LPV\/r monotherapy arm vs 83% in TDF\/3TC\/LPV\/r arm had a viral load <50 copies\/mL, p<0.01.<\/p>\n

Major PI mutations were detected in 1 of 2 LPV\/r monotherapy and 0 of 3 TDF\/3TC\/LPV\/r treated participants with genotype results following treatment failure. There was no significant difference in CD4 count increase between arms: 114 vs 137 cells\/mm3 in the LPV\/r monotherapy and TDF\/3TC\/LPV\/r arms respectively. One death (unrelated to study drugs) was reported in each arm. Serious adverse events were reported in two patients in the LPV\/r monotherapy arm and seven patients in the TDF\/3TC\/LPV\/r arm.<\/p>\n

The investigators concluded that LPV\/r monotherapy should be used with caution as a second-line option, particularly in settings where close viral load monitoring is not available.<\/p>\n

<\/strong><\/p>\n

comment<\/strong><\/p>\n

The ongoing EARNEST Trial (NCT00988039) will answer the question whether or not lopinavir\/r monotherapy is a sufficiently potent regimen compared to lopinavir\/r combined with two NRTIs or raltegravir. <\/strong><\/p>\n

Results from this trial are expected in 2013.<\/strong><\/p>\n

<\/strong><\/p>\n

References<\/p>\n

    \n
  1. Bartlett J et al. A pilot study of LPV\/r monotherapy following virologic failure of first-line NNRTI-containing regimens in resource-limited settings: The Week-24 primary analysis of ACTG 5230. 18th CROI, 27 February\u00962 March 2011, Boston. Poster abstract 583<\/a>.<\/li>\n
  2. Bunupuradah T et al. Second-line LPV\/r monotherapy was inferior to TDF\/3TC\/LPV\/r in patients who failed NNRTI regimen: HIV STAR Study. 18th CROI, 27 February\u00962 March 2011, Boston. Poster abstract 584<\/a>.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base WHO guidelines recommend the use of boosted protease inhibitors second line in resource limited settings. Findings from strategies looking at using lopinavir\/ritonavir (LPV\/r) have been uncertain to date, both in limited and richer resourced settings. Two …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,41,38],"tags":[65],"class_list":["post-15525","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-treatment-strategies","category-treatment-access","tag-croi-2011"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15525","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=15525"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/15525\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=15525"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=15525"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=15525"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}