Apparent Selection against Transmission of Zidovudine-Resistant Human Immunodeficiency Virus Type 1 Variants

Abstract

The sexual transmission of zidovudine-resistant human immunodeficiency virus type 1 (HIV-1) variants was investigated in 5 donor-recipient pairs in which all donors and none of the recipients had received zidovudine treatment. The virus isolates were tested for sensitivity to zidovudine (IC50) in vitro using blood donor lymphocytes. A region of the HIV-1 pol gene was also directly sequenced by a solid-phase sequencing method. Four donors were shown to have zidovudine-resistant HIV-1 variants. Two of these patients had a single mutation (Thr215-->Tyr), and 2 had a double mutation (Met41-->Leu and Thr215-->Tyr) that previously has been shown to confer zidovudine resistance. Zidovudine-resistant virus was found in only 1 of the 4 recipients, which indicates that zidovudine-resistant HIV-1 variants may be selected against during transmission. Thus, the transmission of zidovudine-resistant HIV-1 variants is a complex process that will require consideration whenever zidovudine treatment is initiated in persons who may have been infected by resistant variants.

Sexual Transmission of an HIV-1 Variant Resistant to Multiple Reverse-Transcriptase and Protease Inhibitors

“…Some HIV-1 variants that are resistant to zidovudine may be at a selective disadvantage during transmission as compared with wildtype virus. 27 Although the findings in our case do not rule out the possibility that multidrug-resistant HIV-1 is less readily transmitted, they confirm that an HIV-1 variant with multiple mutations coding for resistance to protease and reverse-transcriptase inhibitors can be transmitted.…”

Public Health Implications of Antiretroviral Therapy and HIV Drug Resistance

“…34 In a comparison of 5 pairs of zidovudinetreated donors and their drug-naive HIV-infected sexual contacts, 4 donors had virus that displayed phenotypic resistance to zidovudine, of which 2 possessed only the T215Y mutation while 2 were doubly mutated in regard to both the T215Y and M41L substitutions. 35 In contrast, virus resistant to zidovudine was identified in only 1 of the 4 recipients, suggesting that the resistant variants may have been less well transmitted than wild type. 35 The studies cited above regarding the restricted nature of perinatal transmission of zidovudine-resistant virus reinforce this point.…”

“…35 In contrast, virus resistant to zidovudine was identified in only 1 of the 4 recipients, suggesting that the resistant variants may have been less well transmitted than wild type. 35 The studies cited above regarding the restricted nature of perinatal transmission of zidovudine-resistant virus reinforce this point.…”

Sexual networks and the transmission of drug-resistant HIV

“…As individuals with ADR harbor a mixture of resistant and wild type viruses, it is possible that wild type viruses are preferentially transmitted, as has been described for zidovudine resistance in both sexual [154] and vertical [155] transmissions. However, in general, transmitted drug-resistant variants do not seem to suffer a 'fitness cost' [156] in terms of replication compared to wild type virus; such variants can persist for many years [32,75,[81][82][83][84][85][86][87][88][89], and individuals with TDR have similar or only slightly lower viral loads to those infected with wild type virus [76,157,158].…”