AIDS Research and Treatment Table 1 (a) Potential ﬁrst- and second-line NRTI backbones for HIV-2 and dual infection First-line Second-line AZT/3TC TDF/AZT/3TC or FTC TDF/FTC or 3TC∗ TDF/AZT/3TC or FTC ABC/3TC TDF/AZT/3TC or FTC ∗ FTC and 3TC are assumed to be essentially equivalent in the table, despite FTC’s possible superiority and 3TC’s possibly lower cost. (b) Potential ﬁrst- and second-line PIs for HIV-2 and dual infection Table 2: Representative daily costs of selected antiretrovirals in West Africa in 2010 [74]. All values represent amounts paid since 01/01/2010 in West Africa except where otherwise noted, in which case the nearest equivalent in terms of year of purchase and income was used. First-line LPV/r SQV/r IDV/r Drug AZT/3TC d4T/3TC ABC/3TC 3TC TDF TDF/FTC LPV/r IDV SQV DRV ddI (400 mg buﬀered) Second-line SQV/r or DRV/r LPV/r or DRV/r LPV/r or SQV/r or DRV/r Cost per daya $0.28–$0.36 $0.12 $1.38b $0.79 $0.08–$0.10 $0.72c $0.87–$0.88c $1.24–$1.56d $0.96d $7.20e $22.12–$28.40f $0.22–$0.96d Ritonavir (100 mg bd) a Costs are given in US dollars for standard doses given twice daily or daily in the case of TDF, ddI, ABC/3TC, and TDF/FTC bDominican Republic; 2008 cRepublic of South Africa, Somalia d2009 eEgypt f Bulgaria, Jamaica; 2009. HIV therapy. Enfurvitide (T20), a fusion inhibitor currently licensed for use in HIV-1, has been found to have no activity against HIV-2 [8] which is not surprising given that HIV-1 and HIV-2 only share an amino acid sequence similarity of less than 30%–40% in the Env protein [80]. Maraviroc, a coreceptor binding inhibitor, works by blocking the CCR5 receptor, thereby inhibiting the virus from further conformational changes that will allow fusion with the host membrane. The activity of maraviroc against HIV-2 has not been formally tested, but since this drug binds to the CCR5 receptor, it should work against R5-tropic HIV- 2 viruses [81, 82]. A recent case report demonstrates the 5 inclusion of maraviroc in a regime used successfully to control resistant HIV-2 infection [83]. However, the ability of HIV-2 eﬃciently to utilize other coreceptors may limit the eﬀectiveness of these antagonists in HIV-2 treatment [84]. Another potential concern is the switch or emergence of X4-tropic viruses, which is associated with faster disease progression [84]. Although R5 to X4 switch has only been reported in a few HIV-2-infected individuals [85], a limited number of X4-tropic viruses have been isolated from symptomatic patients [80]. Integrase inhibitors (INIs) work by interfering with the insertion of HIV DNA into host DNA and raltegravir (RAL), the ﬁrst licensed INI for HIV-1 therapy, appears to be safe and eﬃcacious in both ART na¨ıve [86] and ART- experienced patients [87]. Despite the 40% heterogeneity in HIV-1 and HIV-2 integrase genes, the functionally important motifs (the catalytic triad DDE, the HHCC, and RKK) are 100% conserved in HIV-1 and HIV-2 [88, 89]. In vitro susceptibility of 14 clinical HIV-2 isolates, as well as HIV-2 ROD, to RAL, has showed similar activity for HIV-1 and HIV-2 [88]. In vivo studies on highly treatment-experienced HIV-2-infected individuals, two with group A [88, 90] and one with group B [91], showed promising results, with viral loads reduced to undetectable results, when RAL was used in combination therapy. HIV-2 resistance to RAL in vivo occurs via the N155H mutation [91] which is also associated with phenotypic resistance against RAL in HIV-2 [92]. However, these HIV-2 N155H mutants, like the M184V mutation in the reverse transcriptase, are much less ﬁt than the wild type [75, 92]. This loss in replicative capacity can be exploited when viral suppression is no longer a realistic goal of therapy, and maintaining these mutations through continued selective pressure can slow disease progression. 3. Special Circumstances 3.1. Pregnancy. While the risk of HIV-2 transmission in pregnancy only reaches about 4% (including breast milk transmission) [93], clinical and in vitro data would suggest that AZT monotherapy as part of a prevention of mother to child transmission program poses a considerable threat to the mother, and to the child in the event of infection, of selecting for the Q151M mutation with subsequent pan- NRTI resistance [36]. Boosted PI-based ART through the latter two trimesters of pregnancy and the breastfeeding period should be the mainstay of vertical transmission prevention; however boosted PIs may result in greater nausea or insulin resistance in a small number of patients [94]. Dosing of PIs in pregnancy is not well validated, with evidence of reduced plasma concentrations with several agents, especially when used unboosted [95, 96]. Recent ﬁndings suggest that in the absence of TDM, LPV/r dose should be increased 50% in the second and third trimesters of pregnancy [97]. SQV/r is probably eﬀective at its standard dose of 1000/100 mg twice daily [98, 99] and IDV/r at its standard dose of 800/100 mg twice daily may be adequate, but further clariﬁcation is required [100]. As with HIV-1, concerns exist about the use of TDF as part of the nucle- oside backbone during pregnancy potentially interfering