6 AIDS Research and Treatment with bone mineralization, although it has not as yet been associated with congenital abnormalities [101]. their antiretroviral regimen being appropriate for HIV-2 as described above for adults. 3.2. Tuberculosis (TB) Coinfection. TB is endemic in West Africa, and the problematic drug interactions between PIs and rifampin are well known, with induction of the cytochrome P450 system by rifampin resulting in accelerated metabolism of PIs, making eﬀective dosing of the PIs more diﬃcult to achieve. Provision of rifabutin as part of TB therapy for HIV-2 co-infected patients would therefore be ideal, allowing for the more predictable pharmacokinetic interactions between LPV/r and rifabutin. However TB treat- ment protocols, particularly where TB and HIV treatments are managed by diﬀerent health care providers, might not adopt rifabutin as a result of cost or other considerations. In this case, where ART cannot be safely deferred, a PI- sparing regimen may represent the best balance of safety and eﬃcacy for HIV-2/TB co-infected patients. Increasing the PI dose, for example doubling the dose of LPV/r, may be an alternative, although achieving therapeutic drug levels with tolerable dosing of LPV/r appears challenging [102, 103]. If a triple or quadruple NRTI regime is used, ART should be reassessed once TB treatment is completed and the patient switched to a boosted-PI regimen. 3.3. Chronic Hepatitis B (HBV) Co-Infection. Chronic HBV infection is common in West Africa, with prevalence rates of 8%–20% [104–106]; as a consequence many individuals infected with HIV-2 can be expected to have chronic HBV co- infection and a substantial proportion is likely to have high HBV viremia. Unlike the epidemiology in Western countries, most HBV transmission occurs between children and is not due to shared risk factors for transmission as between sexually active or intravenous drug using adults [107]. Screening protocols for comorbidities in HIV care settings in HBV endemic countries should include HBsAg, either for all new patients or at a minimum for those with evidence of liver disease, such as transaminitis. Where chronic HBV is present, ideally TDF/FTC or TDF/3TC should be in the ﬁrst-line ART regimen [108], although this recommendation may be diﬃcult to follow where HBV diagnostics are limited. Moreover it introduces another layer of complexity into protocol-based sequential ART. Clearly these issues would be addressed if TDF/FTC (or 3TC) were adopted as the preferred NRTI backbone, although it may be necessary to maintain them in succeeding regimens, regardless of the addition of other agents, to avoid the risk of HBV “ﬂare” arising with their discontinuation [109]. 3.4. Childhood. Children with HIV-2 infection present many of the same challenges as those with HIV-1 infection, such as concerns about dosing, formulations, and speciﬁcally TDF toxicity [110]. The principal diﬀerences, that vertical HIV-2 transmission is distinctly less common and that it is not rare for perinatal HIV-2 infections to present in teenagers, do not argue for any speciﬁc diﬀerences in their management compared to children with HIV-1, beyond 4. Operational Issues Endemic HIV-2 brings with it complications in terms of program management in West Africa beyond the necessary alterations in the antiretroviral therapy protocols, speciﬁcally that it complicates HIV testing and management of both stocks and staﬀ. 4.1. Diagnosis. Testing to distinguish HIV-1 from HIV-2 and dual infection can be complicated and expensive due to the presence of cross-reactive antibodies and strain diﬀerences [111, 112]. Screening tests need high sensitivity for HIV- 2, while conﬁrmatory testing may require multiple steps in order to reliably distinguish between HIV-1, HIV-2, and HIV-1/HIV-2 dual infection, detailed review of which is beyond the scope of this paper. The alternative to these more demanding and elaborate testing protocols is misdiagnosis, primarily over-diagnosis of HIV-1/HIV-2 dual infection, resulting in HIV-1 monoinfected people going onto more expensive and cumbersome PI regimens. Diagnostic clarity therefore is a trade-oﬀ between higher upfront costs in testing and savings over the longer term in pharmaceuticals, although no rigorous analysis of costs has yet been made in this context. Misdiagnosis that results in HIV-2 and dually infected patients going on treatment that ignores their HIV-2 carries a greater risk, as discussed earlier. 4.2. When to Start. Compared with HIV-1, more patients with HIV-2 will be long-term nonprogressors or slow progressors. Although this could be used to argue for a later CD4-driven initiation of ART, it has been demonstrated that immunological recovery on ART is worse in HIV-2 com- pared with HIV-1 [113] and excessive delay in initiating ART may carry long-term negative immunological consequences. While the authors support initiating treatment for HIV-2 below a CD4 count of 350/mm3 or possibly higher, instead of below 200/mm3, it may be operationally awkward to apply diﬀerent CD4 cut-oﬀs for starting ART in HIV-1 and HIV-2 where CD4-driven initiation of therapy has not yet advanced to the earlier thresholds. 4.3. Monitoring. There is little evidence to suggest that monitoring of patients on ART should be any diﬀerent for HIV-2 than for HIV-1. In practice the lack of a commercially available viral load assay [114] makes viral load measurements harder to obtain for HIV-2. CD4 recovery has been found to be blunted in HIV-2 [113]; combined with the more limited treatment options for HIV-2 this argues against considering a lack of substantial CD4 gains on ART to be a failure. Other immunologic criteria, including a drop from peak or a return to baseline CD4, may not be any worse for monitoring response to treatment in HIV-2 than in HIV-1. 4.4. Stock Management. In terms of stock management, the more complicated the program, the more diﬃcult it