2.2 Hepatitis

B). 2B 4.2 We recommend patients presenting with an AIDS-defining infection, or with a serious bacterial infection and a CD4 cell count <200 cells/μL, start ART within 2 weeks of initiation of specific antimicrobial chemotherapy. 1B 4.3 We recommend patients presenting with primary HIV infection (PHI) and meeting any one of the following criteria start ART:   • Neurological involvement. 1D • Any AIDS-defining illness. 1A • Confirmed CD4 cell count <350 cells/μL. 1C 4.4 We recommend the evidence that treatment with ART lowers the risk of transmission is discussed with all patients, and an assessment of the current risk of transmission to others is made at the time of this discussion. GPP   We recommend following discussion, if a patient with a CD4 cell INK 128 manufacturer count >350 cells/μL wishes to start ART to reduce the risk of transmission selleckchem to partners, this decision is respected and ART is started. GPP a Abacavir is contraindicated if HLA-B*57:01 positive. 5.3 We recommend therapy-naïve patients start combination ART containing tenofovir (TDF) and emtricitabine (FTC) as the NRTI backbone. 1A   We suggest abacavir (ABC) and lamivudine

(3TC) is an acceptable alternative NRTI backbone in therapy-naïve patients who, before starting ART, have baseline viral load (VL) of ≤100 000 copies/mL. 2A   ABC must not be used in patients who are HLA-B*57:01 positive. 1A 5.4 We recommend therapy-naïve patients start combination ART containing one of the following as the third agent: atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), efavirenz (EFV) or raltegravir (RAL). mafosfamide 1A   We suggest that in therapy-naïve patients lopinavir/ritonavir (LPV/r) and fosamprenavir/ritonavir (FPV/r) are acceptable alternative PIs, and nevirapine (NVP) and rilpivirine

(RPV) are acceptable alternative NNRTIs. 2A 5.5 We recommend against the use of PI monotherapy as initial therapy for treatment-naïve patients. 1C   We recommend against the use of PI-based dual ART with a single NRTI, NNRTI, C–C chemokine receptor type 5 (CCR5) receptor antagonist or INI as initial therapy for treatment-naïve patients. 1C 6.1.1 We recommend adherence and potential barriers to it are assessed and discussed with the patient whenever ART is prescribed or dispensed. GPP   We recommend adherence support should address both perceptual barriers (e.g. beliefs and preferences) and/or practical barriers (e.g. limitations in capacity and resources) to adherence. GPP 6.2.1 We recommend that potential adverse pharmacokinetic interactions between ARV drugs and other concomitant medications are checked before administration (with tools such as http://www.hiv-druginteractions.org). GPP 6.2.2 We recommend against the unselected use of therapeutic drug monitoring (TDM). GPP 6.2.

WHO HIV treatment guidelines now recommend initiating ART when the CD4 count declines to <350 cells/μL instead of <200 cells/μL [23]. Initiation of antiretrovirals at this higher CD4 cell count threshold

is associated with a reduced risk of progression to AIDS or death [37], an improved chance of immune restoration [38], and a lower risk of developing antiretroviral-related toxicities [39] and antiretroviral resistance [40] compared with initiation of antiretrovirals at a CD4 count <200 cells/μL. In resource-limited selleckchem settings where nevirapine is widely used, there has been concern that these benefits may be offset by increased nevirapine-associated hepatotoxicity, especially among women with CD4 counts between 250 and 350 cells/μL. Access to alternative antiretrovirals such as efavirenz or protease inhibitors may be limited because of their potential teratogenicity risks and high cost. Our data support the expansion of nevirapine-based ART to women with a CD4 count <350 cells/μL. Although serious nevirapine-associated hepatotoxicity occurred among women in these resource-limited

settings, the rate of nevirapine-associated hepatotoxicity was low (3–5%). Further, the risk was not uniquely greater for women with higher baseline CD4 counts; women with the lowest CD4 counts (<50 cells/μL) PI3K inhibitor were at similar risk for rash-associated hepatotoxicity to women with high CD4 counts (≥200 cells/μL). Our data also suggest that early transaminase monitoring (baseline and weeks 2 and 4) identifies the majority of women experiencing nevirapine-associated hepatotoxicity. Initiating HIV-infected women with CD4 counts ≥250 cells/μL on an efavirenz-based regimen for at least 6 months and then changing to nevirapine does not appear to lead to a spike in hepatotoxicity or rash when patients are changed to nevirapine, despite CD4 counts that exceed 250 cells/μL Mannose-binding protein-associated serine protease [41–43]. This strategy is an alternative method to minimize the risk of both

hepatotoxicity and teratogenicity. Hepatotoxicity may not occur under these circumstances because nevirapine is introduced after the initial rapid immune recovery on ART has occurred. There were several limitations to our study. First, all of the participants in this study were women and therefore the findings cannot necessarily be extrapolated to men in these settings. However, the issue of nevirapine use and hepatotoxicity might be more relevant to women in resource-limited settings than men. Women who are pregnant or may become pregnant cannot use nevirapine’s alternative, efavirenz, because of that agent’s teratogenic potential. Secondly, rash may have been more difficult to diagnose in participants with dark skin.