HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission

Abstract

Background HIV-1 subtype C has emerged as the most prevalent strain of HIV-1 worldwide, leading to speculation that subtype C may be more transmissible than other subtypes. We compared the risk of HIV-1 transmission for subtype C versus non-C subtypes (A, D, G and recombinant forms) among heterosexual African HIV-1 serodiscordant couples. Methods We conducted a nested case-control analysis using data from two prospective cohort studies of heterosexual HIV-1 serodiscordant couples from 6 countries in eastern and southern Africa. Cases (N=121) included incident HIV-1 transmissions that were established as linked within the serodiscordant partnership by viral sequencing; controls (N=501) were non-transmitting HIV-1 infected partners. Subtype was determined for partial env and gag genes. Multiple logistic regression controlled for age and gender of the HIV-1 infected partner and self-reported unprotected sex. Plasma and genital HIV-1 RNA concentrations were compared between subtype C and non-C subtypes using generalized estimating equations. Results HIV-1 subtype C was not associated with increased risk of HIV-1 transmission compared to non-C subtypes: env adjusted odds ratio (adjOR) 1.14 (95% confidence interval [CI] 0.74–1.75, p=0.6) and gag adjOR 0.98 (95% CI 0.63–1.52, p=0.9). Plasma and genital HIV-1 RNA levels did not differ significantly for subtype C versus non-C. Conclusion In a geographically diverse population of heterosexual African HIV-1 serodiscordant couples, subtype C was not associated with greater risk of HIV-1 transmission compared to non-C subtypes, arguing against the hypothesis that subtype C is more transmissible compared to other common subtypes.

Weighing the Evidence of Efficacy of Oral PrEP for HIV Prevention in Women in Southern Africa

“…In Partners PrEP, 24% of HIV-positive partners had a viral load below 2,000 copies/mL at enrollment, 75 similar to other serodiscordant couple studies. 9,66,76 Surreptitious ART use has been noted in previous serodiscordant couple studies, but explains only a fraction (22%-33%) of the low viral loads. 66,77 Accordingly, the low viral load more likely reflects the selection of long-term sexual partners who have not transmitted HIV and who therefore may be less infectious.…”

“…Regarding subtype C, ex vivo studies have shown that subtype C HIV isolates have higher transmission fitness compared to other group M isolates 61 and higher transmission efficiency across the cervical mucosa compared to subtype A isolates, 62 although Kahle et al did not report a difference in sexual transmissibility in subtype C versus nonsubtype C viruses. 66 Given that much of the work comparing sexual transmissibility of different HIV subtypes has been conducted among serodiscordant couples, who differ from the general population in multiple respects as discussed below, it remains an open question whether there are differences in sexual transmissibility of subtype C versus non-subtype C viruses in the general population.…”

In vitro functional assessment of natural HIV-1 group M Vpu sequences using a universal priming approach

“…Given this diversity, it is not surprising that natural (patient-derived) HIV-1 sequences also exhibit differences in their in vitro function, which may in turn influence viral pathogenesis. For example, it has been hypothesized that HIV-1 subtype C isolates, which comprise more than >50% of infections worldwide (Hemelaar, 2012), may be inherently more transmissible - possibly because of subtype-specific motifs within Env-gp120 that modulate interactions with host cell entry receptors (Walter et al, 2009) - though this remains controversial (Kahle et al, 2014). Subtype-specific differences in HIV-1 entry efficiency (Marozsan et al, 2005), replication capacity (Aralaguppe et al, 2016; Konings et al, 2006), and the function of viral accessory proteins Vif (Binka et al, 2012; Iwabu et al, 2010) and Nef (Mann et al, 2013) have also been described.…”

Polyanionic carbosilane dendrimer-conjugated antiviral drugs as efficient microbicides: Recent trends and developments in HIV treatment/therapy

“…CI values b 0.9 123 indicate a synergistic effect, 0.9 b CI b 1.1 indicate additive activity, 124 and CI N 1.1 indicates antagonism. 125 Tenofovir: clinical studies and efficacy as an HIV-1 microbicide 126 TFV is an adenosine NRTI with potent activity against 127 retroviruses, and it inhibits the synthesis of DNA by inserting 128 into propagating viral DNA. 31 Therefore, TFV prevents initial 94 The biological activity has been ascribed to 441 the cluster effects of randomly sulfated cellobiose, with an EC 50 442 of 3.2 μg/ml (Table 2).…”