Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG.

The magnitude of the HIV-1 epidemic in Nigeria is second only to the subtype C epidemic in South Africa, yet the subtypes prevalent in Nigeria require further characterization. A panel of 50 subtype G and 18 CRF02_AG Nigerian HIV-1 pseudoviruses (PSV) was developed and envelope coreceptor usage, neutralization sensitivity and cross-clade reactivity were characterized. These PSV were neutralized by some antibodies targeting major neutralizing determinants, but potentially important differences were observed in specific sensitivities (eg. to sCD4, MPER and V2/V3 monoclonal antibodies), as well as in properties such as variable loop lengths, number of potential N-linked glycans and charge, demonstrating distinct antigenic characteristics of CRF02_AG and subtype G. There was preferential neutralization of the matched CRF/subtype when PSV from subtype G or CRF02_AG were tested using pooled plasma. These novel Nigerian PSV will be useful to study HIV-1 CRF- or subtype-specific humoral immune responses for subtype G and CRF02_AG.

Prevalence of Mycoplasma genitalium Infection and Macrolide and Fluoroquinolone Resistance Mutations Among US Air Force Service Members With HIV, 2016-2020.

Background: Mycoplasma genitalium (MG) infection is a public health concern due to antimicrobial resistance (AMR). Data are limited on repeat MG infection and AMR among US Air Force service members with HIV. Methods: US Air Force service members seeking HIV care were screened for MG infection during the surveillance period (16 May 2016-16 March 2020). Baseline and repeat MG prevalence rates were estimated. An extended Cox proportional hazards regression model evaluated characteristics associated with repeat MG infection. MG-positive rectal samples were tested for macrolide or fluoroquinolone resistance. Results: Among 299 male patients from a total of 308 patients followed during the surveillance period, baseline prevalence of MG infection was 19.7% (n = 59); among the 101 patients who screened positive for MG at any time during the surveillance period, repeat MG was 35% (n = 36). Characteristics independently associated with increased risk of repeat infection were sexually transmitted infection history vs none (adjusted hazard ratio [aHR], 2.33; 95% CI, 1.26-4.31), a sexually transmitted infection coinfection vs no positive test result in the medical records (aHR, 5.13; 95% CI, 2.78-9.49), and a new HIV diagnosis (<1 vs ≥1 year; aHR, 2.63; 95% CI, 1.45-3.73). AMR in MG-positive rectal specimens was 88% (43/49) indicating macrolide resistance, 18% (10/56) quinolone resistance, and 18% (10/56) both. Conclusions: Macrolide and fluoroquinolone resistance mutations were common. Testing for co-occurring MG infection and AMR mutations may be warranted in guiding treatment for sexually transmitted infections such as chlamydia or gonorrhea detected at HIV diagnosis.

A remarkable genetic shift in a transmitted/founder virus broadens antibody responses against HIV-1.

A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists. An in-depth study of escape variants emerging under host immune pressure during very early stages of infection might provide insights into such a HIV-1 vaccine design. Here, in a rare longitudinal study involving HIV-1 infected individuals just days after infection in the absence of antiretroviral therapy, we discovered a remarkable genetic shift that resulted in near complete disappearance of the original T/F virus and appearance of a variant with H173Y mutation in the variable V2 domain of the HIV-1 envelope protein. This coincided with the disappearance of the first wave of strictly H173-specific antibodies and emergence of a second wave of Y173-specific antibodies with increased breadth. Structural analyses indicated conformational dynamism of the envelope protein which likely allowed selection of escape variants with a conformational switch in the V2 domain from an α-helix (H173) to a ß-strand (Y173) and induction of broadly reactive antibody responses. This differential breadth due to a single mutational change was also recapitulated in a mouse model. Rationally designed combinatorial libraries containing 54 conformational variants of V2 domain around position 173 further demonstrated increased breadth of antibody responses elicited to diverse HIV-1 envelope proteins. These results offer new insights into designing broadly effective HIV-1 vaccines.