Abstract
Background
Maintaining viral suppression in the postpartum period is critical for preventing HIV transmission to sexual partners and breastfed infants. Despite systemic viral suppression, genital HIV shedding may still occur in some women. We examined the association between bacterial vaginosis (BV) and sexually transmitted infections (STIs) and genital HIV shedding in postpartum women.
Methods
In this cross-sectional postpartum study, we hypothesised that BV and other genital tract infections would modulate HIV viral load (VL) in the genital tract. Postpartum women with HIV, aged < 25 years and within 3 months of delivery were enrolled at a research facility located in a a high HIV-prevalence area in Durban, South Africa. Using the NucliSENS® EasyQ® HIV-1 v2.0 assay and a modified Abbott Alinity m HIV-1 assay, HIV VLwas quantified in plasma and cervical vaginal lavage respectively. Stored vaginal swabs were tested for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis. BV and other STIs including HSV-2, Syphilis, and HepBsAg, were tested for in real-time.
Results
Of 82 women, 41 (50.6%) tested positive for BV and 22 (27.2%) for any STIat a median timepoint of 6.7 weeks postdelivery (IQR 1.3, 13.7). Fourteen (63.6%) women testing positive for an STI and 31 (75.6%) positive for BV were asymptomatic. Using the the bioMérieux NucliSENS® EasyQ® HIV-1 v2.0 assay with a lower limit of detection (LLOD) of 10 HIV-1 RNA copies/mL, HIV-RNA was quantifiable in plasma of 25 (30.5%) women with a mean (SD) VL of 69 594 (153 330) copies/ml. HIV-RNA was detected in the genital tract of 9 (11%) women with a mean VL of 3503 copies/ml (range 146 –11 504 copies/ml). We observed a strong positive correlation between plasma and GT VL(r = 0.970). Of the 51 participants with undetectable plasma VL, one had a detectable GT VL of 173 copies/ml. None of the predominantly asymptomatic and untreated genital tract infections were associated with genital tract HIV-1 VL.
Conclusions
Despite receipt of ART, a third of women in the early postpartum women were virally unsuppressed, and one in ten women had evidence of viral shedding in the genital tract. There was no evidence of an association between genital tract infections and genital tract viral shedding. Poor adherence to ART and other genital tract factors will need to be explored in larger studies.
Clinical trial number
Not applicable.
Keywords: Postpartum, Sexually transmitted infections, Bacterial vaginosis, HIV-1, Plasma viral load, Cervical plasma viral load
Background
Aligned with the UNAIDS target of 95–95-95 and U = U (undetectable = untransmissible), wider access to effective antiretroviral treatment (ART) is expected to decrease new HIV infections among men and women [1]. Universal ART in pregnant and breastfeeding women is also expected to reduce vertical transmission; however, maintaining viral suppression is key to preventing transmission to a sexual partner and preventing vertical transmission.
ART in the treatment of HIV during pregnancy and its impact on maternal VL and in-utero and intrapartum transmission has been well studied [2]. In addition, the impact of ART on breastfeeding transmission in postpartum women further underscores the importance of maintaining viral suppression throughout pregnancy and breastfeeding [3–5]. While optimal adherence to ART is crucial for inhibiting viral replication and maintaining viral suppression, other factors that modulate viral replication may include host cell membrane damage, immunomodulation, and co-infections transmitted through sexual contact [6, 7].
The effect of uninterrupted ART on viral suppression is primarily reported through the measurement of HIV-1 copies in plasma [8, 9]. Yet, studies have shown that even when the HIV-1 VL is undetectable in plasma (PVL), genital shedding of HIV can still occur, posing a risk for sexual transmission [10]. Although initiatingART typically leads to a rapid decrease in PVL and HIV-RNA shedding in genital secretions, some women on stable ART continue to intermittently exhibit detectable levels of HIV-RNA in cervicovaginal secretions (CVL) [11]. Persistent HIV shedding in genital secretions despite effective ART and undetectable PVL is not fully understood but is likely influenced by local genital factors that promote viral shedding. Conditions in the genital tract (GT) such as genital ulceration, BV, candidiasis, trichomoniasis, herpes simplex virus (HSV-2) and chlamydia influence cervical-vaginal HIV shedding [12–15]. Additionally genital HIV shedding in women on ART may be influenced by menstrual cycles [16] and potential drug-drug interactions with progestin-based contraceptives, which have been associated with an increased risk of HIV shedding and transmission in ART-naive populations [17, 18]. While ART significantly reduces both PVL and HIV genital shedding, PVL and GT VL do not always correlate perfectly, and genital HIV shedding can persist even when systemic viral levels are controlled. The above studies were primarily conducted among non-pregnant women and had implications for the sexual transmission of HIV. We hypothesized that while women in the early postpartum period who initiated ART during pregnancy will be virally suppressed (plasma VL < 10 copies/ml), they will have persistent genital tract viral shedding in the presence of other genital tract infections. This has implications for sexual transmission to HIV uninfected partners in the early postpartum period when women reengage in sexual intercourse after pregnancy.
In this cross-sectional exploratory study of African breastfeeding women who had delivered within the last 3 months in a setting of high burden of HIV and other genital tract infections, we first examined viral suppression in plasma and the genital tract and then explored the impact of GT co-infections on HIV viral suppression in the genital compartment of postpartum women receiving ART.
Methods
Young African women under 25 years old, living with HIV and having delivered within the last three months, were recruited from a postnatal clinic in Umlazi, Durban, between July 2017 and April 2020. This area in South Africa is known for its high HIV prevalence, and young women ( < 25 years) of reproductive age are mostly affected by the HIV epidemic [19]. Eligible participants provided written informed consent for study participation and storage of biological specimens for future research. During the collection of vaginal samples, the research nurse physically examined the participant for symptoms of genital tract infections including abnormal vaginal discharge and genital sores or blisters. Participants who were symptomatic for STIs were treated empirically with single doses of azithromycin (1 g oral dose), ceftriaxone (250 mg intramuscular injection) and metronidazole (2 g oral dose) as per the National Department of Health Guidelines for STI Management [20].
A research nurse collected vaginal swabs, which were transported to a central laboratory for Gram staining and BV diagnosis using Nugent’s criteria (scores: 0–3 negative, 4–6 intermediate, 7–10 positive). Remaining swabs were stored at −70 °C until the end of the cohort study for future testing of other sexually transmitted infections.
In addition, the study nurse collected cervico-vaginal lavage (CVL) samples for HIV-1 viral quantification using a modified plastic bulb pipette, cut below the bulb and attached to a 10 mL syringe. A 5 mL volume of normal saline was drawn into the syringe. After inserting a lubricated, water-warmed speculum into the vagina, the pipette was introduced through the speculum and directed toward the cervical os. Saline was released to bathe the cervix, allowing fluid to pool in the posterior fornix. This fluid was aspirated into the pipette, and the process repeated 2–3 times without adding additional saline. Finally, the aspirated fluid was collected with the pipette and transferred into a sterile 15 mL conical tube. The CVL sample was then transferred to a 15 mL screw-capped centrifuge tube and transported to the CAPRISA laboratory for processing and storage. At the laboratory, the CVL tube was centrifuged at 800 G (approximately 2000 rpm) for 10 minutes. After centrifugation, 500 μL of supernatant was aspirated and transferred into pre-labeled sterile cryovials marked with the participant identification number (PID). This process was repeated until all supernatant was aliquoted, and samples were stored in an ultra-freezer until testing.
Stored vaginal swabs were analyzed for C. trachomatis, N. gonorrhoea, and T. vaginalis using the Roche Light Cycler® 480 and Roche STI kits (Roche Diagnostics, USA). A second swab was tested for HSV-2 with the Roche Light Cycler 480 and HSV-1/2 detection kit. Blood samples were collected for plasma VL quantification, and testing for Hepatitis B surface antigen (HBsAg), and syphilis. The NucliSENS EasyQ® HIV-1 v2.0 assay was used for HIV-1 PVL and has a lower limit of detection (LLOD) of 10 HIV-1 RNA copies/mL. The same sample was tested for HBsAg using the ARCHITECT HBsAg Confirmatory V1 assay and syphilis using the BD Macro-Vue™ RPR Card Test. RPR-positive syphilis samples were confirmed with the TPHA test.
The Abbott Alinity m HIV-1 assay (Abbott Molecular Inc., Des Plaines, IL) was modified in-house to quantify HIV-1 in CVL specimens. This in vitro reverse transcription-polymerase chain reaction (RT-PCR) assay is typically used to quantify HIV-1 in plasma, serum, and dried blood spots (DBS). After modification for CVL specimens, assay performance was verified by diluting previously quantified specimens in phosphate-buffered saline diluent, which was the lavage fluid used for genital fluid collection. The correlation coefficient for specimens was > 0.99, with even scatter on Bland-Altman analysis (mean difference: 0.08 log10 copies/ml, 95% CI: −0.12–0.27 log10 copies/ml). For the dilution series, the correlation coefficient exceeded 0.99, with even scatter on Bland-Altman analysis (mean difference: 0.08 log10 copies/ml, 95% CI: −0.12–0.27 log10 copies/ml). The assay demonstrated acceptable linearity and100% accuracy with this specimen matrix. The lower limit of detection (LLOD) for this inhouse modified assay was set as 42 copies/ml by probit analysis.
In this study we hypothesised that bacterial vaginosis (BV) and other genital tract infections would modulate HIV viral load in the genital tract. Specifically, we postulated that postpartum women who initiated ART during pregnancy would be systemically suppressed (plasma VL < 10 copies/mL) but may exhibit persistent genital tract HIV-1 RNA shedding in the presence of genital tract infections.
Regulatory oversight for the study was provided by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (BE 482/17).
Statistical analysis
Categorical variables were presented as frequencies and percentages. Associations with cervical-vaginal VL (CVL) and plasma VL (PVL) were analyzed using univariate logistic regression models. Odds Ratios (ORs) and 95% confidence intervals (CIs) estimated the relationship between each GTI and CVL or PVL, categorized as detectable (≥42 copies/ml) or undetectable ( < 42 copies/ml). Fisher’s exact test determined significance due to the small sample size and zero counts in some categories. A p-value less than 0.05 was considered statistically significant. We used the Spearmans Ranked correlation analysis to assess the overall relationship between CVL and PVL.
Results
A total of 82 young women living with HIV and with a median age of 22 years (IQR 19, 24) were enrolled in the postpartum period at a median timepoint of 6.7 weeks postdelivery (IQR 1.3, 13.7). Among the 82 postpartum women, 12 (14.6%), 3 (3.7%) and 3 (3.7%) tested positive for the curable STIs; C. trachomatis, T.vaginalis and N.gonorrhoea respectively (Table 1). In addition, 8 (9.8%), 2 (2.4%) and 2 (2.4%) women tested positive for HSV-2, syphilis and HepBsAg respectively. Forty two (51.2%) women tested positive for bacterial vaginosis. Overall, 52 (63.4%) women tested positive for any GTI. Women who tested positive for any GTI were predominantly asymptomatic (53.8%) and did not receive empirical treatment.
Table 1.
Genital tract infections and HIV viral burden
| Variable | WLHIV N = 82 |
|---|---|
| C. trachomatis | |
| Positive | 12 (14.6%) |
| Negative | 70 (85.4%) |
| T. vaginalis | |
| Positive | 3 (3.7%) |
| Negative | 79 (96.3%) |
| N. gonorrhoea | |
| Positive | 3 (3.7%) |
| Negative | 79 (96.3%) |
| HSV-2 | |
| Positive | 8 (9.8%) |
| Negative | 73 (89.0%) |
| Not Done | 1 (1.2%) |
| Syphilis | |
| Positive | 2 (2.4%) |
| Negative | 68 (82.9%) |
| Not Done | 12 (14.6%) |
| HepBsAg | |
| Positive | 2 (2.4%) |
| Negative | 77 (93.9%) |
| Not Done | 3 (3.7%) |
| Bacterial Vaginosis | |
| Positive | 42 (51.2% |
| Negative | 40 (48.8%) |
| Any GTI | |
| Yes | 52 (63.4%) |
| No | 30 (36.6%) |
| Any GTI | |
| Symptomatic/Received Treatment | 21 (40.4%) |
| Asymptomatic/Not treated | 28 (53.8%) |
| Not Assessed | 3 (5.8%) |
| HIV Antiretroviral Treatment | |
| < 3 months | 3 (3.7%) |
| ≥3 months | 72 (87.8%) |
| Date of commencement unknown | 7 (8.5%) |
| Plasma Viral Load | |
| Detectable (≥20 copies/ml) | 25 (30.5%) |
| Undetectable ( < 20 copies/ml) | 53 (64.6%) |
| Not Done | 4 (4.9%) |
| Viral copies/ml Mean (SD) | 69 594 (153 330) |
| CVL Viral Load | |
| Detectable (≥40 copies/ml) | 9 (11.0%) |
| Undetectable ( < 40 copies/ml) | 67 (81.7%) |
| Not Done | 6 (7.3%) |
| Viral Copies/ml Mean (SD) | 2801 (4031) |
At the postpartum visit, all 82 WLHIV were receiving antiretroviral therapy (ART), with 75 women having a documented date of ART initiation. The regimen consisted of a fixed-dose combination tablet containing 300 mg tenofovir-diphosphate (TDF), 200 mg emtricitabine (FTC) and 600 mg efavirenz (EFV).The median (IQR) time on ART was 7.5 months (IQR 6, 12). The majority of women (87.8%) had been on ART for more than three months. HIV-1 RNA was quantifiable in plasma samples from 25 (30.5%) women and CVL samples from 9 (11.0%) women (Table 1).
Of the 82 postpartum women in this study, 76 had HIV-1 VL results of the GT (including four without matching PVL), and 78 had PVL results (including three without matching GT VL). Due to insufficient volumes, viral load was not tested in six CVL and four plasma samples respectively (Table 1). Correlation analysis included 75 women with both plasma and GT VL. Of 24 (32%) women with quantifiable plasma RNA, seven (29.2%) had quantifiable GT RNA. The mean GT viral load in the seven participants was 3503 copies/ml (range: 146– 11,504), while the mean PVL was 156,657 copies/ml (range: 9600– 700,000). Of the 51 participants with undetectable plasma viral load, one had a detectable GT viral load of 173 copies/ml. We observed a moderate positive correlation between plasma and GT VL (r = 0.48) (Fig. 1).
Fig. 1.
Pearson correlation between plasma and genital tract HIV-1 viral load
In Table 2, we explored whether a quantifiable HIV-1 VL (RNA > 42 copies/ml) in the GT was associated with individual STIs, BV, symptomatic and asymptomatic GT co-infections and ART duration. For STIs, women testing positive for C. trachomatis were two times more likely to have a quantifiable VL in the GT (OR 2.11; 95% CI 0.37–11.9), though not statistically significant (p = 0.337). HIV-1 VL in the GT was unquantifiable for all other STIs (Table 2). Testing positive for BV or any GTI was not associated with HIV-1 VL in the GT. Asymptomatic GTIs were not associated with GT VL. Three of 26 (11.5%) women with any GTI and did not receive empirical treatment (asymptomatic)as opposed to 1 of 20 (5.0%) women treated for a GTI had detectable genital VL Of 75 women with a known antiretroviral commencement date, three had less than three months of treatment, and one among these (33.3%) had a quantifiable VL in the GT (OR 0.28; 95% CI 0.02–3.4) and also had a PVL of 56,000 copies/ml.
Table 2.
Impact of genital tract co-infections and duration of antiretroviral treatment on genital tract HIV-1 viral load categorised as detectable (≥42 copies/ml) and undetectable ( < 42 copies/ml)
| Variable | HIV-1 RNA >42 copies/ml N = 9 |
HIV-1 RNA < 42 copies/ml N = 67 |
Odds Ratio (95%CI) | P Value |
|---|---|---|---|---|
| C. trachomatis | ||||
| Positive | 2 (20.0%) | 8 (80.0%) | 2.11 (0.37–11.9) | 0.337 |
| Negative | 7 (10.6%) | 59 (89.9%) | ||
| T. vaginalis | ||||
| Positive | 0 | 3 (100%) | 0.0 | 1.000 |
| Negative | 9 (12.3%) | 64 (87.7%) | ||
| N. gonorrhoea | ||||
| Positive | 0 | 3 (100%) | 0.0 | 1.000 |
| Negative | 9 (12.3%) | 64 (87.7%) | ||
| HSV-2 | ||||
| Positive | 0 | 8 (100%) | 0.0 | 0.585 |
| Negative | 9 (13.2%) | 59 (86.8%) | ||
| Syphilis | ||||
| Positive | 0 | 2 (100%) | 0.0 | 1.000 |
| Negative | 8 (12.5%) | 56 (87.5%) | ||
| Not Done | 1 | 9 | ||
| HepBsAg | ||||
| Positive | 0 | 2 (100%) | 0.0 | 1.000 |
| Negative | 8 (11.0%) | 65 (89.0%) | ||
| Bacterial Vaginosis | ||||
| Positive | 4 (10.3%) | 35 (89.7%) | 0.73 (0.18–2.96) | 0.733 |
| Negative | 5 (13.5%) | 32 (86.5%) | ||
| Any GTI | ||||
| Yes | 5 (10.2%) | 44 (89.8%) | 0.95 (0.79–1.13) | 0.399 |
| No | 4 (14.8%) | 23 (85.2%) | ||
| Any GTI | ||||
| Symptomatic (Treated) | 1 (5.0%) | 19 (95.0%) | 0.40 (0.04–4.2) | 0.621 |
| Asymptomatic (Not treated) | 3 (11.5%) | 23 (88.5%) | ||
| Missing data | 1 | 2 | ||
| HIV Antiretroviral Treatment | ||||
| < 3 months | 1 (33.3%) | 2 (66.7%) | 0.28 (0.02–3.4) | 0.347 |
| ≥3 months | 8 (12.1%) | 58 (87.9%) | ||
| Missing data | 0 | 7 |
In Table 3, we further examined whether a quantifiable HIV-1 VL(defined as RNA > 42 copies/mL) in plasma was associated with genital tract (GT) co-infections and duration of antiretroviral (ARV) treatment. Women who tested positive for N. gonorrhoeae and Hepatitis B were more likely to have quantifiable plasma VL (PVL), however due to the small numbers these associations were not statistically significant (Table 3). While PVL was quantifiable in two of the three women who initiated ART less than three months ago, notably, 22 (32.3%) women who were on ART for longer than three months also had a quantifiable PVL.
Table 3.
Impact of genital tract co-infections and duration of antiretroviral treatment on plasma HIV-1 viral load categorised as detectable (≥42 copies/ml) and undetectable ( < 42 copies/ml)
| Variable | HIV-1 RNA >42 copies/ml N = 25 |
HIV-1 RNA < 42 copies/ml N = 53 |
Odds Ratio (95%CI) | P Value |
|---|---|---|---|---|
| C. trachomatis | ||||
| Positive | 5 (41.7%) | 7 (58.3%) | 1.64 (0.47–5.81) | 0.507 |
| Negative | 20 (30.3%) | 46 (69.7%) | ||
| T. vaginalis | ||||
| Positive | 1 (33.3%) | 2 (66.7%) | 1.06 (0.09–12.3) | 1.000 |
| Negative | 24 (32.0%) | 51 (68.0%) | ||
| N. gonorrhoea | ||||
| Positive | 2 (66.7%) | 1 (33.3%) | 4.52 (0.39–52.41) | 0.239 |
| Negative | 23 (30.7%) | 52 (69.3%) | ||
| HSV-2 | ||||
| Positive | 1 (12.5%) | 7 (87.5%) | 0.27 (0.03–2.36) | 0.425 |
| Negative | 24 (34.3%) | 46 (65.7%) | ||
| Syphilis | ||||
| Positive | 0 | 2 (100%) | 0.0 | 0.540 |
| Negative | 24 (35.8%) | 43 (64.2%) | ||
| Not Done | 1 | 8 | ||
| HepBsAg | ||||
| Positive | 1 (50.0%) | 1 (50.0%) | 2.17 (0.13–36.12) | 0.541 |
| Negative | 24 (31.6%) | 52 (68.4%) | ||
| Bacterial Vaginosis | ||||
| Positive | 10 (24.4%) | 31 (75.6%) | 0.47 (0.18–1.25) | 0.150 |
| Negative | 15 (40.5%) | 22 (59.5%) | ||
| Any GTI | ||||
| Yes | 15 (29.4%) | 36 (70.6%) | 0.71 (0.26–1.90) | 0.611 |
| No | 10 (37.0%) | 17 (63.0%) | ||
| Any GTI | ||||
| Symptomatic (Treated) | 5 (23.8%) | 16 (76.2%) | 0.74 (0.20–2.72) | 0.750 |
| Asymptomatic (Not treated) | 8 (29.6%) | 19 (70.4%) | ||
| Missing data | 2 | 1 | ||
| HIV Antiretroviral Treatment | ||||
| < 3 months | 2 (66.7%) | 1 (33.3%) | 0.24 (0.02–2.78) | 0.262 |
| ≥3 months | 22 (32.3%) | 46 (67.7%) | ||
| Missing data | 1 | 6 |
Discussion
In this cross-sectional exploratory study of 82 young postpartum women living with HIV and with a high prevalence of genital co-infections (63.4%), HIV-RNA was quantifiable in the plasma of 25 (30.5%) women and the genital tract of 9 (11.0%) women within the first 3 months post-delivery. We observed a strong positive correlation between plasma and genital tract VL. None of the predominantly asymptomatic and untreated genital tract infections were associated with genital tract HIV-1 shedding.
The lack of association between GTIs and HIV viral shedding in the genital tract in our study is not consistent with several early studies that have demonstrated a correlation between the presence of GTIs and increased HIV shedding in the genital compartment, emphasizing the role of co-infections in modulating HIV transmission risk [21]. It must be noted that most of these early studies were in ART naïve populations, while all of our study participants had initiated ART prior to the postpartum visit. However, a cross-sectional study of 128 non-pregnant women living with HIV and receiving ART in Zambia revealed a very high prevalence of BV, and yet it was not BV but a high plasma VL that significantly predicted genital HIV shedding [22]. Our study demonstrated a moderate positive correlation between genital tract VL and plasma VL. HIV-1 RNA was quantifiable in plasma samples from a third of the women and CVL samples from one in ten women despite initiating ART during pregnancy. Other studies have also reported an inconsistent change in viral load in these compartments after changing ART treatment regimens [23, 24].
Although we were unable to correlate the presence of GTIs and plasma or genital tract VL, the high rate of viral non-suppression in this early postpartum period is worrying and has implications for early breastfeeding transmission. The high proportion of postpartum women in our study who were not virally suppressed is consistent with other studies in South Africa. In a large cohort of an estimated 5000 PLWLH in the Gauteng province in South Africa, the authors underscored the lack of compliance in VL testing during pregnancy and postpartum as per national guidelines. Only 12% of this cohort were tested postnatally, and moreover a third among these who had a VL test were not virally suppressed [25]. Using a larger synthetic cohort in South Africa the authors further highlight the astoundingly high proportion of pregnant and postpartum women who are not virally suppressed [26]. The risk for breastfeeding transmission remains high among women who are not virally suppressed ( > 1000 copies/ml) and even among women with a low but detectable plasma VL (40–1000 copies/ml), as demonstrated in a cross-sectional nested study of the Malawian PMTCT Evaluation program [27].
The lack of association between GTIs and genital tract VL in our study could be due to certain GTIs may induce immune responses that do not significantly enhance HIV replication or shedding. For instance, some pathogens might trigger anti-inflammatory pathways or fail to elicit a strong inflammatory response, thereby not creating an environment conducive to increased HIV shedding [28]. Other reasons for the lack of association between GTIs and genital VL in our study could be that HIV-RNA was measured only from the cell-free component of cervicovaginal secretions. If we had measured both HIV complementary DNA and RNA, the results could have been different [29].
Bull et al. (2020) observed that HIV-RNA could still be detected in genital secretions despite plasma viral suppression, with genital co-infections and inflammation identified as significant contributors to this discordance [28]. In our study, only one participant was reported with an undetectable plasma VL and a detectable VL in the genital tract, albeit a low VL. Fiore et al. (2003) reported genital shedding of HIV in 25% of women with undetectable plasma viral loads, suggesting that ART does not uniformly suppress viral replication in all compartments and is less efficacious in reducing genital and rectal viral loads [10]. Moreover, the pharmacokinetics of antiretroviral drugs differ between systemic and genital compartments, with some drugs achieving suboptimal concentrations in genital secretions, potentially permitting localized viral replication [7, 30–35]. In our study, participants received antiretroviral therapy as a fixed-dose combination tablet comprising tenofovir disoproxil fumarate, emtricitabine and efavirenz. Existing literature indicates that these agents show variable penetration into the female genital tract. TDF Shows high concentrations in cervicovaginal secretions, particularly active in mucosal tissues [36], which is why it’s also used in topical PrEP. Emtricitabine (FTC) also achieves good penetration into the genital tract [37], reaches comparable levels as TDF in genital and systemic compartments whilst Efavirenz (EFV) has limited penetration into cervicovaginal fluid [38, 39], this may contribute to suboptimal suppression of local HIV replication, despite systemic suppression. Given that EFV has poor mucosal penetration, it is plausible that this pharmacokinetic limitation could be associated with the persistent genital HIV shedding observed in a subset of participants—even those on ART for over three months. While TDF and FTC likely achieved adequate levels, EFV’s low mucosal penetration could allow compartmentalized viral persistence.
Limitations
Our study has several limitations. This being an exploratory study the small sample size may have limited our ability to detect statistically significant correlations between genital tract infections and genital tract viral shedding. We did not evaluate all genital tract infections such as candidiasis, mycoplasma etc [40] and we could not assess adherence to ART in this cross-sectional evaluation. Lastly, since the study population was restricted to young women < 25 years, may further limit the generalizability of our findings to all postpartum population.
Conclusion
While we were unable to confirm an association between GTIs and genital VL, our study revealed a high proportion of breastfeeding women who were not virally suppressed in the early postpartum period despite initiating ART during pregnancy. We have also provided novel evidence of HIV-1 viral shedding in the genital tract in this early postpartum period. Our findings have important implications for preventing sexual and early breastfeeding transmission among postpartum women and therefore underscore the need for continued VL monitoring in postpartum women to be able to support adherence to ART during this vulnerable period.
Acknowledgements
Research Assistant, Research Nurses and Laboratory technicians, Study Clinician, Global Neuberg Laboratory, CAPRISA Laboratory and NHLS Laboratory, Department of Virology.
Abbreviations
- WLHIV
Women living with HIV
- STI
Sexually transmitted infections
- PVL
Plasma viral load
- CVL
Cervical viral load
- PCR
Polymerase chain reaction
- GTI
Genital tract infections
- CT
Chlamydia trachomatis
- TV
Trichomonas vaginalis
- NG
Neisseria gonorrhoeae
- BV
Bacterial vaginosis
- PVL
Plasma viral load
- OR
Odds ratio
- CI
Confidence interval
Author contributions
VG and DM conceptualized this study and drafted the manuscript. KG validated the laboratory testing of CVL for HIV.
Funding
Funding for STI testing was received from University of KwaZulu Natal.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Eligible women provided written informed consent to participate in the study and store biological specimens for future research, as approved by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BE 194/18) and in keeping with SA GCP guidelines and the declaration of Helsinki 2013.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.